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Q: Testing if the volatility of single stocks and/or indices have risen in the past I'm currently writing my bachelor thesis and the main goal of my paper is to test if the volatility of single stocks and indices have risen in the past. My data consists of all stocks of the SMI and the DAX. In total, I have 50 stocks with monthly volatility data tested between 2005-2015. So, I have 50 $\times$ 12 $\times$ 10 = 6000 data points. Now I've heard of the time series analysis, ARCH, GARCH(1.1) and GARCH(1.2). I have read a bit about those models, but until now, I have only had 2 statistics courses and 1 econometrics course. And with the knowledge I have at the moment, I cannot understand which model would suit the best and/or is the simplest to model in R/Stata. I've read that the models ARCH/GARCH are good to model volatility, but it is not the tool to test my hypothesis. Also I've read that those models are mainly to predict future volatility, but my goal is to analyse past volatility, do I still choose ARCH/GARCH? So my questions are: Which model should I use for this kind of hypothesis (hypothesis: Has the volatility of the financial market represented through the SMI and DAX indices risen significantly in the past?) If I'd use a time series model like ARCH/GARCH, how do I test my hypothesis? A: You don't need a model to show that volatilities are changing. Simply show the time series of squared returns, you'll be able to spot the clusters of high and low volatilities easily. If you want to fit a model, then GARCH(1,1) will do. GARCH is usually not an undergrad topic, by the way, so you can do simpler analysis and get away with it. UPDATE: The simple analysis would be plots and trivial regressions. For instance, plot the squared return (y-axis) against their lagged values (x-axis). This was the GARCH idea to start with. If you see the significant slope, then you can claim autocorelation of returns, i.e. if the stocks were moving a lot recently then they're likely to be moving a lot in near future. That's volatility clustering in its simplest form UPDATE 2: I decided to write your thesis. I got SPX Index prices from Bloomberg: You can't see much from prices, so we get the daily returns: It turns out that the returns are not very infomative either, so let's look at the squared returns: Bingo! There's clearly volatility clustering in effect. So, let's scatter the squared return against itself one day ago: We can now fit the simple regression: $$r_t^2=\beta_0+\beta_1r_{t-1}^2+e_t$$ Here are the results. Note that the slope is significant, so you can claim that you tested the volatility changes. SUMMARY OUTPUT Regression Statistics Multiple R 0.305793227 R Square 0.093509498 Adjusted R Square 0.091085726 Standard Error 0.000175742 Observations 376 ANOVA df SS MS F Significance F Regression 1 1.19156E-06 1.19156E-06 38.58016389 1.4001E-09 Residual 374 1.15511E-05 3.08853E-08 Total 375 1.27427E-05 Coefficients Standard Error t Stat P-value Lower 95% Upper 95% Lower 95.0% Upper 95.0% Intercept 6.72079E-05 1.02634E-05 6.548334991 1.92453E-10 4.70268E-05 8.73891E-05 4.70268E-05 8.73891E-05 X Variable 1 0.305193577 0.049135271 6.211293254 1.4001E-09 0.208577558 0.401809596 0.208577558 0.401809596 You could also show the simple correlation of lagged squared returns: Correlation: Column 1 Column 2 Column 1 1 Column 2 0.305793227 1 Now, all you need is to get a few gallons of water to fill in the space between the Title and the bibliography of the thesis. Don't forget: this is bachelor level work :) A: ARCH/GARCH models are appropriate if there is autoregressive conditional heteroskedasticity in the data. So if there is, and if you also know the shape of change in volatility you want to test for, you may include corresponding terms as extra regressors in the conditional variance equation, something like $$ \sigma^2_t=\omega+\alpha_1 e^2_{t-1}+\beta_1\sigma^2_{t-1}+\gamma x_t. $$ For example, you could include a linear time trend $x=(1,2,\dots)$ if you want to test for a constant increase in volatility over time; or a level-shift variable with zeros followed by unities after the suspected change point, $x=(0,\dots,0,1,\dots,1)$, if you want to test for an abrupt jump. Then you may test the significance of those regressors ($\text{H}_0\colon \, \gamma=0$) and this way test for the rise in volatility. | Mid | [
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Bluesband® Harmonica $8 Packed with all the pathos required to play the blues in the key of C, Hohner's diatonic harmonicas set the industry standard. A maker of premier musical instruments since 1857, Hohner harmonicas offer quality construction, excellent response and unsurpassed tone. | High | [
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Q: Windows 10 and new hardware I recently upgraded my computer to Windows 10 from Windows 7. I am now thinking about installing a new motherboard and processor. Will this require me to purchase a new version of Windows, or will I be able to run my current installation with the new hardware? A: To avoid potential problems, you should format your computer and do a fresh clean install. Windows You might like the new hardware, or may not, but probably "be aware" of changing hardware and some messages ... The fact is that I have not tried it, but do not expect anything good. I'll say again, format the hard drive and do a clean install, you will save headaches. [EDIT] From infopackets.com Rumor has it that in order to do a clean install -and- retain your free license to Windows 10, you must first install Windows 10 using an in-place upgrade; this is done from within an existing Windows desktop environment via "Get Windows 10 app". After that, you can then do a clean install using a Windows 10 DVD as many times as you want. The license for Windows 10 will be valid for the life of the device, and any subsequent clean installs will automatically register with Microsoft without requiring you to enter a serial number ever again. The free Windows 10 license is valid providing that you don't make any major hardware changes (such as a new motherboard, which technically constitutes a new computer). A new hard drive, for example, is not a major hardware change. Therefore the free Windows 10 license is tied to specific hardware (such as motherboard, CPU, RAM, etc). So, no, you lose your "free" license with a major upgrade like the one you asking... | Mid | [
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Handball at the 1990 Asian Games – Men Men's handball at the 1990 Asian Games was held in Beijiao Gymnasium, Beijing from 27 September to 5 October 1990. Results Final standing References Results External links Olympic Council of Asia Men | Low | [
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1. Introduction {#sec1} =============== Cochlear implant (CI) is the primary method to restore hearing in patients with severe sensorineural hearing loss. In China, increasing number of patients achieve satisfactory hearing restoration and speech and spoken language skills through CI surgery. Experience and studies show that strict and comprehensive candidate selection, improved surgical skills, effective rehabilitation training and post-implantation psychotherapy are important for the success of CI. Contraindications to cochlear implantation may include a defect of the auditory nerve, and deafness caused by a severe cochlear malformation, although some cases of inner ear anomalies can achieve satisfactory outcomes. To ensure the success of CI surgery, complete preoperative evaluation should include imaging studies for temporal bone anatomy and the auditory nerve pathway. High resolution computed tomography (HRCT) can clearly reveal the anatomy of the mastoid, outer ear, middle ear, inner ear, bony labyrinth, and internal auditory meatus. Moreover, magnetic resonance imaging (MRI) allows evaluation of the auditory nerve, brain and auditory center, in addition to detecting the bony labyrinth and its pathological changes. Comprehensive evaluation of imaging studies is of important significance in determining the suitable ear for CI, evaluating electrode placement, and predicting intraoperative and postoperative complications ([@bib8]). In this paper, we analyze pre-operative imaging before CI surgery from November in 2005 to April in 2014 in our hospital and discuss the value of combined computed tomography (CT) and MRI in evaluating profound sensorineural deafness patients before CI surgery. 2. Materials and methods {#sec2} ======================== 2.1. Clinic data {#sec2.1} ---------------- We included 1012 patients with profound sensorineural deafness who received CI at the 2nd XiangYa Hospital of Central South University between November 2005 and April 2014 (the research group). Inclusion criteria included auditory examination showing binaural profound sensorineural deafness (PTA \>90 dB HL); age ≥12 months; no significant improvement in hearing and speech after hearing rehabilitation training for 3--6 months and meeting the conditions of hearing and speech rehabilitation training; parents and family members having a strong desire to improve patient\'s hearing and holding realistic expectations of CI. All the subjects and their family members agreed to partake in this research and signed the informed consent form. 2.2. Imaging examination method {#sec2.2} ------------------------------- All the children in the research and control group received HRCT scan and MRI examination. A 64-slice and dual-source layer 256 spiral CT scanner was used for CT scans. Patients took a supine position, with the chin tucked and the orbit line kept parallel with scan baseline. The entire structures of both middle and inner ears were included in the scan range. Volume data were collected to reconstruct cross-sectional, coronal and sagittal plane images and combined with volume rendering technology to show bony labyrinth. Pneumatization of mastoid, the size of sigmoid sinus and jugular fossa, cochlear niche, development of cochlea and internal auditory canal were examined separately. Meanwhile, the length and width of mastoid were measured. We measured the diameter of vestibular aqueduct at its external aperture and midpoint of a line connecting the posterior and anterior semicircular canals. The scan parameters were: 120 kV, 100 mA, beam collimation 0.75 mm, Pitch 1 and FOV 100 mm. We also reconstructed the ear with 0.1 mm reconstruction interval and 50 mm FOV overlapping amplification reconstruction. A GE Twin speed 1.5T superconducting MRI scanner was used for MRI scan. Children who could not cooperate were given 0.5 mg chloral hydrate per kilogram body weight orally or per rectum for sedation. Head scan was performed conventionally. Inner ear and auditory nerve scans were performed twice using FIESTA sequence on standard axial views and the parameters were TR 12.25 ms, TE 59.0 ms, Flip angle 700, effective slice thickness 0.6 mm, matrix 230 × 512, vision 200 mm, that was used to observe the vestibular nerve, cochlear nerve and inner ear membranous labyrinth. To acquire auditory nerve images, MRP was performed perpendicular to the long axis of the internal auditory canal. Referring to the classification criteria of inner ear malformations by Sennaroglu, diagnosis standards were established and inner ear malformations were divided into cochlear malformation, vestibular malformations, semicircular canal malformation, malformation of internal auditory canal, vestibular aqueduct malformations and cochlear aqueduct deformity. Among these malformations, cochlear malformation was divided into Michel deformity, cochlear aplasia, common cavity, cochlear hypoplasia, incomplete partition I and incomplete partition II, also known as Mondini dysplasia. 2.3. Imaging analysis of cochlear translocation malformation {#sec2.3} ------------------------------------------------------------ ### 2.3.1. Case groups {#sec2.3.1} \(1\) Normal controls: temporal bone CT scan from 20 children (40 ears) with normal hearing; (2) Normal cochlear position group: axial temporal bone CT scans before CI surgery from 20 children (40 ears) with binaural profound sensorineural deafness, who matched the inclusion criteria; (3) Abnormal cochlear position group: axial temporal bone CT scans from three 1--3 years old children whose cochleae could not be successfully accessed from the normal position during the CI surgery. ### 2.3.2. Measuring method {#sec2.3.2} Each case was measured as follows: (1) the angle between cochlear basal turn plane and head midsagittal plane (α) ([Fig. 1](#fig1){ref-type="fig"}A), (2) the angle between a line connecting the mid-point of the facial nerve vertical section and the upper edge of the round window niche and head midsagittal plane (β) ([Fig. 1](#fig1){ref-type="fig"}B), (3) in the round window plane, the vertical distance from the surface of facial nerve vertical section to the external canal wall ([Fig. 1](#fig1){ref-type="fig"}C).Fig. 1Imaging analysis of cochlear translocation malformation. A: The angle between cochlear basal turn plane and head midsagittal plane (red lines). B: The angle between a connection line from facial nerve vertical section midpoint to the upper edge of the round window niche and head midsagittal plane (green lines). C: Vertical distance A from the surface of facial nerve vertical section to the external canal wall in a round window plane. In addition, we also evaluated cochlear ossification and fibrosis that could affect CI through radiography. 3. Results and analysis {#sec3} ======================= 3.1. Absence of inner ear abnormalities in majority of cases {#sec3.1} ------------------------------------------------------------ HRCT and MRI results showed normal inner ear structures in 916 of the 1012 cases, with clear imaging of the cochlea, vestibular window, cochlear window and normal development of the internal auditory canal on HRCT and corresponding MRI results with no abnormal radiological changes in the cochlea, vestibule and internal auditory canal. Also, there was no apparent abnormality in the facial nerve from the brainstem to the internal auditory canal, the cochlear nerve or the vestibular nerve. MRI clearly showed cochlear patency and the development of cochlear nerve. 3.2. Imaging findings of large vestibular aqueduct syndrome (LVAS) {#sec3.2} ------------------------------------------------------------------ CT examination from 61 cases revealed cone or trumpet-shaped enlarged vestibular aqueduct bilaterally with sharp edges ([Fig. 2](#fig2){ref-type="fig"}A). MRI showed that all the patients with LVAS had unilateral or bilateral expansion of the endolymphatic sac, as a pouch pocket, flat oval or bar or curved protrusion on the surface of the cerebellum laterally posterior to the internal auditory canal with clear and smooth borders and high signals ([Fig. 2](#fig2){ref-type="fig"}B).Fig. 2Imaging findings of large vestibular aqueduct syndrome. A: CT scan images with a white arrow pointing to enlarged vestibular aqueduct. B: MRI images showing enlarged endolymphatic canal and sac. 3.3. Michel deformity {#sec3.3} --------------------- In the research group, we found 3 cases of Michel deformity. HRCT studies: structures of bilateral cochlea, vestibules and lateral semicircular canals were not clear and showed only an ovoid cystic cavity ([Fig. 3](#fig3){ref-type="fig"}A). MRI studies: on axial, coronal, and sagittal T1W, T2W scans, imaging showed bilateral cochleae, vestibules and lateral semicircular canals forming an oval structure. Meanwhile, the normal morphological development of the brain, the internal auditory canal, and the cochlear nerve was absent ([Fig. 3](#fig3){ref-type="fig"}B).Fig. 3Imaging findings of Michel deformity. A: CT; B: MRI. 3.4. Imaging findings in cochlear incomplete partition I {#sec3.4} -------------------------------------------------------- Two cases of cochlear incomplete partition I were found in the research group. CT scans showed that the actual size of the cochlea was normal bilaterally, but the interval was incomplete or absent, displaying an empty cochlear appearance. Bilateral cochlear and vestibular organs showed an abnormal cystic expansion, although outlines could still be distinguished. We also found an expansion of the vestibule, basal internal auditory canal hypoplasia and a shortened horizontal semicircular canal ([Fig. 4](#fig4){ref-type="fig"}A), but without enlarged vestibular aqueduct. MRI demonstrated that both the cochlea and the vestibule had a cystic appearance ([Fig. 4](#fig4){ref-type="fig"}).Fig. 4Imaging findings of cochlear incomplete partition I. A: CT; B: MRI. 3.5. Imaging findings of cochlear incomplete partition II (Mondini dysplasia) {#sec3.5} ----------------------------------------------------------------------------- We found 6 cases with cochlear incomplete partition II in the research group. This malformation showed missing interval bone between the middle and apical turns of the cochlea bilaterally, leading to a common space or cloaca. Instead of two and one-half turns in the bony cochlea, there were only one and one-half turns in the cochlea. Meanwhile, the length of the cochlear duct and the height of modiolus were significantly less than normal ([Fig. 5](#fig5){ref-type="fig"}A). MRI of the inner ear fluid showed a cochlea with just one and one-half turns, with the middle and apical turns forming a common space or cloaca. Due to low signals, modiolus was not clearly visible ([Fig. 5](#fig5){ref-type="fig"}B).Fig. 5Imaging findings of Mondini dysplasia. A: CT; B: MRI. 3.6. Cochlear hypoplasia combined with vestibular malformation {#sec3.6} -------------------------------------------------------------- In this research group, we found 3 cases of cochlear hypoplasia combined with vestibular malformation. HRCT results suggested severe cochlear dysplasia, vestibular cavity extension, semicircular canals deformity, bony defects in the basal internal auditory canal and vestibules open to the internal auditory canal ([Fig. 6](#fig6){ref-type="fig"}A). MRI showed absence of the cochlear perilymphatic space and vestibular cavity deformity connected with the internal auditory canal ([Fig. 6](#fig6){ref-type="fig"}B).Fig. 6Cochlear hypoplasia combined vestibular malformation. A: HRCT showing undeveloped cochlea, vestibular deformity combined with internal auditory canal. B: MRI showing the vestibule connected with internal auditory canal, and absence of cochlear perilymphatic space. 3.7. Imaging findings of cochlear ossification {#sec3.7} ---------------------------------------------- We found 3 cases of cochlear ossification in our research group. Of the 3 cases, HRCT revealed bilateral cochlear ossification in 2 patients. In one case, the severity of ossification differed between the two sides, severe on the left but mild on the right. Severe ossification in the left ear involved the entire cochlea. The density of the membranous labyrinth was significantly higher, displaying blurred edges and a slightly lower than normal bony labyrinth. Meanwhile, the structures of the modiolus and bony spiral plate appeared fuzzy with obvious narrow base and obscured border between apical and middle turns ([Fig. 7](#fig7){ref-type="fig"}). In contrast to HRCT, MRI results did not detect the presence of bilateral cochlear ossification in neither cases. In another patient, the left cochlea was not visible but perilymph cavity was visible in the right cochlea.Fig. 7CT images of cochlear ossification. A: Axial view; B: Coronal view. 3.8. Imaging findings of internal auditory canal abnormalities {#sec3.8} -------------------------------------------------------------- We found 5 patients with bilateral internal auditory canal obstruction associated with cochlear nerve dysplasia and 2 cases with right internal auditory canal stenosis. Cross-sectional CT showed that internal auditory canal was severely narrowed, the anteroposterior and vertical diameters were clearly minimal and the width of the opening was only 1 mm ([Fig. 8](#fig8){ref-type="fig"}A); Cross-sectional and coronal T2WI MRI showed high signal intensity in the internal auditory canal, indicative of cerebrospinal fluid (CSF). 3D-CISS imaging confirmed the absence of the cochlear and vestibular nerves ([Fig. 8](#fig8){ref-type="fig"}B).Fig. 8Image findings of internal auditory canal obstruction associated with cochlear nerve dysplasia. A: CT scans showing internal auditory canal stenosis. B: axial section MRI images of internal auditory canal showing cochlear nerve aplasia. 3.9. Image analysis results of cochlear translocation malformation {#sec3.9} ------------------------------------------------------------------ In control groups, angles α and β and mean distance A were 60.5 ± 3.6°, 48.5 ± 6.7° and 4.49 ± 0.37 mm, respectively. There were no significant differences between the normal control and the normal cochlear position groups (P \< 0.05). Compared to the normal control and normal cochlear position groups, α and distance A in the 3 cases in the abnormal cochlear position group were not statistically different, although β was greater than in the other two groups. β in the 3 cases were beyond or near the upper limit of reference range bilaterally. In the abnormal cochlear position group, α was smaller than β ([Fig. 9](#fig9){ref-type="fig"}A). In contrast, in the control groups, α was greater than β ([Fig. 9](#fig9){ref-type="fig"}B).Fig. 9α and β angles comparison between normal and cochlear translocation malformation patients. A: Cochlear translocation malformation. B: Normal cochlea. 4. Discussion {#sec4} ============= Congenital sensorineural deafness is mainly due to developmental abnormalities of the inner ear, especially the cochlea. However, the occurrence of any lesions in the auditory pathway, including the cochlear nerve, can cause deafness. The most effective treatment for profound sensorineural deafness is cochlear implantation. Therefore, determining the site of the lesion through preoperative examination is required to formulate the best approach for cochlear implantation surgery, and to achieve optimal results of rehabilitation. Imaging analysis is one of the most important preoperative assessment instruments. Cochlear abnormalities, caused by a variety of congenital malformations in the inner ear, and acquired diseases may affect the efficacy of cochlear implant surgery. According to the literature, the incidence of inner ear malformation is approximately 20% in patients with severe sensorineural deafness ([@bib19]). The inner ear primordium is the derivative of the auditory placode arising from the ectoderm. Inner ear malformations can involve the vestibule, semicircular canals, cochlea, endolymphatic sac and vestibular aqueduct. These malformations occur in the auditory vesicle, and malformations in the internal auditory tract are from non-auditory vesicle. Genetic factors, chromosomal aberrations, congenital infection or exposure to certain medications at an early embryonic age, and other unknown reasons can cause the development of inner ear disorders. At present, large vestibular aqueduct syndrome is one of the inner ear malformations largely caused by genetic factors. Viral infections (such as rubella, measles, and mumps virus) and drugs (such as streptomycin, kanamycin, Miltown, thalidomide and so on) have been known to lead to inner ear malformations. Depending on the embryonic period when an offense occurs, different inner ear malformations may occur. Inner ear malformations can occur in any part of the bony and membranous labyrinth. Approximately 20% are bony labyrinth deformities and about 80% are membranous labyrinth malformation ([@bib6]). The development of embryonic bony labyrinth occurs around 4--8 weeks gestation and the maturation of the membranous labyrinth occurs from 8 to 24 weeks. Therefore, bony labyrinth deformities often accompany membranous labyrinth malformations. Bony labyrinth deformities can be diagnosed by imaging examinations ([@bib13]), but most membranous labyrinth malformation such as Scheibe and Alexander deformities cannot be seen on imaging at this time ([@bib5]). In the past, the classification of congenital inner ear malformations, proposed by [@bib7] in 1987, was most widely used. He divided bony labyrinth deformities into: labyrinth deficiency (Michel deformity), cochlear aplasia, cochlear hypoplasia, incomplete partition (Mondini dysplasia) and common cavity. At that time, temporal bone imaging was mainly taken via multi-track tomography. With the advances in imaging technology, Sennaroglu proposed a new classification based on CT findings and subdivided inner ear malformation into cochlear malformation, vestibular deformity, semicircular canal deformity, internal auditory meatus deformity, vestibular aqueduct deformity and cochlear aqueduct malformation. Cochlear malformation was further divided into: (1) Michel deformity: the most severe inner ear malformation characterized by complete loss of inner ear structure. This deformity correlates to arrested development in the 3rd week of gestation. (2) Cochlear aplasia, i.e. absence of the cochlea, with the vestibule being normal, expanded or showing hypoplasia. It is also caused by arrested development at the end of the 3rd week of gestation. (3) Common cavity: cochlear and vestibular structures showing a cystic structure and indistinguishable from each other because development is halted in the 4th week of gestation. (4) Cochlear hypoplasia: cochlear and vestibular structures indistinguishable from each other, with the structure being smaller than normal. The cochlea often appears as a bud-shaped structure expanding from the internal auditory meatus. This malformation is caused by arrest of development in the 6th week of gestation. (5) Incomplete partition I: cochlea showing a sack-like structure without integral modiolus and ethmoid, usually associated with cystic dilated vestibule. This is due to the stop of development in the 5th week of gestation. (6) Incomplete partition II (also known as Mondini dysplasia): caused by a development arrest in the 7th week of gestation, this malformation usually occurs with an enlarged vestibular aqueduct and vestibule. The cochlea has one and a half coils, and only the basal turn is normal whereas apical and middle turns merge together. Vestibular deformity and semicircular canal deformity are common. The cochlea may be normal, but there is an expansion of the vestibule and a short, thick or absent semicircular canal. Vestibular aqueduct malformations: enlarged vestibular aqueduct is one of the most common types of deformity, which is bell-mouthed or connected with common crus. Internal auditory meatus deformity: internal auditory canal stenosis, absence or expansion. Cochlear aqueduct malformations: enlarged or narrowed cochlear aqueduct is the main feature. During CI surgery in a patient with inner ear malformation, the greatest concern is the location of the facial nerve, as well as whether there is a defect in the lateral wall of the internal auditory canal and during the course of the auditory nerve. The auditory vesicle of inner ear primordium and the Reichert cartilage of the second branchial arch formed the facial nerve canal. Therefore, inner ear malformations can cause abnormal positions of the facial nerve canal. On the other hand, the defect of the lateral wall of the internal auditory can lead to cerebrospinal fluid connected with the lymph of the cochlea. Because of the high pressure of the cerebrospinal fluid, cerebrospinal fluid "gush" phenomenon often occurs during the surgery. Imaging studies can aid an otolaryngologist in deciding the appropriate surgical approach and reducing complications. In displaying inner ear abnormalities, CT and MRI have their own advantages and disadvantages ([@bib20], [@bib22]). High-resolution CT provides good spatial resolution through the thin layer, small field of view, large matrix and bone algorithm. Temporal bone HRCT is generally set at 1--2 mm layers and scanned with continuous or partially overlapping technology. Bilateral scanning is routinely performed and sometimes with partial reconstruction and amplification, if necessary. Application of window technique is very important for showing different middle and inner ear structures. Generally, window width is about 4000 Hu and window level is around 400--1000 Hu. From various scan thickness and calculation methods for image reconstruction, HRCT can significantly increase the display resolution of structures including the ossicular chain and bony labyrinth compared to regular CT, which provides a basis for the accurate measurement of certain structures, diagnosis and surgery design. Meanwhile, HRCT also helps identify the development situation of inner ear bony labyrinth, including each turn of the cochlea, the degree of ossification, the development of the internal auditory canal, and the expansion of vestibule and vestibular aqueduct. MRI technology provides better soft tissue resolution. Especially in recent years, the application of water imaging technology makes intuitive, three-dimensional display of the fine structure of the inner ear membranous labyrinth possible, compensating deficiencies of CT examination. MRI is capable of showing inner chambers containing fluid within the bony labyrinth. Furthermore, MRI three-dimensional MIP image more vividly reflects inner ear structural details, especially regarding semicircular canals morphology and their three-dimensional relationship. For cases with cochlear ossification, it is difficult to see ossification and fibrosis lesions within the membranous labyrinth on HRCT, whereas MRI can show the lesion as local low density. This proves that MRI has more advantages when studying the membranous labyrinth, the endolymph and the cochlear and vestibular nerves in the internal auditory canal. In addition, direct scanning with HRCT is limited to cross-sectional and coronal planes, but less so on sagittal or other tilted angle planes. Therefore, display of some structures is less satisfactory compared to MRI, which has its advantages in this regard. In this study, the most common inner ear malformation was large vestibular aqueduct syndrome, which accounted for 63.5% of inner ear malformations (61/96) in this series. In our experience, CI surgery in enlarged vestibular aqueduct syndrome patients is rarely complicated by cerebrospinal fluid leakage. The characteristic finding of enlarged vestibular aqueduct on imaging is expansion of the distal vestibular aqueduct in the endolymphatic sac region on CT. The diameter of bony vestibular aqueduct is determined by measuring the distance between the common crus and the midpoint of the outside export on axial CT images. When greater than 1.5 mm, it is considered an enlarged vestibular aqueduct. This standard was proposed by Valvassori and has been widely used ([@bib18], [@bib17]; [@bib10]). It was also used in our study for diagnosis of large vestibular aqueduct syndrome. However, a new diagnostic criterion has been suggested recently, also known as the Cincinnati criteria ([@bib2]), which calls for diagnosis of enlarged vestibular aqueduct when the middle section vestibular aqueduct diameter is greater than 1.0 mm or outside diameter is greater than 2.0 mm. The endolymphatic sac appeared enlarged on MRI in most of our patients. However, Okamodo et al. found that the size of the vestibular aqueduct on MRI did not always correspond to its actual size. Thus, Okamodo et al. believed that it was more appropriate to name this disease as "large lymphatic sac syndrome" ([@bib9]). Under normal circumstances, the size of the endolymphatic sac is about 1 mm, and difficult to detect on MRI. Also, endolymphatic sac is hard to see in normal adults and children. [@bib16] thought that CT might show false positive or false negative results. However, MRI can clearly show the endolymphatic sac, and thus help more accurately determine whether it is in conjunction with enlarged vestibular aqueduct syndrome. Incomplete partition II is also known as inner ear hypoplasia or Mondini dysplasia that is caused by the stop of development in the 7th week of gestation. It was first described by Mondini in 1791 and usually shows as bony labyrinth and membranous labyrinth hypoplasia that is often accompanied by middle ear abnormalities and aberrant courses of the facial nerve. [@bib12] reported the temporal bone pathology of Mondini malformation, including one and a half coils of the cochlea with only the base turn being normal and absent apical and middle turns, or the whole cochlea being a single ring. It may also include expansion of vestibular pool, endolymphatic sac and endolymphatic canal. Other abnormalities may include variation in size or absence of the semicircular canal, cochlear and vestibular receptors hypoplasia, incomplete stapedial plate in some patients, closed vestibular window, and swollen round window membrane that can lead to spontaneous rupture. In our study, 8 patients were diagnosed with Mondini malformation through high-resolution CT and MRI of the temporal bone, and 6 of them received cochlear implantation surgery. CSF "gush" phenomenon occurred intraoperatively but cochlear electrode was implanted successfully and CSF leak repair was done at the same time. There were no facial paralysis, CSF leakage, intracranial infection, or other serious complications post-operatively. Cochlear translocation deformity, however, can hamper cochlear implant surgery. Three were found to have cochlea backward translocation among the 1012 cases. All of them received cochlear implantation. With cochlear translocation, the turning and the position of the promontory of cochlear basal turn is changed, making it difficult to open the window through the ordinary approach. In order to adjust to the new location of cochlear window opening and the directionality of electrode placement, attention must be paid to this deformity through preoperative detection. Abnormal cochlear positions can be divided into cochlea translocation and cochlear shift. α (the angle between cochlear basal turn plane and head midsagittal plane) and β (the angle between a connection line from facial nerve vertical section midpoint to the upper edge of the round window niche and head midsagittal plane) measured on temporal bone CT scans can help determine whether the cochlear position is abnormal and to what degree. 95% reference range of α is 53.4°--67.6° with the average being 60.5° ± 3.6°. 95% reference range of β is 35.4°--61.6° with an average of 48.5° ± 6.7°. When the angle is not within the normal range, a forward or backward cochlear translocation is indicated. Internal auditory canal malformations include absent, narrowed or dilated internal auditory canals. The normal width of the internal auditory canal is about 4--6 mm. Less than 2 mm should be considered as narrow and is usually associated with auditory nerve and/or facial nerve abnormalities. If the width is greater than 6 mm but without any clinical symptoms, it is usually not diagnosed as abnormal or expanded. For patients with internal auditory canal malformations who are being considered for cochlear implantation, attention should be focused on presence of stenosis that accounts for about 12% of congenital temporal bone deformities ([@bib4], [@bib1], [@bib3]). The diagnosis of internal auditory canal stenosis depends on temporal bone high-resolution CT. CT can show the diameter of the internal auditory canal, but not the details inside the canal or the integrity of the auditory nerve. However, high-resolution MRI three-dimensional scanning images, combined with oblique sagittal thin layer reconstructed images perpendicular to the internal auditory canal, can clearly demonstrate the morphology of the internal auditory nerve. In our group, CT results showed \<2 mm diameter of the internal auditory canal in 1 patient, and MRI also showed developmental abnormalities of the auditory nerve. However, the diameter of the internal auditory canal is not always consistent with auditory neurodevelopmental situation. Some cases have normal sized internal auditory canal, but auditory nerve hypoplasia. Therefore, for all cochlear implantation applicants, MRI examination is needed to determine auditory neurodevelopmental situation with or without internal auditory canal stenosis to ensure the efficacy of hearing rehabilitation after surgery. Cochlear ossification and fibrosis directly affect cochlear electrode implantation. Therefore, preoperative examination is necessary to determine the patency of the cochlear cavity. However, identification of cochlear ossification may present certain degrees of difficulty. At present, the rate of diagnosis of severe cochlear ossification is up to 100% through high-resolution temporal bone CT examination, and lateral semicircular canal ossification is the most sensitive indicator in the diagnosis of cochlear ossification. But for cochlear fibrosis and early stage ossification, the rate of missed diagnosis remains very high ([@bib21]). [@bib14] found up to 57% of misdiagnosis rate for early ossification with cochlear fibrosis on CT. Therefore, for patients with suspected cochlear ossification, additional MRI examination is necessary. Three-dimensional MR water imaging technology can show the patency of the cochlear cavity very well. As it can clearly show the outline of the structure of the membranous labyrinth and can be rotated 360°, it helps distinguish cochlear soft tissue abnormalities, cochlear fibrosis, and other internal auditory canal and retrocochlear soft tissue abnormalities that CT has failed to identify. It is therefore very helpful in selection of appropriate surgical ears ([@bib11]). This study was supported by the Cochlear Implantation Program of Hunan, National Basic Research Program of China (2012CB967904). We thank the patients, their families and deaf-mute school children who participated in this study. Peer review under responsibility of PLA General Hospital Department of Otolaryngology Head and Neck Surgery. [^1]: The first two authors contributed equally to this paper. | High | [
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Oral administration of collagen conjugated with cholera toxin induces tolerance to type II collagen and suppresses chondritis in an animal model of autoimmune ear disease. B10.RIII (H-2r) mice were orally administered cyanogen bromide peptide 11 (CB11) or cholera toxin B (CTB)-conjugated CB11 to induce tolerance in collagen-induced autoimmune ear disease. Oral administration of a high dosage of CB11 provided partial protection from chondritis. However, administration of a tiny amount of CTB-CB11 conjugate effectively suppressed chondritis. Oral administration of CTB-CB11 conjugate did not alter the stimulation of T cells in vitro or the fine specificities of B cells. The oral administration of CTB-CB11 caused a higher level of type II collagen-specific IgG and its subclass. Interestingly, increases of TH1 cytokine (interferon-gamma) in Peyer's patches and of TH1/TH2 cytokines (interleukin-2 and interleukin-4) in lymph nodes were detected in mice that had been fed CTB-CB11. An increase of CD8+ T cells in the Peyer's patches with a decrease of CD8+ T cells in lymph nodes was seen in mice that had been fed CTB-CB11. These results suggest that protection from chondritis by oral administration of minute amounts of CTB-CB11 conjugate can be achieved by a mechanism distinct from that of conventional oral tolerance induction. | Mid | [
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/************************************************************* * * MathJax/fonts/HTML-CSS/TeX/png/AMS/Regular/GeometricShapes.js * * Defines the image size data needed for the HTML-CSS OutputJax * to display mathematics using fallback images when the fonts * are not availble to the client browser. * * --------------------------------------------------------------------- * * Copyright (c) 2009-2013 The MathJax Consortium * * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. * */ MathJax.OutputJax["HTML-CSS"].defineImageData({ "MathJax_AMS": { 0x25A0: [ // BLACK SQUARE [5,5,0],[6,6,0],[8,7,0],[9,9,0],[10,10,0],[12,12,0],[15,14,0],[17,16,0], [20,20,0],[24,23,0],[29,27,0],[34,32,0],[40,39,0],[48,46,0] ], 0x25A1: [ // WHITE SQUARE [5,5,0],[6,6,0],[7,7,0],[9,8,0],[10,10,0],[12,12,0],[14,14,0],[17,16,0], [21,20,0],[24,23,0],[29,27,0],[34,32,0],[40,39,0],[48,46,0] ], 0x25B2: [ // BLACK UP-POINTING TRIANGLE [5,5,1],[6,6,1],[7,7,1],[8,8,1],[9,9,1],[11,11,1],[13,13,1],[15,15,1], [18,17,1],[21,20,1],[25,24,1],[30,28,1],[36,34,2],[42,40,2] ], 0x25B3: [ // WHITE UP-POINTING TRIANGLE [5,5,0],[6,5,0],[7,6,0],[8,8,1],[9,10,1],[11,11,1],[13,13,1],[15,15,1], [18,17,1],[21,20,1],[25,24,1],[30,28,1],[36,34,2],[42,41,2] ], 0x25B6: [ // BLACK RIGHT-POINTING TRIANGLE [5,5,1],[6,6,1],[7,7,1],[9,8,1],[10,9,1],[12,10,1],[14,12,1],[17,14,1], [20,17,2],[23,20,2],[28,24,2],[33,28,2],[39,33,3],[46,39,3] ], 0x25BC: [ // BLACK DOWN-POINTING TRIANGLE [5,5,1],[6,6,1],[7,7,1],[8,8,1],[9,9,1],[11,11,1],[13,13,1],[15,15,1], [18,17,1],[21,20,1],[25,24,1],[30,28,1],[36,33,1],[42,40,2] ], 0x25BD: [ // WHITE DOWN-POINTING TRIANGLE [5,5,1],[6,6,1],[7,7,1],[8,8,1],[9,9,1],[11,11,1],[13,13,1],[15,15,1], [18,17,1],[21,20,1],[25,24,1],[30,28,1],[36,33,1],[42,40,2] ], 0x25C0: [ // BLACK LEFT-POINTING TRIANGLE [5,5,1],[6,6,1],[7,7,1],[9,8,1],[10,9,1],[12,10,1],[14,12,1],[17,14,1], [20,17,2],[23,20,2],[28,24,2],[33,28,2],[39,33,3],[46,39,3] ], 0x25CA: [ // LOZENGE [5,6,1],[6,8,2],[7,10,2],[8,11,2],[9,12,2],[11,15,3],[12,17,3],[15,21,4], [17,24,4],[21,29,5],[25,35,6],[29,41,7],[34,48,8],[41,57,9] ] } }); MathJax.Ajax.loadComplete(MathJax.OutputJax["HTML-CSS"].imgDir+"/AMS/Regular"+ MathJax.OutputJax["HTML-CSS"].imgPacked+"/GeometricShapes.js"); | Low | [
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owner = MEX
controller = MEX
add_core = MEX
metal = 6.00
infra = 5
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[Parent-child treatment in general psychiatry]. German psychiatry has been using parent-child treatment for only a few years-in contrast to Anglo American countries. Now, however, similar modalities are now on the rise in Germany, and it is time to list experiences and considerations of possible quality standards for such treatment units. To account for the necessary broadening of perspectives including the whole family system, the term "parent-child treatment" is used instead of the frequently used "mother-child treatment." | High | [
0.673521850899742,
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Q: how connect this table to MySQL I have this user table files php from easyui http://www.jeasyui.com/tutorial/app/crud.php , but i not know how connect to MySQL users.php <style type="text/css"> #fm{ margin:0; padding:10px 30px; } .ftitle{ font-size:14px; font-weight:bold; color:#666; padding:5px 0; margin-bottom:10px; border-bottom:1px solid #ccc; } .fitem{ margin-bottom:5px; } .fitem label{ display:inline-block; width:80px; } </style> <script type="text/javascript" src="http://code.jquery.com/jquery-1.6.min.js"></script> <script type="text/javascript" src="http://www.jeasyui.com/easyui/jquery.easyui.min.js"></script> <script type="text/javascript"> var url; function newUser(){ $('#dlg').dialog('open').dialog('setTitle','New User'); $('#fm').form('clear'); url = 'save_user.php'; } function editUser(){ var row = $('#dg').datagrid('getSelected'); if (row){ $('#dlg').dialog('open').dialog('setTitle','Edit User'); $('#fm').form('load',row); url = 'update_user.php?id='+row.id; } } function saveUser(){ $('#fm').form('submit',{ url: url, onSubmit: function(){ return $(this).form('validate'); }, success: function(result){ var result = eval('('+result+')'); if (result.success){ $('#dlg').dialog('close'); // close the dialog $('#dg').datagrid('reload'); // reload the user data } else { $.messager.show({ title: 'Error', msg: result.msg }); } } }); } function removeUser(){ var row = $('#dg').datagrid('getSelected'); if (row){ $.messager.confirm('Confirm','Are you sure you want to remove this user?',function(r){ if (r){ $.post('remove_user.php',{id:row.id},function(result){ if (result.success){ $('#dg').datagrid('reload'); // reload the user data } else { $.messager.show({ // show error message title: 'Error', msg: result.msg }); } },'json'); } }); } } </script> <h2>Basic CRUD Application</h2> <div class="demo-info" style="margin-bottom:10px"> <div class="demo-tip icon-tip"> </div> <div>Click the buttons on datagrid toolbar to do crud actions.</div> </div> <table id="dg" title="My Users" class="easyui-datagrid" style="width:700px;height:250px" url="get_users.php" toolbar="#toolbar" pagination="true" rownumbers="true" fitColumns="true" singleSelect="true"> <thead> <tr> <th field="firstname" width="50">First Name</th> <th field="lastname" width="50">Last Name</th> <th field="phone" width="50">Phone</th> <th field="email" width="50">Email</th> </tr> </thead> </table> <div id="toolbar"> <a href="#" class="easyui-linkbutton" iconCls="icon-add" plain="true" onclick="newUser()">New User</a> <a href="#" class="easyui-linkbutton" iconCls="icon-edit" plain="true" onclick="editUser()">Edit User</a> <a href="#" class="easyui-linkbutton" iconCls="icon-remove" plain="true" onclick="removeUser()">Remove User</a> </div> <div id="dlg" class="easyui-dialog" style="width:400px;height:280px;padding:10px 20px" closed="true" buttons="#dlg-buttons"> <div class="ftitle">User Information</div> <form id="fm" method="post" novalidate> <div class="fitem"> <label>First Name:</label> <input name="firstname" class="easyui-validatebox" required="true"> </div> <div class="fitem"> <label>Last Name:</label> <input name="lastname" class="easyui-validatebox" required="true"> </div> <div class="fitem"> <label>Phone:</label> <input name="phone"> </div> <div class="fitem"> <label>Email:</label> <input name="email" class="easyui-validatebox" validType="email"> </div> </form> </div> <div id="dlg-buttons"> <a href="#" class="easyui-linkbutton" iconCls="icon-ok" onclick="saveUser()">Save</a> <a href="#" class="easyui-linkbutton" iconCls="icon-cancel" onclick="javascript:$('#dlg').dialog('close')">Cancel</a> </div> conn.php <?php $conn = @mysql_connect('127.0.0.1','root','root'); if (!$conn) { die('Could not connect: ' . mysql_error()); } mysql_select_db('mydb', $conn); ?> get_users.php <?php $page = isset($_POST['page']) ? intval($_POST['page']) : 1; $rows = isset($_POST['rows']) ? intval($_POST['rows']) : 10; $offset = ($page-1)*$rows; $result = array(); include 'conn.php'; $rs = mysql_query("select count(*) from users"); $row = mysql_fetch_row($rs); $result["total"] = $row[0]; $rs = mysql_query("select * from users limit $offset,$rows"); $items = array(); while($row = mysql_fetch_object($rs)){ array_push($items, $row); } $result["rows"] = $items; echo json_encode($result); ?> and this MySQL database CREATE TABLE `users` ( `id` int(11) NOT NULL auto_increment, `firstname` varchar(50) default NULL, `lastname` varchar(50) default NULL, `phone` varchar(200) default NULL, `email` varchar(200) default NULL, PRIMARY KEY (`id`) ) ENGINE=InnoDB DEFAULT CHARSET=utf8; A: Glad that it didn't connect. Stop using mysql_* functions as they are deprecated. Switch to PDO. Rewrite your connection like this. try { $dbh = new PDO("mysql:host=localhost;dbname=$dbname",$dbuser,$dbpass); $dbh->setAttribute(PDO::ATTR_ERRMODE, PDO::ERRMODE_EXCEPTION); } catch (PDOException $e) { echo 'Connection failed: ' . $e->getMessage(); } How to write queries using PDO ? | Mid | [
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The Mexican representative for immigrant issues will ask U.S. legislators to grant posthumous citizenship to the Mexicans that died in the terrorist attacks of September 11th, as well as to their surviving family members. Juan Hernandez, appointed by President Vicente Fox to campaign for better treatment of Mexican immigrants, traveled to New York to meet with U.S. Representative Jose Serrano, a Democrat who supported a measure to grant citizenship to the victims of the attacks. Hernandez told the press that he would ask Serrano to concede citizenship to the victims and their families, as well as allow that they be eligible to receive aid granted to U.S. citizens. Hernandez_s office has given an initial payment of $3,300 to every Mexican family who lost a member in the attacks. Hernandez said he is confident that Congress sensitivity will allow for a quick and favorable decision over this issue which the Fox administration considers a priority. The Mexican community was the one group that was most affected by the September 11th attacks. Several Mexican nationals worked in the restaurants of the bottom floors of the World Trade Center Towers. Others labored as janitors and some were employed in the computer companies that disappeared when the twin towers were destroyed after two commercial airliners filled with passengers and fuel crashed into the buildings. | Mid | [
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Towradgi in Sydney South is an exposed beach break that has very consistent surf, although summer tends to be mostly flat. Ideal winds are from the west. Waves just as likely from local windswells as from distant groundswells and the best swell direction is from the southeast. The beach break provides left and right handers. Good surf at all stages of the tide. A fairly popluar wave that can sometimes get crowded Watch out for sharks. Canberra Airport (CBR), also in Australia is the fifth nearest airport to Towradgi and is 182 km (113 miles) away. This is the Surf-Forecast page for Towradgi, NSW - Illawarra. Use the tab navigation above to view Towradgi sea temperature, Towradgi photographs, Towradgi detailed swell predictions, wind and weather forecasts, Towradgi webcams, current wind from NSW - Illawarra live weather stations and Towradgi tide predictions. The Australia swell maps link will open up the big picture showing Australia and the surrounding seas. These swell maps can be animated to show the different swell components, wave energy, wave period, wave heights, together with wind and weather forecasts, current weather and sea state observations from Australia wave-buoys, passing ships and coastal weather stations. Each of the forecast pages for this surf break feature a global and regional wavefinder tool to locate the best surf conditions in the area around Towradgi. | High | [
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// Copyright 2017, 2019 ETH Zürich, Thomas Schöps // // Redistribution and use in source and binary forms, with or without // modification, are permitted provided that the following conditions are met: // // 1. Redistributions of source code must retain the above copyright notice, // this list of conditions and the following disclaimer. // // 2. Redistributions in binary form must reproduce the above copyright notice, // this list of conditions and the following disclaimer in the documentation // and/or other materials provided with the distribution. // // 3. Neither the name of the copyright holder nor the names of its contributors // may be used to endorse or promote products derived from this software // without specific prior written permission. // // THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" // AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE // IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE // ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDER OR CONTRIBUTORS BE // LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR // CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF // SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS // INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN // CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) // ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE // POSSIBILITY OF SUCH DAMAGE. #pragma once #ifndef M_PI
#define M_PI 3.14159265358979323846
#endif #include <Eigen/StdVector> #include <sophus/rxso3.hpp> #include <sophus/se2.hpp> #include <sophus/se3.hpp> #include <sophus/sim3.hpp> #include <sophus/so2.hpp> #include <sophus/so3.hpp> #include "libvis/libvis.h" #ifdef __CUDA_ARCH__ #error "Compiling Eigen code with nvcc is not supported properly, therefore Eigen headers should not be included from .cu / .cuh files." #endif namespace vis { // Using the full namespace was discarded as it conflicted with importing the // Eigen namespace: Matrix was defined in both. using Sophus::RxSO3f; using Sophus::RxSO3d; using Sophus::SE2f; using Sophus::SE2d; using Sophus::SE3f; using Sophus::SE3d; using Sophus::Sim3f; using Sophus::Sim3d; using Sophus::SO2f; using Sophus::SO2d; using Sophus::SO3f; using Sophus::SO3d; } EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::RxSO3f) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::RxSO3d) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SE2f) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SE2d) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SE3f) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SE3d) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::Sim3f) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::Sim3d) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SO2f) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SO2d) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SO3f) EIGEN_DEFINE_STL_VECTOR_SPECIALIZATION(Sophus::SO3d) | Mid | [
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Self-perceived motivation for benzodiazepine use and behavior related to benzodiazepine use among opiate-dependent patients. Clinical observations have shown a high prevalence of benzodiazepine use among opiate-dependent patients. Our objective was to identify if distinct patterns of behavior could be associated with three different self-perceived motivations for benzodiazepine use: (a) exclusive self-therapeutic motivation, (b) exclusive hedonic motivation, and (c) combined self-therapeutic and hedonic motivation. Data were collected through a self-administered questionnaire in 92 opiate users in treatment in France (Aquitaine). The behaviors associated with exclusive self-therapeutic motivation included the search for an anxiolytic effect, oral administration, use within the context of a medical prescription, and use without other substances. The behaviors associated with exclusive hedonic motivation were use in combination with other substances, the obtaining of benzodiazepines by the black market, and use of other routes of administration in search of a "blackout." Among patients who reported both motivations, there were distinct trends of behavior according to motivation. | Mid | [
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Theory and practice of conventional adventitious virus testing. CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) For decades conventional tests in cell cultures and in laboratory animals have served as standard methods for broad-spectrum screening for adventitious viruses. New virus detection methods based on molecular biology have broadened and improved our knowledge about potential contaminating viruses and about the suitability of the conventional test methods. This paper summarizes and discusses practical aspects of conventional test schemes, such as detectability of various viruses, questionable or false-positive results, animal numbers needed, time and cost of testing, and applicability for rapidly changing starting materials. Strategies to improve the virus safety of biological medicinal products are proposed. The strategies should be based upon a flexible application of existing and new methods along with a scientifically based risk assessment. However, testing alone does not guarantee the absence of adventitious agents and must be accompanied by virus removing or virus inactivating process steps for critical starting materials, raw materials, and for the drug product. | High | [
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import PeoplePage from './people-page'; import PlanetsPage from './planets-page'; import StarshipsPage from './starships-page'; export { PeoplePage, PlanetsPage, StarshipsPage }; | Low | [
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Polymersome In biotechnology, polymersomes are a class of artificial vesicles, tiny hollow spheres that enclose a solution. Polymersomes are made using amphiphilic synthetic block copolymers to form the vesicle membrane, and have radii ranging from 50 nm to 5 µm or more. Most reported polymersomes contain an aqueous solution in their core and are useful for encapsulating and protecting sensitive molecules, such as drugs, enzymes, other proteins and peptides, and DNA and RNA fragments. The polymersome membrane provides a physical barrier that isolates the encapsulated material from external materials, such as those found in biological systems. Synthosomes are polymersomes engineered to contain channels (transmembrane proteins) that allow certain chemicals to pass through the membrane, into or out of the vesicle. This allows for the collection or enzymatic modification of these substances. The term "polymersome" for vesicles made from block copolymers was coined in 1999. Polymersomes are similar to liposomes, which are vesicles formed from naturally occurring lipids. While having many of the properties of natural liposomes, polymersomes exhibit increased stability and reduced permeability. Furthermore, the use of synthetic polymers enables designers to manipulate the characteristics of the membrane and thus control permeability, release rates, stability and other properties of the polymersome. Preparation Several different morphologies of the block copolymer used to create the polymersome have been used. The most frequently used are the linear diblock or triblock copolymers. In these cases, the block copolymer has one block that is hydrophobic; the other block or blocks are hydrophilic. Other morphologies used include comb copolymers, where the backbone block is hydrophilic and the comb branches are hydrophobic, and dendronized block copolymers, where the dendrimer portion is hydrophilic. In the case of diblock, comb and dendronized copolymers the polymersome membrane has the same bilayer morphology of a liposome, with the hydrophobic blocks of the two layers facing each other in the interior of the membrane. In the case of triblock copolymers the membrane is a monolayer that mimics a bilayer, the central block filling the role of the two facing hydrophobic blocks of a bilayer. In general they can be prepared by the methods used in the preparation of liposomes. Film rehydration, direct injection method or dissolution method. Uses Polymersomes that contain active enzymes and that provide a way to selectively transport substrates for conversion by those enzymes have been described as nanoreactors. Polymersomes have been used to create controlled release drug delivery systems. Similar to coating liposomes with polyethylene glycol, polymersomes can be made invisible to the immune system if the hydrophilic block consists of polyethylene glycol. Thus, polymersomes are useful carriers for targeted medication. For in vivo applications, polymersomes are de facto limited to the use of FDA-approved polymers as most pharmaceutical firms are unlikely to develop novel polymers due to cost issues. Fortunately there are a number of such polymers available, with varying properties, including: Hydrophilic blocks Poly(ethylene glycol) (PEG/PEO) Poly(2-methyloxazoline) Hydrophobic blocks Polydimethylsiloxane (PDMS) Poly(caprolactone (PCL) Poly(lactide) (PLA) Poly(methyl methacrylate) (PMMA) If enough of the block copolymer molecules that make up a polymersome are cross-linked, the polymersome can be made into a transportable powder. Polymersomes can be used to make an artificial cell if hemoglobin and other components are added. The first artificial cell was made by Thomas Chang. See also Cell (biology) Liposome Polymer Copolymer Artificial cell References Category:Biomolecules Category:Polymers Category:Immunology Category:Pharmacokinetics | High | [
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Adobe Systems has confirmed it will help sponsor the work of the SQLite database project, joining a new consortium alongside Mozilla and Symbian. SQLite, which is an embedded SQL database engine with core source code in the public domain, has been built into the firm's newly released Adobe Integrated Runtime (AIR) software. So it's perhaps of little surprise that Adobe's announcement to sponsor SQLite has coincided with the launch of AIR, which has tools for programmers to build apps that run inside an internet browser and integrate with the desktop. The San Jose-based company's open source boss Dave McAllister said in a blog post on Sunday: "Adobe's support of the SQLite Consortium demonstrates Adobe's commitment to open source, and belief that technologies such as SQLite should remain independent and free in the best interests of the community." Members of the consortium, which was launched in December 2007, receive a number of benefits that include extra support provided by SQLite developers, which amounts to "undivided attention" of at least 23 staff days per year. ® | Mid | [
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"I want to confess as best I can, but my heart is void. The void is a mirror. I see my face and feel loathing and horror. My indifference to men has shut me out. I live now in a world of ghosts, a prisoner in my dreams. " -Antonius Block from The Seventh Seal heh, well do you expect to get an intelligent answer out of a stupid question? Logged "I want to confess as best I can, but my heart is void. The void is a mirror. I see my face and feel loathing and horror. My indifference to men has shut me out. I live now in a world of ghosts, a prisoner in my dreams. " -Antonius Block from The Seventh Seal the reason why these people started the comic was because of penny-arcade, and that was their inspiration, instead of gaming they wanted to do movies. Logged "I want to confess as best I can, but my heart is void. The void is a mirror. I see my face and feel loathing and horror. My indifference to men has shut me out. I live now in a world of ghosts, a prisoner in my dreams. " -Antonius Block from The Seventh Seal "I want to confess as best I can, but my heart is void. The void is a mirror. I see my face and feel loathing and horror. My indifference to men has shut me out. I live now in a world of ghosts, a prisoner in my dreams. " -Antonius Block from The Seventh Seal The scene where Philip Baker Hall starts lecturing the zombies is classic. i don't think so, Soldier was beautiful and the best, but Paul Thomas Anderson will hit big is with Alien vs. Predator. Logged "I want to confess as best I can, but my heart is void. The void is a mirror. I see my face and feel loathing and horror. My indifference to men has shut me out. I live now in a world of ghosts, a prisoner in my dreams. " -Antonius Block from The Seventh Seal there's a lot of talk of the best movie, best shots, best scenes, best actors, best scores, best drug scene, best sex scene, et cetera. there's not a lot of talk about the worst, unless someone can prove me wrong. lock this if you can find something that's about the worst movie ever (to avoid further embarassment on my part). my idea is to understand the best, you need to see both sides, the good and the bad. what's the worst movie you've ever seen? i mean actually seen, not like gigli, we know it's bad, but no one has seen it. no one i'll start it off... Plan 9 From Outer Space Seriously. The Adventures of Pluto Nash. Knowing what I know now, you couldn't pay me the ticket price to sit there and watch it again. almost terrible but so hilarious is Mr. T's Be Somebody or Be Somebody's Fool. it's a hilarious movie, he gives such advice as "If you don't walk around with any clothes, then you could get arrested""Use your anger, don't lose it.""It's always good to daydream." Logged "I want to confess as best I can, but my heart is void. The void is a mirror. I see my face and feel loathing and horror. My indifference to men has shut me out. I live now in a world of ghosts, a prisoner in my dreams. " -Antonius Block from The Seventh Seal "In Serbia a lot of people hate me because they want to westernise, not understanding that the western world is bipolar, with very good things and very bad things. Since they don't have experience of the west, they even believe that western shit is pie."-Emir Kusturica | Mid | [
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Uptake by rat liver and intracellular fate of plasmid DNA complexed with poly-L-lysine or poly-D-lysine. Efficiency of transfection is probably dependent on the rate of intracellular degradation of plasmid DNA. When a non-viral vector is used, it is not known to what extent the plasmid DNA catabolism is subordinated to the catabolism of the vector. In the work reported here, the problem was approached by following the intracellular fate in rat liver, of plasmid [35S]DNA complexed with a cationic peptide poly-L-lysine that can be hydrolyzed by cellular peptidases or with its stereoisomer, poly-D-lysine, that cannot be split by these enzymes. Complexes of DNA with poly-L-lysine and poly-D-lysine are taken up to the same extent by the liver, mainly by Kupffer cells, but the intracellular degradation of nucleic acid molecules is markedly quicker when poly-L-lysine is injected. The association of DNA with the polycations inhibits DNA hydrolysis in vitro by purified lysosomes but similarly for poly-L-lysine and poly-D-lysine. The intracellular journey followed by [35S]DNA complexed with poly-L- or poly-D-lysine was investigated using differential and isopycnic centrifugation. Results indicate that [35S]DNA is transferred more slowly to lysosomes, the main site of intracellular degradation of endocytosed macromolecules, when it is given as a complex with poly-D-lysine than with poly-L-lysine. They suggest that the digestion of the vector in a prelysosomal compartment is required to allow endocytosed plasmid DNA to rapidly reach lysosomes. Such a phenomenon could explain why injected plasmid DNA is more stable in vivo when it is associated with poly-D-lysine. | Mid | [
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// OpenVPN -- An application to securely tunnel IP networks // over a single port, with support for SSL/TLS-based // session authentication and key exchange, // packet encryption, packet authentication, and // packet compression. // // Copyright (C) 2012-2017 OpenVPN Inc. // // This program is free software: you can redistribute it and/or modify // it under the terms of the GNU Affero General Public License Version 3 // as published by the Free Software Foundation. // // This program is distributed in the hope that it will be useful, // but WITHOUT ANY WARRANTY; without even the implied warranty of // MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the // GNU Affero General Public License for more details. // // You should have received a copy of the GNU Affero General Public License // along with this program in the COPYING file. // If not, see <http://www.gnu.org/licenses/>. #ifndef OPENVPN_OPENSSL_CRYPTO_API_H #define OPENVPN_OPENSSL_CRYPTO_API_H #include <openvpn/openssl/crypto/cipher.hpp> #include <openvpn/openssl/crypto/ciphergcm.hpp> #include <openvpn/openssl/crypto/digest.hpp> #include <openvpn/openssl/crypto/hmac.hpp> namespace openvpn { // type container for OpenSSL Crypto-level API struct OpenSSLCryptoAPI { // cipher typedef OpenSSLCrypto::CipherContext CipherContext; typedef OpenSSLCrypto::CipherContextGCM CipherContextGCM; // digest typedef OpenSSLCrypto::DigestContext DigestContext; // HMAC typedef OpenSSLCrypto::HMACContext HMACContext; }; } #endif | Mid | [
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The state agency responsible for the certification of educators had received complaints from former GCPS teachers who say Wilbanks and other district officials lied about why they lost their jobs earlier this year. The teachers have said they were laid off for financial reasons, but district officials have maintained the teachers were not rehired due to performance reasons. During its meeting Wednesday, the PSC decided the matter was an employment issue, said Gary Walker, the director of the ethics division. “We took copies (of the complaints) to the Professional Standards Commission for the Commission to review,” Walker said. “They decided it was primarily an employment issue. ... The Commission normally does not investigate employment issues.” At the end of last school year, the contracts of 155 teachers were recommended for nonrenewal. Of those, 139 were in their first three years of teaching in Gwinnett, which means they were nontenured and had fewer due process rights. A number of the teachers chose to resign, leaving 63 nontenured teachers whose contracts were not renewed by the school system. The 16 tenured teachers recommended for nonrenewal all resigned. District officials have said the nonrenewal process is an annual process that addresses employee performance issues. They have maintained that the complaints filed by former employees are without merit. Pete Toggerson, a UniServe director with the Georgia Association of Educators, has spoken with many of the teachers who lost their jobs. He’s not a spokesman for the group, but he’s familiar with the complaints. “It never was about getting their jobs back,” Toggerson said. “That has been a constant misunderstanding of the PSC of what this was about. Either the teachers didn’t communicate what they were saying clearly or the PSC didn’t hear it. The question was, ‘Did they tell the truth?’” Patricia Oakes, a former Gwinnett County Public Schools employee, said she thinks the school system is lying about the situation. She also said it was more than just teachers who were affected. She was an attendance administrator at Lilburn Middle School, and she was let go in June. Oakes said the reason given to her for her termination was poor job performance. However, the year before, she said her performance had been rated as superior. She was also able to collect unemployment. Although not one of the 155 teachers recommended for nonrenewal, Oakes said she has been in touch with many who were on that list. “These were Teachers of the Year. They designed curriculum,” she said. “These were top-notch teachers.” Top-notch teachers who were earning too much money, Oakes said. She said the school system hired new people at a lesser pay rate. “It wasn’t just teachers that the school system did this way,” she said, “and how are they getting away with that? “... We need to pull together. We may need to do a class-action suit.” | Mid | [
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Q: Detect differences between two lists of data.frames Background/Underlying problem: I have a data extraction job from a production database that generates a dataset used as reference for further analytics work . Between every build of the dataset I want to be able to detect if anything has changed in the dataset. The dataset is stored as a list of dataframes. Question: The following code is a simplified version of my dataset account_1 <- data.frame(id = c(1,2), name=c("Andy", "Ben")) account_2 <- data.frame(id = c(1,2,3), name=c("Andy", "Ben2","Ceasar")) bill <- data.frame(id=c(101,102,103), account_id = c(1,2,3), amount=c(100,100,100)) db_1 = list(account=account_1, bill=bill) db_2 = list(account=account_2, bill=bill) I want to be able to detect the delta between db_1 and db_2, which is in the account data frame. Pseudo code: delta(db_1, db_2) Should return account id name 2 Ben2 3 Ceasar bill <<NULL>> The response is read by human, not a machine, so there a no tight formal requirements on the response. Other items to consider: relatively small data sets, no need to bother about memory/speed I like tidyverse code If we can have git-style comments around new records (Ceasar) and modified (Ben) that is great Edit: Data frame comparison can be done by anti_joins (thanks Linus) OR the response in Compare two data.frames to find the rows in data.frame 1 that are not present in data.frame 2 (thanks Vivek) BUT what is the best way of looping through the list of data.frames A: the base function mapply() with let you iterate through multiple objects (lists or vectors): mapply(function(x, y) dplyr::anti_join(x, y), db_2, db_1) # order matters for the result, since it returns rows in x that don't have a match in y $account id name 1 2 Ben2 2 3 Ceasar $bill [1] id account_id amount <0 rows> (or 0-length row.names) if you want to use tidyverse functions then use purrr::map2(): purrr::map2(db_2, db_1, ~ anti_join(.x, .y)) there is also pmap() function if you have more than two lists to compare. | Mid | [
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In the largest study of bisexual Australians to date, researchers at La Trobe University have sought to understand why bisexual people face poorer mental health than either their straight or gay counterparts. What they uncovered was that internalized biphobia, having a less supportive partner, and even being in a heterosexual relationship contribute to psychological distress for bisexual people. “While there has been an increased focus on lesbian and gay health in recent years, general practitioners may be less familiar with the specific health needs of bisexual people,” reads the paper, published in the March issue of the Australian Journal of General Practice. “This is the largest study of bisexual Australians to date and provides detailed information about the relationships between bisexual life experiences and poor mental health.” The “Who I Am” study consisted of a cross-sectional survey of 2,651 bisexual-identified adults living in Australia. Analysis of the participants also showed numerous issues with poor mental health. Related: Bisexual youth are the most likely to be bullied & consider suicide “Bisexual people have consistently been found to have poorer mental health than their gay, lesbian or heterosexual counterparts,” said the paper. “They are significantly more likely than those of other sexual orientations to be diagnosed with a mental health disorder, have symptoms of depression and anxiety, harm themselves, and report suicidal ideation.” Depression and anxiety disorders were the most commonly self-reported issues by those who participated in the “Who I Am” survey, followed by eating disorders and post-traumatic stress disorder. Self-Harm and suicidal ideation were also extremely common amongst study participants. As to why this is, the paper first dispelled a myth, stating that “managing and maintaining monogamy or non-monogamy within relationships” was not a significant contributing to bisexual mental health, instead pointing to internalized biphobia. “The present study supports this, finding that experiencing ‘feeling your sexuality is bad or wrong’ increases the odds of having higher psychological distress,” read the paper. “These findings suggest that self-acceptance of one’s sexuality is an important aspect of mental wellbeing for bisexual people.” Researchers also discovered, perhaps unsurprisingly, that when a bisexual person’s partner is supportive of their sexuality, their mental health benefits. They noted, too, that unlike straight or gay relationships, a bisexual person’s “sexual orientation is not inferred by the gender of their partner nor is it necessarily obvious to their partners when in a relationship.” That said, the study also showed that bisexual people in same-sex relationships seemed to fare better overall than those in straight relationships. “Participants in the ‘Who I Am’ study who were in heterosexual relationships reported significantly poorer mental health than those in same-sex relationships,” reads the study. “This phenomenon has similarly been observed in previous research, with bisexual women finding those in same-sex relationships fared best emotionally while those with a male partner were particularly vulnerable to depressive symptoms and bi-negativity.” The paper added, “this finding challenges the long-promulgated belief that bisexual people in heterosexual relationships are afforded ‘heterosexual privilege’ because they are less exposed to the stressors associated with being in a same-sex relationship, such as having a more visible sexual minority status.” A follow-up study, to be released later this year, will focus on transgender and gender diverse bisexual people. | High | [
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Document Actions Bohne Bohne is a symbolic shape analysis tool. It infers loop invariants of programs manipulating heap-allocated data structures. Bohne is integrated into the Jahob verification system. A standalone version of Bohne will be available, soon. For more information, please contact Thomas Wies. | High | [
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Q: php getting values from session Hey guys I have a quick question I have a session and when I do a print_r of the session this is what I get... Array ( [items] => a:1:{s:2:"1_";a:5:{s:2:"id";s:1:"1";s:4:"name";s:9:"Product 3";s:5:"price";s:5:"20.00";s:6:"option";N;s:3:"qty";N;}} ) I am trying to echo out the price and the name (price = 20.00, name = Product 3) I've tried.. <?php echo $_SESSION['price']; ?> and <?php echo $_SESSION['items']['price']; ?> nothing works...any ideas? A: The contents of $_SESSION['items'] seems to be serialized. Try $items = unserialize($_SESSION['items']); echo $items['1_']['price']; var_dump($items); http://php.net/manual/en/function.unserialize.php | Mid | [
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Q: RegEx: Catch block start with "something" in a text I need a regex to chatch 2 groups: Success (the start of text block) and all the folow, untill next Success Text sample with 3 success block: Success blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla Success blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla Success blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla blablabla This regex stop the block to first \n: (Success|Error|Critical|Warning)\s{8}((.*|\n*?|\r*?|[\r\n]*?)*) A: One of many possibilities would be (with multiline, verbose and singleline enabled): ^(Success|Error|Critical|Warning) .+? (?=^(?:Success|Error|Critical|Warning)|\Z) See a demo on regex101.com. | Mid | [
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Food A cake from a land of cultural confluence The round cake is said to symbolise fullness and family reunion (Photo: VNA) The confluence of three ethnicities in the Mekong Delta province of Soc Trang, that of the Kinh, the Hoa and the Khmer, makes it a great place to discover the beauty of different cultures and observe distinct customs. The distinctive festivals, landmarks and other features also open a door to the Mekong Delta province’s unique culinary specialties influenced by its cultural diversity. For hundreds of years, the Pia cake (a cake filled with durian, shredded lard, salted egg yolk and mung bean paste), originally of the Hoa people, has been served and given as gifts by Soc Trang residents. The Pia cake is served on special occasions during the year, including weddings and the Full Moon Festival. This round cake is seen as a symbol of fullness and family reunion. The cake has a thin crust made of flour and a filling of durian, mung beans and taro with or without salted duck egg. The outer part can be uncovered layer by layer. As the cake is cut, the aroma of the filling is appetising. It’s said that the Pia cake first appeared in Soc Trang in the 17th century when Hoa people migrated to the south of Vietnam. Over the years, Pia cake was adjusted to match the taste buds of other people and it developed into a provincial specialty. Traditionally, the Pia cake was made only for the Full Moon Festival and Tet (Lunar New Year). As with other such food items, the cake is now made and sold all year round. It has a shelf life of up to two months, instead of a fortnight. In order to make an attractive, tasty Pia cake, bakers have to exercise sophisticated skills at several stages. To make the crust, they mix the flour with sugar and finely mill the mixture into very thin layers. The filling of durian, mung bean, taro and salted duck egg, or durian, steamed mung bean, taro and sugar is ground into fine paste and added with a bit of pork fat before being used to cover salted duck egg. The baker then applies a layer of oil to the cake before putting it in the oven at an average of about 270 degrees Celsius. After 5-7 minutes, it is turned over, and baked for another 10 minutes until it turns yellow. The Soc Trang Pia cake is special because the aroma of fresh durian is irreplaceable. Soc Trang now has more than 50 Pia bakeries. Currently, with improved quality and promotion, many enterprises have started selling their product not only in other areas of Vietnam, but also in foreign countries like the US and Cambodia. Today’s Pia cake varies a lot from the traditional version. It fillings now include not only mung bean, taro, durian, salted egg, but also lotus seeds and pineapple. -VNA | Mid | [
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Dopamine D(1) receptor deletion strongly reduces neurotoxic effects of methamphetamine. Methamphetamine (METH) is a potent, highly addictive psychostimulant consumed worldwide. In humans and experimental animals, repeated exposure to this drug induces persistent neurodegenerative changes. Damage occurs primarily to dopaminergic neurons, accompanied by gliosis. The toxic effects of METH involve excessive dopamine (DA) release, thus DA receptors are highly likely to play a role in this process. To define the role of D(1) receptors in the neurotoxic effects of METH we used D(1) receptor knock-out mice (D(1)R(-/-)) and their WT littermates. Inactivation of D(1)R prevented METH-induced dopamine fibre loss and hyperthermia, and increases in gliosis and pro-inflammatory molecules such as iNOS in the striatum. In addition, D(1)R inactivation prevented METH-induced loss of dopaminergic neurons in the substantia nigra. To explore the relationship between hyperthermia and neurotoxicity, METH was given at high ambient temperature (29 °C). In this condition, D(1)R(-/-) mice developed hyperthermia following drug delivery and the neuroprotection provided by D(1)R inactivation at 23 °C was no longer observed. However, reserpine, which empties vesicular dopamine stores, blocked hyperthermia and strongly potentiated dopamine toxicity in D(1)R(-/-) mice, suggesting that the protection afforded by D(1)R inactivation is due to both hypothermia and higher stored vesicular dopamine. Moreover, electrical stimulation evoked higher DA overflow in D(1)R(-/-) mice as demonstrated by fast scan cyclic voltammetry despite their lower basal DA content, suggesting higher vesicular DA content in D(1)R(-/-) than in WT mice. Altogether, these results indicate that the D(1)R plays a significant role in METH-induced neurotoxicity by mediating drug-induced hyperthermia and increasing the releasable cytosolic DA pool. | High | [
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Luigi And The New Quest (SMB1 Hack) [a2] ROM Download for Nintendo (NES) on Emulator Games. Play Luigi And The New Quest (SMB1 Hack) [a2] game that is available in the United States of America (USA) version only on this website. Luigi And The New Quest (SMB1 Hack) [a2] is a Nintendo emulator game that you can download to your computer or play online within your browser. You can also download free ROMs such as Super Luigi Bros (SMB1 Hack), New Ghostbusters 2 and Dragon Quest as shown below. Luigi And The New Quest (SMB1 Hack) [a2] works on all your devices in high quality. | Mid | [
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Q: Fade WS_EX_LAYERED form I have a form which I make click-through using the following function calls: SetWindowLong(Handle, GWL_EXSTYLE, (IntPtr)(GetWindowLong(Handle, GWL_EXSTYLE) ^ WS_EX_LAYERED ^ WS_EX_TRANSPARENT)); SetLayeredWindowAttributes(Handle, 0, 0xFF, LWA_ALPHA); This works fine, however when I try to fade that window using the System.Windows.Forms.Form.Opacity property I get the following exception: System.ComponentModel.Win32Exception (0x80004005): The parameter is not valid at System.Windows.Forms.Form.UpdateLayered() at System.Windows.Forms.Form.set_Opacity(Double value) How can I achieve both things at the same time? A: The following works on a windows form using System; using System.Collections.Generic; using System.ComponentModel; using System.Data; using System.Drawing; using System.Linq; using System.Text; using System.Windows.Forms; using System.Runtime.InteropServices; namespace WindowsFormsApplication30 { public partial class Form1 : Form { [DllImport("user32.dll", SetLastError = true)] static extern System.UInt32 GetWindowLong(IntPtr hWnd, int nIndex); [DllImport("user32.dll", EntryPoint = "SetWindowLong")] private static extern int SetWindowLong32(IntPtr hWnd, int nIndex, uint dwNewLong); [DllImport("user32.dll", CharSet = CharSet.Ansi, SetLastError = true)] static extern int SetLayeredWindowAttributes(IntPtr hWnd, int crKey, byte bAlpha, uint dwFlags); public const int GWL_EXSTYLE = -20; public const uint WS_EX_LAYERED = 0x80000; public const uint LWA_ALPHA = 0x2; public const uint LWA_COLORKEY = 0x1; public Form1() { InitializeComponent(); IntPtr Handle = this.Handle; UInt32 windowLong = GetWindowLong(Handle, GWL_EXSTYLE); SetWindowLong32(Handle, GWL_EXSTYLE, (uint)(windowLong ^ WS_EX_LAYERED)); SetLayeredWindowAttributes(Handle, 0, 128, LWA_ALPHA); } } } | Mid | [
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Ouvrage Croupe du Reservoir Ouvrage Croupe du Réservoir is a lesser work (petit ouvrage) of the Maginot Line's Alpine extension, the Alpine Line. Located on the heights of Roquebrune at an elevation of 139 meters, the ouvrage consists of one entry block and one observation block facing Italy and covering the Grande Corniche road. The fortification was manned by 60 troops of the 58th Demi-Brigade Alpin de Forteresse (DBAF) under the command of sous-lieutenant Roman. Description Croupe-du-Réservoir is located in a hill above Ouvrage Cap Martin, positioned to prevent infiltration along the corniche road. Two blocks are connected by a gallery with short side passages. Block 1 (entry): One machine gun port and one grenade launcher port. Block 2 (infantry): One machine gun cloche. There were no other ports or firing positions. The ouvrage is privately occupied and has been kept in an excellent state of preservation. See also List of Alpine Line ouvrages References Bibliography Allcorn, William. The Maginot Line 1928-45. Oxford: Osprey Publishing, 2003. Kaufmann, J.E. and Kaufmann, H.W. Fortress France: The Maginot Line and French Defenses in World War II, Stackpole Books, 2006. Kaufmann, J.E., Kaufmann, H.W., Jancovič-Potočnik, A. and Lang, P. The Maginot Line: History and Guide, Pen and Sword, 2011. Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 1. Paris, Histoire & Collections, 2001. Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 4 - La fortification alpine. Paris, Histoire & Collections, 2009. Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 5. Paris, Histoire & Collections, 2009. External links Croupe du Réservoir (petit ouvrage) at fortiff.be RESE Category:Maginot Line Category:Alpine Line | High | [
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Buemi: Big expectations for 2011 Sebastien Buemi says he has big expectations about the 2011 season after Toro Rosso launches the new STR6 Sebastien Buemi says he has 'big expectations' about the 2011 F1 season after Toro Rosso launched its STR6 on the opening day of pre-season testing in Valencia. The Swiss driver will lead Toro Rosso for a third season this year having been retained over the winter, with the team being one of those on the grid to have kept an unchanged line-up for the new campaign. With two years of experience now behind him, Buemi said he was aiming high for the year ahead although admits that he will need to push to the maximum to achieve his target of scoring more championship points than in 2010. "I have big expectations to be honest, as I have quite a lot of experience now," he said. "I know all the circuits, I know how Formula 1 works and we also have quite a lot of experience in terms of building up the car. So, if all goes well and hopefully it will, we should be able to score many points and finish in the top eight of the Constructors' championship. "I have to give the maximum, getting the most out of myself and I need to have a good car, which is obvious as it is actually the same for all the drivers. The team is doing a good job to get everything working better than before and hopefully produce a quicker car. We switched the focus to the 2011 car pretty early in the season last year, so I have big hopes for the start of the season and how things will work out." Like many of his rivals, Buemi admitted it was difficult to judge how Toro Rosso will perform against the other teams due to the various changes being implemented in the sport, with the return of KERS, a moveable rear wing and a switch to Pirelli tyres being the major changes made for the year ahead. "This season with all the rule changes, it could be a bit difficult, especially in the early stages at the first few races," he said. "It is not yet really clear how we will use the rear wing and the KERS as we are still awaiting a rule clarification. It will take a bit of time to get used to it, but that will be the job of the drivers to be on top of it to the maximum by the start of the season. We will be trying to get up to speed during the winter tests to see what we can do and how we can improve it. "We had two test days in Abu Dhabi at the end of the last championship [to test the Pirelli tyres] and it will be important to understand them quickly, because this might make a big difference when you get to the first race. We will learn how they work in cold conditions with all the testing in Europe, but as soon as we get to Bahrain the four days of testing will be very important in terms of understanding their behaviour in our qualifying and race simulations." | High | [
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Q: Patten matching to check for non-empty argument list I'm learning Elixir. while building a trivial cli application (as seen here http://asquera.de/blog/2015-04-10/writing-a-commandline-app-in-elixir/) I'm defining a module that implements a main/1 function that accepts a List as an argument. My question is: What is the best way to pattern match a method against a non-empty list ? This is what i did and it seems to work but i was wondering if the elixir community has better suggestions ( maybe def main(args) when is_list(args) and length(args) > 0 do is considered better ? ) defmodule Cli do def main([]) do IO.puts "arguments are needed" end def main([_|_] = args) do options = parse_args(args) input = options[:name] size = options[:size] output(input, size) end def parse_args(args) do {options, _, _} = OptionParser.parse args, switches: [name: :string, size: :integer] options end def output() do IO.puts "Missing required --name parameter" end def output(input) do # defaulting size to 50 output(input, 50) end def output(input, block_size) do IO.puts "you entered #{input} and #{block_size}" end end A: You've implemented it by pattern matching against empty lists with def main([]). If an empty list is passed to main, it will be caught here. In the second def main(args), args should never be an empty list. If you want to make sure that args is a list, you could use a guard clause: def main(args) when is_list(args). (You should then write a catch-all third definition: def main(_)). | Mid | [
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harvmac epsf Martijn Wijnholt and Slava Zhukov .1in *Jefferson Laboratory of Physics, Harvard University* *Cambridge, MA 02138, USA* .5in **Abstract** We examine the attractor mechanism for extremal black holes in the context of five dimensional $N = 2$ supergravity and show that attractor points are unique in the extended vector multiplet moduli space. Implications for black hole entropy are discussed. .3in BPS black holes in four and five dimensional $N = 2$ supergravity have been much studied using the attractor mechanism. To construct a black hole solution, one specifies the charges and asymptotic values of the moduli. The moduli then evolve as a function of the radius until they reach a minimum of the central charge at the horizon. This minimum value determines the entropy of the black hole. Consequently, it is important to know if different values of the central charge can be attained at different local minima, or perhaps even more basically if multiple local minima are allowed. If uniqueness fails, one would be led to believe that the degeneracy of BPS states does not solely depend on the charges. As it turns out, in the five dimensional case we can show that at most one critical point of the central charge can occur; that is the subject of this paper. The structure of the argument is simple. Remarkably, the extended Kähler cone turns out to be convex. Therefore we can take a straight line between two supposed minima and analyse the (correctly normalised) central charge along this line. The central charge cannot have two minima when restricted to this line, yielding a contradiction. We would like to emphasize that although Calabi-Yau spaces will be in the back of our minds for most of this paper, the geometric statements have clear analogues in five dimensional supergravity, so that our arguments are independent of the presence of a Calabi-Yau. We will point out some of the parallel interpretations where they occur. In section two we provide two arguments for uniqueness in a single Kähler cone. In section three we tackle the extended Kähler cone, and in section four we discuss some of the implications. The reader may wish to start with section four before moving on to the arguments of sections two and three. Let us recall the basic setting for the five-dimensional attractor problem. We consider M-theory compactified on a Calabi-Yau threefold. As the low-energy effective theory we obtain five dimensional $N=2$ supergravity with $h^{1,1}-1$ vector multiplets, $h^{2,1}+1$ hypermultiplets and the gravity multiplet\[\]. The vector multiplets each contain one real scalar, so the vector moduli space is $h^{1,1} - 1$ dimensional. From the point of view of Calabi-Yau compactification these scalars have a simple geometrical interpretation. Let us denote the Calabi-Yau three-fold by $X$ and expand two-cycles $Q$ of $X$ as $Q = Q_i \, e^i$, where $e^i$ is a basis for $H_2(X,\bf{Z})$. The dual basis for $H^2(X,\bf{Z})$ will be written with lower indices, $e_j$, so that $\left< e_j e^i \right> =\delta^i_j$. The Calabi-Yau Kähler class $k$ can be expanded as $k = k^i \, e_i$ which gives an $h^{1,1}$ dimensional space of parameters. One parameter corresponding to the total volume of the Calabi-Yau is part of the universal hypermultiplet and the rest of the parameters corresponding to the sizes of cycles in the Calabi-Yau describe precisely the moduli space of vector multiplets. The dynamics of vector multiplets in $N=2$ supergravity is completely governed by the prepotential $F(k)$, which is a homogeneous cubic polynomial in vector moduli coördinates $k^i$. It is a special property of five dimensional supergravity that there are no nonperturbative quantum corrections to this prepotential\[\]. Geometrically the prepotential is simply the volume of $X$ in terms of $k$ where $d_{ijl}$ denote the triple intersection numbers of $X$ $$d_{ijl} = \int_X e_i \wedge e_j \wedge e_l.$$ In order to abbreviate the formulae, let us introduce the following notation: $$\eqalign{ a \cdot b &\equiv a_m b^m \cr a \cdot b \cdot c &\equiv a^i b^j c^l d_{ijl} \cr k^3 &\equiv k \cdot k \cdot k }$$ To decouple the universal hypermultiplet coördinate we need to impose the constraint $F(k)=1$ which gives us the vector moduli space as a hypersurface inside the Kähler cone. Alternatively, we will sometimes think of the moduli space as a real projectivisation of the Kähler cone. In this case we have to consider functions invariant under overall rescaling of $k$’s. The prepotential defines the metric on moduli space as well as the gauge coupling matrix for the five-dimensional gauge fields. Including the graviphoton, there are exactly $h^{1,1}$ $U(1)$ gauge fields in the theory and their moduli-dependent gauge coupling matrix is given by\[\] The moduli space metric $g_{ij}$ is just the restriction of $G_{ij}$ to the hypersurface $F(k)=1$. In the supergravity Lagrangian $G_{ij}$ and $g_{ij}$ multiply kinetic terms for the gauge fields and the moduli fields respectively. It is then very important that both metrics should be positive-definite inside the physical moduli space. The tangent space to the $F(k)=1$ hypersurface is given by vectors $\Delta k$ such that $k \cdot k \cdot \Delta k =0 $. Then positivity of $g_{ij}$ requires Next we consider BPS states with given electric charges. The vector of electric charges with respect to the $h^{1,1}$ $U(1)$ gauge fields can be thought of as an element $Q$ of $H_2(X,\bf{Z})$. In M-theory language these BPS states are M2-branes wrapped on a holomorphic cycle in the class $Q$. For large charges we can represent them in supergravity by certain extremal black hole solutions\[\].The structure of these solutions is as follows. As one moves radially towards the black hole the vector multiplet moduli fields $k^i$ vary. They follow the gradient flow of the function $Z \equiv Q \cdot k$: $$\eqalign{ \partial_{\tau} U &= + {1\over 6} e^{-2 U} Z \cr \partial_{\tau} k^i &= -{1\over 2} e^{-2U} G^{ij} D_j Z }$$ Here $U \equiv U(r)$ is the function determining the five dimensional metric $$ds^2 = - e^{-4U} dt^2 + e^{2U} (dr^2 + r^2 d\Omega^2),$$ $\tau = 1/ r^2$ and the covariant derivative is $$D_j = \partial_j - {1\over 6} k^i k^l d_{ijl}.$$ Geometrically $Z$ is just the volume of the holomorphic cycle $Q$ in the Calabi-Yau with Kähler class $k$. We will refer to $Z(k)$ as the central charge because when evaluated at infinity, $Z$ is indeed the electric central charge of the $N = 2$ algebra. As we approach the horizon of the black hole at $r = 0$ or $\tau = \infty$, the central charge rolls into a local minimum and the moduli stabilise there, let us call that point $k_0$. The area of the horizon and thus the entropy of the black hole are determined only by the minimal value of the central charge : Those points in the moduli space where the central charge attains a local minimum for a fixed electric charge $Q$ are called attractor points. The microscopic count of the number of BPS states with given charge has been performed for the special case of compactifications of M-theory on elliptic Calabi-Yau threefolds\[\].There the attractor point for any charge vector $Q$ was found explicitly and the resulting entropy prediction agreed with the microscopic count for large charges. It was pointed out in\[\] that in the case of general Calabi-Yau compactifications an attractor point is not necessarily unique, and in principle for making an entropy prediction one needs to specify not only the charges of the black hole, but also an attractor basin, that is one needs to specify a region in moduli space in which all the points flow to a given attractor point along a path from infinity to the horizon. In the remainder of this article we show that if a minimum of the central charge exists, the attractor basin for this minimum covers the entire moduli space. There cannot be a second local minimum and so the specification of the charges of the black hole is sufficient for determining the attractor point. To find an attractor point explicitly, one needs to extremise the central charge subject to the constraint ${k \cdot k \cdot k = 1}$, which leads directly to the five dimensional attractor equation $$Q_i = (Q \cdot k)\, k^j\, k^l\, d_{ijl}$$ In differential form notation, it reads Here $[Q]$ is a four-form which is Poincaré dual to the two-cycle $Q$. For convenience, we will leave out the square brackets in what follows. Let us recall some standard facts about the Lefschetz decomposition (see for instance\[\]). On any Kähler manifold the Kähler class is a harmonic form of type (1,1). It can therefore be used to define an action on the cohomology. We define the raising operator to be the map from $H^{p,q}(X, {\bf C})$ to $H^{p+1,q+1}(X, {\bf C})$ obtained by wedging with $k$ $$L_k \alpha = k \wedge \alpha$$ and similarly the lowering operator to be the map from $H^{p,q}(X, {\bf C})$ to $H^{p-1,q-1}(X, {\bf C})$ obtained by contracting with $k$ $$\Lambda_k \alpha = \iota_k \alpha.$$ The commutator sends forms of type (p,q) to themselves up to an overall factor: where $n$ is the complex dimension of $X$. Thus $L$, $\Lambda$ and $(p + q - n) {\bf I} $ form an $sl(2,{\bf R})$ algebra and the cohomology of $X$ decomposes as a direct sum of irreducible representations. When $X$ is a Calabi-Yau threefold, the decomposition is $$H^*(X,{\bf C}) = 1({\bf {3/2}}) \oplus (h^{1,1} - 1)({\bf {1/2}}) \oplus (2 h^{2,1} + 2)({\bf 0}).$$ The spin 3/2 represenatation corresponds to $\{1, k, k^2, k^3\}$. There can be no spin 0 representations in $H^{1,1}(X,{\bf C})$ because if $\alpha$ is of type (1,1) and $L_k \alpha = 0$ then by equation we deduce that $\alpha$ is zero. In particular, the raising operator $L_k$ maps classes of type (1,1) isomorphically onto classes of type (2,2). We will use this fact in the following argument. To prove that a single Kähler cone supports at most one attractor point, assume to the contrary that there are two such points, $k_0$ and $k_1$, satisfying . Then we may rescale $k_0$ or $k_1$ by a positive factor such that First we fix the sign in the above equation. Since ${1\over 2}(k^0 + k^1)$ is inside the Kähler cone, $k^0 + k^1$ is an admissible Kähler class and $\int_X (k^0 + k^1)^{\wedge 3}$ is positive. Assuming the sign in is minus, one may expand $(k_0 + k_1)^{\wedge 3}$ and deduce that $$\int (k_0 + k_1)^{\wedge 3} = -2\int (k_0)^{\wedge 3} -2\int (k_1)^{\wedge 3} < 0 \;,$$ which is impossible, so the sign is a plus. Therefore we have $$(k_0 + k_1) \wedge (k_0 - k_1) = 0.$$ As discussed above, $L_{k_0 + k_1}$ cannot annihilate any classes of type (1,1) because $k^0 + k^1$ is an allowed Kähler class. We conclude that $k_0 - k_1$ must vanish. One doesn’t really need the attractor equation to prove that in a single cone multiple critical points cannot occur. Another argument makes use of the simple properties of the prepotential and gives further insight into the behaviour of the central charge function. Let us examine the behaviour of the central charge along straight lines in the Kähler cone. First take any two points $k_0$ and $k_1$ in the Kähler cone. By convexity of the cone we can take a straight line from $k_0$ to $k_1$, For $t$ between $0$ and $1$ and a little bit beyond those values $k(t)$ certainly lies in the Kähler cone, but it no longer satisfies $k(t)^3=1$. To cure this we think of the moduli space as a real projectivisation of the Kähler cone and define the central charge everywhere in the cone by normalising $k$: Then the central charge along the straight line is just Let us also assume that the central charge is positive at $k_0$, i.e. $Z(0)>0$. Otherwise we would consider the same problem with the opposite charge. Differentiating $Z(t)$, one finds for the first derivative Now suppose $Z(t)$ has a critical point $t_c$ where $Z'(t_c) = 0$. Then the second derivative at $t_c$ can be expressed as $$\eqalign{ Z''(t_c) &= 2 (k^3)^{-4/3} (Q \cdot k) \left( {(\Delta k \cdot k \cdot k)^2 \over k^3} - \Delta k \cdot \Delta k \cdot k \right) \cr &= 2 (k^3)^{-4/3} (Q \cdot k) (B_{ij} \, \Delta k^i \Delta k^j).}$$ The bilinear form $B_{ij}$ has the following properties: exactly one of its eigenvalues is zero (namely in the $k$-direction) and the other eigenvalues are positive. In the language of Calabi-Yau geometry this holds because $\int_X k \wedge \Delta k \wedge \Delta k < 0$ for any $\Delta k$ that satisfies ${\int_X k \wedge k \wedge \Delta k = 0}$. Now if $\Delta k$ would be proportional to $k(t) = k_0 + t \Delta k$ for some $t$, we would find that $k_0$ and $k_1$ are in fact equal. Thus $\Delta k$ necessarily has a piece that is orthogonal to $k(t)$ and so $$B_{ij} \, \Delta k^i \Delta k^j > 0 \; \; {\rm strictly}.$$ In the language of supergravity the above statement follows from the fact that the form $B$ is proportional to the metric when restricted to directions tangent to the moduli space, for which $k \cdot k \cdot \Delta k = 0$, see . The zero eigenvalue in the $k$-direction is simply the scale invariance of $Z(k)$. The above inequality can be expressed in the following words: for positive central charge [*any critical point along any straight line is in fact a local minimum!*]{} For negative $Z$ every critical point along a straight line is a local maximum. It is well known that a critical point of the central charge is a minimum when considered as a function of all moduli. Here we have a much stronger statement. We see that on a one-dimensional subspace (a projection of a straight line) any critical point is in fact a local minimum. We can use the above observation as follows. The central charge $Z$ has a local minimum at the attractor point $k_0$ by definition. Therefore it must grow continuously on any straight line emanating from $k_0$ and can never achieve a second local minimum. Moreover, we see that the central charge has a global minimum at $k_0$ in the entire Kähler cone. Let us remark on another consequence of our observation. Consider level sets of the central charge function, i.e sets where $Z<a$ for some constant $a$. Note that all such sets are necessarily convex. For otherwise, if we could connect two points inside a level set by a line segment venturing outside it, there would be a maximum of the central charge on that line segment, which contradicts the above observation. The single Kähler cone we have just discussed is only a part of the full vector moduli space. Some of the boundaries of the Kähler cone correspond to actual boundaries of the moduli space. At other boundaries the Calabi-Yau undergoes a flop transition, that is a curve collapses to zero size, but one may continue through the wall and arrive in a different geometric phase. There one has another Calabi-Yau which is birationally equivalent to the original one. They share the same Hodge numbers but have different triple intersection numbers. In terms of the original Kähler moduli, the collapsed curve has a finite but negative area on the other side of the wall. In five dimensions this has the interpretation of a phase transition where a BPS hypermultiplet goes from positive to negative mass. The union of the Kähler cones of all Calabi-Yaus related to each other through a sequence of flop transitions is called the extended Kähler cone. Geometrically one cannot go beyond the boundaries of this extended cone. It has also been argued that at the boundaries that are at finite distance the physical vector moduli space ends . After we cross the wall into an adjacent cone we may take linear combinations of Kähler parameters $k^i$ in order to get an acceptable set of moduli that yield positive areas for two- and four-cycles. But we will find it more convenient to stick to the original $k^i$, even though they can sometimes yield negative areas outside the original cone. By induction, we may still use the $k^i$ if we pass through a second flop transition into a third cone, and so on. The Calabi-Yau in the adjacent cone has different intersection numbers, which means that we have to adjust the prepotential for the new cone. It is well known how the prepotential changes when one passes through a wall: if we denote by $m$ the area of the collapsing curve that is negative on the other side of the wall, then\[\] Here $\# {\bf P}^1$ stands for the number of ${\bf P}^1$’s shrinking to zero size at the wall. Intuitively, the growing curve should contribute a positive number to the volume of the Calabi-Yau for $m < 0$, hence the minus sign in . This sign is crucial for proving uniqueness of attractor points in the extended Kähler cone. Physical quantities experience only a mild change at the flop transition . In particular from we see that the prepotential is twice continuously differentiable. The central charge $Z$ is also twice continuously differentiable. The metric, which involves second derivatives of the prepotential, is only continuous. The extended Kähler cone has an alternative description in terms another cone, as we will explain below. The advantage of this description comes from the fact that this other cone is manifestly convex, hence so is the extended Kähler cone. We will only give a brief sketch of the argument here and simply use the result in the remainder of the paper. For a detailed proof, one may consult the mathematics literature \[\] (see also ). There is a one to one correspondence between real cohomology classes of type (1,1) and line bundles. Namely, given such a class $[\omega]$, one may find a line bundle $L_{[\omega]}$ such that its first Chern class is $[\omega]$, and conversely. In order to apply some standard constructions in algebraic geometry, we will assume that $[\omega]$ is a rational class, that is it is a class in the intersection of $H^{1,1}(X,{\bf C})$ and $H^2(X,{\bf Q})$. With appropriate restrictions, some high tensor power of $L_{[\omega]}$ will have sufficiently many holomorphic sections to define a ‘good’ map to some projective space, as follows: choose a basis of holomorphic sections ${s_0, s_1, \ldots, s_n}$. Then we get a map $f_{[\omega]}$ from $X$ to ${\bf P}^n$ by sending a point $p$ in $X$ to the equivalence class $[s_0(p), s_1(p), \ldots , s_n(p)]$. Let us call the image $Y$. Some points $p$ may be a common zero for all the $s_i$’s. The collection of such points is called the [*base locus*]{} of $L_{[\omega]}$. Under $f_{[\omega]}$ the base locus is mapped to the origin in ${\bf C}^{n + 1}$, so when one projectivises ${\bf C}^{n + 1}$ cycles in the base locus may get contracted and points may get smeared out. Away from the base locus the map $f_{[\omega]}$ is an isomorphism. In order to insure that the image will be a Calabi-Yau that is related to $X$ by flop transitions at most, we require that $[\omega]$ is [*movable*]{}, which means that the base locus is of complex codimension at least two in $X$. This condition means that the map $f_{[\omega]}$ is an isomorphism in codimension one, i.e. the most that can happen is that some two-cycles contract or some points expand to two-cycles. In particular, the canonical class of $Y$ must be trivial, so $Y$ is a Calabi-Yau. Finally, by construction the holomorphic sections of (some multiple of) $L_{[\omega]}$ get transformed into hyperplane sections, which are the sections of the line bundle corresponding to the Kähler class on $Y$. So the pull-back of the Kähler class on $Y$ is precisely (some multiple of) $[\omega]$. It is well known that when $[\omega]$ is taken to be in the original Kähler cone of $X$, $f_{[\omega]}$ will give a smooth embedding of $X$ in projective space. Hopefully we have made it plausible that for any rational class $[\omega]$ of type (1,1) on $X$, provided it is movable, we can find a Calabi-Yau $Y$ which has Kähler class (a multiple of) $[\omega]$ and is related to $X$ by flop transitions. Conversely, given a Calabi-Yau $Y$ with rational Kähler class $[\varpi]$ and related to $X$ by flops, it can been shown that the transform of $[\varpi]$ on $X$ is movable. Therefore the extended rational Kähler cone is precisely the rational cone generated by movable classes of type (1,1). We want to discuss why the property of movability is preserved under positive linear combinations. To see this, take two classes $[\omega_1]$ and $[\omega_2]$ and consider the sum $[\omega] = m [\omega_1] + n [\omega_2]$ where $m$ and $n$ are positive rational numbers. Since we may multiply $[\omega]$ by any integer, we may assume that $m$ and $n$ are themselves integer and moreover large enough for the following argument to apply. The corresponding line bundle is $$L_{[\omega]} = {L_{[\omega_1]}}^{\otimes m} \otimes { L_{[\omega_2]}}^{\otimes n} .$$ Take a basis of holomorphic sections $s_i$, $i = 0 \ldots n_1$, for ${L_{[\omega_1]}}^{\otimes m}$. This defines a map to ${\bf P}^{n_1}$. Similarly choose basis $t_j$, $j = 0 \ldots n_2$, for ${L_{[\omega_2]}}^{\otimes n}$. Then $L_{[\omega]}$ defines a map to ${\bf P}^{n_1 n_2 + n_1 + n_2}$ by means of the sections $s_i \otimes t_j$. Thus the base locus of $L_{[\omega]}$ is the union of the base loci of ${L_{[\omega_2]}}^{\otimes m}$ and ${L_{[\omega_2]}}^{\otimes n}$, and in particular is of codimension at least two. So we conclude that the cone generated by movable classes is convex, and therefore that the extended Kähler cone is convex. Armed with the knowledge that the extended Kähler cone is convex, we may try to employ the argument that was used successfully in section two. We start with the local minimum of the central charge at the attractor point $k_0$. Then on straight lines emanating from $k_0$ the critical points of $Z$ are all minima as long as they are [*inside*]{} some Kähler cone. However, a critical point may lie on the boundary between two cones in which case our argument that it must be a minimum doesn’t apply. Recall that we needed the form $B_{ij}$ to be positive in the direction of the line. This followed from the physical requirement of the positivity of the metric inside the moduli space, so that $B_{ij}$ is positive-definite for all directions tangent to the moduli space. But continuity of the metric alone does not prevent it from acquiring a zero eigenvalue on the flopping wall and so in principle $B_{ij}$ may become degenerate there. We are not aware of a proof of nondegeneracy of the metric (or a counterexample). Thus it may be possible for a critical point of the central charge along a straight line to have vanishing second derivative when it lies on the wall between two Kähler cones. Depending on the details of the behaviour of $Z'$ such a critical point may be a local minimum, maximum or an inflection point. By the same token, it may even be that an attractor point $k_0$ is not a local minimum of the central charge on the extended moduli space, but rather a saddle point. We therefore switch to a more direct argument. We will first consider the case when $k_0$ itself is not on the wall and consequently it is a local minimum. Let us again examine the central charge function along a straight line between an attractor point $k_0$ and some other point $k_1$ inside the extended moduli space. If $k_1$ were another attractor point, then it would also be a critical point of $Z(t)$ at $t=1$, which is why we will be looking at the critical points of $Z(t)$. As we know, the only source of trouble are the points where our line crosses walls of the Kähler cone. Let us first consider the case where only a single wall is crossed between $t = 0$ and $t = 1$. Suppose that the intersection is at $t = t_f$. Rather than looking at the central charge $Z(t)$ itself, we will examine its derivative. The derivative of $Z$ was The cubic terms in the second term of $Z'$ cancel, so we put $$Z'(t) = (k^3)^{-4/3}R(t)$$ where $R(t)$ is a polynomial of degree two. As $(k^3)^{-4/3}$ is nonnegative, we will focus on $R(t)$. By assumption $t = 0$ is a local minimum for $Z$, i.e. it is a root for $R(t)$ where $R' > 0$. Recall that at the attractor point we start with a positive value of the central charge. It is important that for positive $Z$ the only physical root of $R(t)$ is the one where the first derivative is positive or possibly zero if such a root is on the flopping wall. The other root of $R(t)$ is not physical, i.e. it lies outside the original Kähler cone. Thus $Z(t)$ has only one critical point in a cone, which is another proof of uniqueness for a single cone. Now we will see what happens in the adjacent cone. First we need to know the point where $Z(t) \sim Q \cdot k(t)$ vanishes, call it $t_0$. With this definition we may write When we cross the flopping wall at $t = t_f$ the prepotential changes as $$k^3 \to k^3 + c( t - t_f)^3$$ where $c>0$. So we must also modify $Z'(t)$ for $t > t_f$: $$\eqalign{ Z'(t)\big|_{t>t_f} &= (k^3 + c( t - t_f)^3 )^{-4/3} \left( R(t) + c(Q \cdot \Delta k - Q \cdot k_0) ( t - t_f)^2 \right) \cr &=(k^3 + c( t - t_f)^3 )^{-4/3} \left( R(t) + c\ Q \cdot k_0 \left( {t_f \over t_0} - 1 \! \right)( t - t_f)^2 \right) \cr &=(k^3 + c( t - t_f)^3 )^{-4/3} P(t) .}$$ We are interested in the physical roots of $P(t)$ for $t \ge t_f$. As long as $Z(t)$ is positive those are the roots where $P' \ge 0$. $Z(t)$ is positive for all $t>0$ if $t_0 < 0 $ while if $t_0 > 0$ it is only positive for $t < t_0$. In both cases the constant $ A \equiv c\ Q \cdot k_0 \left( {t_f \over t_0} - 1 \! \right) $ is negative. First we show that for $A<0$ there are no physical roots of $P(t)$ for $t \ge t_f$. For that we simply find the root $t_r$ where $P' \ge 0$ and show that $t_r < t_f$. It will also imply that $Z(t)$ may not start decreasing and therefore cannot become negative inside the extended moduli space. We write $R(t) = a t^2 +b t$ where $b>0$ since $t=0$ is a minimum of $Z$. Then we need to find roots of the quadratic equation $$P(t) = a t^2 +b t + A (t-t_f)^2 = 0$$ The root where the derivative $P'(t)$ is nonnegative, if it exists, is always given by $$t_r = { 2 A t_f - b + \sqrt{b^2+4 t_f(-A)(b+a t_f)}\over 2(a+A)}$$ Then there are four cases to consider depending on the value of the coefficient $a$. [1.]{} $a \leq -b/t_f < 0 $, note that $a + A <0$ and $b + a t_f < 0$, see Fig.1. In this case there may be no roots, but if there are, we have $$t_r < { 2 A t_f - b \over 2(a+A)} \leq { 2 A t_f + a t_f \over 2(a+A)} < t_f.$$ This case is not physical, because the second root of $R(t)$ is inside the original Kähler cone which gives unphysical maximum of the central charge. We include this case for future reference. Fig. 1 [2.]{} $-b/t_f < a < -A$, still $a + A < 0$ but $b + a t_f > 0$. Now there are always roots and we have [3.]{} $a = -A > 0$. In this case $P(t)$ is linear. It has only one root, which satisfies $$t_r = {a\, t_f^2 \over b + 2 a t_f} < t_f.$$ [4.]{} $-A < a$, see Fig.2. As in item $2$ we replace $-A$ by $a$ inside the square root. The resulting equations are exactly the same as in . Fig. 2. What we have found is that $P(t)$ doesn’t have physical roots in the new Kähler cone. This means that $Z(t)$ doesn’t have critical points there and therefore continues to grow as we go away from the attractor. It follows that we need not consider the case when the central charge is negative. Crossing several walls can now be handled by induction. The polynomial $P(t)$ after the wall plays the role of $R(t)$ for the next crossing. We have shown that $P(t)$ has a root where $P'>0$, but it lies to the left of the new wall, therefore we are in the same situation as we started. Let us comment on the (im)possibility of the critical point of $Z(t)$ which lies on the flopping wall and is a local maximum. It would correspond to the situation where $R$ and $R'$ both vanish (recall that $R'$ cannot be negative at the critical point by continuity and positivity of the metric away from the flopping wall). Such a point can be described by a situation in item 4 above with $b=0$, $t_f = 0$ and both roots of $R(t)$ at $0$. As $R(t)$ is positive to the left of the wall and $P(t)$ is negative to the right of it, this critical point is a local maximum. However, $R(t)$ cannot have a double zero at $t_f$ because we have shown that it always has one root strictly to the left of the wall. Therefore such critical points do not arise. Finally, we are left to consider the case when $k_0$ itself lies on the flopping wall. Then $P(t)$ may be either positive or negative to the right of the wall. In the former case $Z(t)$ starts growing for $t>0$ and the analysis we have made earlier carries over with no changes. In the latter case $k_0$ may be a local maximum in some directions precisely as described in the previous paragraph. The difference is that we now begin in this situation and cannot argue that $R(t)$ does not have a double root on the wall. In such a case the central charge decreases from $t=0$ and it may eventually become negative. While it is still positive the first wall crossing is described essentially by the situation in item 1 above, with $b=0$. It is then clear that $P(t)$ will have no roots after all subsequent wall crossings while $Z(t)>0$. Moreover, in every cone $P(t)$ will be a downward-pointing parabola with the apex to the left of the left wall. After the central charge becomes negative the discussion changes in two ways. First, when crossing the wall the constant $A$ in the change from $R(t)$ to $P(t)$ becomes positive: $$R(t) \to P(t) = R(t) + A(t-t_f)^2, \quad A>0.$$ And second, the physical critical points are now the roots of $R(t)$ where the first derivative is negative or possibly zero if the root is on the flopping wall. Now, $Z(t)$ is decreasing when it becomes negative, therefore the first critical point after that may only be on the wall of some cone such that $R(t)$ has a double zero. If we assume that this critical point exists, right before it $R(t)$ would be a downward pointing parabola with a double zero on the wall. We can move backwards from it and reconstruct the polynomials $R(t)$ and $P(t)$ in all the preceding cones. Taking into account that the constant $A$ is now positive but has to be subtracted, we see that while $Z$ is negative $R(t)$ in every cone is a downward pointing parabola with no roots and apex to the right of the right wall. In the cone where $Z$ crosses zero we obtain a conradiction with the previous analysis where we have found that the apex of the parabola should be to the left of the left wall. Therefore, there cannot be multiple attractor points even when they lie on the walls between Kähler cones. In this paper we have demonstrated that a critical point of the central charge $Z$ is unique if it exists. Moreover, if $Z$ has a minimum (maximum) at the critical point then it will grow (decrease) along straight lines emanating from the critical point. In this section we will discuss two implications of our result. If one restricts the moduli to lie inside a single Kähler cone then uniqueness is not surprising. The reason for this derives from the microscopic interpretation of entropy: it should be possible to reproduce the entropy of a BPS black hole by a microscopic count of degenerate BPS states. For the Calabi-Yau black holes considered in this paper, we would have to count the degeneracy of holomorphic curves within the class specified by the charge vector. As we have seen in section two, the macroscopic entropy predicted by the attractor mechanism is $S = {\pi^2 \over 12} \, Z_0^{3/2}$. Thus one expects that the degeneracy of BPS states for large charges, when supergravity should give a good description, asymptotically approaches $e^{{\pi \over 24} Z_0^{3/2}}$. In the count was done for the special case of elliptic threefolds. The attractor equation in that case could be solved explicitly and the attractor point was therefore unique (at least in a single Kähler cone). But even for a general Calabi-Yau one should not have expected multiple attractor points to occur in a single Kähler cone. Supergravity is well-behaved when the moduli vary only over a single cone and so the existence of two black hole solutions with different entropy should have its origin in the possibility of counting different BPS state degeneracies. But the number of holomorphic curves does not change inside a Kähler cone, so neither should the number of BPS states. So at least inside a single Kähler cone, it is clear that the entropy should be completely fixed by specification of the charges of the black hole. In the extended moduli space however this is not so clear: the number of curves does change as one crosses a flopping wall. One could therefore interpret the walls of a Kähler cone as a hypersurface of marginal stability, analogous to the curve of marginal stability in Seiberg-Witten theory. The puzzle is this: suppose one starts with asymptotic moduli at some point very far away from the attractor point. Then somehow the attractor point seems to be aware of the degeneracy of BPS states for the Calabi-Yau associated with the asymptotic moduli. But when we choose the asymptotic moduli in a cone that is different from the cone where the attractor point lies, the degeneracies in the two cones will in general not be the same, so there is no a priori reason for the absence of multiple critical points. In the light of our result, one possibility is that the number of curves changes only very mildly across a transition, mild enough so that the asymptotic degeneracy in the limit of large charges is not affected. It would be interesting to check this mathematically. The existence of multiple attractor points was also thought to be desirable for the construction of domain walls in five dimensional $N = 2$ gauged supergravity, along the lines of \[\]. In that setup the goal is not to minimise the central charge, but to find extrema of the scalar potential of gauged supergravity, which is $$V = - 6 ( W^2 - {3\over 4} g^{ij} \partial_i W \partial_j W).$$ In the above, $W = Q_i k^i$ where $k^i$ are the usual Kähler moduli and $Q_i$ are the gravitino and gaugino charges under the $U(1)$ that is being gauged. Even though the interpretation is different, $W$ is numerically the same as what we have called $Z$ before and the supersymmetric critical points of $V$ are also critical points of $W$ . At a critical point $W_0$ of $W$ the five dimensional supergravity solution is anti-De Sitter space with cosmological constant equal to $-6 W_0^2$. To construct a domain wall, one would like to have two critical points $k_0$ and $k_1$ of $W$. Then one could write down a supergravity solution that interpolates between two different anti-De Sitter vacua, with the asymptotic values of the moduli being $k_0$ on one side of the wall and $k_1$ on the other. It was hoped that this might lead to a supergravity realisation of the Randall-Sundrum scenario \[\]. Unfortunately as we have seen, this construction does not appear to be possible, at least in its simplest form, because of the absence of multiple (supersymmetric) critical points. Finally, the attractor mechanism in four dimensions is somewhat similar to the five dimensional mechanism considered in this paper. It would be interesting if our methods could be used to shed some light on this important problem as well. [**Acknowledgements:**]{} We would like to thank M. Bershadsky, R. Gopakumar, S. Nam, A. Klemm, T. Pantev, and especially D. Morrison and C. Vafa for valuable discussions and support. The work of SZ was supported in part by the DOE grant DE-FG02-91ER40654. | Mid | [
0.607929515418502,
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[Forensic age estimation in juveniles and young adults: Reducing the range of scatter in age diagnosis by combining different methods]. The dramatic rise in the number of refugees entering Germany means that age estimation for juveniles and young adults whose age is unclear but relevant to legal and official procedures has become more important than ever. Until now, whether and to what extent the combination of methods recommended by the Study Group on Forensic Age Diagnostics has resulted in a reduction of the range of scatter of the summarized age diagnosis has been unclear. Hand skeletal age, third molar mineralization stage and ossification stage of the medial clavicular epiphyses were determined for 307 individuals aged between 10 and 29 at time of death on whom autopsies were performed at the Institutes of Legal Medicine in Berlin, Frankfurt am Main and Hamburg between 2001 and 2011. To measure the range of scatter, linear regression analysis was used to calculate the standard error of estimate for each of the above methods individually and in combination. It was found that combining the above methods led to a reduction in the range of scatter. Due to various limitations of the study, the statistical parameters determined cannot, however, be used for age estimation practice. | Mid | [
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33.5,
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Late antibody-mediated rejection by de novo donor HLA-DP-specific antibody after renal transplantation: a case report. The role of donor HLA-DP-specific antibodies after renal transplantation is controversial, and only preformed HLA-DP-specific antibodies have been shown to mediate rejection. Here we present a case of late humoral rejection mediated by de novo donor HLA-DP-specific antibodies in a non-sensitized recipient. This unique case demonstrates the pathogenic role of de novo anti-DP antibodies and suggests that HLA-DP matching might be relevant for renal transplantation. | High | [
0.690161527165932,
29.375,
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Being a big fan of smoking and grilling, I am always out to try new things. This time I decided to throw some shrimp into the smoker. It turned out to be a pretty easy thing, but I’m not sure if I would throw them in the smoker again. It seemed like they were in there for to little amount of time. I think skewered on the grill is the way to go. But, if your interested in trying it yourself, here is what I did. I took around a pound of unpeeled jumbo shrimp. I peeled them, deveined them, and lined them inside a 9 x 13 aluminum pan. In the bottom of the pan, I poured about a stick of melted butter. I would do a half stick next time. Here is the rub I used for the shrimp. 2 Tablespoons Old Bay Seasoning 2 Tablespoons Salt 2 Tablespoons Paprika 2 Tablespoons (I would use way less next time) 2 Tablespoons 2 Tablespoons Garlic 1 lb Jumbo Shrimp 1 Lime 1 Stick Unsalted Butter I put the cleaned shrimp in a bowl, poured the seasoning over them, placed a plate over the bowl and shook until all the shrimp were coated. I lined them flat in the pan and let them sit in the fridge for about 2 hours. I set the temp for the smoker at 225 degrees and I used some hickory wood chips. I put the pan of shrimp on the middle rack and closed the door. The nice thing about shrimp is that they have their very own built in timer. They will go from a bland grey color to a bright pink color when they are done. This only took about 20 minutes, so don’t run to far from your smoker. If you wait to long, they start to get rubbery, and no one will be happy with them. At the 20 minute mark, I scooped the shrimp out of the left over butter and put them onto a paper towel on a plate to drain. Once they were drained, I squeezed fresh lime over them and they were awesome! Keep an eye out for future recipes! | Mid | [
0.573737373737373,
35.5,
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SphinxOS 4.0 Home Edition Screenshot Tour SphinxOS is a commercial offspring of MEPIS Linux developed for the German-speaking market. The "Home Edition" of the product (without CrossOver, Cedega and support) can now be downloaded free of charge. OSDir took advantage of this great opportunity and took SphinxOS through it's paces. | High | [
0.662473794549266,
39.5,
20.125
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Time trends in the incidence and disease location of Crohn's disease 1980-1995: a prospective analysis in an urban population in Germany. To determine the incidence and clinical pattern of Crohn's Disease in a defined area in Germany, a prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995. All patients newly diagnosed with Crohn's disease within the respective study period who were resident in the study area were included in the study. The results from both study periods were then compared to detect time trends. Altogether 288 (156 and 132, respectively) incident cases were identified yielding an almost unchanged incidence over the years (1980-84: 4.9/10(5); 1991-95 5.2/10(5)). While the peak of incidence is still in the 15-24-year-old group, 1 out of 5 incident patients is now age 50 years and older. Median age at onset of symptoms increased to 30 years (20 years in the former period). Time from onset of symptoms was reduced from a median of 20 months in the 1980s to 5 months. Symptoms did not change significantly, although there seems to be less complicated disease recently. Distal migration of the inflammation in the intestinal tract was observed with significantly more involvement of the sigmoid and rectum in the recent period. | High | [
0.6781326781326781,
34.5,
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Eden Prairie Foreclosure Homes For Sale Welcome to the newest Eden Prairie real estate source for foreclosure Eden Prairie homes and listings available. Looking for Minneapolis foreclosure information and the newest MLS listings? Use our easy-to-use search tool to find Eden Prairie Lakefront Homes, New Construction Homes, and Short Sale Homes for sale. Contact one of our local real estate professionals to get insider information about the local Eden Prairie community, schedule a private showing, or begin the process of buying a foreclosed home that meets your wants, needs, and lifestyle. For the most accurate information about foreclosure homes for sale in Eden Prairie or to schedule a private home tour, contact your Eden Prairie real estate experts today. Want to purchase a unique foreclosed house in Eden Prairie? Call your Eden Prairie real estate team, The Kris Lindahl Team at (612) 315-9223. Your neighborhood Eden Prairie REALTORS® and agents are here to help with the Eden Prairie foreclosure housing market. Eden Prairie Real Estate Agents Preparing for the purchase of a foreclosure home in Eden Prairie? Let our local Eden Prairie real estate experts work with you to navigate the purchase of or expertly negotiate the sale of your Eden Prairie home. Our expert knowledge will give you access to up-to-date information about the unique dynamics of the Eden Prairie foreclosure real estate market. We're ready to help you today! ContactThe Kris Lindahl Team to learn more about buyer and seller representation for Eden Prairie foreclosed homes. Visit our comparative market analysis page to receive a free home value estimate in Eden Prairie within minutes. The data relating to real estate for sale on this site comes in part from the Broker Reciprocity program of the Regional Multiple Listing Service of Minnesota, Inc. Real Estate listings held by brokerage firms other than RE/MAX Results are marked with the Broker Reciprocity logo or the Broker Reciprocity house icon and detailed information about them includes the names of the listing brokers. RE/MAX Results is not a Multiple Listing Service MLS, nor does it offer MLS access. This website is a service of RE/MAX Results, a broker Participant of the Regional Multiple Listing Service of Minnesota, Inc. | Mid | [
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constant dog = 'Benjamin'; sub Dog() { 'Samba' } my &DOG = { 'Bernie' } say "The three dogs are named {dog}, {Dog}, and {DOG}." | Low | [
0.454326923076923,
23.625,
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Results of treating Hodgkin's disease without a policy of laparotomy staging. Results of the treatment of 780 primary patients with Hodgkin's disease at the Princess Margaret Hospital (PMH) between 1968 and 1977 are analyzed. Treatment decisions were based on the evaluation of the extent of disease by clinical methods. A marked improvement in relapse-free survival and overall survival was observed for 1973-1977 as compared to 1968-1972. This improvement did not result from differences in the distribution of important prognostic attributes (clinical stage, pathology, and age) between the two periods, and there was no improvement in our ability to rescue relapsed patients. Improved relapse-free and overall survival during the second period was observed for all stages in patients less than 50 years of age, but not in the older group. The improved survival of patients treated between 1973 and 1977 is attributed to more effective initial therapy, which reduced the fraction of patients who relapsed. These observations provide indirect evidence that relapse has a negative effect on prognosis, and that the initial treatment of patients with Hodgkin's disease should be designed to reduce the risk of relapse to a minimum without causing an unacceptable increase in late complications. The observed/expected incidence of acute leukemia and non-Hodgkin's lymphoma in the PMH series was increased to 41.9 and 13.9 respectively. The question of whether a policy of doing routine staging laparotomies improves the results of treatment of patients with Hodgkin's disease is considered only in general terms by comparing the total PMH series with the total Stanford Medical Center series of patients treated between 1968 and 1977. Relapse-free survival at 10 years is 48.9% and 66.8% respectively, at the two institutions, while overall survival at 10 years is identified. | Mid | [
0.633569739952718,
33.5,
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Insects rely on stimuli detection to explore the environment for a variety of primary activities, ranging from food localization and mate choice to predator avoidance. Social and environmental chemical cues are perceived and processed through the chemosensory system, resulting in a variety of downstream responses. Thus, genes related to chemosensation are likely to be involved in the evolution of new behaviors and the adaptation to new ecological niches. Taste and smell are the two main mechanisms of chemosensation and they are mostly mediated by three receptor gene families: the highly divergent GR family, found in all arthropods and generally involved in taste; the more recently evolved olfactory receptor (OR) family ([@bib10]; [@bib18]; [@bib49]), which is found only in insects and is mainly involved in olfaction ([@bib36]; [@bib41]); and the ionotropic receptor (IR) family, composed of two distinct subfamilies involved in both taste and olfaction ([@bib6]; [@bib12]; [@bib24]; [@bib47]). Taste is used by insects for a variety of key processes, such as detection of toxins present in food, identification of secondary metabolites associated with host plants, and recognition of nonvolatile cuticle pheromones. In insects, and likely in various other arthropods, tastant compounds are detected by specialized hair-like structures, called gustatory sensilla, located in different parts of the insect body (*e.g.*, mouthparts, legs, pharynx, and wings) ([@bib48]). These sensilla house gustatory neurons (GRNs) that express specific transmembrane receptors, which enable the detection of external contact molecules ([@bib16]; [@bib23]). Initially discovered in 1999 ([@bib11]), GRs are the first and most extensively studied family of chemoreceptors to be found to be expressed in GRNs in insects. Efforts to elucidate the molecular details of their function have been steadily increasing in the past few years, but to date only a limited number of GRs have been deorphanized in a few insect species ([@bib44]; [@bib15]; [@bib16]; [@bib17]; [@bib23]). In *D. melanogaster*, the GR family includes 60 genes encoding 68 receptor proteins ([@bib42]; [@bib19]; [@bib2]). Unlike ORs, some GRs are characterized by exhibiting functional plasticity beyond gustatory perception: for example, GR28bD is involved in thermosensation ([@bib37]), while GR21a and GR63a are expressed in specific antennal sensilla and are associated with CO~2~ detection ([@bib22]; [@bib26]). Such functional diversification is also revealed by the observation that, in *D. melanogaster*, GRs are expressed not only in GRNs, but also in other neurons scattered in different tissues ([@bib17]). The IRs are a divergent lineage of the ionotropic glutamate receptors (iGluRs), an ancient gene family with a synaptic role in neuronal communication ([@bib6]). In *D. melanogaster* there are 57 genes coding for IRs, and they have been divided into two subfamilies depending on their expression, which putatively reflect their ecological role ([@bib12]). The first subfamily, antennal IRs (aIRs), is highly conserved among species; it is expressed in olfactory organs and is mainly involved in the detection of air-borne molecules. The second subfamily, dIRs, comprises most the IR genes (around 40 genes in *D. melanogaster*); they are mainly expressed in GRNs and involved with taste, either alone or in association with GRs ([@bib12]; [@bib24]; [@bib47]). In contrast to aIRs, dIRs evolved under species-specific patterns, with local expansions and/or losses of family members in certain lineages, likely mirroring the natural history of species. The evolutionary history of GRs and dIRs in *Drosophila* has been studied by exploiting the 12 annotated sequenced genomes ([@bib42]; [@bib34]; [@bib35]; [@bib19]; [@bib12]; [@bib2]). In this work, we expanded these studies with the aim of characterizing the evolution of GRs and dIRs in *D. suzukii*, a pest of soft fruits characterized by a peculiar reproductive ecology. This species lays eggs inside ripening unwounded soft fruits, providing an interesting case of shift in oviposition preferences when compared to most other drosophilids, which instead oviposit on fermenting substrates ([@bib43]; [@bib4]). We hypothesize that such behavioral change may have been accompanied by duplications and/or losses in taste receptor genes that allowed gravid females to recognize suitable oviposition sites and/or that enabled larvae to feed on fresh fruits. The availability of the genomes of *D. suzukii* and of its closely related species *D. biarmipes*, which does not share oviposition preferences with *D. suzukii*, enabled us to examine the evolutionary diversification of GRs and dIRs associated with this new ecological context. We previously exploited this comparison to reveal a peculiar evolution of ORs and odorant binding proteins (OBPs) in *D. suzukii*, and to identify various genes and ligands that likely play an active role in its attraction toward fresh rather than fermenting fruits ([@bib40]). The role of taste receptors in *D. suzukii* behavior is, on the other hand, still completely unexplored. Here, we have characterized GR and dIR families in *D. suzukii* and *D. biarmipes*, studied their evolution in a 14 *Drosophila* phylogenetic framework, and further analyzed expression profiles of duplicate genes in *D. suzukii*. We used our results to address three major questions. Is there any evidence of lineage-specific differentiation of GR or dIR repertoires in *D. suzukii* that may correlate with its peculiar behavior? Are the two taste perception modalities (GRs *vs.* dIRs) evolving with similar patterns? Finally, do recently duplicated genes have nonredundant spatio-temporal expression patterns that avoid a possible overlap in their function? Our results revealed an unusual burst of gene copies in both GR and dIR families in the branch leading to the suzukii subgroup (which includes both *D. suzukii* and *D. biarmipes*), whereas only few genomic changes uniquely characterize *D. suzukii* taste gene repertoire. We found evidence of a similar evolution pattern for GRs and dIRs not only in *D. suzukii*, but also in all the analyzed *Drosophila*. Lastly, reverse transcription PCR (RT-PCR) showed a tissue-specific expression pattern for some duplicate gene families which supports a role of some of them as pheromone receptors. Overall, our dataset is the first describing the complete *D. suzukii* taste receptor repertoire and suggests that the diversification of bitter receptors has played a central role in the evolution of the suzukii subgroup lineage. Materials and Methods {#s1} ===================== Annotation of GRs and IRs {#s2} ------------------------- We used tBLASTn (cut-off values 10^−5^) to iteratively search against *D. suzukii* ([@bib9]; [@bib38]) and *D. biarmipes* genomes using *D. melanogaster* GRs and dIRs (obtained from FlyBase release FB2015_02) as query sequences. Coding sequences (CDS) were manually predicted *in silico* by mapping exons identified in tBLASTn searches using BioEdit ([@bib21]). Introns (following the GT-AG rule) were removed and the remaining sequences were checked for an in-frame coding sequence. *D. suzukii* or *D. biarmipes* sequences with indels leading to a premature stop codon were considered pseudogenes. In *D. suzukii*, GRs and IRs were retrieved from both the Italian ([@bib38]) and the American ([@bib9]) genomes. Paralogous duplications were cross-checked between the two genomes; genes that were represented by more copies located in different scaffolds and in only one genome, and which diverged for only a few SNPs, were considered allelic variants that were not well assembled during genome assembly. Genes were named based on the reconstructed phylogenetic tree (see below) and following the *D. melanogaster* nomenclature, while adding a two-letter prefix corresponding to the species' names. Orthologs in *D. suzukii* and *D. biarmipes* were named with consecutive numbers: for example, *IR47a* has two copies in *D. suzukii* and *D. biarmipes*, which were named as *DsIR47a1*, *DsIR47a2*, *DbIR47a1*, and *DbIR47a2*. Paralogs whose orthologs could not be clearly identified in the other species were named with consecutive numbers after a point: for example, *GR59d8* has three copies in *D. suzukii* which were named *DsGR59d8.1*, *DsGR59d8.2*, and *DsGR59d8.3*. We did not rename genes with previously published names (*e.g.*, in *D. ananassae IR94j* or *IR94k*). Phylogenetic analysis {#s3} --------------------- Nucleotide sequences of GRs from *D. melanogaster*, *D. pseudoobscura*, *D. ananassae*, and *D. erecta* were downloaded from FlyBase (release FB2015_02) according to datasets used before ([@bib19]; [@bib2]), whereas dIR sequences were obtained from [@bib12] (Supplemental Material, [Table S2](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS2.xls)). These species were chosen to recreate the taxon sampling of [@bib40], which proved to be useful for comparative studies. In cases of mis-annotated genes in species other than *D. suzukii* and *D. biarmipes*, sequences retrieved from databases were manually reannotated from whole-genome sequencing data to unify gene structure prediction across species ([Table S2](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS2.xls)). These sequences, together with *D. suzukii* and *D. biarmipes* genes, were aligned with TranslatorX ([@bib1]) using the Muscle algorithm ([@bib14]), and the resulting alignments were manually checked and edited. Maximum likelihood amino acid-based trees were then calculated with RAxML ([@bib46]) using the PROTGAMMA+LG+F model and bootstrapping the dataset with 100 pseudoreplicates. Trees were viewed and graphically edited using iTOL ([@bib28]). Pseudogenes were excluded from the alignments. Gene birth and death estimation {#s4} ------------------------------- To infer the number of GRs and dIRs duplications and losses along *Drosophila* phylogeny, we used Badirate ([@bib29]), which reconciles gene trees onto the species tree. The species tree, which included divergence dates for 14 drosophilid species, was the one proposed by [@bib38]. The data matrix with the gene numbers for each species was taken and slightly modified from [@bib2], except for data for *D. persimilis* that were added from [@bib12] and [@bib19] ([Table S3](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS3.xls)). To obtain β (birth rate) and γ (death rate) estimates we applied the BDI-FR-CML method, which uses a full maximum-likelihood approach and assumes independent evolution for each branch along each lineage. Analysis of selective forces {#s5} ---------------------------- We used PAML 4.7 ([@bib52]) to infer the rate of nonsynonymous, *d~N~*, and synonymous nucleotide substitution, *d~S~*, as well as the level of selective pressure acting on a gene (ω *= d~N~*/*d~S~*). We first created multiple sequence alignments of orthologous genes from six *Drosophila* species (*D. suzukii*, *D. biarmipes*, *D. melanogaster*, *D. erecta*, *D. pseudoobscura*, and *D. ananassae*) with PRANK ([@bib31]) and TranslatorX. In case of paralogs in species other than *D. suzukii* or *D. biarmipes*, we used the most conserved isoform compared to the other lineages. In case of duplications in *D. suzukii* and *D. biarmipes*, the analysis was repeated for each of the paralogs using the closest ortholog from the other species. Pseudogenes were excluded from the analysis. To estimate ω values in *D. suzukii* and *D. biarmipes*, PAML was run using the "free-ratio" model, which allows branch-specific values for ω over all branches of the unrooted phylogenetic tree. Tree topology was taken from [@bib38]. To evaluate heterogeneity in the selective pressure on *D. suzukii* or *D. biarmipes*, we used a branch test that compared the likelihood of a model that assumed a single ω across branches (model = 0 and NSsites = 0) to a second that assumed a distinct ω for the focal branch (*D. suzukii* or *D. biarmipes*). To identify the occurrence of positive selected sites along *D. suzukii* or *D. biarmipes* branches, we used the branch-site test (branch-site model A, test 2; model = 2 and NSsites = 2; null model has parameters fix\_ ω = 1, ω = 1; the positive selection model fix\_ ω = 0, ω = 1). In both branch and branch-site tests, the value of twice the difference between the two alternative likelihoods was tested using a χ^2^ test with one degree of freedom. To account for multiple testing, we estimated the false discovery rate (FDR) using the Benjamini and Hochberg correction ([@bib5]). RT-PCR {#s6} ------ Gene expression analysis was carried on *D. suzukii* adults from a population collected in Trento Province (Italy) and maintained in our laboratory on a standard *Drosophila* semiartificial diet (*Drosophila* species stock center, <https://stockcenter.ucsd.edu/info/food_cornmeal.php>) at a temperature of 23--25°, relative humidity of 65 ± 5%, and 16L:8D photoperiod. We dissected flies from both sexes using forceps, and we pooled males and females to obtain four different samples: heads (*n* = 20), thoraxes (including wings and legs; *n* = 10), abdomens (*n* = 10), and antennae (*n* = 300 pairs). A fifth sample was composed of third instar larvae (*n* = 10) that were processed as whole body samples. Additionally, two more samples consisting of female forelegs and male forelegs (*n* = 100 legs each) were prepared. All samples were placed immediately in cold RNAlater (LifeSciences) and stored at −80° until crushed in Trizol (LifeSciences) using Tissue Lyser II (QIAGEN). Total RNA was extracted followed the Trizol manufacturer's instructions. Extracted RNA was treated with RNAse-free DNAse (LifeSciences) and then used for first strand cDNA synthesis using Superscript RT III (LifeSciences). One µl of cDNA diluted 1:5 was amplified by PCR with GreenTaq (Promega) according to the manufacturer's instructions using 32 amplification cycles. To control for genomic DNA contamination, each batch of total RNA underwent a parallel mock reverse transcription step in which the reverse transcriptase was omitted. The cDNA quality was checked by tubulin amplification. PCR primers (listed in [Table S4](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS4.xlsx)) were first checked against genomic DNA. Two biological replicates were done for each sample, and each amplification was repeated at least twice. Data availability {#s7} ----------------- Sequence data are presented as [File S1](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS1.7z) and [File S2](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS2.7z), and their scaffold locations are listed in [Table S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS1.xls). Alignments used to build [Figure 1](#fig1){ref-type="fig"} and [Figure 2](#fig2){ref-type="fig"} are contained in [File S3](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS3.7z) and [File S4](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS4.7z). [File S5](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FileS5.pdf) contains supplementary figures. ![Gene phylogeny of GRs from six drosophilid genomes. Maximum likelihood tree calculated with RAxML and based on Muscle nucleotide alignment implemented in TranslatorX. Bootstrap support is out of 100 replicates and support \> 80 is indicated by black dots whose sizes are according to bootstrap values. Gray half circles identify the gene groups used in birth-death analysis. Branches highlighted in red show *D. suzukii* genes, and branches highlighted in blue show *D. biarmipes* genes. *D. melanogaster* genes are colored in black whereas other *Drosophila* lineages are shown with different gray shades. Color legends refer to GRs whose function has been deorphanized in *D. melanogaster* ([@bib23]). Clades highlighted in yellow have undergone specific gene expansion in the suzukii subgroup. GRs, gustatory receptors.](4185f1){#fig1} {#fig2} Results {#s8} ======= Annotation of GRs and dIRs in the genomes of D. suzukii and D. biarmipes {#s9} ------------------------------------------------------------------------ We manually annotated 77 GRs in *D. suzukii* and 76 in *D. biarmipes*. Genomic evidence of alternative splicing was found for three genes in both species (*GR23a*, *GR28b*, and *GR39a*), bringing the total of predicted GR proteins to 85 ([File S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FileS1.zip)) and 84 ([File S2](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FileS2.zip)), respectively; in *D. biarmipes*, we identified three pseudogenes ([Table S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS1.xls)). All genes have identical intron--exon structures in the two species: exons range from 1 to 9, but most genes have one or two exons, and only two genes are intronless (*GR94a* and *GR68a*) ([Table S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS1.xls)). We identified 50 dIRs in the *D. suzukii* genome and 49 in the *D. biarmipes* one, and a pseudogene in *D. biarmipes* ([File S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FileS1.zip), [File S2](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FileS2.zip), and [Table S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS1.xls)). Similar to GRs, intron--exon structures of dIRs were the same for both species. dIRs were characterized by less introns than GRs; most genes (around 70%) were intronless, and the remaining ones had one to four introns per gene ([Table S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS1.xls)). GR and dIR evolution in the suzukii subgroup {#s10} -------------------------------------------- To obtain a detailed insight into gene duplication and loss in *D. suzukii*, we inferred the phylogenetic relationships of GRs and dIRs from *D. suzukii* to that of five other *Drosophila* species (*D. biarmipes*, *D. melanogaster*, *D. erecta*, *D. pseudoobscura*, and *D. ananassae*) ([Figure 1](#fig1){ref-type="fig"} and [Figure 2](#fig2){ref-type="fig"}). Using the *D. melanogaster* orthologs as reference, 66% of GRs have a one-to-one orthologous relationship across the six species, while copy number variation occurs for the remaining genes. In particular, 15 genes are missing in at least one of the six species, whereas 10 have multiple copies in at least one species. Among dIRs, most copy number variation events are mostly species-specific (*i.e.*, families IR52, IR60, and IR94). Considering only the 41 dIRs present in *D. melanogaster* genome, 68% of them have a one-to-one orthologous relationship across the six species studied. Five GR genes (*GR36a*, *GR36b*, *GR59a*, *GR59d*, and *GR93d*) have multiple copies in *D. suzukii* and *D. biarmipes* genomes compared to other drosophilids (a total of 17 and 16 more genes than *D. melanogaster*, respectively) ([Figure 1](#fig1){ref-type="fig"} and [Table 1](#t1){ref-type="table"}). Based on their orthological relationships, we observed that some triplications and duplications (*GR36a*, *GR36b*, *GR59a*, and *GR93d*) are clearly shared between *D. suzukii* and *D. biarmipes*, and thus they likely originated in the common ancestor of the suzukii subgroup. Other duplications or losses are instead species-specific, such as that observed for *GR59a4*, which is present only in *D. suzukii*. The duplication pattern of *GR59d* is particularly complex ([Figure 3](#fig3){ref-type="fig"}). Some duplicated copies of *GR59d* show a one-to-one orthologous relationship, and their synteny is conserved between the two species (*GR59d2*, *GR59d3*, *GR59d4*, and *GR59d5*) ([Figure S1](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS5.pdf)) indicatingTable 1Representative GR and dIR genes characterized by duplication events and signatures of differential selective pressure in *D. suzukii*GeneType of DuplicationSignificant Branch Test at FDR \< 0.05Expression in *D. suzukii*Ortholog Expression in *D. melanogasterGR36a2*Suzukii subgroupω = 1.25, FDR \< 0.0001Head*GR36a*: labellar sensilla[*^a^*](#t1n1){ref-type="table-fn"}*GR36b2*Suzukii subgroupω = 1.02, FDR = 0.021Head*GR36b*: labellar sensilla[*^a^*](#t1n1){ref-type="table-fn"}, larval sensilla innervating terminal distal group[*^b^*](#t1n2){ref-type="table-fn"}*GR59a3*Suzukii subgroupω = 0.23, FDR = 0.030ND*GR59a*: labellar sensilla[*^a^*](#t1n1){ref-type="table-fn"}, foreleg sensilla[*^c^*](#t1n3){ref-type="table-fn"}, larval sensilla innervating terminal distal group[*^b^*](#t1n2){ref-type="table-fn"}*GR59a4*Unique to *D. suzukii*ω = 0.27, FDR = 0.021ND*GR59d2*Suzukii subgroupω = 0.48, FDR = 0.011Head, foreleg, larva*GR59d*: labellar sensilla[*^a^*](#t1n1){ref-type="table-fn"}, foreleg sensilla[*^c^*](#t1n3){ref-type="table-fn"}, larval sensilla innervating terminal distal group[*^b^*](#t1n2){ref-type="table-fn"}*GR59d3*Suzukii subgroupω = 1.2, FDR \< 0.0001Head, abdomen, larva*GR59d5*Suzukii subgroupω = 0.66, FDR \< 0.0001Head*GR59d7.1*Unique to *D. suzukii*ω = 0.41, FDR = 0.0066ND*GR59d7.2*Unique to *D. suzukii*ω = 0.39, FDR = 0.0114ND*GR59d8.1*Unique to *D. suzukii*ω = 1.00, FDR \< 0.0001Head, larva*GR59d8.2*Unique to *D. suzukii*ω = 1.72, FDR \< 0.0001Head, larva*GR59d8.3*Unique to *D. suzukii*ω = 1.28, FDR \< 0.0001Head, larva*IR47a2*Suzukii subgroupω = 0.57, FDR = 0.0105Abdomen, thorax, foreleg, head, larva*IR47a*: labellar sensilla[*^d^*](#t1n4){ref-type="table-fn"}, foreleg sensilla[*^d^*](#t1n4){ref-type="table-fn"}[^1][^2][^3][^4][^5]Figure 3Gene phylogeny of GR59c and GR59d families from 14 *Drosophila* species. Maximum likelihood tree calculated with RAxML and based on Muscle nucleotide alignment implemented in TranslatorX. Phylogenetic relationships of all genes included in gene family GR59c-d used in birth-death analysis are displayed in the tree. Bootstrap support is out of 100 replicates and support \> 80 is indicated by black dots whose sizes are according to bootstrap values. Branches highlighted in red show *D. suzukii* genes, and branches highlighted in blue show *D. biarmipes* genes. Branches without *D. suzukii* or *D. biarmipes* genes are collapsed. GRs, gustatory receptors. that duplication events occurred in the common ancestor of suzukii subgroup. Within the same gene cluster, *D. biarmipes* possesses an additional copy (*GR59d6*) ([Figure S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FigureS1.pdf)) that is not present in the *D. suzukii* genome. Another copy of *GR59d*, *GR59d7*, also originated from duplication in the common ancestor of the suzukii subgroup and later diverged in the two species: in *D. biarmipes GR59d7* is likely a pseudogene, whereas in the *D. suzukii* genome it is present in two paralogous (functional) copies. *GR59d8* evolution is extremely problematic; there are three distinct copies in *D. suzukii* and in *D. biarmipes* (plus a pseudogene in the latter). In both species, the three copies cluster together in a different scaffold to those containing *GR59d1--6* and *GR59d7* ([Figure S1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FigureS1.pdf)). Although not well resolved, their phylogenetic affinities inferred by ML tree ([Figure 3](#fig3){ref-type="fig"}) suggest various rounds of duplication in the common ancestor of *D. suzukii* and *D. biarmipes* followed by various rounds of deletion in *D. suzukii*, and a recent triplication in *D. suzukii*. Alternatively, it is possible that the three copies in *D. suzukii* are evolving in a concerted fashion and experienced gene conversion by homologous recombination, therefore showing high similarity among them. Three dIR families (*IR47a*, *IR52*, and *IR94*) belonging to the IR20a clade ([@bib24]) experienced higher turnover in either *D. suzukii* and *D. biarmipes* genomes compared with the rest of *Drosophila* species ([Figure 2](#fig2){ref-type="fig"}); IR47a2 and IR52f2 are two new duplicates in both species whereas IR52i is a receptor found only in *D. suzukii* and *D. biarmipes* ([Figure S2](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/FigureS2.pdf)). *IR52c* is duplicated only in *D. suzukii*, while *D. biarmipes* does not have *IR52g* ([Figure 2](#fig2){ref-type="fig"} and [Figure S2](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS5.pdf)). Finally, the IR94 family experienced multiple cases of gene loss and duplication; while *D. biarmipes* and *D. suzukii* possess multiple orthologs copies compared to the other *Drosophila* species (*IR94i*, *IR94r*, and *IR94s*), *D. suzukii* specifically lost *IR94c* whereas *D. biarmipes* lost *IR94a* ([Figure 2](#fig2){ref-type="fig"} and [Figure S3](http://www.g3journal.org/content/suppl/2016/10/19/g3.116.036467.DC1/FileS5.pdf)). Outburst of taste receptor duplication in the branch leading to the suzukii subgroup {#s11} ------------------------------------------------------------------------------------ To quantify the number of GR and dIR gain and loss events, we analyzed the gene phylogeny in the context of species phylogeny using Badirate ([Figure 4](#fig4){ref-type="fig"}). Because we could not resolve the orthological relationships of *GR59d7* duplicates with confidence, we have used a conservative view that implies duplications in the common ancestor of *D. suzukii* and *D. biarmipes*. Badirate estimated that along the whole *Drosophila* phylogeny, GRs experienced 38 losses (global death rate of 0.0022 losses per gene per millions of years, l/g/m) and 87 gains (global birth rate of 0.0045 gains per gene per millions of years, g/g/m), whereas dIRs experienced 43 losses (global death rate of 0.0029 l/g/m) and 38 gains (global birth rate of 0.0025 g/g/m) ([Figure 4A](#fig4){ref-type="fig"}). Notably, the highest birth rate for GRs occurs in the branch leading to the suzukii subgroup, where we can observe the gain of 15 GRs (birth rate 0.0439 g/g/m, tenfold higher than the average, [Figure 4B](#fig4){ref-type="fig"}). On the same branch, we can observe the second highest birth rate for dIRs (the highest is for *D. simulans*), characterized by four dIR gains (birth rate 0.0153 g/g/m, sixfold higher than the average, [Figure 4B](#fig4){ref-type="fig"}). Particularly high death rates occur for both gene families in the branch leading to the specialist *D. sechellia* ([Figure 4C](#fig4){ref-type="fig"}). ![Gene loss and gain in GR and dIR drosophilid repertoires. (A) Estimates of gene birth and death on internal nodes of *Drosophila* phylogeny \[based on [@bib38]\]. Numbers on each node represent the estimated number of genes at that internal node whereas numbers on branches represent gene gains and losses. Gains and losses referred to birth rates (β) or death rates (γ), which are an outlier in Tukey boxplots, are highlighted with colors referring to the corresponding Tukey boxplot. (B) Tukey boxplot showing birth rates (β) calculated by Badirate under the BDI-FR-CML model. (C) Tukey boxplot showing death rates (γ) calculated by Badirate under the BDI-FR-CML model. (D) Correlation among number of GR and dIR gene copies along *Drosophila* phylogeny. dIR, divergent ionotropic receptor; GR, gustatory receptor.](4185f4){#fig4} Interestingly, in the 14 drosophilid genomes, the family size of GRs correlates with the family size of dIRs ([Figure 4D](#fig4){ref-type="fig"}). *D. suzukii* and *D. biarmipes* are the species with the highest number of genes in both families, whereas the two species from the obscura group (*D. pseudoobscura* and *D. persimilis*), the specialists *D. sechellia* and *D. mojavensis*, and *D. virilis* have the lowest number of both GRs and dIRs. Signatures of different selective pressure on genes encoding taste receptors in D. suzukii and D. biarmipes {#s12} ----------------------------------------------------------------------------------------------------------- We studied the overall selective pressure acting on GRs and dIRs in *D. suzukii* and *D. biarmipes* by examining the *d~N~/d~S~* ratio (ω) at each locus. All tested GRs and dIRs in both species are under a gene-wide moderate to strong purifying selection regime (ω \< 1), with the notable exception of six duplicate genes in *D. suzukii* (from the GR59d, GR36a, and GR36b families) and one (GR36b2) in *D. biarmipes* ([Figure 5A](#fig5){ref-type="fig"}, [Table 1](#t1){ref-type="table"}, and [Table S5](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS5.xls)). In both species, ω ratios are always higher for duplicate genes compared to nonduplicate ones ([Figure 5B](#fig5){ref-type="fig"}). Within both species, the level of selective pressure of GRs is similar to that of dIRs (medians of 0.170 and 0.202 for *Ds*GRs and *Ds*dIRs, respectively; 0.159 and 0.132 for *Db*GR and *Db*dIR, respectively), and both are larger than those estimated for ORs (medians of 0.114 and 0.112 for *Ds*OR and *Db*OR, respectively). Within each class of receptors, no differences between species are evident ([Figure 5A](#fig5){ref-type="fig"}). The synonymous substitution rate (*d~S~*) does not vary among GRs, dIRs, and ORs within each species (medians for *D. suzukii*: *Ds*GR = 0.164, *Ds*dIR = 0.164, and *Ds*OR = 0.166; medians for *D. biarmipes*: *Db*GR = 0.202, *Db*dIR = 0.223, and *Db*OR = 0.214), whereas *d~S~* values in *D. biarmipes* are higher than *D. suzukii* for all receptors ([Figure 5C](#fig5){ref-type="fig"}). The nonsynonymous substitution rate (*d~N~*) does not vary among species and taste receptors (medians: *Ds*GR = 0.031, *Ds*dIR = 0.032, *Db*GR = 0.033, and *Db*dIR median = 0.032), whereas ORs have the lowest values in both species (medians: *Ds*OR = 0.018 and *Db*OR = 0.021) ([Figure 5D](#fig5){ref-type="fig"}). ![Selective pressure acting on *D. suzukii* and *D. biarmipes* chemoreceptor genes. All boxplots were built using values estimated for genes present in the six lineages. OR dataset was taken from [@bib40]. (A) Tukey boxplots showing *d~N~/d~S~* (ω) for GRs, dIRs, and ORs in *D. suzukii* (pink) and *D. biarmipes* (green). Significant differences among groups were highlighted by Kruskal--Wallis test (*H* = 25.33, 5 d.f., and *P* \< 0.0001) followed by Dunn's multiple comparison *post hoc* test (different letters indicate significance levels at *P* \< 0.05). (B) Tukey boxplots showing the *d~N~/d~S~* ratios (ω) for singleton (empty plots) or duplicate (striped plots) GRs and dIRs in *D. suzukii* (pink) and *D. biarmipes* (green). Differences between singleton and duplicate gene were tested only for GRs in both *D. suzukii* and *D. biarmipes* by Wilcoxon test using a Bonferroni-corrected *P*-value (*P* \< 0.025). (C) Tukey boxplots showing synonymous substitution rate (*d~S~*) for GRs, dIRs, and ORs in *D. suzukii* (pink) and *D. biarmipes* (green). Significant differences among groups were highlighted by Kruskal--Wallis test (*H* = 39.61, 5 d.f., and *P* \< 0.0001) followed by Dunn's multiple comparison *post hoc* test (*P* \< 0.05). (D) Tukey boxplots showing nonsynonymous substitution rate (*d~N~*) for GRs, dIRs, and ORs in *D. suzukii* (pink) and *D. biarmipes* (green). Significant differences among groups were highlighted by Kruskal--Wallis test (*H* = 23.89, 5 d.f., and *P* \< 0.0005) followed by Dunn's multiple comparison *post hoc* test (different letters indicate significance levels at *P* \< 0.05). (E) Venn diagrams depicting the number of genes under a differential selective pressure in *D. suzukii* (pink) and *D. biarmipes* (green) identified by PAML branch-test at FDR \< 0.05. dIR, divergent ionotropic receptor; FDR, false discovery rate; GR, gustatory receptor; OR, olfactory receptor.](4185f5){#fig5} Branch tests identified 28 GRs in *D. suzukii* (22 at FDR \< 0.05) and 23 in *D. biarmipes* (15 at FDR \< 0.05) that are evolving under differential selective pressure in either of these species compared to the rest of the phylogeny. Ten of these genes are shared between the two species, seven of which are duplicate genes ([Figure 5E](#fig5){ref-type="fig"} and [Table S5](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS5.xls)). Among dIRs, 12 genes in *D. suzukii* (nine at FDR \< 0.05) and five in *D. biarmipes* (three at FDR \< 0.05) have signatures of differential selection pressure, and one of them is shared between the two species ([Figure 5E](#fig5){ref-type="fig"}). This corresponds to 38 and 29% of GRs and dIRs under differential selection pressure, respectively, suggesting a very dynamic selective regime in this class of genes. To test if few sites inside GRs or dIRs are evolving under positive selection (but are masked by purifying or relaxed selection acting on the other parts of the gene), we applied a branch-site test and obtained evidence for site-specific selection in *D. suzukii* and *D. biarmipes*. Eight GRs (one at FDR \< 0.05) and two dIRs (none at FDR \< 0.05) were detected as having sites under positive selection in *D. suzukii*, whereas in *D. biarmipes* five GRs (two at FDR \< 0.05) and one dIR (at FDR \< 0.05) were identified ([Table S5](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.116.036467/-/DC1/TableS5.xls)). Spatio-temporal expression of duplicate GRs and IRs in D. suzukii {#s13} ----------------------------------------------------------------- Expression patterns of the genes that underwent duplication in *D. suzukii* are reported in [Figure 6](#fig6){ref-type="fig"}. Family IR52 is mainly expressed in the thorax, specifically in forelegs of both females and males. One IR52 (*DsIR52e*) is also clearly expressed in larvae; interestingly, no members of this family are expressed in adult heads. *DsIR47a2* shows the broadest expression pattern since it is expressed in all tissues and stages tested, whereas expression of *DsIR47a1* was mainly detected in the head (a slight band is also observed for thorax and forelegs). Families IR94, GR36a, GR36b, GR59a, and GR59d are mainly expressed in heads, although some specific members are expressed in other tissues or during the larval stage; the three members of the GR59d family (GR59d8.1, GR59d8.2, and GR59d8.3) under positive selection are expressed in the head and in larvae ([Table 1](#t1){ref-type="table"}). Finally, all the three members of family GR93d are ubiquitously expressed in heads (but not antennae), thorax, and abdomen, as well as in larvae. None of the tested dIRs or GRs (except for IR47a2) were detected in antennae. {#fig6} Discussion {#s14} ========== Evolution of taste genes on the Drosophila phylogeny {#s15} ---------------------------------------------------- In the last few years, the availability of numerous *Drosophila* genomes has allowed several comparative studies to be carried out that have described the evolution of chemosensory genes along the *Drosophila* phylogeny. Their results have highlighted lineage-specific expansions and contractions that have occasionally been associated with phenotypical differences between species ([@bib20]; [@bib34]; [@bib35]; [@bib19]; [@bib12]; [@bib2]; [@bib40]). Some of these studies suggested that the evolutionary properties of genes encoding chemosensory receptors correlate with their putative function. For example, genes involved in taste, but belonging to phylogenetically distinct families (GRs and dIRs), evolve under evolutionary constraints that are different from those of genes involved with smell (such as ORs and aIRs) ([@bib12]). Our results confirm this trend by further showing that GRs and dIRs are characterized by a similar lineage-specific turnover rate along the *Drosophila* phylogeny ([Figure 4](#fig4){ref-type="fig"}). Other confirmation comes from our molecular evolution studies; in *D. suzukii*, GRs and IRs are characterized by a more relaxed selective pressure than that observed in ORs ([Figure 5A](#fig5){ref-type="fig"}). Overall, our average ω values are consistent with purifying selection acting in both chemosensory gene families, as reported for other *Drosophila* ([@bib19]; [@bib12]). Furthermore, faster molecular evolution was found for genes that underwent gene duplication, supporting the hypothesis that recently duplicate genes experience lower selective constraints and thus can be a source of genetic novelty ([@bib32]; [@bib25]). Outburst of taste receptors supports a generalist feeding behavior in the suzukii subgroup {#s16} ------------------------------------------------------------------------------------------ Previous work in *Drosophila* and other insect species indicated that GR losses are often associated with host specialization. The specialists *D. sechellia*, which feeds only on Morinda fruits, and to a lesser extent *D. erecta*, which feeds on *Pandanus* spp., are losing GRs more rapidly than generalists ([@bib34]; [@bib35]). In the butterflies of the genus *Heliconius*, whose members are specialized on different *Passiflora* species, there have been a number of species-specific gene losses in bitter-related GRs ([@bib8]). In all such cases, it seems that specialization on a novel host plant is generally associated with a contraction of the GR family. *D. suzukii*, although being characterized by a peculiar larval feeding ecology, cannot be defined as a specialist; adults feed on fermenting substrates like other *Drosophila* generalists, and females lay eggs in a great variety of fruits. Accordingly, *D. suzukii* is not characterized by a reduced number of taste receptors as is seen in specialist species, but rather by the highest number of both GRs and IRs among the sampled *Drosophila* lineages. This is compatible with a generalist feeding habit, as expanded molecular taste machinery would allow perception of a large assortment of tastants from a wide variety of food sources. This is supported by experimental evidence showing that *D. suzukii* can oviposit in extremely different fruit species ([@bib54]; [@bib53]; [@bib39]). Such an increase in taste receptors is shared between *D. suzukii* and *D. biarmipes*, suggesting that an ancestral generalist feeding behavior characterized the whole suzukii subgroup, rather than *D. suzukii* alone. The association between the burst in number of taste receptor genes and a change in ecology fits well with the observation that gene duplication is a major source of genetic, and phenotypic, novelty. After duplication, redundant genes may experience relaxed selection; their fate will then be defined by a combination of drift and selection, with retained duplications that will experience a distinct regime of purifying selection ([@bib32]). Therefore, we can hypothesize that the proportion of duplicate genes in a genome is an excellent genetic proxy for adaptation to new habitats ([@bib33]). The burst of GR and dIR duplications in the branch leading to the suzukii subgroup has a magnitude comparable only with the losses that occurred in GRs in the endemic and highly adapted *D. sechellia* lineage ([@bib34]; [@bib35]); this suggests an adaptive role of GR and dIR duplications in expanding *D. suzukii* distribution to heterogeneous environments, likely promoting a generalist feeding behavior. Do selective constraints act on D. suzukii gustative receptors? {#s17} --------------------------------------------------------------- One interesting observation that emerges from our molecular evolution analysis is that, in *D. suzukii*, all chemoreceptor families (GRs, dIRs, and ORs) have a higher rate of nonsynonymous site evolution (*d~N~*) compared to that of 1021 nuclear genes estimated in a previous study ([@bib38]). In contrast, this was not observed for *D. biarmipes* chemoreceptor genes. Results obtained by [@bib38] showed that *d~N~* and *d~S~* rates were both higher in *D. biarmipes* compared to *D. suzukii* and no differences in ω ratio existed between the two species. In our study, we observed an increased *d~S~* rate in *D. biarmipes* for all the gene families tested but, unexpectedly, no differences at *d~N~* rate distributions emerged between *D. biarmipes* and *D. suzukii*. This points toward an increased evolution rate acting on *D. suzukii* chemosensory proteins. The increased amino acid substitution rate might be explained by the presence of fewer selective constraints acting on *D. suzukii* chemoreceptors or by an increase in positive selection shaping the molecular evolution of specific GRs, dIRs, and ORs. In the second case, the fixation of specific genes would lead to a high dispersion in the distribution of *d~N~* across the gene family ([@bib7]). When we compared ω variances for each gene family between *D. suzukii* and *D. biarmipes*, we observed that such a hypothesis accounts only for GR*s* (Levene's test: *F* = 5.40; df = 1131; and *P* = 0.022). In particular, gene targets of positive selection that are responsible for the higher variance are four duplicate *Ds*GRs (including the three GR59d8, see below) having a ω \> 1 (Levene's test without the four *Ds*GRs: *F* = 1.33; df = 1131; and *P* = 0.251). In cases of dIRs and ORs, whose variance do not differ between *D. suzukii* and *D. biarmipes*, the increased rate of amino acid substitutions may be due to pervasive relaxed selection, in accordance with what has been observed at the intra specific level in *D. melanogaster* ([@bib3]). Bitter taste receptors putatively relevant for the biology and control of D. suzukii {#s18} ------------------------------------------------------------------------------------ In terms of gene number, *D. suzukii* has only one more GR and one more dIR compared to *D. biarmipes*. However, differences are more pronounced because of species-specific isoforms characterizing some of the duplicate families. The most striking case is the extra duplications of GR59d8 which seems unique to *D. suzukii* ([Figure 3](#fig3){ref-type="fig"}); the exact affinity of these genes to their orthologs in *D. biarmipes* is hard to decipher and we cannot exclude an ancient origin on the common ancestor followed by different evolutionary histories in the two species. Regardless of their origin, these three genes are characterized by an ω \> 1 only in *D. suzukii*, indicating strong positive selection acting on them ([Table 1](#t1){ref-type="table"}). We speculate that these paralogs may have played an active role in the adaption of *D. suzukii* to its fresh fruit polyphagous ovipositing behavior; we therefore consider them good candidates for functional studies and downstream practical application. Notably, these genes are expressed in heads and in the larval stage; therefore, we suggest that they may be involved in oviposition host choice and larval feeding behavior. The limited knowledge (mostly restricted to *D. melanogaster*) about the function of most GRs and dIRs makes it difficult to propose a functional ecological role for duplications unique of *D. suzukii*, as well as for the other duplications shared with D. *biarmipes*. In fact, most genes whose function has been deorphanized in *D. melanogaster* do not exhibit copy number variation, with the notable exception of the L-canavanine receptor GR98b ([@bib45]), which is duplicated only in *D. biarmipes*. However, most of the GRs duplicated in *D. suzukii* and/or in *D. biarmipes* (GR36b, GR59a, GR59d, GR93b, and GR98b) are expressed in bitter-sensing neurons in *D. melanogaster* ([@bib51]; [@bib30]). This is concordant with what has been observed in *Heliconius* spp. and *D. sechellia*, where adaptive gene gain and loss appear to primarily affect GRs presumed to respond to bitter compounds ([@bib34]; [@bib35]; [@bib8]). Moreover, the proportion of putative bitter-related genes that experience a different selective pressure in both *D. suzukii* and *D. biarmipes* is particularly high (75 and 78% genes, respectively). In general, specialists tend to have a lower number of bitter receptors than generalists, since the latter enter into contact with a larger array of toxic molecules ([@bib34]; [@bib35]; [@bib8]). However, exceptions to this rule exist: *Bombyx mori*, which feeds exclusively on mulberry leaves, has an increased number of bitter-receptors probably used to detect the bitter compounds typical of its host plant ([@bib50]). We can hypothesize that the ancestor of the suzukii subgroup experienced a transition from one ecological niche to another that required the neo/subfunctionalization of newly duplicated genes to allow a wider recognition of bitter-related compounds. Even more difficult is the prediction of the ecological function of duplicate dIRs, since less information is available compared to GRs. A family that is particularly enriched in *D. suzukii* (IR52), is mainly expressed in pheromone-sensing neurons located on forelegs in *D. melanogaster*, and *DmIR52c* is indeed required for normal copulation behavior ([@bib24]). Duplication in *DsIR52c* in *D. suzukii* may be related to a different mating communication system specific for this species, since *D. suzukii* does not produce the sex pheromone *cis*-11-octadecenyl acetate (cVA), which is a pheromone basal to *Drosophila* species ([@bib13]). Expression studies also support the role of members of family IR52 as putative pheromone receptors in *D. suzukii*; the expression of all IR52 isoforms has been observed in thorax segments of *D. suzukii* adults, and more specifically in adult forelegs, but never in heads. Expression of duplicate dIRs and GRs in different parts of the *D. suzukii* body (mainly in the head) is consistent with their role as taste receptors, since in the model *D. melanogaster* they are expressed in GRNs scattered along the body ([@bib23]). Within each family, each member was expressed with a different pattern, with the exception of the GR93d family, whose three members are expressed together in the three parts of the *D. suzukii* body. Considering the limitations of using RT-PCR to studying the expression of chemoreceptor genes (which only enabled us to examine tissue-specific and not neuron-specific patterns), our results suggest that duplicate GRs and dIRs in *D. suzukii* might have diverged their temporal and/or spatial expression after duplication, in response to neo-functionalization events. Conclusions {#s19} ----------- The analysis of gene gains/losses, molecular evolution, and expression patterns of *D. suzukii* tastant receptors has shown that GR and dIR gene families experience rapid gene family evolution. In particular, comparison with the closely related species *D. biarmipes* revealed a high number of gene gains occurred on the branch leading to the suzukii subgroup, whereas few specific genomic events (for instance the GR59d duplications) characterized the *D. suzukii* lineage. Overall, our results bring us one step closer to understanding *D. suzukii* innovative ecological behavior and provide a foundation for further studies aiming to disentangle the mechanisms of oviposition preferences, for example providing candidate taste receptors specific for *D. suzukii*, which may be tested for their ligand affinity and their role in the oviposition behavior of this species. Supplementary Material ====================== ###### Supplemental Material We thank the editor and two anonymous reviewers for their fruitful suggestions. This work was funded by Project LExEM (Laboratory of excellence for epidemiology and modeling, <http://www.lexem.eu>). C.M.C. is recipient of a Marie-Curie FP7-PEOPLE-2013-IEF grant. S.R. has been funded by a PhD fellowship from the FIRS \> T \[FEM (Fondazione Edmund Mach) International Research School-Trentino\] program at FEM, Italy. Supplemental material is available online at [www.g3journal.org/lookup/suppl/doi:10.1534/g3. 116.036467/-/DC1](http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.115.024505/-/DC1). Communicating editor: Y. Kim [^1]: FDR, false discovery rate; ND not detected. [^2]: [@bib51]. [^3]: [@bib30]. [^4]: [@bib27]. [^5]: [@bib24]. | Mid | [
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News Borderfree looks to raise $86 million in an initial public offering February 19, 2014 12:59 PM Borderfree Inc., which provides e-retailers with international shipping services, including displaying shipping fees, duties and taxes to foreign shoppers at checkout, is looking to raise $86.25 million in an initial public offering of stock, according to a filing with the U.S. Securities and Exchange Commission. Borderfree, which changed its name from FiftyOne Global Ecommerce last year, handles international shipping for at least 37 e-retailers ranked in the 2013 Top 500 Guide. They include Gilt Groupe, No. 49; Crate and Barrel, No. 59; and David’s Bridal Inc., No. 344. The company plans to list on the NASDAQ exchange under the symbol BRDR. Borderfree reported in its filing more than $110 million in revenue during 2013 and a loss of $654,000. It says it works with more than 150 e-commerce sites, accepts more than 60 currencies and delivers to more than 100 countries and territories. Borderfree makes money from fees it collects from retailers based on a percentage of their sales generated through Borderfree. Customer contracts typically range from one to four years, followed by one-year renewal periods, according to the SEC filing. It also generates additional revenue from fulfillment services, foreign exchange and other transaction fees. In 2013 it facilitated $448 million in gross merchandise sales volume on behalf of its customers, reaching 76% of the world outside the U.S. Credit Suisse and RBC Capital Markets are main underwriters for the offering. | Low | [
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Few things attract more attention in the business world than new ways of making groups work well. As any fool knows, groups are a pain. They argue, dither, drift off course, waste time and resources, and produce loads of rubbish. Worse, all those participants draw salaries, so treasure is wasted. Surely, bosses think, any technique that promises to make groups productive will be better than what they have now: a dysfunctional collection of pointless individuals, wasting their time by rushing off in aimless directions? They reject the absurd notion that one person should do the job, and that the dysfunctional team should be disbanded. Leadership: that is what is required, they proclaim. So, the poor hapless managers are sent off to Leadership courses, and come back with interesting theories which get nowhere, because the rest of the staff have not been sent off to Followership courses. Leaders always require followers. While everyone loves Leadership courses, being recommended for a Followership course would probably cause great offence. A pity. It is fatal to any enterprise when people can neither command nor obey. While the supposed leaders have been away at an expensive hotel ,the remaining staff have sorted out the problem to their own satisfaction, sometimes with good effect, and most often by cobbling together a patch to protect their own interests. So, it is with grim satisfaction that one learns of Group Performance Enhancement Theory No 347, namely that people working in groups on complex problems: “show a strong general-ability or IQ factor, with significant differences between groups on this factor. Surprisingly, group-IQ, or “collective intelligence” is not strongly correlated with the average or maximum individual intelligence of group members but is correlated with the average social sensitivity of group members, the equality in distribution of conversational turn-taking, and the proportion of females in the group.” So, if I have understood this correctly, the individual IQs do not matter too much, so long as the group is socially sensitive, takes turns in speaking, and includes women. Personally, having heard this proposal I would have thought it unlikely. Bates and Gupta, however, are truer to the spirit of empiricism, and embody Carl Sagan’s injunction (my summary) that scientists should be kind to hypotheses and tough on proofs. What is more, since the original study by Woolley et al in 2010 was cited over 700 times, this finding is likely to be the cornerstone of a myriad of training courses, as participants attempt to be sensitive, willing to wait their turn, and womanly. Bates and Gupta have bothered to find out if collective intelligence (group IQ) actually exists. https://drive.google.com/open?id=0B3c4TxciNeJZLWFibW9jYnlFQVU They point out: For some time, it has been known that work-groups whose team-members have higher IQ out-perform teams of less-able members (Devine & Philips, 2001). Against this background, Woolley et al. (2010) asked whether groups themselves exhibit a general-factor of intelligence, if this might be distinct from individual IQ, and, if so, what the origins of such a collective intelligence might be. To assess group-IQ, subjects were allocated to small groups and performed tasks including brainstorming, matrix reasoning, moral reasoning, planning a shopping trip, and collaborative text editing. They did all this in 3 studies, so there is a lot of detail in the paper about the findings from their individual studies, and further work on the combined results, usually studies 2 and 3. Woolley et al. (2010) came to the conclusions described above, namely that it is the collective IQ which develops (due to sensitivity, turn taking in conversation, and women members) which is important, and not the IQ of the members of the group. Bates and Gupta sum up the findings of their replication thus: What allows groups to behave intelligently? One suggestion is that groups exhibit a collective intelligence accounted for by number of women in the group, turn-taking and emotional empathizing, with group-IQ being only weakly-linked to individual IQ (Woolley, Chabris, Pentland, Hashmi, & Malone, 2010). Here we report tests of this model across three studies with 312 people. Contrary to prediction, individual IQ accounted for around 80% of group-IQ differences. Hypotheses that group-IQ increases with number of women in the group and with turn-taking were not supported. Reading the mind in the eyes (RME) performance was associated with individual IQ, and, in one study, with group-IQ factor scores. However, a well-fitting structural model combining data from studies 2 and 3 indicated that RME exerted no influence on the group-IQ latent factor (instead having a modest impact on a single group test). The experiments instead showed that higher individual IQ enhances group performance such that individual IQ determined 100% of latent group-IQ. Implications for future work on group-based achievement are examined. After doing their 3 studies and re-analysing the results, they conclude: Smart groups are (simply) groups of smart people. By contrast, we found little to no evidence for two proposed causes of group-IQ: numbers of women in the group and turn-taking, and found evidence for a weak and specific impact of RME on one group task, but not on latent group-IQ. Here is the relationship between the IQs of the individuals in the group, and the resultant group intelligence. If particular group IQs develop, then the group IQs will differ from the mere sum of the individual IQs. In fact, there is a close match. Here are all their results summarised in a best fitting model. Individual’s IQs lead to the group average IQ, which explains the performance the group achieves on all of the tasks. On one task, Missing letters, the Mind in the Eyes task makes a small additional contribution. They add: The present findings cast important doubt on any policy-style conclusions regarding gender composition changes cast as raising cognitive-efficiency. Their findings should not be interpreted as meaning that groups are useless. On the contrary, given that the management of clever people is so important for success, care must be taken to let the best thinkers concentrate on the hardest problems. Also, it implies that organizations should pay close attention to the intelligence of their staff members, and very probably to pay more attention to the opinions of their brighter workers. And there the silly story would end, but there is a sting in the tail. Not only was the original paper cited 700 times, but it was cited without the benefit of a replication. All researchers may be tempted to do that, particularly when a study buttresses a position they like. However, since so many psychological studies fail to replicate, there is now general agreement that replications should be given as much attention as the original claims. So, how did reviewers respond to Bates and Guptas’s replication? With considerable reservations, it appears. While every paper has to run the gauntlet of reviewer criticism, this one seems to have experienced unusual opposition. In their discussion section the authors reply to the objections raised by unnamed reviewers. A reviewer complained about lack of statistical power, but the main analysis of studies 2 and 3 had a power of 95%. This is a technical discussion, but I think the reviewer got it wrong. A reviewer judged that the replication was not a replication. Bates and Gupta used the same IQ tests, the same test of empathy, and those tests of successful team work which had best shown the effects which Woolley et al. claimed in the original research. Looks like a replication to me. Turn-taking was measured by a simpler technique in the replication, but turn-taking was not shown to be independently predictive of group IQ, rendering the point moot. An anonymous reviewer suggested that (paraphrasing) there clearly must be an unidentified moderator which accounts for why individual IQ and collective intelligence correlated so strongly. Readers should evaluate this claim for themselves. It is far from clear to us that an unidentified moderator “must” exist. Bates and Gupta were polite, but they could have responded “You show us why you think there has to be a moderator. Evidence, please”. A friend of the authors, speaking to me in a dark car park on condition of reviewer-type anonymity, said: The back story is that this paper went through 4 revisions, in which one reviewer every time demanded 10, 20, or even 38 new changes, none of which involved a single new analysis. They demanded that Bates and Gupta remove study 2, remove variables, include a statement that they had not done a replication, and conclude that this area is vigorous and needs more research. They claimed the work was sloppy, error-filled, and so under-powered no one should publish it. They suggested that no peer-reviewed journal would ever publish such awful work. So, if you think science is an efficient hunt for the truth…Think again. The impression I get is that the reviewers were being unreasonable, and even obstructive. You might like to look at this link: https://www.unz.com/jthompson/does-peer-review-give-too-much-power-to All this further silliness aside, in what I consider to be one of the most important findings about team work, the authors identify a crucial result: It is interesting also that groups did not perform better than individuals – a genuine group-IQ might be expected to enable problem solving to scale linearly (or better) with number of subjects. In group-IQ tasks, coordination costs appear to prevent group problem-solving from rising even to the level of a single individual’s ability. This implicates not only unsolved coordination problems, which are well-known barriers to scale (Simon, 1997) but also reiterates the finding that the individual problem-solver remains the critical reservoir of creativity and novel problem solution (Shockley, 1957). So, if you want a problem solved, don’t form a team. Find the brightest person and let them work on it. Placing them in a team will, on average, reduce their productivity. My advice would be: never form a team if there is one person who can sort out the problem. As regards team work and collective intelligence, another idea bites the dust, at least until a new hypothesis comes along, claiming you can boost team productivity by a training in…(insert something warm and friendly). No teams were assembled to write this post. | Mid | [
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Q: pointer to function compilation error I am trying to call the function using the pointer to function above but it keeps showing this error:expression preceding parentheses of apparent call must have (pointer-to-) function type. any help? #include<iostream> using namespace std; class a { public: a(){} int f(float m){cout<<"called.\n";return 1;} }; int main() { int (a::*ptr2)(float m) = &a::f; a *p ,obj; p = &obj; obj.*ptr2(.8); p->*ptr2(.5); } A: You are simply missing some parenthesis around your function pointer calls. #include<iostream> class a { public: a(){} int f(float m) { std::cout<<"called."<<std::endl; return 1; } }; int main() { int (a::*ptr2)(float m) = &a::f; a *p ,obj; p = &obj; (obj.*ptr2)(.8); //note the difference (p->*ptr2)(.5); } It is in situations like this that std::invoke can be extremely handy: std::invoke Reference | Mid | [
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Q: How to unwrap return value at function call? I am trying to simplify the problem, the simple code is below. how can I pass two/any arguments(which comes from another function return value) to the test method? Is it possible, or we can't do it in python? def values(x, y): return (x,y) def test(x, y): print(x,y) # error at below test(value(1,2)) A: Unpack using *: test(*value(1,2)) # >>> test(1, 2) | Mid | [
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Q: Hibernate connection provider issue We are facing a strange issue. We are having a web application with spring and hibernate persistence. We are facing issue while deploying our application on Jboss with below error Caused by: org.hibernate.HibernateException: Could not instantiate connection provider [org.springframework.orm.hibernate3.TransactionAwareDataSourceConnectionProvider] at org.hibernate.service.jdbc.connections.internal.ConnectionProviderInitiator.instantiateExplicitConnectionProvider(ConnectionProviderInitiator.java:192) [hibernate-core-4.1.9.Final.jar:4.1.9.Final] at org.hibernate.service.jdbc.connections.internal.ConnectionProviderInitiator.initiateService(ConnectionProviderInitiator.java:114) [hibernate-core-4.1.9.Final.jar:4.1.9.Final] at org.hibernate.service.jdbc.connections.internal.ConnectionProviderInitiator.initiateService(ConnectionProviderInitiator.java:54) [hibernate-core-4.1.9.Final.jar:4.1.9.Final] at org.hibernate.service.internal.StandardServiceRegistryImpl.initiateService(StandardServiceRegistryImpl.java:69) [hibernate-core-4.1.9.Final.jar:4.1.9.Final] at org.hibernate.service.internal.AbstractServiceRegistryImpl.createService(AbstractServiceRegistryImpl.java:176) [hibernate-core-4.1.9.Final.jar:4.1.9.Final] ... 37 more Caused by: java.lang.ClassCastException: org.springframework.orm.hibernate3.TransactionAwareDataSourceConnectionProvider cannot be cast to org.hibernate.service.jdbc.connections.spi.ConnectionProvider at org.hibernate.service.jdbc.connections.internal.ConnectionProviderInitiator.instantiateExplicitConnectionProvider(ConnectionProviderInitiator.java:189) [hibernate-core-4.1.9.Final.jar:4.1.9.Final] ... 41 more Looks like it is conflicting with existing jar in jboss. SAme setup is working fine in windows but not working in linux server. Please help. A: You're using Hibernate 4.1.9 with classes from the org.springframework.orm.hibernate3 package. You shouldn't. Classes in this package must be used with Hibernate 3.x. To use Hibernate 4 with Spring, use classes from the org.springframework.orm.hibernate4package. | High | [
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Impressive idea matratze 90 x 200 hausdesign suchergebnis auf amazon de für cm 31pj hdyrbl ac us218 is one of our best pictures of matratze 90 x 200 hausdesign peaceful ideas and its resolution is 218x218 pixels. Find out our other pictures similar to this impressive idea matratze 90 x 200 hausdesign suchergebnis auf amazon de für cm 31pj hdyrbl ac us218 at gallery below and if you want to find more ideas about matratze 90 x 200 hausdesign peaceful ideas, you could use search box at the top of this page. | Low | [
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Microalbuminuria and casual and ambulatory blood pressure monitoring in normotensives and in patients with borderline and mild essential hypertension. Several reports suggest that urinary albumin excretion may be elevated in patients with essential hypertension and that this index may be a good predictor for cardiovascular complications. The aim of this study was to compare 24-hour urinary albumin excretion in a group of normotensives, borderline, and untreated mild hypertertensives and to assess, in a subgroup of them, the possible relations between microalbuminuria and arterial blood pressure. Fifteen normotensives, 16 borderline, and 19 mild hypertensive patients were studied. Slightly but significantly higher values of microalbuminuria were observed in the mild hypertensives compared to the other two groups. In 21 borderline and mild hypertensive patients 24-hour microalbuminuria was related to casual blood pressure and noninvasive ambulatory blood pressure monitoring. A significant correlation was found between microalbuminuria and average day-time diastolic blood pressure. Our data suggest that albumin excretion is slightly increased in mild arterial essential hypertension; the direct association between microalbuminuria and arterial diastolic blood pressure during daily activities seems to confirm a pathophysiological link between transcapillary protein escape and arterial blood pressure that warrants further studies. | High | [
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Even if we are not deeply versed in the theatre, most of us share an understanding of the familiar social script of going to a play. On the stage, actors move around, talk, touch a set, props, and each other, and maybe dance or sing. On the other side of the fourth wall, the audience voluntarily sits still, silently, in the dark, facing forward. Immersive may be a buzzword right now (if I see another ad for an immersive television set, I’ll scream), but to practitioners, immersive theatre means something pretty specific: a style of performance in which audience members are in the “world” of the play, not separated from it by the boundary of a stage. Nina Simon, the Executive Director of the Santa Cruz Museum of Art and History, observes that cultural institutions traditionally are unidirectional, with the audience absorbing content that has been wholly crafted by an institution (or artist, or curator, etc.). The same goes for theatre. In immersive theatre however, the audience participates in creating the very content of the experience. It's not just bidirectional, fostering interaction between audience and actor, but multidirectional: the audience interacts with actors, with other audience members, even with the physical space, creating feedback loops that affect everyone involved. When you take away something as deeply engrained to the theatre experience as the stage, and give the audience more agency, it’s easy to get disoriented. As an audience member at an immersive show, you might ask yourself, where do I look? Where do I sit or stand? Can I talk? Even to seasoned audience members, each immersive they attend can feel like the Wild West. Enter experience design, a frame of mind that is the lifeblood of great immersive theatre. A term also frequently used in tech, in immersive, experience design is a holistic approach to crafting the audience’s journey from the moment they buy a ticket, to the moment they leave the show, integrating front of house, performance, and production. Experience design considers how we help the audience understand their role and how we convey the rules they should follow - rules that keep everyone safe and on the best track toward a meaningful experience. Experience design also includes creating a physical space and designing points of interaction that reinforce those roles and rules, and the big picture "idea" or narrative of the work. At its core, experience design is about seeing through the eyes of the audience. Dr. Temple Grandin, a professor of Animal Science at Colorado State University, famously reconceived the design of livestock facilities by paying close attention to the behavior of animals, considering the “cattle’s eye view” of farm systems and reducing animal stress in the process. Immersive artists apply the same principles, carefully considering and testing audience responses and impulses. Every event can benefit from the experience design thinking we use in immersive work. Here are some takeaways for your next event: 1. Make sure that the audience is top of mind. It sounds obvious enough, but guests can tell when you’ve contemplated and prepared for their every move and when they’re an afterthought. Do guests need to bring their phones for mobile bidding? Did you tell them in advance – and provide charging stations? Details count. 2. Treat everything that happens between ticket purchase and arrival in the playing space as part of the experience. How many times have you had an evening out marred by not being able to find parking? Or by a bad check-in experience? Pay special attention to these early encounters with the guest. After all, there’s no way to make a new first impression. 3. Embrace the creativity that comes when you realize you don’t “have” to do anything. Familiar social scripts are there if you need them, but there’s room to adapt event formats even in traditional institutions. If you plan carefully and conscientiously, communicate clearly, and walk a mile in the shoes of an audience member, you can always write a new script for a great event. I used to hate setting goals. As a kid, setting goals meant being prodded to make absurd promises or declarations about a future that to me never seemed terribly distinct (I vividly remember writing “I will never swear” on a piece of paper that was then burned in a fire on a 5th grade retreat. Don’t ask me how that one turned out). As I progressed in my career as a producer, I came to understand how important goal setting is, especially when you’re working with a team. Goals aren’t magical predictions or promises; they’re a set of shared expectations about what defines success. Delineating objectives, and writing them down, at the beginning of a project helps keep your team working with shared purpose and keeps people accountable to each other and to higher ups. So where to begin? As I’m still recovering from my childhood goal-setting angst, I like a little structure when it comes to planning. I usually turn to the SMART Goal framework. First developed by a consultant named George T. Duran in the early 1980’s, SMART is a rubric designed to help craft “meaningful objectives,” using the acronym to identify the five qualities shared by (most) goals that spur action. Over time, some letters have taken on multiple interpretations, but in my work, I use: specific, measurable, achievable, relevant, and time-bound. These are the questions I ask myself as I approach a new project: Specific: What is the exact objective? Can it be broken into smaller, individual objectives that are more discrete? Measurable: How will the success of the objective be quantified? (Not every goal easily lends itself to quantifiable measurement, but many do.) Achievable: Can this goal reasonably be accomplished in the time allotted and with available resources? Relevant: Is this goal pertinent? Does it matter to the mission of the organization, or the larger career trajectory of an individual artist? Time-Bound: When should this objective be reached? Are there any milestones along the way? In future posts I’ll delve deeper into some of the individual SMART elements. For now, think about the projects on your plate in 2018. Have you started mapping out your goals for the coming year? I’d love to hear about them – and help you bring them to fruition! | Mid | [
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Brief communication: paleopathology of the Kiik-Koba 1 Neandertal. The Kiik-Koba 1 Neandertal partial skeleton (canine, partial hands, partial leg, and feet), of a approximately 40-year-old probable male, exhibits a suite of pathological lesions, including hypercementosis, minor fibrous ossifications, pedal phalangeal fracture, and pronounced enthesopathies on the patella and calcanei in the context of no articular degenerations. The first two sets of lesions are related to age in the context of advanced dental attrition and physical strains. The third lesion joins a series of healed minor traumatic lesions among the Neandertals. The last represents either pronounced tendinous inflammation, albeit in the context of no articular degenerations, or a case of diffuse idiopathic skeletal hyperostosis (DISH) in the Late Pleistocene. Kiik-Koba 1 therefore adds to the high incidence of pathological lesions among the Neandertals and, if a diagnosis of DISH is correct, to a high frequency of this disorder among older Neandertals. | High | [
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209 B.R. 714 (1997) In re Srinivasan KRISHNAMURTHY; Annapoorna Krishnamurthy, Debtors. Srinivasan KRISHNAMURTHY; Annapoorna Krishnamurthy, Appellants, v. Prasad NIMMAGADDA; Lih Guin Nimmagadda, Appellees. BAP No. NC-96-1409-MeOV, Bankruptcy No. 94-47652, Adv. No. 94-4751. United States Bankruptcy Appellate Panel of the Ninth Circuit. Argued and Submitted January 23, 1997. Decided February 27, 1997. Amended April 3, 1997. *715 *716 Srinivasan and Annapoorna Krishnamurthy, Santa Clara, CA, pro se. Roger T. Ritter, Law Offices of Joel D. Adler, San Francisco, CA, for Prasad and Lih Guin Nimmagadda. Before: MEYERS, OLLASON and VOLINN, Bankruptcy Judges. AMENDED OPINION MEYERS, Bankruptcy Judge: I OVERVIEW The appellants' disorganized and nonsensical arguments notwithstanding, this case is quite simple. A state court jury assessed punitive damages against the appellants under Section 3294 of the California Civil Code which requires a finding of "oppression, fraud or malice." A finding of oppression or malice satisfies Bankruptcy Code § 523(a)(6). A finding of fraud coupled with the undisputed fact that appellants and appellees were partners, and hence fiduciaries, satisfies § 523(a)(4). Either way the state court judgment established that appellees have a valid claim and that such claim is nondischargeable. The Freeman & Mills case relied upon by the appellants does not apply to the facts of this case. The appellants' claim of extrinsic fraud was supported by neither sufficient evidence nor satisfactory factual allegations. The appellees were entitled to collateral estoppel and summary judgment. We AFFIRM. II FACTS A. State Court Litigation On January 20, 1988, Prasad and Lih Guin Nimmagadda, ("Nimmagaddas"), filed a "Second Amended Complaint," ("Complaint"), in Superior Court asserting seven causes of action against Srinivasan and Annapoorna Krishnamurthy, ("Debtors"): dissolution and accounting; breach of contract; fraud; constructive fraud; breach of covenant of good faith and fair dealing; and breach of fiduciary duty the Debtors and the Nimmagaddas were, at the time of the Debtors' misdeeds, partners. The trial took more than a month. The jury returned general verdicts against the Debtors and in favor of the Nimmagaddas. The verdicts did not indicate upon which cause(s) of action damages were awarded, however, the jury did award punitive damages under California's "oppression, fraud or malice" standard.[1] On April 1, 1988, judgment was entered on the general verdicts awarding damages in the amount of $234,847 and punitive damages in the amount of $25,000 against each of the Debtors. The Debtors filed motions for a new trial and for judgment notwithstanding the verdict, both of which were denied. The Nimmagaddas filed a motion for a new trial with *717 respect to damages, which was granted "because of inadequate damages."[2] In June of 1988, the Debtors appealed the April 1, 1988 judgment and the order granting the Nimmagaddas a new trial. The California Court of Appeals affirmed the trial court on both issues and awarded the Nimmagaddas costs on appeal. In September of 1992 a new trial was held on the issue of the amount of damages. The jury was instructed that "Defendants have been found liable to plaintiffs for punitive damages." The jury was instructed on fraud and breach of fiduciary duty; the breach of contract cause of action had been dismissed against both of the Debtors no instructions were given for breach of contract. In this second trial the jury awarded, in addition to compensatory damages, punitive damages in the amount of $125,000 against both of the Debtors. On September 17, 1992, the Nimmagaddas obtained a state court judgment against the Debtors. The Debtors appealed, attacking both the determination of liability and the award of damages. On November 20, 1992, the trial judge found that the award of punitive damages with respect to Srinivasan Krishnamurthy was excessive and granted a new trial on that issue. On January 28, 1994, the California Court of Appeals dismissed the Debtors' appeal with respect to the determination of liability stating: On the merits, Krishnamurthy first argues that the punitive damages award is void as a matter of law because there was no clear and convincing evidence of fraud, oppression or malice. At the first trial, the issue of entitlement to punitive damages was determined. The jury was instructed on the need for clear and convincing evidence of oppression, fraud or malice to support its finding that punitive damages were warranted. Its finding of liability including the determination to award punitive damages was affirmed in our previous appeal. That decision constitutes the law of the case, conclusively establishing the liability issue for our purposes. At the second trial, the only issue was the amount of damage that the Nimmagaddas suffered. The Court of Appeals affirmed the judgment awarding the compensatory and punitive damages and provided the following evaluation of the Debtors' appeal: On appeal, Krishnamurthy raises a myriad of contentions. Having reviewed the record of this appeal and several of Krishnamurthy's earlier appeals, we are satisfied that the trial court's sanctions order was well justified. Krishnamurthy has engaged in a systematic practice of filing meritless motions and appeals that only thinly disguise her intention to delay satisfaction of all judgments and orders entered against her. We will not countenance her disrespect of the judicial system by allowing any further delay. . . . In particular, Annapoorna Krishnamurthy's briefs in this appeal establish repeated attempts to inject new life into issues that have already been resolved by this court. By ignoring well-established doctrine of law of the case as well as fundamental principles of jurisprudence, Krishnamurthy has forced the Nimmagaddas to defend against all aspects of this case that have been put to rest years ago. Subject to review by our Supreme Court, this opinion should put to rest, for all eternity, any and all issues relating to this litigation, and with the finality of this opinion, there should be no further delays in the ultimate disposition of this cause. That decision was filed nearly three years ago. B. Bankruptcy Proceedings On November 15, 1994, the Debtors filed a petition under Chapter 7. On December 7, 1994, the Nimmagaddas filed a nondischargeability action under Bankruptcy Code §§ 523(a)(4) and 523(a)(6). *718 The Debtors filed a motion to strike and motion to dismiss, both of which were denied. The Debtors answered on March 27, 1995. Both the Debtors and the Nimmagaddas filed motions for summary judgment. The Bankruptcy Court granted the Nimmagaddas' motion determining that all of the necessary findings had been made by the state court and that the Debtors were collaterally estopped from relitigating those issues. The Debtors filed a motion for reconsideration which was denied. III ISSUES PRESENTED First we will address the impact of the intervening case, Freeman & Mills, Inc. v. Belcher Oil Co., 11 Cal.4th 85, 44 Cal.Rptr.2d 420, 900 P.2d 669 (1995), on the Nimmagaddas entitlement to collateral estoppel. Next we will consider whether the Bankruptcy Court properly granted summary judgment in light of the Debtors' bald allegations of extrinsic fraud. Finally we will determine whether the record supported a grant of summary judgment in favor of the Nimmagaddas. IV STANDARDS OF REVIEW The Panel determines its jurisdiction sua sponte. In re Peters, 191 B.R. 411, 416 (9th Cir.BAP1996). The availability of collateral estoppel is a question of law reviewed de novo. In re Nourbakhsh, 67 F.3d 798, 800 (9th Cir.1995). The bankruptcy court's findings of fact are reviewed under the "clearly erroneous" standard while conclusions of law are reviewed de novo. In re A & C Properties, 784 F.2d 1377, 1380 (9th Cir.1986). The granting of summary judgment is reviewed de novo, making all reasonable inferences in favor of the non-movant to determine whether there exists any genuine issue of material fact precluding judgment in favor of the movant as a matter of law. In re Lewis, 97 F.3d 1182, 1185 (9th Cir.1996). V DISCUSSION A. Jurisdiction On April 18, 1996, the Debtors filed their "Notice of Appeal," purporting to appeal from the following orders: 1. The April 9, 1996 judgment determining that the Nimmagaddas' claim is nondischargeable; 2. the April 9, 1996 order granting the Nimmagaddas' motion for summary judgment, denying the Debtors' cross-motion for summary judgment and denying the Debtors' motion to dismiss the Nimmagaddas' complaint; 3. the June 16, 1995 order granting the Nimmagaddas' motion to dismiss the Debtors' counterclaim; and 4. the April 12, 1995 order extending the last date for the Nimmagaddas to file objections to discharge under Bankruptcy Code § 727. The orders and judgment entered on April 9, 1996, were timely appealed the period did not begin running until the Debtors' timely motion for reconsideration was denied, April 17, 1996. In re D.W.G.K. Restaurants, Inc., 42 F.3d 568, 569 (9th Cir.1994); In re Watson, 192 B.R. 739, 742 n. 3 (9th Cir. BAP 1996). With respect to the June 16, 1995 order granting the Nimmagaddas' motion to dismiss the Debtors' counterclaim, the Debtors had filed a "timely" notice of appeal on June 26, 1995. On August 10, 1995, the Panel, finding the order to be interlocutory, entered an order denying the Debtors "Motion for Leave to Appeal," and dismissing the appeal. The June 16, 1995 order became final upon entry of the motion for summary judgment and was thus timely appealed with the April 9, 1996 orders. The order entered April 12, 1995, extending the time to file a complaint objecting to discharge under § 727, on the other hand, remains interlocutory. In re Travers, 202 B.R. 624, 626 (9th Cir. BAP 1996). Since the judgment was limited to the causes of action under § 523 no final judgment has been entered with respect to the § 727 causes of *719 action. 28 U.S.C. § 158(a) authorizes the Panel to grant leave to appeal an interlocutory order, treating the notice of appeal as a motion for leave to appeal. Id.; Fed. R.Bankr.P. 8003(c). As a practical matter, however, in light of their successful § 523 action, the Nimmagaddas may not wish to pursue their § 727 action. The Panel thus declines to grant leave to appeal the April 12, 1995 order. On April 23, 1996, the Debtors filed an amended notice of appeal to include for appellate review the Bankruptcy Court's denial of the motion for reconsideration. The appeal from that order, which was entered on April 17, 1996, was timely. B. Collateral Estoppel The Debtors argue that the Bankruptcy Court improperly applied the principles of collateral estoppel to the state court judgment for two reasons: First, the Debtors argue that intervening case law has stripped the judgment of its power to bind, and second the state court judgment was obtained through extrinsic fraud. Neither of the Debtors' arguments are supported by the record. 1. Application of Subsequent Case LawFreeman & Mills The Debtors' primary argument is that the state court's judgment in favor of the Nimmagaddas may not be afforded res judicata consequences as it was preempted by a state court decision, Freeman & Mills, Inc. v. Belcher Oil Co., 11 Cal.4th 85, 44 Cal.Rptr.2d 420, 900 P.2d 669 (1995), in which the California Supreme Court held that damages in tort would not lie for bad faith denial of contract. According to the Debtors, "[t]he main issue for this court to determine is whether the doctrine of collateral estoppel can be invoked in a case as here, where there has been an overruling decision in favor of a general rule precluding tort recovery for noninsurance breach of contract actions." The Debtors have misinterpreted the Freeman & Mills case. In Freeman & Mills, the California Supreme Court addressed the issue of "whether, and under what circumstances, a party to a contract may recover in tort for another party's bad faith denial of the contract's existence." Id. at 88, 44 Cal.Rptr.2d 420, 900 P.2d 669. The court ultimately determined that it had, in Seaman's Direct Buying Service, Inc. v. Standard Oil Co., 36 Cal.3d 752, 206 Cal.Rptr. 354, 686 P.2d 1158 (1984), "incorrectly recognized a tort cause of action based on the defendant's bad faith denial of the existence of a contract between the parties." Id. The rule of Freeman & Mills is simply and exclusively that breach of a noninsurance contract and denial of its existence, "in the absence of violation of `an independent duty arising from principles of tort law,'" does not give rise to a tort claim. Id. at 102, 44 Cal.Rptr.2d 420, 900 P.2d 669. The mere fact, however, that the conduct of the Debtors may also have amounted to a breach of contract, does not, under California law, preclude an independent finding that the Debtors committed a tort. Applied Equipment Corp. v. Litton Saudi Arabia Ltd., 7 Cal.4th 503, 515, 28 Cal.Rptr.2d 475, 869 P.2d 454 (1994) ("Conduct amounting to a breach of contract becomes tortious only when it also violates an independent duty arising from principles of tort law.") (Cited with approval in Freeman & Mills, 11 Cal.4th at 102, 44 Cal.Rptr.2d 420, 900 P.2d 669.) As the Nimmagaddas and the Bankruptcy Court explained to the Debtors, the Nimmagaddas' state court judgment was not based on breach of contract and hence Freeman & Mills has no application. The Nimmagaddas dropped their breach of contract claim before obtaining the judgment upon which their nondischargeability action is based before the jury instructions were given, counsel for the Nimmagaddas explained to the trial court: Now, for reasons that needn't concern you, just tactical, my clients have decided to present this case to you on the fraud and breach of fiduciary duties issues. So instructions on the contract issues won't come in. All the damages I described at the beginning of the case, are damages for fraud and breach of fiduciary duty. *720 The Debtors' argument that Freeman & Mills "prohibits tort recovery for breach of a fiduciary duty between partners that is founded on the partnership agreement," finds no support in the Freeman & Mills decision. In the case at hand the California courts found that the Debtors committed the independent torts of breach of fiduciary duty and fraud. The Bankruptcy Court clearly found that the state court judgments were based upon non-contractual causes of action. The Bankruptcy Court properly found that these state court findings necessarily satisfied the Bankruptcy Code requirements of §§ 523(a)(4) and 523(a)(6). The Bankruptcy court specifically addressed the Debtors' "Freeman & Mills" argument, and correctly found the case to be inapplicable. 2. Extrinsic Fraud Since shortly after the state court judgment was entered the Debtors have been making unintelligible allegations of "extrinsic fraud." The Debtors first made the argument fruitlessly to the state trial court in their "Memorandum of Points and Authorities in Support of Motion for Equitable Relief From Judgment Obtained by Reason of Extrinsic Fraud or Mistake." Next the Debtors made the argument in vain to the California Court of Appeals. Having had no success in the state courts the Debtors made the argument to the Bankruptcy Court. One of the Debtors' twenty-three affirmative defenses in their answer to the Nimmagaddas' nondischargeability complaint was that the state court judgment was obtained "through extrinsic fraud perpetrated by plaintiffs on the state courts." The Debtors repeated their allegations of extrinsic fraud in their counterclaim which was dismissed by the Bankruptcy Court. Finally, the Debtors provided the following "ILLUSTRATION OF PLAINTIFFS' EXTRINSIC FRAUD" to the Bankruptcy Court in their reply in support of their motion for reconsideration: Defendants' claim of extrinsic fraud arises from the fact that defendants have been prevented from presenting all of their case to the court and the attorney regularly employed by defendants corruptly sold out his clients' interests to the other side, with the result that there has never been a real contest in the trial. . . . Defendants' allegations are real and not amorphous as argued by plaintiffs. In addition, extrinsic fraud resulted also from "corruption of or duress upon the court or the attorney for the party against whom the judgment was rendered" and the judgment was "based on a claim that the party obtaining the judgment knew to be fraudulent."[3] It appears from the record that this is the most the Debtors ever produced as evidence or argument of extrinsic fraud. The BAP has recently held that a state court judgment is subject to attack if the judgment was procured through extrinsic fraud: A state court judgment is subject to collateral attack if. . . . the judgment was procured through extrinsic fraud. Equity will set aside a judgment on the basis of extrinsic fraud if the judgment resulted from circumstances of unfairness or injustice where the aggrieved party was not afforded an opportunity to participate in the proceedings or to present his case to the court. The basic requirement for invoking the extrinsic fraud exception is that there has been no fair adversary trial at law, either because the aggrieved party was kept in ignorance of the action or proceeding, or in some other way fraudulently prevented from presenting his claim or defense. In re Lake, 202 B.R. 751, 758 (9th Cir. BAP 1996). However, in order to establish a case for vacating a California state court judgment the movant must plead and prove that he has a meritorious case. Lake, supra, 202 B.R. at 759 citing New York Higher Educ. Assistance Corp. v. Siegel, 91 Cal.App.3d 684, 689, 154 Cal.Rptr. 200 (1979). In Lake the debtor plead specific instances of extrinsic fraud which had permitted *721 claimant to unwittingly obtain a default judgment.[4] In the case at hand the Debtors offered no similar proof they simply set forth more of their convoluted and unsupported argument. To survive summary judgment the Debtors were obliged to produce some "significant probative evidence." Lewis, supra, 97 F.3d at 1187, citing Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 249, 106 S.Ct. 2505, 2510, 91 L.Ed.2d 202 (1986). Conclusory arguments unsupported by factual statements or evidence do not meet this burden. Lewis, supra, 97 F.3d at 1187. Nothing alleged by the Debtors would support a finding that "there has been no fair adversary trial at law." To the contrary, the Debtors litigated and appealed these issues for over six years in the state courts. The Bankruptcy Court properly addressed the Debtors' claim of extrinsic fraud. C. Summary Judgment Was Supported By the Record That punitive damages were awarded and that the Debtors and the Nimmagaddas were partners at all relevant times are apparent from the record. These undisputed facts, standing alone, dictate that the decision of the Bankruptcy Court be affirmed. Section 3294 of the California Civil Code, which governs the imposition of punitive or exemplary damages, provides in relevant part: (a) In an action for the breach of an obligation not arising from contract, where it is proven by clear and convincing evidence that the defendant has been guilty of oppression, fraud, or malice, the plaintiff, in addition to the actual damages, may recover damages for the sake of example and by way of punishing the defendant. Cal.Civ.Code § 3294(a). "Malice" is defined as "conduct which is intended by the defendant to cause injury to the plaintiff or despicable conduct which is carried on by the defendant with a willful and conscious disregard of the rights or safety of others"; "oppression" is defined as "despicable conduct that subjects a person to cruel and unjust hardship in conscious disregard of that person's rights"; and "fraud" means "an intentional misrepresentation, deceit, or concealment of a material fact known to the defendant with the intention on the part of the defendant of thereby depriving a person of property or legal rights or otherwise causing injury." Cal.Civ.Code § 3294(c).[5] The terms "malice" and "oppression" are often used by the California courts interchangeably without any distinction. In re Aubrey, 111 B.R. 268, 275 (9th Cir. BAP 1990). The BAP has held that the statutory definition of the term "oppression" as defined in the California courts is equivalent to "malice", and that either satisfies the requirements of § 523(a)(6).[6]Id.; In re Giangrasso, 145 B.R. 319, 323 (9th Cir. BAP 1992). In In re Moore, 186 B.R. 962 (Bkrtcy.N.D.Cal. 1995), the court concluded: As discussed above, however, it appears that because "conscious disregard" is required for a finding of malice under the California statute since the 1980 amendment, "reckless disregard" is no longer sufficient to sustain a punitive damage award under California law. It therefore appears that under California law, punitive damage awards under Cal.Civ.Code § 3294 can only properly be made in response to wrongful acts that would, by definition, also violate 11 U.S.C. § 523(a)(6). *722 Id. at 973. If the court can determine that the state court jury found "oppression" or "malice", then a judgment for punitive damages satisfies the willful and malicious requirements under § 523(a)(6). Giangrasso, 145 B.R. at 323. Since, however, the phrase "oppression, fraud, or malice" in Civil Code § 3294 is in the disjunctive; an award of punitive damages could be based upon fraud alone. Glendale Fed. Sav. & Loan Assn. v. Marina View Heights Dev. Co., 66 Cal.App.3d 101, 135, 135 Cal.Rptr. 802 (1977); Las Palmas Associates v. Las Palmas Center Associates, 235 Cal. App.3d 1220, 1239, 1 Cal.Rptr.2d 301 (1991). In this case, however, a finding of fraud is also sufficient to render the obligation nondischargeable because the Debtors and the Nimmagaddas were fiduciaries. Whether a relationship is fiduciary within the meaning of § 523(a)(4) is a question of federal law.[7]Lewis, supra, 97 F.3d at 1185. The issue can be resolved by looking to state law. Id.; Ragsdale v. Haller, 780 F.2d 794, 796-97 (9th Cir.1986); In re Short, 818 F.2d 693 (9th Cir.1987). As the Bankruptcy Court explained at the hearing, under California law a partner is a fiduciary within the meaning of § 523(a)(4). Thus, even if the punitive damages were based upon a finding of fraud, it was fraud while acting as a fiduciary, and the elements of § 523(a)(4) are unquestionably established. The willful and malicious elements under § 523(a)(6) or the fraud as a fiduciary elements of § 523(a)(4) were specifically determined in the state court proceeding. It would have been unjust to require the Nimmagaddas to relitigate these issues before the Bankruptcy Court. Incurring these costs anew is precisely the evil the doctrine of collateral estoppel was designed to prevent. See Allen v. McCurry, 449 U.S. 90, 94, 101 S.Ct. 411, 414-15, 66 L.Ed.2d 308 (1980); In re Bugna, 33 F.3d 1054, 1057 (9th Cir. 1994). VI CONCLUSION That punitive damages were awarded under California law necessarily establishes that the jury found "oppression, fraud or malice." Oppression or malice satisfy § 523(a)(6). Fraud, while acting as a fiduciary, satisfies § 523(a)(4). The Bankruptcy Court properly granted summary judgment in favor of the Nimmagaddas and against the Debtors. The orders and judgments from which appeal was properly taken are hereby AFFIRMED. NOTES [1] See, Section 3294 of the California Civil Code set out below. [2] In lieu of a new trial Nimmagaddas were offered, by the court, additur raising the awards to $375,000 and $25,000, jointly and severally against Debtors. Apparently the Nimmagaddas did not accept the offer and elected to go on to trial on damages. [3] The claim of extrinsic fraud in the counterclaim is lengthier, but no more lucid. [4] In Lake the plaintiff had threatened the life of the defendant causing the defendant to move out of the state. The plaintiff then obtained a default judgment serving the summons by publication. The defendant did not learn of the lawsuit until several months after the default judgment had been entered. 202 B.R. at 754-55. [5] At the 1988 trial, the one in which punitive damages were initially awarded, the jury was read an instruction which tracked § 3294, ("BAJI 14.72.1"). [6] Section 523(a)(6) provides: (a) A discharge under section 727, 1141, 1228(a), 1228(b), or 1328(b) of this title does not discharge an individual debtor from any debt . . . . (6) for willful and malicious injury by the debtor to another entity or to the property of another entity; [7] Section 523(a)(4) provides: (a) A discharge under section 727, 1141, 1228(a), 1228(b), or 1328(b) of this title does not discharge an individual debtor from any debt . . . . (4) for fraud or defalcation while acting in a fiduciary capacity, embezzlement, or larceny; | Mid | [
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Amadou Diallo, Abner Louima, Anthony Baez, Patrick Dorismond. New York City has been rocked in recent years by the fate of these four men at the hands of the police. But police brutality in New York City is a multi-dimensional phenomenon that refers not only to the hyperviolent response of white male police officers as in these cases, but to an entire... more... | Mid | [
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Toronto — A man whose family said he suffered from psychosis and depression fired a handgun into restaurants and cafes in a lively Toronto neighborhood, killing a 10-year-old girl and an 18-year-old woman and wounding 13 others in an attack that has shaken the confidence of many in the normally safe city. Authorities on Monday evening identified the suspect as Faisal Hussain, 29, of Toronto, who died in an exchange of gunfire with police. It was not immediately clear whether he killed himself or was killed by police. The mass shooting in Toronto's Greektown district Sunday night came just three months after a van struck and killed 10 people in an apparent attack directed at women. A statement from the family of Hussain said their son had severe mental health challenges that the struggled with psychosis and depression. They said medications did not help him and the interventions of professionals were unsuccessful. "While we did our best to seek help for him throughout his life of struggle and pain, we could never imagine that this would be his devastating and destructive end," the Hussain family said. "Our hearts are in pieces for the victims and for our city as we all come to grips with this terrible tragedy. We will mourn those who were lost for the rest of our lives." Police Chief Mark Saunders earlier said he would not speculate on a motive but did not rule out terrorism. "It's almost inconceivable that these things can happen," said Mayor John Tory. "We were so used to living in a city where these things didn't happen and as we saw them going on in the world around us (we) thought they couldn't happen here." "This is an attack against innocent families and our entire city." The slain 18-year-old was identified as Reese Fallon, a recent high school graduate who volunteered for Canada's Liberal party and was due to attend McMaster University in the fall. Her family said in a statement they were devastated. "She was ... smart, passionate and full of energy. It is a huge loss," said Canadian Member of Parliament Nathaniel Erskine-Smith, who knew Fallon. Flags at Toronto City Hall as well as at Fallon's former high school, Malvern CI, and at school board buildings were lowered to half-staff. " An engaging student, Reese Fallon graduated from Malvern CI just last month and was highly regarded by staff and loved by her friends," the school board said in a statement, adding that support was being offered to students. The 13 wounded ranged in age from 10 to 59, and suffered injuries ranging from serious to minor, Saunders said. He did not name the victims, who included eight women and girls, and seven men. Dr. Najma Ahmed of St. Michael's Hospital said five patients had been admitted in serious or critical condition and that three of the five underwent immediate lifesaving operations. A video taken by a witness showed a man dressed all in black walking quickly down a sidewalk and firing three shots into at least one shop or restaurant in Toronto's Greektown, a residential area crowded with Greek restaurants and cafes. Witnesses heard many shots and described the suspect walking past restaurants and cafes and patios on both sides of the street and firing into them. Ontario's police watchdog said there was an exchange of gunfire between the assailant and two officers on a side street before the gunman was found dead near Danforth Avenue where the shootings occurred.. A spokeswoman for the Special Investigations Unit, Monica Hudon, said an autopsy would be performed Tuesday on the suspect. Det.-Sgt. Terry Browne said police had sought a search warrant for an address related to the suspect but didn't say where. Tanya Wilson was closing her tattoo shop on the street when she heard gunshots and a mother and her son ran into her store with gunshot wounds to their legs "They said they were walking and a man told them to get the hell out his way and he just shot them," Wilson said. Wilson said she tied and elevated their wounds and tried to keep them calm while they waited for paramedics. She locked the door and shut off the lights, not knowing what was happening outside. Jody Steinhauer was celebrating her birthday with family at Christina's restaurant on Danforth Avenue when they heard 10 to 15 shots. They ran to the back to the restaurant and hid under a table. "We heard a woman yell, 'Help!' My partner went outside the restaurant and the woman was right there. She had been shot," she said. Her boyfriend and a doctor who was in the restaurant attended to the woman who was shot in the thigh. "She was screaming and yelling and in shock. Nobody was with her. That was the scary part," Steinhauer said. Police, paramedics and other first responders descended on the scene, while people, some in their pajamas, emerged from their homes to see what was happening. Though mass shootings are rare in Canada's largest city, Toronto police had deployed dozens of additional officers over the weekend to deal with a recent rise in gun violence in the city, which has seen 23 gun homicides so far this year, compared to 16 fatal shootings in the first half of 2017. Toronto Councilor Paula Fletcher said the attack was "not gang related" and that the gunman shot "indiscriminately" into restaurants and into a park. "I know we always say, 'That can't happen here,' when we see those gunmen in the States doing the same thing and it has happened here now," Fletcher said. Ontario Premier Doug Ford said the confidence that Toronto is a safe city had been shaken. Toronto has long prided itself as being one of the safest big cities in the world. Prime Minister Justin Trudeau tweeted: "The people of Toronto are strong, resilient and brave — and we'll be there to support you through this difficult time." In April, the driver of a van plowed into pedestrians on a Toronto sidewalk, killing 10 people and injuring 14. Authorities have not disclosed a motive, but said the arrested driver, Alek Minassian, posted a message on social media referencing a misogynistic online community before the attack. A now-deleted Facebook post indicated anger toward women and saluted Elliot Rodger, a community college student who killed six people and wounded 13 in shooting and stabbing attacks near the University of California, Santa Barbara, in 2014. "The Incel Rebellion has already begun!" read the post, using the term incel to refer to "involuntarily celibate." Meanwhile, Ottawa police arrested a 24-year-old man with a knife on Monday during the Changing of the Guard on Parliament Hill in Ottawa. No one was injured. It was unclear if the incident was related to the mass shooting in Toronto. ___ | Low | [
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Police said a 29-year-old man was taken to the hospital Saturday night after an instance of road rage led to a shooting.The man had been driving west along Silver Spring Drive around 10:15 p.m. He and another driver got into a road rage incident near 103rd Street.The other driver began shooting at the man. Officers arrived soon after.The man was taken to the hospital. Police did not say whether the shooter had been arrested or whether the victim's injuries were life threatening.Check back with WISN.com for updates.Get the WISN 12 NEWS app Police said a 29-year-old man was taken to the hospital Saturday night after an instance of road rage led to a shooting. The man had been driving west along Silver Spring Drive around 10:15 p.m. He and another driver got into a road rage incident near 103rd Street. The other driver began shooting at the man. Officers arrived soon after. The man was taken to the hospital. Police did not say whether the shooter had been arrested or whether the victim's injuries were life threatening. Check back with WISN.com for updates. | Low | [
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Modern Lifestyles Are Trying To Kill You Translation: 94% of the people who get this disease either do not notice or do not think it significant enough to report. They concluded that on average about 6 per cent of cases were detected in the 40 countries studied, and the only way to prevent a renewed outbreak of Covid-19, the disease caused by the coronavirus, was to do widespread testing followed by isolation of infected people. The mAbs, made based on antibodies in B cells of the patients, are 13 strains targeting the spike protein (S) of the coronavirus and 12 strains targeting the nucleocapsid protein (N) of the virus. Monoclonal antibodies (mAbs) are immune system proteins that are created in the lab. They are made by identical immune cells that are all clones of a unique parent cell. Like the body’s own antibodies, mAbs recognize specific targets. It turns out that building up basic immunity makes the immune system more likely to be able to fend off unknowns. If drivers start testing positive, there could be a tremendous reduction in drivers willing to risk everything, Spencer said. Hindsight is 20-20 but actually blind. When you receive many reports of possible crises, with each organization emphasizing its pet crisis in order to gain more importance in the hierarchy, many important things get overlooked in the constant flow of hysteria, panic, and mania. Do you trust this system to ever get it right? “Analysts concluded it could be a cataclysmic event,” one of the sources said of the NCMI’s report. “It was then briefed multiple times to” the Defense Intelligence Agency, the Pentagon’s Joint Staff and the White House. Following the swine flu and SARS, it makes some people sick and avoids others, and of those sick, most have a nasty flu but the unhealthy pop off. The CDC was able to analyze 7,162 laboratory-confirmed COVID-19 cases and found that 656 of them, or 9.2%, reported having a chronic lung condition. No surprise there. We know that air pollution damages brains, lungs, and bodies. When a stressor like COHIVID-19 comes around, it will kill those most affected. This probably also explains the bump in African-American results in part, since inner city communities have terrible air. A small increase in long-term exposure to PM2.5 leads to a large increase in COVID-19 death rate, with the magnitude of increase 20 times that observed for PM2.5 and all-cause mortality. The majority of the pre-existing conditions that increase the risk of death for COVID-19 are the same diseases that are affected by long-term exposure to air pollution. We investigate whether long-term average exposure to fine particulate matter (PM2.5) increases the risk of COVID-19 deaths in the United States. The Secondary Effects Checkpoints have gone up along the TX/LA state line In accordance with a recent order from Texas Governor Greg Abbott, Texas State Troopers are advising those who try to travel from Louisiana into Texas that they must quarantine themselves for a 14 day period upon enter the Lone Star State. This should be normal for American states. Places are different; encouraging travel between them just erases those differences. The pre-Constitution government under The Articles of Confederation and the Confederacy just won a big historical point here. You can win the war, but can you win the cause-effect fact pattern? Why African Americans are dying at higher rates from Covid-19 “We know that blacks are more likely to have diabetes, heart disease, lung disease,” the nation’s top doctor, Surgeon General Jerome Adams told CBS News on Tuesday. These chronic illnesses, which are in turn linked to poverty and structural racism, can lead to more serious forms of the Covid-19 disease. Structural racism? More likely, they are genetic, exacerbated the tendency of inner city communities to be awash in pollution. The best option for the impoverished comes in the form of ghettos, which by their nature as worthless land, lower their housing costs. Defective masks were sent to Toronto long-term care home where residents died of COVID-19 “After reports of ripping and tearing, further inspection of the masks determined that the masks ordered did not meet the city’s standard and specifications,” the city said, adding that Toronto’s occupational health safety staff has been contacted This pandemic has revealed the flip side of modernity: the fragility and incompetence of just about everything. Even while Trump leads well, he is commanding a vast system comprised of bureaucrats. Each one of them is thinking only about how to promote himself by avoiding risk and seizing opportunities to draw attention to himself. Social mobility leads to the condition, where everyone is trying to advance his individual power, wealth, and status at the expense of society at large. Consequently, everything we have is surface-level, based in appearance, and nothing is durable; all of the bean-counters that we have promoted through our meritocracy are good at school and tests, but unable to think outside of what they have been taught. The Prole Kingdom of Democracy has failed. For more ineptitude comedy, check out how democracy has been destroying medical supplies to make room for migrants. Coronavirus: Video footage shows inmates burying coffins in New York The newly released footage shows more than a half-dozen white-clad prisoners lower wooden coffins into the ground, then stand by as a bulldozer and backhoe dump mounds of dirt on at least 20 of the boxes, which are lined up at the end of a long trench. Burials are a common sight on the island, where the city has used inmates to inter the Big Apple’s anonymous and unclaimed dead for 150 years. Large cities filled with diversity seem to get hit hard by this epidemic. Perhaps genetic differences have a lot to do with it. Trump threatens to defund WHO as US coronavirus deaths surge past 12,800 In Washington, Trump told reporters that he was “going to put a very powerful hold” on funding to the WHO, the UN body whose biggest contributor is the US, accusing it of being “very biased towards China.” “They called it wrong,” he said of a WHO travel warning on China. “They could have called it months earlier.” Following revelations that the WHO and UN are effectively controlled by China, Trump wants us out of these organizations. Connection to the coronavirus is incidental: the WHO, like other international organizations, operates on the basis of wealth transfer from the first world to the third, in order to keep up our ideological commitment to equality. We can lose them with no risk to ourselves. Coronavirus: When using the c-word gets you blacklisted The New York Times estimates that it will lose 10% of its digital revenues this year because brands are refusing to advertise on pages with coronavirus-related stories. In 2019, NYT achieved total digital revenues of $800 million. A watchdog for Britain’s national newspaper sector reports that, if the pandemic lasts another three months, publishers will have 50 million pounds ($62 million, €57 million) less to fund quality journalism at a time when reliable, timely information is critical. That represents nearly 30% of total digital revenue, according to Newsworks, the UK industry’s marketing body. Brands do not want to see their logos next to coronavirus news, since who wants to be associated with disease, panic, and systemic failure? Newspapers dealt with this problem by letting big companies buy more expensive ads closer to the front of the newspaper, but online firms work not by a linear page-order but by keyword-linked ads. This means that some news, and some topics, will sell zero ads. With this revelation, the idea of internet advertising takes another hit. Soon we will realize that the dot-com boom is just as fake as climate change or most claims in your newspaper about Donald Trump. 70 percent of fake COVID-19 news from China: Investigation Bureau Of the 271 fake news cases the MJIB was investigating, 196 originated from China, and 35 suspects have been handed over to prosecutors, according to Chang. Zero surprise. Leftist societies run on propaganda. How much of our news will turn out to be fake once all the facts are out? The links in the PPE supply chain “have been broken” as hospitals battle coronavirus “We are all shopping China to try to get these materials and we’re all competing against each other,” New York Governor Andrew Cuomo said at a press conference. Better if everything you need is produced locally. In addition, that way you can put up the roadblocks and avoid any crisis that originates somewhere else. Black, Asian and Hispanic House caucus chairs unite in ‘no tolerance’ for coronavirus racism Leaders also took a stand against rhetoric that promoted the racist association between the disease and location or ethnicity, including terms like “Chinese virus” and “Wuhan virus,” saying it could cause people to misdirect their anger and put Asian Americans in harm’s way. When times get tough, minorities unite against the majority, even if many of these anti-Asian hate crimes are committed by fellow minority groups. California county threatens $1,000 fine for not wearing face masks in public Frederico said the tough mandate, which went into effect Sunday at midnight, was aimed at slowing the spread of the highly contagious virus in the county, about 60 miles east of Los Angeles, and beyond. Again we see the advantage of culture: when people perceive themselves as group united by similarity, they work for the health and sanity of that group, which means that they enforce good practices by ostracizing those who refuse to obey. With civil rights, culture went out the window, and now instead we have Sugar Daddy government coming in to force people to conform to obvious needs. Sweden took the opposite approach and told each citizen to be responsible, avoiding the enforcement crisis that will now expand across the USA as local communities one-up each other for headlines. Fauci: ‘Looks like’ US deaths will be lower than original projection A closely watched University of Washington model is now projecting about 60,000 deaths in the U.S. Most of these were on their way out anyway. Sad, but not a game-ender. Now that we have created a second Great Depression in response, can we admit that modernity is inept? Officials warned Canada couldn’t enforce coronavirus quarantine for travellers from China Federal, provincial and territorial health departments agreed not to order tens of thousands of travellers arriving in Canada from China to quarantine in February in order to reduce pressure on public health resources, according to a memo addressed to Health Minister Patty Hajdu and signed by the Public Health Agency of Canada’s president and chief public health officer. Triage comes to you with socialized medicine. The system has only so many resources, so to make their figures look good, they dump infected people into the population in order to cause a crisis so that they can get the funding that they need. | Low | [
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package com.github.zxh0.luago.binchunk; import java.nio.ByteBuffer; import java.nio.ByteOrder; import java.util.Arrays; public class BinaryChunk { private static final byte[] LUA_SIGNATURE = {0x1b, 'L', 'u', 'a'}; private static final int LUAC_VERSION = 0x53; private static final int LUAC_FORMAT = 0; private static final byte[] LUAC_DATA = {0x19, (byte) 0x93, '\r', '\n', 0x1a, '\n'}; private static final int CINT_SIZE = 4; private static final int CSIZET_SIZE = 8; private static final int INSTRUCTION_SIZE = 4; private static final int LUA_INTEGER_SIZE = 8; private static final int LUA_NUMBER_SIZE = 8; private static final int LUAC_INT = 0x5678; private static final double LUAC_NUM = 370.5; public static Prototype undump(byte[] data) { ByteBuffer buf = ByteBuffer.wrap(data) .order(ByteOrder.LITTLE_ENDIAN); checkHead(buf); buf.get(); // size_upvalues Prototype mainFunc = new Prototype(); mainFunc.read(buf, ""); return mainFunc; } private static void checkHead(ByteBuffer buf) { if (!Arrays.equals(LUA_SIGNATURE, getBytes(buf, 4))) { throw new RuntimeException("not a precompiled chunk!"); } if (buf.get() != LUAC_VERSION) { throw new RuntimeException("version mismatch!"); } if (buf.get() != LUAC_FORMAT) { throw new RuntimeException("format mismatch!"); } if (!Arrays.equals(LUAC_DATA, getBytes(buf, 6))) { throw new RuntimeException("corrupted!"); } if (buf.get() != CINT_SIZE) { throw new RuntimeException("int size mismatch!"); } if (buf.get() != CSIZET_SIZE) { throw new RuntimeException("size_t size mismatch!"); } if (buf.get() != INSTRUCTION_SIZE) { throw new RuntimeException("instruction size mismatch!"); } if (buf.get() != LUA_INTEGER_SIZE) { throw new RuntimeException("lua_Integer size mismatch!"); } if (buf.get() != LUA_NUMBER_SIZE) { throw new RuntimeException("lua_Number size mismatch!"); } if (buf.getLong() != LUAC_INT) { throw new RuntimeException("endianness mismatch!"); } if (buf.getDouble() != LUAC_NUM) { throw new RuntimeException("float format mismatch!"); } } static String getLuaString(ByteBuffer buf) { int size = buf.get() & 0xFF; if (size == 0) { return ""; } if (size == 0xFF) { size = (int) buf.getLong(); // size_t } byte[] a = getBytes(buf, size - 1); return new String(a); // todo } private static byte[] getBytes(ByteBuffer buf, int n) { byte[] a = new byte[n]; buf.get(a); return a; } } | Mid | [
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Let me tell you I love Victoria’s Secret and everything it stands for. Here is an early look at some of the girls’ outfits taken at this year’s fittings. An inside look should be released monthly just cause! Alright, Alright enough of that – click below to check out the girls. Victoria’s Secret show they miss me… – Kanye. | Low | [
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May the Lord be Generous to You In an 1894 letter to her newlywed cousin, St. Therese of Lisieux wrote: “I am asking our Lord to be as generous to you as He was to the bridal pair at Cana. May He invariably change the water into wine! I mean, may He prolong His gift of happiness, and as far as possible sweeten the bitter trials you will meet on your way. Trials! Fancy introducing that word into my letter—how could I?—at a moment when I realize that life for you is all sunshine.” This morning, I begin with these words spoken by this great Doctor of the Church 122 years ago partly because she references the Wedding at Cana, but mostly because her words contain great insight and wisdom. How so? Well, for those who are married or presently contemplating marriage, St. Therese delivers the goods absent a sugar coating: In marriage, there will be both happiness and trials! Now for those of us who are married, we sit in absolute understanding of this. We have loved and cherished and built a life. On the day of our marriage, we stood before God, family, and friends and said ‘I do.’ And on the arrival of our children, we were struck with awe. And for those of us blessed with grandchildren and even great-grandchildren, even deeper feelings well up inside of us. In a certain sense, as the Little Flower promised, these blessings become like an armor for us when heartbreak alley unfolds before our eyes or the song, I beg your pardon, I never promised you a rose garden, begins to play. This past week, I have been thinking of these things and came to remember meeting an older couple who many years ago greeted me after Mass. At the time, I was just days separated from my ordination. With an awareness that my wife and I were raising four young daughters, they noted that they had four grown daughters. With her husband standing beside her, the woman spoke first and kindly asked me their names and how each of them was doing. When it came time for the man to speak, however, his facial expression changed and his two words for me were these: Good luck! Today, I mention the reality of ups-and-downs in our lives for a simple reason: such twists-and-turns of our daily lives are best navigated in relationship with Jesus Christ! And on this Second Sunday in Ordinary Time, the Holy Scriptures given us for this liturgical celebration provide us with some important insights for living out and making sense of our lives. In them, we will find three powerful movements: joining, rejoicing, and pouring. For humans, there is perhaps no more powerful image than the joining of a man and woman in Holy Matrimony. In Natural and Divine law, this truth is crystal clear and eternal and, despite efforts to the contrary, will forever withstand the unwise winds that blow in our time. As Creator, God’s law will always trump Man’s law! Given that marriage is the foundation of society and that the marital act cooperates with God in bringing about new human life, do any of us think it a surprise that Jesus’ first public miracle occurs at a wedding? In the Gospel of John (2:1-11), we are invited to this wedding ceremony where Jesus and Mary are invited guests. At a certain point of the celebration, we are told that Mary becomes aware of a difficulty and declares to Jesus: “They have no wine.” After this, one question and a series of important instructions begin to unfold: “How does your concern affect me?”…”Do whatever He tells you.” …”Fill the jars with water.” In the end, St. John tells us that “Jesus did this as the beginning of his signs at Cana in Galilee and so revealed his glory, and his disciples began to believe in him.” Through this newfound belief, the disciples would eventually come to see Jesus as the Bridegroom and the Church as His bride. And if we remember, this imagery was earlier spoken by the Prophet Isaiah (62:1-5): “As a young man marries a virgin, your Builder shall marry you; and as a bridegroom rejoices in his bride, so shall your God rejoice in you.” And so, as the wine is poured at the Wedding at Cana, the disciples come to see Jesus, albeit imperfectly, as the wine that will be poured out for the many. And in regard to the grapes used to create the wine, Jesus is not simply the vine grower, but rather, He is the vine itself; a vine that from the day of our baptism, Jesus calls us to join and remain forever attached. After joining, the second movement, rejoice, is clearly reflected in the title of a book I read years ago: God Acts-We React. Having joined ourselves to the life of God, what more can we do but—rejoice! Like the Psalmist (96), we break into song. We sing to the Lord a new song! We sing to the Lord to bless his name! We tell his glory to the nations! We give to the Lord glory and praise that is due his name! But sadly, how many of us do this each day? A deacon friend and I meet regularly for lunch and I confess that I look forward to his memorable words before the food is delivered: Shall we thank the boss? Each time, I reflect whether I thank the boss enough—each day of my life. After joining ourselves to the Lord and rejoicing, how often do we praise Him for the gifts He pours out upon us? As St. Paul (1 Cor 12:4-11) notes, God pours out His gifts of love upon us through the Holy Spirit: wisdom, knowledge, faith, healing, mighty deeds, prophecy, discernment of spirits, and tongues. Having distributed these according to His Divine Will, I confess that as one who has taught thousands of students through the years, I am continually amazed by the different and varied gifts given others and that I constantly remind them that these gifts are given not just for you, but for the many. But, I wonder. In our ever-increasing techie world, so many of us seem joined at the hip, 24/7, with devices of every kind. Having allowed our iPhones and Fitbits to shape every waking moment of our lives, what time is left to discern the voice of the Lord, let alone join ourselves to Him, rejoice in Him, and praise Him for the gifts He has poured out upon us? While I do not advocate that we fully separate ourselves from the progress of our time, I do wonder whether we are losing our capacity to hear God’s voice. This past Wednesday, the Old Testament reading (1 Sam 3:1-10, 19-20) at daily Mass recalled the story of Samuel and Eli. If you remember that scripture passage, the young Samuel, over and over, reminds the wise Eli that he is hearing a voice. Eventually, Eli tells Samuel that if he hears the words again to say: “Speak, for your servant is listening.” And of course, he does. This is good advice for us, as well. Through daily prayer, weekly Mass attendance, celebration of the sacraments, and following our baptismal vocation, may we be granted the grace of hearing the Lord speak to us deep within our hearts. By doing so, we will be assured that Jesus is always close to us and that He walks with us through our happiness and trials. In walking with us, He continues to pour out his many blessings and graces upon us— if we but recognize them. Today and every day, may the words of St. Therese to her newlywed cousin also be for you and me: “I am asking our Lord to be as generous to you as He was to the bridal pair at Cana. May He invariably change the water into wine! …May He prolong His gift of happiness, and as far as possible sweeten the bitter trials you will meet on your way.” Deacon Kurt Godfryd REVEREND MR. KURT GODFRYD is editor of Catholic Journal and a permanent deacon of the Archdiocese of Detroit. Married and the father of five children, Deacon Kurt was ordained to the diaconate on October 4, 2008 by His Eminence Adam Cardinal Maida and is assigned to St. Clement of Rome parish in Romeo, Michigan. A native Detroiter, he was educated at the Jesuit-run University of Detroit Mercy, where he received a B.S. in finance, M.B.A., and M.A. in economics. His theological training was taken at Detroit's Sacred Heart Major Seminary, where he earned an M.A. in pastoral ministry. About Author REVEREND MR. KURT GODFRYD is editor of Catholic Journal and a permanent deacon of the Archdiocese of Detroit. Married and the father of five children, Deacon Kurt was ordained to the diaconate on October 4, 2008 by His Eminence Adam Cardinal Maida and is assigned to St. Clement of Rome parish in Romeo, Michigan. A native Detroiter, he was educated at the Jesuit-run University of Detroit Mercy, where he received a B.S. in finance, M.B.A., and M.A. in economics. His theological training was taken at Detroit's Sacred Heart Major Seminary, where he earned an M.A. in pastoral ministry. About Catholic Journal And given that this site emanates from the Motor City, it is our hope that we will be a unique place where reflections upon the present and past will offer ideas so that a brighter future might be realized. | Mid | [
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Weather Forecast I think back to a Red Carpet Service workshop in which several employees in area communities took part. The purpose focused on the front line people in the community who can make the first and only impression of a town. If someone passing through stops for a purchase and the person who they pay is unfriendly, they can go away from that town with a negative image simply by that one contact. Or if the person has a question and the employee makes no effort to find an answer, an impression is made. On the contrary, if someone is super friendly and goes above and beyond in offering service with a smile, the travelers might decide to stop for a bite to eat or even spend the night. Or they might continue to move on but take the impression with them about a friendly town (having talked to just a few people). Such is the same when someone visits a church. No matter how much the sermon affected them, it’s generally the way they are greeted and treated that makes the difference in their worship experience. Looking back, my grandson absolutely loved the days when he got to ride the county handi-bus from preschool to daycare. Marv, the driver, was like a hero to him. One thing you didn’t want to do was change the plan and pick him up instead when he was counting on the ride. And in talking to Marvin Hamilton, you could tell it was a highlight for him. He watches the clock, taking his responsibility seriously to be at the right place at the right time to take these youngsters safely to their next destination. It’s not uncommon for Marv to offer treats, and he has had a lot of laughs about comments or songs from his young buddies. Every year, he provides pizza for each of the preschools where he makes stops. When he won a ginger bread house, all the kids joined in the fun of his win. Kids aren’t his only riders. He helps the elderly and any age in between with tasks like carrying groceries or helping someone put on their jewelry before venturing out. Other drivers take on these tasks as well, however I’ve been made aware of the difference Marv makes in many young lives because of my grandchildren. He definitely offers an extra special touch in carrying out his responsibilities. Our grandchildren were living in another community when Tayvin, age 3, saw a handi-bus there. “Is that Marv?” she exclaimed, somewhat disappointed to learn that it wasn’t. She had never actually been a passenger on one of Marv’s journeys, but she felt the delight of it all through her older brother. Austin, age 6, rides the handi-bus to school on a regular basis now. I asked him the driver’s name. He doesn’t know. There are several. He’s been forgotten three times, making him late to school. I’ve heard his mother say more than once, “I miss Marv!” Here’s to Marv and all the other Marvs in the world who go above and beyond in providing a positive spark and making a difference by going the extra mile with kindness and compassion. Chances are when you make someone else’s day, it will also feel good for you. There’s just nothing like service with a smile!! | Mid | [
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Frequently Asked Questions Question: What's the ETA on these? - Raymond (07/08/2020) Response: Hello Raymond, as of today we do not have an ETA on this Speer Lawman 9mm ammo and when we will have it back in stock again. Please sign up to get notified via email or text. Thank you for visiting TargetSportsUSA.com Question: Hey when will the next shipment be in? - Carl (06/22/2020) Response: Hi Carl, next shipment of this Speer Lawman 9mm ammo is scheduled to arrive this Friday. Thank you for your patience. Question: When will this be back in stock? - Luis (05/30/2020) Response: Hi Luis, we will add more Speer Lawman 9mm 124 Grain ammo back in stock on Monday. Thank you for your patience. Question: I didn’t receive any notifications this week? - Johnny (04/24/2020) Response: we will add more Speer Lawman 9mm 124 Grain ammo back in stock on Monday. Thank you for your patience. Question: Hi guys hope you all are well . Question ,when do you think will be more speed lawman 9mm luger ammo 124 grain TMJ in stock . Thank you - Jorge (04/21/2020) Response: Hi Jorge, we will add more Speer Lawman 9mm 124 Grain ammo back in stock on Monday. Thank you for your patience. Question: Haven't seen this ammo come back in stock, when do you plan to put it back online? - Alfonso (04/18/2020) Response: Yes we will add some back in stock this week. Thank you Question: Any idea when this will be loaded onto the website. Have notifications on but afraid I missed last stock - David (03/26/2020) Response: next week ... Question: Next restock/ quantity incoming? Thanks - David (03/14/2020) Response: Hi David, we will have more of this Speer Lawman 9mm 124 Grain ammo back in stock this week Wednesday. Thank you for your patience. Question: Did I miss restock on this, had updates turned on. Thanks - David (03/18/2020) Response: no not yet, end of this week or next.. we have it here, we just need to wait until we catch up on shipping current back log of orders. Thank you for your patience. Question: Restock update? - Luis (03/13/2020) Response: Hi Luis, we will have more Speer Lawman 9mm ammo back in stock today, do not wait long as it will sell out fast. Thank you for your patience. Question: Any idea on restock time? - David (02/29/2020) Response: Hi David, Monday.... we will have another shipment of 150 cases of Speer Lawman 9mm 124 Grain ammo. Thank you for buying bulk 9mm ammunition at TargetSportsUSA.com Question: When do you expect this item to be back in stock? - Stephen (02/14/2020) Response: Hi Stephen, we are getting another shipment of Speer Lawman 9mm 124 Grain in today around noon time. Thank you for your patience. Question: When will these be back in stock? - Stephen (01/24/2020) Response: Hi Stephen, We will have more if this 9mm ammo back in stock sometime this upcoming week, Tuesday or Wednesday. Thank you for buying bulk 9mm ammunition online at TargetSportsUSA.com Question: Any major difference in the TMJ vs FMj? Is it safe for stock Glock 17 and HK vp9sk? - Luis (01/10/2020) Response: Hi Luis, the TMJ bullet has the bottom of the bullet enclosed with copper, whereas the FMJ bullet does not and the core lead is exposed. Both will function just fine. Thank you for buying bulk 9mm ammunition online at TargetSportsUSA.com Question: When will these be back in stock?? - Stephen (01/06/2020) Response: HI Stephen, we got another shipment of 500 cases of this Speer Lawman 9mm 124 Grain TMJ ammo in route to us and should be here sometime this week. Thank you for buying bulk 9mm ammo online at TargetSportsUSA.com Question: These just came in and now gone. When will these be back in stock. Thank You - Stephen (01/13/2020) Response: Hi Stephen, we have another batch of 300 cases in route to us and should be here by Wednesday. Thank you for your patience. Question: Hi, what’s the ETA for getting stock for this item? Thank you. - Joseph (11/11/2019) Response: Hi Joseph, This Speer Lawman 9mm ammo is in stock right now. Thank you for buying bulk 9mm ammunition online at TargetSportsUSA.com Question: Thank you, just ordered! - Joseph (11/11/2019) Response: Awesome, we will send it right out ... Question: Same question as before, ETA for getting stock for this? - Joseph (12/11/2019) Response: Yes we have more Speer Lawman 9mm 124 Grain in route to us and should be here in about 2 days/Friday. Thank you for your patience. Question: My recent purchases of 124 grain have been shooting a lot dirtier than purchases made prior to 3 to 4 months ago. Has Speer changed its powder formula? - Richard (07/26/2019) Response: Hi Richard, We will send your inquiry to Speer and update you as soon as they respond. Thank you for buying Speer Lawman 9mm in stock ammo at TargetSportsUSA.com Question: Recently, there has only been sporadic availability. Any idea when this product will become available again? - Richard (04/01/2019) Response: HI Richard, YES we have more Speer Lawman 9mm 124 Grain ammo coming our way from CCI/Speer and should be here by the end of this week. Thank you for buying in stock 9mm ammo online at TargetSportsUSA.com Question: How come the price increased by $20.00 a case now that you have it back in stock????? - larry (03/07/2019) Response: Hi Larry, We were unable to get the same pricing like last time since we are using a different supplier and we wanted to get some back in stock before the end of March because of the rebates. Hopefully we will get some directly from Federal again and lower your cost as well. Thank you for buying in stock Lawman 9mm ammo at TargetSportsUSA.com Question: Any eta yet?? Thanks! - Ken (03/06/2019) Response: Hi Ken, nothing yet..sorry..We are working hard to secure more Speer Lawman 9mm 124 Grain ammo at a good price. Thank you for buying 9mmm ammo at TargetSportsUSA.com Question: Still no delivery date? Do you know if they will be back in stock before the rebate promo is over? - Brandyn (03/03/2019) Response: Hi Brandyn, YES we just got a confirmation that some of this Lawman 124 Grain 9mm ammo got realized to us and should be at our warehouse any day. Thank you for your patience and thank you for buying in stock 9mm ammo at TargetSportsUSA.com Question: Any idea when it will be back in stock? - Brandyn (02/25/2019) Response: Hi Brandyn, we are overdue to get more Speer lawman 9mm back in stock, just don't have the delivery date as or today. thank you for buying 9mm ammo at TargetSportsUSA.com Question: Is this supposed to come back in stock soon? Previous response send Wednesday by the latest. - Christopher (02/20/2019) Response: Hi Christopher, 115 Grain Speer Lawman 9mm ammo arrived instead of 124 Grain. We are working hard on getting more soon. Thank you for your patience Question: expected restock? thanks - Beau (02/18/2019) Response: Hi Beau, we will have more Speer Lawman 9mm 124 Grain ammo tomorrow or Wednesday latest. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: When are you expecting your next shipment? - Nicholas (02/11/2019) Response: Hi Nicholas, any day we should receive a large shipment of Speer Lawman 9mm 124 Grain ammo. Thank you for your patience Question: Any update on a new shipment of 124gr? Been waiting near a month now and im about to just order elsewhere. - Nicholas (02/25/2019) Response: Hi Nicholas, we would not want you to wait and miss out on the rebate opportunity. As of today we do not have a scheduled deliver date for Speer Lawman 9mm 124 Grain ammo. Thank you for buying ammo at TargetSportsUSA.com Question: I appreciate the honesty. Ill always be checking here first. - Nicholas (02/25/2019) Response: You are welcome, we are working hard here and doing our best to get more !! Question: When will you have more in stock? - larry (02/09/2019) Response: Hi Larry We have more Speer Lawman 9mm 124 Grain on order and should be here any day now. Snow is for sure delaying some shipments to North East here. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: Is this 9mm ammunition completely not magnetic? The responses clearly show a brass case. The FMJ should be copper or bronze jacketed with no components that will be picked up by a magnet. The earlier responses leave a tiny bit of ambiguity. Statements mention the core but leave one to assume the jacket is also non magnetic. - Dan (01/26/2019) Response: Hi Dan, This Speer Lawman 9mm Luger 124 Grain TMJ is 100% complexity non-magnetic. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: When should this return to stock? - Matt (01/10/2019) Response: Hi Matt, Speer Lawman 9mm ammo 124 grain is in stock now.. Thank You Question: Does this round have a copper plating or is it a true Copper jacket? I need plated bullets. - BENJAMIN (01/09/2019) Response: Hi Benjamin, Speer Lawman 9mm ammo features a plated copper jacket bullet. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: When will you be getting more in stock? - Matt (01/04/2019) Response: Hi Matt, We have more Speer Lawman 9mm 124 Grain ammo coming in early next week. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: When do you expect stock again? - Anthony (12/19/2018) Response: Hi Anthony, we will have more Speer Lawman 9mm ammo in stock tomorrow December 20th. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: When will you be getting more in stock? I see that it’s sold out - James (12/05/2018) Response: Hi James, we will have more Speer Lawman 9mm ammo in stock tomorrow December 20th. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: When should this be returning to stock? - Michael (11/30/2018) Response: Hi Michael, We will have more Speer Lawman 9mm 124 Grain ammo in stock on Monday. Thank you for buying 9mm ammo online at TargetSportsUSA.com Question: Is this ammo loaded with round nose bullets, or with flat nose bullets as depicted in the photo? - John J (03/05/2017) Response: Speer Lawman 9mm Luger 124 Grain TMJ features a round nose Total Metal Jacket Non-Magnetic Lead Core bullet. Thank you for visiting TargetSportsUSA.com | Low | [
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Netflix faces European content quota - protomyth https://thestack.com/world/2016/05/19/netflix-european-commission-20-percent-content/ ====== PaulHoule 20% is not that much. It's a sign that they are being "not shut out" as much as it is that they are being included. | Low | [
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Sex and Sexuality in Islam, Part 4 Child marriage and having sex with a minor Many countries have banned child marriage, which is a scourge to humanity. This type of marriage was quite common in the ancient Hindu system of marriage in India. In many ancient literatures we find that children, as little as five or six years of age, were engaged in marriages by their parents. When those children grew up to become adults, they were forced to live a conjugal life that, in many cases, they abhorred. This practice was nothing but the child abuse of the worst kind. However, with reforms in Hinduism by its pioneering humanist activists, this utterly despicable custom is now a thing of the past, at least in the legal sense. But how about Islam? Islamists often proclaim that their religion is the most up-to-date and the most progressive of all religions. Therefore, one may legitimately conclude that the system of child/infant marriage must be illegal in Islam. This, however, is a big deception! The truth is, in Islam there is no minimum age for marriage. Thus, marrying an infant, even a newly born suckling baby is very much halal or an approved thing. The cruelest part of this tyrannical child-sex slavery is that the marriage is absolutely binding if contracted by the parents. That is, the couple must consummate the marriage when they become adult. Here are the Sha'ria rules on infant marriage: Hedaya (ref. 11, p.36) Infant marriage permitted Case in which the marriage of infants continues binding after puberty If the marriage of infants be contracted by the father or grandfathers, no option after puberty remains to them; because the determination of parents in this matter cannot be suspected to originate in sinister motives as their affection for their offspring is undoubted; wherefore the marriage is binding upon the parties, the same as if they had themselves entered into it after maturity. Case which admits an option of acquiescence after puberty But if the authority of others than their parents should have executed the contract, each is respectively at liberty, after they become of age, to choose whether the marriage shall be confirmed or annulled. The Prophet of Islam, Muhammad (pbuh), himself married a child of six (or seven) years old. Many articles have recently been written about this child bride of Muhammad. I shall refer the readers to read those articles elsewhere. Here are two hadith from the Sahi (authentic) of all ahadith to confirm the marriage of Muhammad (pbuh) with a child who was still playing with her dolls when the Prophet of Islam took her to his house to consummate (to have sex with her) the marriage. Sahih Muslim Book 008, Number 3311: 'A'isha (Allah be pleased with her) reported that Allah's Apostle (may peace be upon him) married her when she was seven years old, and he was taken to his house as a bride when she was nine, and her dolls were with her; and when he (the Holy Prophet) died she was eighteen years old. Sahih Bukhari Volume 5, Book 58, Number 236: Narrated Hisham's father: Khadija died three years before the Prophet departed to Medina. He stayed there for two years or so and then he married 'Aisha when she was a girl of six years of age, and he consumed that marriage when she was nine years old. Here is how the Prophet used to have fun and sex with his child bride. Sahih Bukhari Volume 1, Book 6, Number 298: Narrated 'Aisha: The Prophet and I used to take a bath from a single pot while we were Junub. During the menses, he used to order me to put on an Izar (dress worn below the waist) and used to fondle me. While in Itikaf, he used to bring his head near me and I would wash it while I used to be in my periods (menses). Sahih Muslim Book 3, Number 0629: 'A'isha reported: I and the Messenger (may peace be upon him) took a bath from the same vessel and our hands alternated into it in the state that we had had sexual intercourse. Can we ever imagine how an over fifty years old man could fondle his pre-teen wife during her menstrual cycle! By the way, the meaning of Junub is sexual defilement, that is, the state after having sex. If you thought that marrying a girl of six years old and having sex with her when she turns nine is too much to digest then there is more surprise for you! In the Sirat Rasul, we read the incredible story that Muhammad, himself, wanted to marry a crawling baby girl a few years before his death. This happened after he married A'isha. The following citation is from the book of Sirat Rasul Allahby Ibn Ishak, the most authentic biographer of Muhammad (pbuh) Most other biographies are based on this monumental work by Ibn Ishak/Ibn Hisham: (Suhayli, ii.79: In the riwaya of Yunus I.I recorded that the apostle saw her (Ummu'l-Fadl) when she was baby crawling before him and said, 'If she grows up and I am still alive I will marry her.' But he died before she grew up and Sufyan b. al-Aswad b. Abdu'l-Asad al-Makhzumi married her and she bore him Rizq and Lubaba....(ref.10, p. 311) Elsewhere, we note that even Hazrat Omor or Umar (spelling variation) married Umm Kulthum, the four years old half-sister of Bibi A'isha!How fantastic! These are the examples that the noblest of the nobles of Islam have left for their followers to emulate! Riza or fosterage by suckling Have you ever thought of an adult Muslim man marrying an infant (less than two years old) as well as an adult woman who has a suckling baby? What happens if the baby that is married has no one to suckle her (say, she is an orphan) except the adult lactating wife? Of course, the solution in today's world is to bottle-feed the infant wife with formula milk. However, this may not be the true Islamic solution. Here is the Islamic answer: Hedaya (ref. 11, p.71) Case of one of two wives suckling the other IF a man marry an infant and an adult and the latter should give milk to the former, both wives become prohibited with respect to that man [their husband], because if they were to continue united in marriage to him, it would imply the propriety of joint cohabitation with the foster-mother and her foster-daughter, which is prohibited, in the same manner as joint cohabitation with a natural mother and daughter. IT is to be observed on this occasion, that if the husband should not have had carnal connexion with the adult wife, she is not entitled to any dower whatever because the separation has proceeded from her, before consummation:-- but the infant has a claim to her half dower, the separation not having proceeded from her. So far, what I mentioned above relates to an adult man marrying an infant girl. How about an infant boy marrying a grown up girl (nine years and above)? As per Islamic Sharia, there is, of course, no restriction on this practise. The only means by which a child can be prevented from marrying a grown up girl (that is to make him halal to visit her and be with her in privacy) is through a peculiar system in Islam known as RIZA or Rid'a. The Dictionary of Islam (ref. 6, p.546) defines RIZA thus: RIZA. A legal term, which means sucking milk from the breast of a woman for a certain time. The legal definition of RIZA is given in HEDAYA(ref. 11 ) as follows: RIZA, or fosterage (Ibid, p.67) Definition of the term Riza, in its legal sense, means a child suckling milk from the breast of a woman for a certain time, which is termed the period of fosterage. This is the Islamic name for suckling through fosterage. It is the practice by which a newly born baby is handed over to another woman who is able to suckle the infant. It was (and still is) a practice by the rich Arabs by which they hand over their newly born infants to be suckled by Beduin women. Even Prophet Muhammad (pbuh) was suckled, initially, by Thueiba, a slave woman of his uncle Abu Lahab for a very brief period, and then, by his foster mother, Halima. Here is a hadith proclaiming the restrictions by fosterage: What is haram by birth is also haram by suckling...30.3.15 Malik's Muwatta: Book 30, Number 30.3.15: Yahya related to me from Malik from Abdullah ibn Dinar from Sulayman ibn Yasar and from Urwa ibn az-Zubayr from A'isha umm al-muminin, that the Messenger of Allah, may Allah bless him and grant him peace, said, " What is haram by birth is haram by suckling This practice will make the child being suckled to be haram to the foster mother. That is, the child, when he grows up, has unhindered access to his foster mother. It is, as if, the foster mother is the 'real mother' of the child. There is no problem with this noble provision, of course. So, where is the trouble? Let us examine the situation up close. In Islam, a woman can be married at any age even when she is a newly born baby. A foster mother can be any woman, nine years or older, other than her own biological mother. Imagine, a six-month old infant boy is suckled by a foster mother who is slightly above nine years of age. Now, when the infant boy becomes an adult of eighteen years (which is the age of Islamic puberty for male) the foster mother is slightly above twenty-seven years old, still a very youthful age for marriage, love, sex and childbearing. According to the Islamic law, the foster mother is completely forbidden to marry this newly turned adult male. He cannot even marry his foster sister. Here are a few rules on Islamic suckling or fosterage from the 'Reliance of the Traveller', the most authentic Sha'ria book (ref. 8,pp.575-576) n12.0 BECOMING UNMARRIAGEABLE KIN BY SUCKLING (RIDA') n12.1 An infant becomes the "child" of the female who breast-feeds him (A: in respect to being unable to marry her, to the permissibility of looking at her and being alone with her, and inhis ablution (wudu) not being nullified by touching her) when: (a)the milk comes from a female at least nine years old whether it is occasioned by sexual or something else; (b)and she breast-feeds a child who is less than two full years old; (c)in at least five separate breast-feedings (O:a restriction that excludes anything less than five; which is of no consequence. Separate breast-feedings means whatever is commonly acknowledged (def: f4.5) to be separate) n12.2 In such a case: (1)It is unlawful for the wet nurse to marry the child and its subsequent descendants (O: by familial relation or by suckling) exclusively (O: exclusively meaning that only the child's descendants become unlawful for her to marry, not the child's ancestors (N: or brothers)): (2)She becomes the child's "mother," and it is unlawful for the child to marry her, her ancestors (O: by familial relation or by suckling), her descendants (O: who become as if they were brothers and sisters (O: though the child is not forbidden to marry the latter's children). In ahadith we read a few interesting stories about RIZA. Here are some samples. Aisha's sister Umm Kulthum suckled Salim ibn Abdullah ibn Umar only three times; that is why it was haram for him to visit Aisha; if suckled ten times by Kulthum then he would be halal for her...30.1.7 Malik's Muwatta: Book 30, Number 30.1.7: Yahya related to me from Malik from Nafi that Salim ibn Abdullah ibn Umar informed him that A'isha umm al-muminin sent him away while he was being nursed to her sister Umm Kulthum bint Abi Bakr as-Siddiq and said, "Suckle him ten times so that he can come in to see me." Salim said, "Umm Kulthum nursed me three times and then fell ill, so that she only nursed me three times. I could not go in to see A'isha because Umm Kulthum did not finish for me the ten times." Ten suckle is required for a boy to be halal to visit a woman...30.1.8 Malik's Muwatta :Book 30, Number 30.1.8: Yahya related to me from Malik from Nafi that Safiyya bint Abi Ubayd told him that Hafsa, umm al-muminin, sent Asim ibn Abdullah ibn Sad to her sister Fatima bint Umar ibn al-Khattab for her to suckle him ten times so that he could come in to see her. She did it, so he used to come in to see her. (Please note that ten suckling was later abrogated by five suckles) Malik's Muwatta:Book 30, Number 30.3.17: Yahya related to me from Malik from Abdullah ibn Abi Bakr ibn Hazm from Amra bint Abd ar-Rahman that A'isha, the wife of the Prophet, may Allah bless him and grant him peace, said, "Amongst what was sent down of the Qur'an was 'ten known sucklings make haram' - then it was abrogated by 'five known sucklings'. When the Messenger of Allah, may Allah bless him and grant him peace, died, it was what is now recited of the Qur'an." Yahya said that Malik said, "One does not act on this." Needless to say that in an Islamic paradise, RIZA will be a perfectly rightful method to solve the problem of milk supply for the babies. Now, imagine what will happen to the marriage market if most women give up their infants to their foster mothers for a limited period of time! The marriage market will come to a halt, no joke. Most potential suitors will be forbidden for each other due to RIZA or suckling by fosterage, isn't it? Of course, I cited an extreme scenario of Islamic fosterage.Modern world is not at all dependent on RIZA or suckling by fosterage. We have formula milk for those infants whose mothers are unable to breast-feed them for one reason or other. However, I could not find any Sha'ria rule where bottle-feeding can be used as an alternative to RIZA. See, in the seventh century medieval period, there was no baby formula milk, nor was there any concept of bottle-feeding as an alternative to suckling. Therefore, those Bedouin Arabs resorted to RIZA to solve the mother's milk supply problem. An interesting argument will be to know if a lactating woman can suckle an adult man or not? Tauba! Tauba!What a preposterous idea!Islam can never allow such a thing. It is a thought only provoked by Satan, the Islamists will declare. It is true that we find no mention of legitimacy of suckling an adult man or an adult woman in Sha'ria. Neither there is any mention of its illegality.In a few ahdith, we find mind-boggling episodes on RIZA. Let us review a few of them. A woman can suckle a young boy so that he becomes haram for her... 8.3426 Sahih Muslim: Book 008, Number 3426: Ibn Abu Mulaika reported that al-Qasim b. Muhammad b. Abu Bakr had narrated to him that 'A'isha (Allah be pleased with her) reported that Sahla bint Suhail b. 'Amr came to Allah's Apostle (may peace be upon him) and said: Messenger of Allah, Salim (the freed slave of Abu Hudhaifa) is living with us in our house, and he has attained (puberty) as men attain it and has acquired knowledge (of the sex problems) as men acquire, whereupon he said: Suckle him so that he may become unlawful (in regard to marriage) for you He (Ibn Abu Mulaika) said: I refrained from (narrating this hadith) for a year or so on account of fear. I then met al-Qasim and said to him: You narrated to me a hadith which I did not narrate (to anyone) afterwards. He said: What is that? I informed him, whereupon he said: Narrate it on my authority that 'A'isha (Allah be pleased with her) had narrated that to me. Sex with slave-girls/captive women is a perfectly valid Islamic way for a Muslim man to satisfy his sexual appetite. How about his wife?No, his wife can never indulge in such sex orgies. Therefore, it is quite natural for the unfortunate wife to be jealous (read mad) to prevent her husband from indulging in such vulgarity. Can RIZA be successfully applied here? Well, an extremely jealous woman did just that. She went to the young adult slave-girl and suckled her with her breast. This made the slave-girl haram to her husband. What a novel idea it was to prevent her amorous husband from having further intercourse with the slave-girl! Alas! It did not work out well for her. Who received the punishment? Yes, it was the lactating wife of the Muslim man! Hazrat Umar asked her to be flogged, thus protecting the right of her husband to have unhindered sex orgy with his slave-girl. It sounds mind boggling, isn't it? Here is the story from Malik's Muwatta, the founder of Maliki School of Islamic jurisprudence. Umar told a man to beat his wife for suckling a slave-girl with whom he used to have sex; kinship by suckling is only by the suckling of the young...30.2.13 Malik's Muwatta: Book 30, Number 30.2.13: Yahya related to me from Malik that Abdullah ibn Dinar said, "A man came to Abdullah ibn Umar when I was with him at the place where judgments were given and asked him about the suckling of an older person. Abdullah ibn Umar replied, 'A man came to Umar ibn al-Khattab and said, 'I have a slave-girl and I used to have intercourse with her. My wife went to her and suckled her. When I went to the girl, my wife told me to watch out, because she had suckled her!' Umar told him to beat his wife and to go to his slave-girl because kinship by suckling was only by the suckling of the young.' " Is it possible to extend the concept of RIZA to a husband and his wife/s? Wastagferullah! Wastagferullah! Naujubillah! No sane Muslim can even think of committing this despicable act, Islamists will say. However, what we find in the Holy Scripture is quite upsetting, to say the least. If you drink your wife's milk than that does not make the relationship haram, there is only kinship by suckling in the first two years...30.2.14 Malik's Muwatta:Book 30, Number 30.2.14: Yahya related to me from Malik from Yahya ibn Said that a man said to Abu Musa al-Ashari, "I drank some milk from my wife's breasts and it went into my stomach." Abu Musa said, "I can only but think that she is haram for you." Abdullah ibn Masud said, "Look at what opinion you are giving the man." Abu Musa said, "Then what do you say?" Abdullah ibn Masud said, "There is only kinship by suckling in the first two years." Abu Musa said, "Do not ask me about anything while this learned man is among you." Who was Abdullah ibn Masud? He was among the closest ten companions of Muhammad (pbuh) who was promised paradise by him. Every word uttered by ibn Masud is considered to be completely authentic. In fact, his position could be easily considered next to Muhammad. Now, what did ibn Masud say in the above hadis? Readers, please think about its implication. Yes, a husband can drink his wife's milk and still can remain her sex partner. Strange Islamic rules! Here is another silly hadis: It is permissible to have intercourse with a suckling lady...8.3391 Shahih Muslim:Book 008, Number 3391: Judaima daughter of Wahb al-Asadiyya (Allah be pleased with her) reported that she heard Allah's Messenger (may peace be upon him) as saying: I intended to prohibit cohabitation with a suckling woman until I considered that the Romans and the Persians do it without any injury being caused to their children thereby. (Imam Muslim said: Khalaf reported it from Judamat al-'Asadiyya, but the correct wording is what has been stated by Yahya.) The reason why suckling the milk of a woman by her adult husband is quite alright is explained in the following lines by Malik. When the adult drinks the milk of his wife, the milk is treated as a food and not as foster milk! This, indeed is the bizarre Islamic rule, to say the least. Suckling is for the first two years, even if it is only a drop; whatever is after two years is only food that is eaten...30.1.10, 11 Malik's Muwatta:Book 30, Number 30.1.11: Yahya related to me from Malik that Yahya ibn Said said that he heard Said ibn al-Musayyab say, "Suckling is only while the child is in the cradle. If not, it does not cause flesh and blood relations." Yahya related to me from Malik from Ibn Shihab that he said, "Suckling however little or much, makes haram. Kinship by suckling makes men mahram." Yahya said that he had heard Malik say, "Suckling, however little or much when it is in the first two years, makes haram. As for what is after the first two years, little or much, it does not make anything haram. It is like food." And finally, we have this gem of all ahadith. Please read the following hadis and decide whom shall you bash first, before you call me an Islam basher. Mohammad disliked withdrawing the penis before semen was discharged; he also disliked having intercourse with a woman suckling a baby; but these were not forbidden...34.4210 Sunaan Abu Dawud: Book 34, Number 4210: Narrated Abdullah ibn Mas'ud: The Prophet of Allah (peace_be_upon_him) disliked ten things: Yellow colouring, meaning khaluq, dyeing grey hair, trailing the lower garment, wearing a gold signet-ring, a woman decking herself before people who are not within the prohibited degrees, throwing dice, using spells except with the Mu'awwidhatan, wearing amulets, withdrawing the penis before the semen is discharged, in the case of a woman who is wife or not a wife, and having intercourse with a woman who is suckling a child; but he did not declare them to be prohibited. | Mid | [
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Marie-Pierre Gramaglia Marie-Pierre Gramaglia is a member of the Council of Government of Monaco, on which she serves as Counsellor of the Ministry of Equipment, Environment, and Urban Planning since 2011. She is the second woman in Monaco's history to be appointed to the Council, behind Sophie Thevenoux, who served as Counsellor of Finance and Economy from 2009 to 2011. Gramaglia possesses a DEA in International Public and Private Law, a DESS in Notarial Law, a Higher Diploma in Notarial Studies, and a diploma from the Center for International Intellectual Property Studies. She has served in Monaco's civil service in a variety of functions since 1993. In 2001 she was named Deputy Director of the Business Development Agency, and in 2005 she became a technical advisor in the Ministry of Finance and Economy. Beginning in 2008 she served as the director of electronic communications, and in 2010 she joined a working group designed to facilitate Monaco's economic development. She was appointed to the Council of Government on January 15, 2011. In 2013 she announced plans for the development of a new neighborhood, the "Éco-Quartier", to be built on reclaimed land along the Monegaasque coast. She addressed the United Nations Climate Change Conference in 2017, on the subject of greenhouse gas emissions; she had previously addressed the same body in 2013, and has shown herself during her ministerial career to be particularly concerned with environmental issues and matters affecting women entrepreneurs. References Category:Year of birth missing (living people) Category:Living people Category:Government ministers of Monaco Category:Women government ministers of Monaco Category:21st-century women politicians | High | [
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Q: Select from table A if not exist then table B I have two tables as bellow, table A: +------+----------------+ | TYPE | EMAIL | +------+----------------+ | 0 | [email protected] | | 1 | [email protected] | | 2 | [email protected] | table B: +------+----------------+ | ID | EMAIL | +------+----------------+ | 1 | [email protected] | | 2 | [email protected] | | 3 | [email protected] | I need to check the email address from both table with following criteria, Check in the table A, IF EXISTS select the TYPE IF it is not in table A, then check it in table B select the ID even it is not in table B empty results as normal select query I can do this with two quires, But my question is whether there is any possibility to do it with one single query ? Thanks in advance. A: This is an alternative: I hope it can be useful anyway. (SELECT NULL AS ID, EMAIL, TYPE FROM A WHERE EMAIL=<email>) UNION (SELECT ID, EMAIL, NULL AS TYPE FROM B WHERE EMAIL=<email>) In your application you will retrieve from 0 to 2 results. If you got 1 result, use it (note that you will have a NULL value in ID or TYPE). If you got 2 results, use the one where the TYPE is not NULL. Using your dataset and "[email protected]" as the query parameter, this would be the result of the query: ID EMAIL TYPE NULL [email protected] 0 1 [email protected] NULL | Mid | [
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interesting house in Lyme regis Marine Parade, Lyme Regis, Dorset has this fascinating house by architect, Arnold Mitchell, built in 1903 in the Arts & Crafts style. The property is Listed Grade II as being of Significant Architectural Importance and Historic Interest. It's a 6 bedroom imposing house Sea views make this house extra stunning! It has an Entrance hall, drawing room, dining room, study, kitchen and 5 bedrooms, one with en suite bathroom and separate dressing room, bedroom 6/study, family bathroom 4th floor roof terrace with superlative views They want £1 million for it! | Low | [
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1. Field of the Invention The present invention relates to the packaging of electronic components such as integrated circuits or other electronic devices. In particular, this invention relates to an improved semiconductor device package wherein at least one semiconductor die is encapsulated on a substrate and another volume of encapsulant material is added to the opposing side of the substrate in a configuration to assist in control of the stresses in the package. 2. State of the Art Conventionally, semiconductor dice have been packaged in plastic or, less commonly, in ceramic packages. Packages may support, protect, and dissipate heat from semiconductor dice. Packages may also provide external connective elements for providing power and signal distribution to and from semiconductor dice, as well as for facilitating electrical testing, such as burn-in testing and circuit evaluation, of semiconductor dice prior to or after assembly thereof with higher-level components, such as carrier substrates or circuit boards. FIG. 1A schematically illustrates a section of a conventional board-on-chip (BOC) semiconductor device assembly 100A with electrical contacts which conventionally comprise a ball grid array (BGA) of discrete conductive elements 12 such as solder balls. FIG. 1A shows substrate 4, typically a printed circuit board, mounted to semiconductor die 2. Semiconductor die 2 is placed in electrical communication with substrate 4 by bond wires 6 extending between bond pads 3 of semiconductor die 2 and terminal pads 5 through slot 7 in substrate 4 using conventional wire bonding techniques. Both semiconductor die 2 and bond wires 6 are encapsulated in a transfer molded, filled polymer volume of encapsulant material shown by die encapsulation region 8 and wire bond cap 10. FIG. 1B illustrates a side view and FIG. 1C illustrates a plan view of the semiconductor device assembly 100A of FIG. 1A. FIG. 2A schematically illustrates a conventional chip-on-board (COB) assembly 200A fabricated using conventional wire bonding techniques. FIG. 2B shows a flip-chip configured semiconductor device assembly 200B that utilizes solder bumps 14 instead of wire bonds to electrically connect semiconductor die 2 to substrate 4. A semiconductor die, the encapsulation material, the adhesives or other bonding agents used to connect the semiconductor die to the substrate, the substrate, and the electrical connection mechanisms between the semiconductor die and the substrate of a semiconductor device assembly are usually each made from a different material or combination of materials. These different materials usually have different thermomechanical properties due to differing coefficients of thermal expansion (CTE), which differences result in stresses developing during manufacture or use of the semiconductor device assembly, the latter due to thermal cycling. Several problems can result during manufacture and use of semiconductor device assemblies due to the development of these thermomechanical-related stresses. For instance, bowing of the semiconductor device assembly can occur due to internal bending stresses, causing cracking in the encapsulant materials and subjecting components to environmental degradation, debonding of the semiconductor die from the substrate, solder joint failure, or cracking in the substrate itself. Even if minimal bowing is manifested initially, residual tensile stresses can still be present, eventually resulting in the same problems after a period of time due to thermal cycling-induced fatigue experienced during normal operation. Residual tensile stresses develop during manufacture from the aforementioned mismatch of material CTEs, as well as from shrinkage of the encapsulation material during curing and hardening thereof. FIG. 3 shows an exaggerated view of bowing in a wire bonded BOC assembly 100A as previously depicted in FIG. 1A due to the thermomechanical stresses. The bowing occurs in significant part due to the imbalance of the volume of encapsulant material between the two opposing sides of substrate 4. As shown in FIG. 3, there is significantly more encapsulant material volume present in die encapsulation region 8 than in wire bond cap 10. Further, die encapsulation region 8 extends completely across substrate 4, while wire bond cap 10 runs primarily longitudinally over substrate 4, extending laterally only a sufficient distance to cover bond wires 6 and slot 7. The resulting predominant tensile stress developed near substrate 4 and on one side thereof due to shrinkage of the substantially different volumes and extents of the encapsulant material applied to the opposing sides of substrate 4 can cause significant problems with respect to package integrity. One particularly notable problem is cracking in wire bond cap 10, which exposes the wires to environmental degradation and may itself cause breakage of the thin, delicate bond wires 6. The prior art has attempted to address the issues of undesirable stresses in semiconductor packaging. For example, U.S. Pat. No. 5,627,407 to Suhir et al. purportedly solves the problem of unwanted thermomechanical stresses by using a thin xe2x80x9csurrogate layerxe2x80x9d on the entire substrate side opposite the encapsulated semiconductor die. However, this method utilizes significantly more material in the surrogate layer than may be needed and involves the use of a different material than the encapsulant. Also, by covering an entire side of the substrate with the surrogate layer, it is difficult, if not impossible, to place discrete conductive elements, such as a BGA, on the substrate side bearing the surrogate layer. Further, adding this surrogate layer may be required to be performed as an additional process step. Little guidance is provided as to how the encapsulant and the surrogate layer might be applied concurrently, as is indicated by Suhir as being a desirable approach. In addition, placement of a surrogate layer proximate each substrate and prior to encapsulation will itself require additional cost and alignment considerations. U.S. Pat. No. 6,294,831 to Shishido et al. attempts to reduce bowing in a flip-chip type semiconductor device assembly by bonding a structure over the back side of a flip-chip configured semiconductor die and on the opposing side of the semiconductor die to an interposer substrate to which the semiconductor die is mechanically secured and electrically connected, the structure having a CTE similar to that of the substrate. U.S. Pat. No. 6,291,899 to Wensel et al. addresses bowing in a COB BGA semiconductor device assembly by applying a so-called stabilizing plate to a side of the substrate opposite that to which the semiconductor die is back side-attached and wire bonded. The stabilizing plate is formed of a rigid material different from that used to encapsulate the semiconductor die and is applied before the encapsulant is applied over the semiconductor die. Placement of the stabilizing plate on the side of the substrate carrying the discrete conductive elements of the BGA also requires fairly precise alignment of the stabilizing plate during placement. Other U.S. Patents have addressed the issue of stresses in semiconductor packages but only with regard to bowing in lead frame assemblies. For example, U.S. Pat. No. 6,384,487 to Smith and U.S. Pat. No. 6,258,624 to Corisis attempt to equalize the volume of encapsulant material on both sides of a lead frame to minimize bowing. U.S. Pat. No. 6,316,829 to Boon et al. attempts to solve the same problem, but by molding grooves and ridges in an encapsulated lead frame. While the prior art has attempted to address bowing and other stress-related problems in semiconductor device assemblies, a need exists for a semiconductor device assembly of a design whereby the stresses in the assembly can be controlled effectively while not requiring added process steps or the use of substantial additional materials, expensive materials or complex structural configurations, each of which increase fabrication cost. Further, it would be desirable to provide a semiconductor device assembly design which easily accommodates the use of a BGA for connection to higher-level packaging. The present invention provides a structural configuration which substantially balances stresses in semiconductor device assemblies through selective placement of encapsulant material on opposing sides of a substrate. The semiconductor device assembly includes at least one semiconductor die mounted to a substrate in either a board-on-chip (BOC) or chip-on-board (COB) configuration. Flip-chip, wire bonding, or any other technique known in the art may be used to electrically connect the semiconductor die to the substrate. The semiconductor die is attached and electrically connected to one side of a substrate with discrete conductive elements such as a ball grid array (BGA) on the opposing side of the substrate. In a broad embodiment, at least one stem member and at least one transversely extending branch member may be placed on the side of a carrier substrate such as an interposer substrate opposite the side on which a semiconductor die and die encapsulation region extending over them are placed. The combined volumes of the stem and branch member may be substantially equal to the volume of the die encapsulation region. One exemplary embodiment of the present invention comprises a wire bonded BOC semiconductor device assembly where the wire bonds extending between the bond pads of the semiconductor die and terminal pads of the substrate are encapsulated with a longitudinally extending wire bond cap in a conventional manner with at least one laterally extending branch member of encapsulant material formed over the same side of the substrate as the wire bond cap. The wire bond cap and at least one branch member may be formed simultaneously with an encapsulation region formed over the semiconductor die. Another exemplary embodiment of the present invention comprises a wire bonded COB assembly wherein the semiconductor die and wire bonds are encapsulated on one side of the substrate and at least one additional longitudinally extending stem member having at least one laterally extending branch member of encapsulant material may be formed on the opposing side of the substrate and simultaneously with encapsulation of the semiconductor die and wire bonds. Yet another exemplary embodiment of the present invention comprises a semiconductor device package wherein a flip-chip configured semiconductor die is attached and electrically connected to a substrate. The semiconductor die may be encapsulated on one side of the substrate simultaneously with application of encapsulant material to the opposing side of the substrate in a configuration providing at least one longitudinal member and at least one laterally extending member. The present invention offers the advantage, among others, of reducing internal bending stresses on an encapsulated semiconductor device assembly by moving the neutral axis, where such bending stresses are slight to nonexistent, closer to or even within the center of the substrate. Further, the stress-balancing structures of the present invention are formed using an insubstantial volume of additional encapsulant material and simultaneously with molding of an encapsulant envelope over the semiconductor die and, if applicable, a wire bond cap. The present invention also encompasses a method of making the above semiconductor packages and a method of modifying a mold segment for use in the method. | Mid | [
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With an incidence rate of 7.86% per year, meningiomas are the most frequent tumors within the central nervous system (CNS) in the US. The majority of schwannomas arises from the vestibular branch of the eighth cranial nerve within the CNS and represents nearly all nerve sheath tumors found within the CNS ([@bb0035]). Schwannomas are slow-growing low grade tumors. Around 80% of meningiomas are also low grade. However either due to difficult localization or tumor re-growth as a consequence of incomplete resection, tumors may cause considerable morbidity to the patients. Unfortunately, treatment options in these patients with complicated clinical course are restricted to radiotherapy, as systemic therapy has failed to deliver clear benefit so far. The key molecular aberration found in both meningiomas and schwannomas affect the Neurofibromatosis type 2 gene (*NF2*), with more than 50% of sporadic meningiomas harboring *NF2* alterations ([@bb0045]). Most schwannomas harbor mutation of both alleles or allelic loss of one allele and mutation of the other ([@bb0005]). The essential role of *NF2* is evident from the frequent occurrence of meningiomas and vestibular schwannomas in patients suffering from germline mutations in *NF2* ([@bb0015]). The protein product of the *NF2* gene is merlin (also referred to as schwannomin), and is a critical regulator of contact-dependent inhibition of tumor cell proliferation. Thus, loss of merlin contributes to both tumor growth, tumor cell invasion, and metastasis ([@bb0040]). Clinical trials taking *NF2* alterations into account have been rarely undertaken. In one trial, the mTOR inhibitor Everolimus was able to delay the time to tumor progression in *NF2*-associated vestibular schwannomas, while tumor growth itself was not affected significantly ([@bb0020]). The dual mTORC1/mTORC2 inhibitor AZD2014 is currently being tested in patients with progressive or symptomatic *NF2*-related meningiomas ([NCT02831257](ctgov:NCT02831257){#ir0005}). However, there is a clear need to identify additional targets active and treatable in *NF2*-related meningiomas and schwannomas. The paper from [@bb0010] contributes an important step forward to fill this gap. Using proteome and phospho-proteome approaches, they analyzed both primary cells from merlin deficient meningiomas and schwannomas in comparison to non-tumorous Schwann cells and meningeal cells. One of a number of proteins upregulated in both tumor cell types was PDZ and LIM domain protein 2 (PDLIM2), and the authors nicely confirmed its upregulation in primary tumor samples. Downregulation of PDLIM2 by shRNA reverted the increased tumor cell proliferation, suggesting that targeting PDLIM2 might be beneficial in treating aggressive *NF2*-associated tumors. Thus, one important finding is the identification of potential merlin-interacting proteins which can be targeted. The link between merlin and PDLIM2 is facilitated by the function of PDLIM2 as an adaptor protein of several cytoskeleton proteins (actinin, filamin A, myosin) ([@bb0050]). PDLIM2 suppression acts as a tumor-inhibiting factor in other cancers ([@bb0025]). Moreover, PDLIM2 suppresses NFkappaB-mediated inflammation ([@bb0030]), suggesting that drug-based targeting of PDLIM2 might have a positive function in cancer, inflammation, or even tumor-associated inflammatory processes. One idea to modulate PDLIM2 was recognized by the observation that vitamin D induces demethylation of the PDLIM2 promoter ([@bb0055]). However, a more detailed analysis of PDLMI2 is necessary in the context of *NF2*-related animal tumor models, as well as other *NF2*-associated tumor cells lines, such as mesothelioma cells. Given the pleiotropic function of PDLIM2, drug-based modulation of this protein is challenging. **Disclosure** The author declared no conflicts of interest. Meningioma research of CM is supported by grants from the DFG (grant \#MA2530/6-1 and MA253/8-1), from the Wilhelm Sander-Stiftung (grant \#2014.092.1), and the Deutsche Krebshilfe (grant \#111853). | High | [
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INTRODUCTION {#s1} ============ With 238,700 new cases worldwide, ovarian cancer was the seventh most frequently occurring cancer among women in 2012, and was responsible for 151,900 deaths. In developing countries, newly diagnosed cases of ovarian cancer have exceeded those of cervical cancer \[[@R1]\]. Moreover, mortality from ovarian cancer has decreased by only 1.29 per 100,000 over the past several decades due in large part to the paucity of effective screening methods and chemopreventive agents, and to its being asymptomatic during early stages \[[@R2], [@R3]\]. Although active surgical treatment and adjuvant chemotherapy have been applied to the treatment of advanced ovarian cancer, the prognosis of the patients remains poor with a 5-year survival rate of only 23% \[[@R4], [@R5]\]. Considerable research has focused on explaining the molecular mechanisms underlying ovarian cancer, but in the absence of an appropriate progression model, they remain far from clear \[[@R6], [@R7]\]. Thus, identification of a sensitive and early-detected biomarker useful for cancer prediction and prevention is badly needed. *TP53* is a tumor suppressor gene is located on the chromosome 17p13 short arm and encodes a protein with 393 amino acids \[[@R8]\]. Its product, p53, is regarded as a major inhibitor of tumorigenesis, which is involved in cycle arrest, DNA repair, apoptosis or cellular aging \[[@R9], [@R10]\]. Mutations in *TP53* can result in Li--Fraumeni syndrome, which increases the risk of diverse cancers, including breast cancer, carcinosarcoma, leukemia and brain tumors, among others \[[@R11]\]. In addition to the tumor-associated *TP53* mutations, polymorphisms also have an important impact on the susceptibility to cancer \[[@R12]--[@R15]\]. The well-studied *TP53* polymorphism is at codon 72 of exon 4 (CGC to CCC) and corresponds to a change from arginine to proline \[[@R16], [@R17]\]. The two polymorphic forms of *TP53* exhibit differences in their biological function. Whereas the Arg72 form induces cell apoptosis upon stress and inhibits tumorigenesis, the Pro72 inhibits the G1 phase of cell cycle progression \[[@R18]\]. There has been much research on the relationship between *TP53* codon 72 polymorphism and ovarian cancer risk, but the results are conflicting and inconsistent. Some studies have shown that the *TP53* Arg allele is associated with a higher risk of ovarian cancers \[[@R19]--[@R21]\], while others found that the *TP53* Pro allele is likely a risk factor for ovarian cancer \[[@R22]--[@R24]\]. In addition, there are also publications suggesting the *TP53* Arg72Pro polymorphism is not associated with susceptibility to ovarian cancer \[[@R25], [@R26]\]. The reasons for the contradictory results may be attributable to inadequate sample size, different sources of DNA, ethnicity, different environmental exposures, or the borderline effect of genetic variant. In an effort to increase clarity, we collected all eligible studies and analyzed the potential effect of TP53 codon 72 polymorphism on the susceptibility to ovarian cancer. RESULTS {#s2} ======= Study characteristics {#s2_1} --------------------- Through searches of the PubMed, EMBASE and Chinese Biomedical (CBM) databases, a total of 424 potentially relevant articles were initially identified. Of those, 386 were excluded, and 38 were chosen for further evaluation through checking of the title and abstract (Figure [1](#F1){ref-type="fig"}). Based on the inclusion criteria described below in the Methods, 18 articles were included in the final analysis \[[@R19], [@R20], [@R22]--[@R36]\]. Among those 18, the publication by Schildkraut et al. \[[@R26]\] investigated the genotype distributions of the *TP53* Arg72Pro polymorphism in different areas, so it was divided into seven separate studies. Overall, 24 case-control studies with 3271 cases (13 to 626 per study) and 6842 controls (13 to 1045 per study) were included in the present meta-analysis. The main characteristics of all the included studies are presented in Table [1](#T1){ref-type="table"}. Among these studies, 19 were conducted with Caucasians, four with Asians, and only one with Africans. Because detailed information about the source of the controls were not been provided in the study by Peller et al. \[[@R36]\], only 12 articles were classified as population-based, and 11 were hospital-based. In addition, 15 studies with a quality score ≥ 9 were considered to be high quality, while nine with a score \< 9 were regarded as low quality. Table [1](#T1){ref-type="table"} also summarizes the distribution of genotypes, minor allele frequencies (MAFs) and the Hardy--Weinberg equilibrium (HWE) in the controls. {#F1} ###### Characteristics of studies included in the current meta-analysis Surname Year Country Ethnicity Design Genotyping method Case Control MAF HWE Score ------------------- ------ -------------- ----------- -------------- ------------------- ------ --------- ----- ----- ------- ----- ----- ------ ------ ------- ---- Buller 1997 USA Caucasian PB PCR-SSCP 98 79 13 190 30 18 4 52 0.25 0.579 10 Peller 1999 Israel Caucasian Not detailed DS 7 6 0 13 8 5 0 13 0.19 0.447 5 Hogdall 2002 Denmark Caucasian PB PCR-RFLP 118 73 20 211 48 27 8 83 0.26 0.165 9 Li 2002 China Asian PB PCR-RFLP 14 20 5 39 29 67 35 131 0.52 0.920 10 Qie 2002 China Asian HB PCR-RFLP 10 18 2 30 12 16 2 30 0.33 0.273 5 Pegoraro 2003 South Africa African HB AS-PCR 9 29 25 63 32 147 161 340 0.69 0.852 6 Agorastos 2004 Greece Caucasian HB PCR 26 22 3 51 6 19 5 30 0.48 0.142 5 Kang 2004 China Asian HB PCR 28 60 36 124 37 64 27 128 0.46 0.945 9 Morari 2006 Brazil Caucasian PB AS-PCR 23 46 0 69 117 91 14 222 0.27 0.505 9 Santos 2006 Portugal Caucasian HB AS-PCR 49 40 10 99 117 58 13 188 0.22 0.128 7 Ueda 2006 Japan Asian HB PCR-RFLP 21 41 6 68 34 54 7 95 0.36 0.021 6 Schildkraut-POCS 2009 Poland Caucasian PB TaqMan 51 63 4 118 368 207 45 620 0.24 0.038 11 Schildkraut-NCOCS 2009 USA Caucasian PB IGGA 132 104 16 252 231 182 24 437 0.26 0.122 13 Schildkraut-MAYO 2009 USA Caucasian PB IGGA 96 82 14 192 261 157 37 455 0.25 0.057 13 Schildkraut-AUS 2009 Australia Caucasian PB MassARRAY 121 59 14 194 219 110 31 360 0.24 0.002 11 Schildkraut-HAW 2009 USA Caucasian PB TaqMan 18 12 0 30 78 60 8 146 0.26 0.416 12 Schildkraut-MAL 2009 Denmark Caucasian PB TaqMan 134 94 25 253 564 371 78 1013 0.26 0.123 14 Schildkraut-SEA 2009 New-England Caucasian PB TaqMan 119 75 18 212 461 326 55 842 0.26 0.796 14 Matei 2012 Roman Caucasian HB PCR-RFLP 9 6 6 21 7 7 7 21 0.50 0.127 4 Dholariya 2013 North India Caucasian HB ASO-PCR 33 50 17 100 62 32 6 100 0.22 0.499 9 Malisic 2013 Serbia Caucasian HB PCR-RFLP 22 22 3 47 45 22 3 70 0.20 0.881 6 Medrek 2013 Poland Caucasian PB TaqMan 302 265 59 626 537 436 72 1045 0.28 0.191 12 Tecza 2015 Poland Caucasian HB PCR-RFLP 130 79 16 225 167 150 24 341 0.29 0.213 11 Benhessou 2016 Morocco Caucasian HB AS-PCR 33 10 1 44 43 27 10 80 0.29 0.095 5 AA, Arg/Arg; AP, Arg/Pro; PP, Pro/Pro; MAF, minor allele frequency; HWE, Hardy-Weinberg equilibrium; PB, population based; HB, hospital based; PCR, polymerase chain reaction; PCR-RFLP, PCR-restriction fragment length polymorphism; AS-PCR, allele-specific PCR; ASO-PCR, allele specific oligonucleotide; IGGA, Illumina golden gate assay; DS, direct sequencing; PCR-SSCP, PCR-single-strand conformation polymorphism assay. Meta-analysis {#s2_2} ------------- As shown in Table [2](#T2){ref-type="table"} and Figure [2](#F2){ref-type="fig"}, the overall pooled analysis indicated no significant association between *TP53* Arg72Pro polymorphism and ovarian cancer risk in any of the five genetic models \[homozygous: odds ratio (OR)=1.04, 95% confidence interval (CI)=0.81-1.34; heterozygous: OR=1.14, 95% CI=0.96-1.36; recessive: OR=1.05, 95% CI=0.90-1.22; dominant: OR=1.12, 95% CI=0.94-1.33 and allele comparing: OR=1.06, 95% CI=0.93-1.20). In addition, when we performed subgroup analyses based on ethnicity, source of controls, and quality of studies, there were again no significant results indicating a relationship between the *TP53* Arg72Pro polymorphism and ovarian cancer risk. ###### Meta-analysis of the association between *TP53* codon 72 (rs1042522 G\>C) polymorphism and ovarian cancer risk Variables No. ofstudies Samplesize Homozygous Heterozygous Recessive Dominant Allele ------------------- --------------- ------------ ------------------ -------------- ------------------ ---------- -------------------- ------- ------------------ --------- ------------------ --------- All 24 3271/6842 1.04 (0.81-1.34) 0.015 1.14 (0.96-1.36) \<0.001 1.05 (0.90-1.22) 0.131 1.12 (0.94-1.33) \<0.001 1.06 (0.93-1.20) \<0.001 Ethnicity Caucasians 19 2947/6118 1.09 (0.84-1.43) 0.035 1.18 (0.97-1.43) \<0.001 1.09 (0.91-1.29) 0.177 1.15 (0.95-1.39) \<0.001 1.09 (0.95-1.25) \<0.001 Asians 4 261/384 0.99 (0.40-2.42) 0.070 1.08 (0.75-1.56) 0.508 1.07 (0.70-1.65) 0.166 1.06 (0.67-1.68) 0.190 1.02 (0.69-1.49) 0.062 Africans 1 63/340 0.55 (0.24-1.29) --- 0.70 (0.30-1.63) --- 0.73 (0.42-1.27) --- 0.62 (0.28-1.38) --- 0.76 (0.51-1.12) --- Source of control PB 12 2386/5406 1.08 (0.86-1.36) 0.306 1.18 (0.98-1.41) 0.006 1.03 (0.86-1.25) 0.200 1.15 (0.98-1.34) 0.030 1.09 (0.99-1.19) 0.262 HB 11 872/1423 1.06 (0.61-1.84) 0.004 1.05 (0.71-1.55) \<0.001 1.08 (0.83-1.40) 0.135 1.03 (0.67-1.57) \<0.001 1.02 (0.75-1.39) \<0.001 Quality score ≥9 15 2835/5975 1.13 (0.88-1.47) 0.054 1.19 (0.98-1.44) \<0.001 1.11 (0. 94-1. 32) 0.124 1.17 (0.98-1.41) \<0.001 1.11 (0.98-1.25) 0.002 \<9 9 436/867 0.77 (0.39-1.49) 0.064 0.98 (0.63-1.50) 0.033 0.81 (0.56-1.16) 0.425 0.91 (0.56-1.47) 0.004 0.91 (0.64-1.29) 0.002 Het, heterogeneity; OR, odds ratio; CI, confidence interval; HB, hospital based; PB, population based. {#F2} Heterogeneity and sensitivity analyses {#s2_3} -------------------------------------- As shown in Table [2](#T2){ref-type="table"}, significant heterogeneities were observed among studies in the homozygous (*P* = 0.015), heterozygous (*P* \< 0.001), recessive (*P* = 0.131) and dominant (*P* \< 0.001) models, as well as with allele comparing (*P* \< 0.001). We adopted the random-effects model to solve the significant heterogeneity between studies, because it generated wider CIs to estimate genetic susceptibility. To confirm the impact of each study on summary ORs, sensitivity analysis was conducted by separately omitting each single study involved in the analysis and recalculating ORs and the 95% CIs. This analysis showed our results to be statistically robust, as the corresponding pooled ORs and 95% CIs were not materially changed by any of the omissions (data not shown). Publication bias {#s2_4} ---------------- In this meta-analysis, publication bias was assessed using Begg\'s and Egger\'s tests (Figure [3](#F3){ref-type="fig"}). The results demonstrated that there was no potential publication bias present in the included articles under three genetic models (heterozygous: *P* = 0.945; dominant model: *P* = 0.752 and allele comparing model: *P* = 0.371). However, it was important to note that obvious bias existed in the other two models (homozygous: *P* = 0.027 and recessive model: *P* = 0.032). The reason for the bias may be related to the small sample size so that no single study was considered to be the cause of the publication bias. {#F3} DISCUSSION {#s3} ========== The tumor-suppressor protein p53 is a well-known deterrent to cell growth, which inhibits tumorigenesis by activating apoptotic machinery \[[@R37]\]. *TP53* Arg72Pro, a common *TP53* polymorphism, induces certain conformational p53 mutants and binds stably to another tumor suppressor, p73 \[[@R38], [@R39]\]. The two polymorphic variants of *TP53* exert different biochemical and biological effects on cell cycle progression. The Arg72 form induces higher levels of apoptosis than the Pro72 form, while the Pro72 form has the ability to induce growth arrest during the G1 phase of the cell cycle \[[@R40]\]. We therefore hypothesized that *TP53* Arg72Pro polymorphism may be closely related to the risk of ovarian cancer. Although numerous studies have investigated the relationship between the *TP53* Arg72Pro polymorphism and ovarian cancer risk, the results have been inconsistent. Hence, the current meta-analysis of 24 studies was employed further investigate the association between *TP53* Arg72Pro polymorphism and ovarian cancer, which is the most comprehensive analysis to date. The overall pooled results suggest there is no significant connection between the *TP53* Arg72Pro polymorphism and ovarian cancer risk in five genetic models. This result was further confirmed in analyses stratified based on ethnicity, source of control and quality score. Consistent with the results of present meta-analysis, some earlier studies found that there is little or no association between *TP53* Arg72Pro polymorphism and ovarian cancer risk. Likewise, an previous meta-analysis conducted by Francisco et al. \[[@R41]\] detected no association between the *TP53* Arg72Pro polymorphism and ovarian cancer risk under any genetic model, and stratified analyses also failed to validate a genetic association. On the other hand, a study by Shen et al. \[[@R42]\] concluded that the *TP53* Arg72 allele was associated with a modest, but significantly reduced risk of ovarian cancer when the included studies were classified as high quality. In yet another analysis, the main findings of 19 case-control studies, including 2,240 cases and 5,246 controls, were similar to those of the present study, though the subgroup analysis indicated a marginal association between the *TP53* Arg72Pro polymorphism and ovarian cancer risk in the heterozygote model in Caucasians \[[@R43]\]. One possible explanation for why it is difficult to detect an effect of *TP53* codon 72 polymorphism on ovarian cancer based on these epidemiological results is that there was loss of heterozygosity (LOH) at the *TP53* locus. Based on the previous publications, the *TP53* Arg allele is preferentially mutated and expressed, while the Pro allele is lost in *TP53* Arg72/Pro72 heterozygotes across several cancer types \[[@R44], [@R45]\]. Thus the results of these genetic association studies may be biased by preferential LOH of the Pro allele. In addition, the results were probably influenced by individual infections with tumor-associated human papillomaviruses (HPVs). Storey found that the Arg 72 isoform was more susceptible to degradation by E6 protein of HPV16 than Pro 72 isoform in a heterozygous situation \[[@R46]\]. However, the original data on HPV infection were unavailable from the included studies, so further stratified analysis based on HPV infection status was not done. The merits of the present meta-analysis in the context of the previously published ones are as follows. (a) We used an expanded retrieval range that included the latest studies and minimized selection bias. (b) There was a larger sample size and greater statistical power. (c) Our study is further verification that the *TP53* Arg72Pro polymorphism has no impact on ovarian cancer risk. Nonetheless, there are still several limitations to the present meta-analysis. First, the sample sizes of many of the included studies were small, which contributed to reducing the statistical power of the genetic association estimate. Second, this meta-analysis only included publications in English and Chinese, which could lead to selection bias. Third, there were three studies in which the detected genotype frequencies deviated from the HWE \[[@R26], [@R31]\], making biased results inevitable. Fourth, significant heterogeneity was present under four genetic models, which may be attributable to ethnic differences and/or variation in sample size, study design or genotyping methods. Fifth, the well-known protective factors for ovarian cancer, such as bearing children, oral contraceptives and breastfeeding, were not taken into account due to a lack of individual information. Finally, we did not consider the possibility of the gene-gene interaction. Despite of these limitations, the pooled results demonstrated that there was no significant association between the *TP53* Arg72Pro polymorphism and ovarian cancer risk. Future well-designed studies that include large samples and take environmental factors into account will be necessary to validate our findings. MATERIALS AND METHODS {#s4} ===================== Identification of relevant studies {#s4_1} ---------------------------------- We conducted a search of the PubMed, EMBASE and Chinese Biomedical (CBM) databases using the following keywords: "*TP53* or *p53*", "polymorphism or variant or variation" and "ovarian" (prior to May 1, 2017). In addition, the references lists of the original articles and reviews were checked manually to identify additional studies. For overlapping data and republished studies, only the latest and largest studies were included in the current meta-analysis. Inclusion and exclusion criteria {#s4_2} -------------------------------- Inclusion criteria for studies were as follows: (a) evaluation of the association between the *TP53* gene Arg72Pro polymorphism and ovarian cancer risk, (b) case-control design, (c) sufficient and adequate data provided to calculate crude OR and 95% CI, (d) the data were reported in English or Chinese. Studies were excluded for the following reasons: (a) duplicate publication, (b) cases only studies, or (c) article was a review, case report, editorial or expert opinion. Data extraction {#s4_3} --------------- Two reviewers (Anqi Zhang and Jing He) assessed weather the retrieved studies met the inclusion criteria, and extracted data from each eligible study. If the two reviewers did not separately reach a unanimous decision on any one item, the dispute was resolved by joint review and consensus. The information retrieved from each study was as follows: the first author\'s surname, publication data, country of origin, ethnicity, source of control, total number of cases and controls, genotype methods, and numbers of cases and controls for the *TP53* Arg72Pro. Based on differently stratified analyses, ethnicity was divided into three categories: Asians, Caucasians and Africans, and controls were divided into hospital-based and population-based. Statistical methods {#s4_4} ------------------- The strength of the association between *TP53* Arg72Pro polymorphism and ovarian cancer susceptibility was recalculated using crude ORs with the corresponding 95% CIs. The pooled ORs were calculated for the homozygous (Pro/Pro vs. Arg/Arg), heterozygous (Arg/Pro vs. Arg/Arg), dominant \[(Arg/Pro + Pro/Pro) vs. Arg/Arg\], and recessive \[Pro/Pro vs. (Arg/Pro + Arg/Arg)\] models, as well as allele comparison (Pro vs. Arg). The Chi square-based Q test was used to calculate the heterogeneity between studies. If the *P* value was less than 0.1, the pooled ORs were calculated using a random-effects model (the DerSimonian and Laird method) \[[@R47]\]. Otherwise, a fixed-effect model (the Mantel--Haenszel method) was chosen for further calculation \[[@R48]\]. Subgroup analyses were classified into three parts: ethnicity, study design and quality score. The quality score for each study was assessed in accordance with the evaluation criteria, as described previously \[[@R49]--[@R51]\]. The quality scores ranged from 0 to 15, with scores ≥ 9 defined as high quality, while \< 9 were defined as low quality. Publication bias was assessed by constructing a funnel plots, after which the asymmetry of the funnel plots was assessed using Egger\'s linear regression test \[[@R52]\]. HWE was evaluated using the chi-square-based Q-test, values of *P* \< 0.05 were regarded as deviations from the HWE. All statistical tests were conducted using STATA software (version 11.0; Stata Corporation, College Station, TX). Values of *P* \< 0.05 was considered significant, and all tests were two-sided. This study was supported by grants from the Natural Science Foundation of Zhejiang Provincial (LY16H160054, LY16040011, and Y16H160214), the Public Welfare Science and Technology Project of Wenzhou City (Y20150044), and National Natural Science Foundation of China (81401184). **CONFLICTS OF INTEREST** The authors declare no competing financial interests. | Mid | [
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Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic Acid Testing Status: Time for Change. Previous studies have grouped all donors positive for hepatitis C virus (HCV) antibody (Ab). Only recently has donor HCV nucleic acid testing (NAT) become routine, and the impact of Ab and NAT status on organ utilization is unknown. Using the United Network for Organ Sharing database, we identified 9290 donors from 2015 to 2016 for whom both HCV Ab and NAT data were available and compared organ utilization by HCV status. Overall, 93.8% of donors were Ab negative and NAT negative (Ab-NAT-), 0.15% were Ab negative and NAT positive, 1.8% were Ab positive and NAT negative (Ab+NAT-), and 4.2% were both Ab and NAT positive (Ab+NAT+). Ab-NAT- donors donated at the highest rate for all organs except livers, of which Ab+NAT- donors donated at a higher rate (81.2% vs 73.2%, p = 0.03). Livers were discarded for reasons related to abnormal biopsies in Ab+NAT+ donors, whereas kidneys from Ab- or NAT-positive donors were discarded for reasons related to HCV status. Using a propensity score-matched model, we estimated that using Ab+NAT- donors at the same rate as Ab-NAT- donors could result in 48 more kidney donors, 37 more heart donors, and 15 more lung donors annually. We urge the use of HCV Ab+NAT- donors for appropriately selected and consenting recipients. | Mid | [
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Family perspectives on integrated child health information systems. The perspectives of families, and especially parents of children with special health care needs, need to be better understood by the government agencies, health care providers, associations, and information systems vendors that are integrating child health information systems. To date, research on children with special health care needs has not included the perspectives of parents on integrated child health information systems. Interviews were conducted with a limited number of parents of children with special health care needs and a young adult with special health care needs about their perspectives on integrated health information systems needs. The interviews revealed common themes: (1) parents have experienced the benefits of information technology for health care purposes, (2) parents believe integrated health information systems could help to coordinate their children's health care, (3) parents believe information technology can help improve accuracy and timeliness of information, (4) parents of children with special health care needs believe their children's health information should be available to those who need it, but safeguards must be in place, (5) parents believe health information systems can improve health care, but it is not the highest priority health care issue for them, and (6) parents believe that their involvement in issues related to children with special health care needs, including information technology, is critical. Parents of children with special health care needs hold strong opinions about their children's health care, including health information systems. Parents need to be central to discussions about development of integrated child health information systems if we are to develop information systems that serve the needs of children with special health care needs and their families. | Mid | [
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Q: Convergence of $\sum_{n=1}^{\infty} \frac{n^3}{\ln(2)^n}$ would the sum from 1 to infinity of $\frac{n^3}{(\ln{2})^n}$ converge? In the limit n tends to infinity the denominator grows more quickly and so the terms go to zero. Using the ratio test I get $\frac{(n+1)^3}{n^3\ln{2}}$ but im not sure if $(n+1)$ grows fast enough to make the ratio greater than one. A: Observe that $\ln 2\simeq 0.69$, and in particular $\ln 2 \in (0,1)$. Therefore, $\frac{n^3}{(\ln 2)^n} > n^3$ (actually much bigger), and you can conclude easily that the series diverges. | Low | [
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2017 Finalists Meet the teams that made the 2017 Finals STENTiT “Minimally-invasive vascular regeneration” ** GOLD PRIZE ** The stent market is a multibillion-dollar landscape where technological developments have led to more effective treatments that saved the lives of millions of patients. With the emerging trend of bioabsorbable technologies as a temporary therapy for obstructive vascular diseases, another giant leap has just been taken. To improve vascular treatment, current stent developments focus on combining the strength, flexibility and low profile of metal structures with the temporary nature of bioabsorbable materials. However, impossible as it may sound, the ideal stenting therapy would not only treat, but even heal the diseased artery. STENTiT developed a unique product, called the regenerative stent, which will be the only device on the market to bring vascular regeneration to the patient without requiring surgical procedures. Made out of a fully bioabsorbable porous structure, this product provides minimally-invasive support to the diseased artery and promotes healing from the inside-out by using the patient’s own cells to restore the vasculature. The vision of STENTiT is to provide the next generation in stent technology and become the preferred therapy for cardiovascular diseases. CytoChroma “Revolutionising preclinical toxicity screening” ** SILVER PRIZE ** The cost of developing a new drug is £1.15 billion. Greater than 90% of drugs fail to make it to market but fail during the latter stages of the development process. This is due to poor, inaccurate models that do not predict toxicity. Our business proposition uses stem cell derived liver cells and a sensitive screening method to identify drugs toxicity. We transform stem cells into liver cells via a defined and patent protected protocol. Potential drugs are tested using these cells; if the drugs or the metabolites are toxic the cells will be damaged or killed. Using coloured tags we can identify how the compounds damage/destroy the cells. Ultimately we aim to significantly reduce the cost of bringing new drugs to market by identifying toxic drugs early in the drug development process. Our unique ability to deliver large quantities of cells reproducibly, gives us the capacity to screen large numbers of compounds, at a cost effective price. Denovo Matrix “Redefining Cell Culture” ** BRONZE PRIZE & PEOPLE'S CHOICE AWARD ** Current in vitro cell culture methods do not reflect normal in vivo cell surroundings and behaviour. In order to achieve biological relevance, the in vitro microenvironment should recapitulate key parameters of the in vivo microenvironment. Moreover, these parameters vary between different tissue types. Therefore, it is crucial to provide individual cell types with cell-specific in vitro microenvironments. We have developed a proprietary technology to create modular biomimetic matrices that can be tailored to recreate a large variety of microenvironments for any cell type by incorporating biophysical cues and sensory information. In contrast to current solutions, our biomatrices are modular, biologically relevant, self-assembling hydrogels that are chemically defined and GMP-certifiable. We aim to reveal new avenues in research, enable challenging cell culture and facilitate standard cell culture practices for research institutes, SMEs and drug screening companies. We are denovoMATRIX, a team with interdisciplinary expertise in biochemistry, material engineering, cell culture, and business administration. We are currently validating the technology and develop our products in an EXIST Forschungstransfer-funded project at Technische Universität Dresden. We aim to spin-off in 2018. At TERMIS, we wish to identify scientists to co-develop our materials as well as industrial partners for joint product development. CartInject “We regenerate your cartilage” Articular cartilage covers the articular surfaces of the bones and has a unique structure and composition which provide the joints with shock absorption and load bearing. It is particularly subjected to deteriorations and injuries. Cartilage has a very limited capability to repair itself, notably due to the lack of vascularization. The current gold standard for cartilage repair is the total replacement of the joint. Alternative and less invasive treatments have been shown to successfully reduce pain and improve joint function, but long-term results are unfortunately still unsatisfactory. As a spin-off of ETH Zürich, we want to bring the promising results of the research conveyed in Prof Zenobi-Wong’s laboratory to patients and we work hand-in-hand with orthopedic surgeons to develop the ideal treatment for articular cartilage lesions. Our unique bioengineered product is a combination of allogeneic cells and a hyaluronic acid-based biomaterial. The use of an off-the shelf cell source allows a one-step surgery procedure, while the injectable and adhesive material permits a minimally invasive surgery and supports a fast, pain-free recovery of the patient. In the USA alone, 1.2 million patients are affected by cartilage injuries annually and we believe our product can address 500’000 immediately. CLEX “Bringing Hydrogels Alive” Hydrogels represent a hugely important class of materials that are used in everyday items such as desserts and food pastes to high-tech biomedical applications in medicine, diagnostics and biotechnology. However a significant barrier to the realization of many high tech applications is a lack of control over the way hydrogels crosslink – i.e. transition from a free flowing liquid to a solid gel. This may sound easy, but this represents a profound challenge to achieve on the microscale and in a way that is compatible with sensitive molecules and biological cells. CLEX offers an elegant solution to this problem by enabling precise control over the speed of gelation and does so in a mild chemical environment that is friendly to living cells and can be tailored for specific high-tech applications. The vision of CLEX it to provide gel kits which are tailored for 3 key application areas: Microfluidics, 3D bioprinting and Injectables. This will significantly enhance the workflow of scientists working in these areas by providing gelation strategies of unprecedented control in an affordable and easy to use kit form. | Mid | [
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Pregnancy in dark winters: implications for fetal bone growth? To prospectively examine the prevalence of hypovitaminosis D in pregnancy and to correlate maternal and fetal vitamin D to fetal anthropometry. A prospective cohort study. Tertiary referral maternity hospital. Sixty pregnant women. Serum 25-hydroxyvitamin D (25OHD) was measured in early pregnancy, at 28 weeks, and in cord blood at delivery. The prevalence of hypovitaminosis D and the relationship between fetal growth and serum 25OHD concentrations. Two subgroups were analyzed to examine results in the context of seasonal variation in 25OHD: a winter and a summer cohort. Fetal anthropometry was assessed at 20 and 34 weeks, and at delivery the neonatal anthropometry was recorded. There was a high prevalence of hypovitaminosis D ranging from 33% to 97%, with a marked seasonal variation. Fetal 25OHD concentrations correlated with all biometry at 20 weeks. In the winter cohort, a correlation was found between early pregnancy 25OHD and femur length at 20 weeks, and between 28-week 25OHD and femur length at 34 weeks. Infant length was shorter in those with early pregnancy 25OHD less than the median (52.1 vs. 53.6 cm). The high prevalence of maternal hypovitaminosis D during winter months in northern latitudes may have detrimental effects on fetal skeletal growth. | High | [
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Video: Who Holds the Key to Peace? The Chairman of the Yesha Council will determine whether there will be peace, according to Al-Jazeera TV. By Elad Benari First Publish: 11/13/2011, 3:33 AM A video by Al-Jazeera’s English television network is claiming that the one person who will decide whether there will be peace in between Israel and the Palestinian Authority is none other than Yesha Council chairman Danny Dayan. The video claims that conventional wisdom, which claims that Prime Minister Binyamin Netanyahu, PA Chairman Mahmoud Abbas, and U.S. President Barack Obama are the ones who hold the key to peace, is wrong. It goes on to say that Dayan has the power to either prop up the Israeli government or threaten to bring it down. “The Yesha settlement council refuses to even consider the possibility of a Palestinian state,” the video says, “and it boasts strong and growing support both within the Knesset and the Cabinet.” That support, Al-Jazeera claims, provides Netanyahu “with the convenient excuse to do nothing.” | Mid | [
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"I give you a new commandment: love one another. As I have loved you, so you also should love one another." John 13:34 34 NAB Stripped down to its bare essence, following Christ means making the Love Commandment one's way of life. In concrete, it is loving God above all things with our whole being; and loving our neighbor as we love ourselves (cf. Mt 22:35-40). In the Gospel of John, it is given yet another compelling aspect: mutual love in the manner that Jesus has loved us. The life, passion, death and resurrection of Jesus sum it up for all of us. All of Jesus is an expression of his love to each one of us in a very particular way, and to the one body that we comprise, the one human community. His whole existence is a communication of that love. Hence, we are to love one another to the fullest, to the best of our potentials, to the full extent of our giftedness. Every breath, every beat of our heart, every thought, every feeling, every decision, every action can be an expression of that divine-human love of Jesus. The utmost fulfillment of human identity and existence would be in the total love of all. When life seems complicated, and we are burdened by the demands of the daily grind, we just have to remember: LOVE ONE ANOTHER! When our relationships are challenged, and we feel betrayed, we just have to remember the words of the one crucified: LOVE ONE ANOTHER! When human institutions seem heartless, and injustice prevails, we have to remember that there is still a way: LOVE ONE ANOTHER! Prayer Jesus, our friend and brother, you gave us a new commandment to love one another as you have loved us. Grant us the grace that our hearts and awareness may be opened to the reality of your love that in coming to know how much you love us, we may be moved to love you in your presence in one another. In loving one another, may we realize that building personal relationships, communities and societies of peace, justice and integrity of creation are all but part of our response to follow you! Amen. | High | [
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Comedian Louis CK has proved a point: People are willing to pay a reasonable amount of money for DRM-free content from a performer they love, even though it would be trivial for them to pirate the same content for free. Twelve days ago, Louis CK decided to skip the distribution, DRM, ads and everything else that goes into marketing and sale of a video, and simply offer the video of his latest performance on his website for $5. It took four days for Louis to earn $200,000, and another eight days to earn a whopping $1 million. So how did he do it? And what can you learn from his approach? The questions One thing that I find interesting is the questions that Louie hoped his test would answer. It’s not so much the content of the questions, but that he asks them at all. Would people buy at a drastically low price? – If you price something too low, people may not think it has value, so they ignore it. Five dollars is way less than the normal price for such a video ($20), so people wonder if it’s just copied material or just bad production. Will everyone steal it? – Putting a video on your website leads to hackers stealing it and then torrenting it. Will this approach avoid that? Will anyone even pay for it? – Because this was an experiment where the middle man was removed, Louis wondered if anyone would even think it worth paying for. Customers might be thinking Louis is no longer wanted by the big people, thus reducing the value of what he offers. Will it be easy to buy and download? – Louis wanted to make the process as easy as possible…would all the time he spent on it make the difference? How much can one person make off of an experiment like this? – At the base of this test was a desire/need to make money… so the question was how much could be made? And would it be worth repeating again? I’ll answer those questions in a few minutes, so keep reading… The Pre-Launch The product that Louie eventually sold on his website was a video of never-before seen footage he recorded with six cameras during a live show at the Beacon Theater, an upscale venue in Manhattan. The total cost to record the footage was $170,000. This doesn’t include Louie’s time, which he invested in by directing the show, then editing the footage for countless hours up to the launch. One thing that is immediately noticeable is that the “buy” button is at the top and obvious. What else is there for you to do but “buy the thing?” Testing is so important when it comes to making a website. I don’t know if Louie tested different wording like “Buy the video” or “Buy it now.” Once they felt the site was ready and the video was ready they launched. But for you site it’s worth testing, as Optimizely did in a test they ran on their site and during Obama’s campaign which both proved the power of one word on conversions. Launch Louis and his team released the video on noon December 12th. They were selling it for $5, allowing people to pay for it through PayPal and download it immediately. There were no restrictions, meaning people could do with it what they wanted. They could watch it anywhere in the world, copy it and share it without fear of getting in legal trouble… Four days later Louis had made over $500,000, pocketing $250,000 in profit. Then that number doubled in the next eight days, bringing Louie to the magic number: $1 million dollars. Granted, Louie admits that this would’ve been a whole lot less if he had done it through a large company. But there would’ve been a whole host of restrictions placed on the material…and the direct connection with the audience would’ve been missing. Post launch In his latest blog posting, Louie talks about how much he’s enjoyed the success of the experiment and how much he’s really enjoyed seeing people get involved and interested in it. He likes making the money, but what he really seems to enjoy is the interaction with his audience. This is not surprising for a comedian who generally depends on intimacy with the audience to make his or her show work. The success has given Louis the idea to continue by selling just about anything on the site, including CDs, videos and tickets to shows. If it works for videos, what about other products? Smells like another test to me. My guess is that he’ll also continue to tinker with the current site, improving the call to action. This is not a new approach In Rainbows. Album cover via Wikipedia Louis CK may be the first comedian to use this approach, but he’s not the first person. According to some sources, about a third of the downloads paid the lowest premium price…one penny. It was the pre-release sales that proved more profitable. It’s revealing that Radiohead has never repeated this process. Following Radiohead’s lead, another band, this time Nine Inch Nails tried the same experiment, but with some notable differences. They offered other options to get the music, like a 2-CD boxed set for $10 or a deluxe limited edition for $70, but one truly remarkable move was to uploaded the partial album to BitTorrent themselves. Here’s what they said about that move: “Now that we’re no longer constrained by a record label, we’ve decided to personally upload Ghosts I, the first of the four volumes, to various torrent sites, because we believe BitTorrent is a revolutionary digital distribution method, and we believe in finding ways to utilize new technologies instead of fighting them.” They even offered it under a Creative Commons license that allowed anyone to share or remix it. How did this approach work? Bypassing the middle man and offering the album for free, the band managed to make $750,000 on sales from the different collections they offered. Their approach generated enough interest that at one point their servers were knocked offline. This worked because the strategy was different than Radiohead’s in a number of ways: There was no “set your own price” model. Part of the album was simply free. There was no way that fans could get the entire album free, even on the band’s site. The strategy was more like “free sample.” Each transaction led to a piece of consumer information, typically an email address that the band could use for future promotions. Conclusion Let’s finish this article by going back to Louis CK and see if his experiment answered the questions he asked. Remember, he wondered: Would people buy at a drastically low price? Will everyone steal it? Will anyone even pay for it? Will it be easy to buy and download? How much can one person make off of an experiment like this Yes, to the first question. In Louis’ next experiment he might test to see if he could lower or raise the price point and see what kind of impact that would have on sales. He should do it on a smaller scale, however, or try it with a minimum viable product. Some people did steal the video. But not very many…at least not enough to concern Louis. Obviously over a 200,000 people paid for it. People will continue to buy even if there isn’t a middle man. I think one of the reasons the video did so well was the ease of buying and downloading it. And finally, his test showed that a person could become a millionaire by selling this way. Louis doesn’t want to be a millionaire, however…he says he’ll be splitting that money four ways, with a fourth of the profits going to him. Still, a $250,000 pay out in 12 days is not bad. What other lessons do you think we can learn from Louis CK’s online experiment? Neil Patel is the co-founder of KISSmetrics, an analytics provider that helps companies make better business decisions. Thats really awesome! However, why did it cost his film crew 170,000 to film one night??? Was Spielberg filming for him? Anonymous While the story is informative, it misses the most important factor for the average person. You must have a following. The biggest challenge for most artists and authors is building that community. The rest, by comparison, is easy. http://robiganguly.com/blog Robi Ganguly Ritaashley you’re right on. The most important lesson from Louis CK’s success is that this “new” media age has the same principles: you have to develop your audience and that takes time, patience, hard work and an investment in your brand. Louis CK has spoken at length about how much time and effort he’s put into his craft, into working hard and honing his act, about hustling on the road in order to grow his audience and about the value of generating points of leverage for himself as his popularity grew. Today’s digital environment affords us lots of channels to grow our brands and popularity and Neil, you’re a great example of someone utilizing these channels to do so, but it takes hard work and commitment and a focus on building that core asset: your loyal audience. Tjmartin66x Louis C.K. is brilliant. He understands file sharing is a real culture and priced his digital product accordingly without DRM. He also possesses charisma and that has a great way of motivating buyers. He’s brutally honest and Carlinesque; and anyone that can make you laugh as much as C.K. will surely create a following that will want a digital piece of him in their collection. However, what about the new and obscure ebook author? I am a technical consultant at File Secure Pro, a drm vendor. IP protection of PDF ebooks is our business. Many of our clients find DRM essential. The Megauploads of the Internet threaten the return on investment of IP for our clients. It’s delicate balance. Louis C.K. drm free distribution was almost risk free because he’s made his work personal for his audience. They tacitly know that if they want more C.K., he needs a paycheck. I think Louis should do a skit on SOPA and PIPA, explaining why he would file share. It would probably go something like this: “I’d steal a car, for example. I’d steal a car if the owner got to keep the car… and if everyone I ever met never bought a car in their entire life.” Ryan Mindy Kaling already did that bit. http://www.youtube.com/user/tracksquad169?feature=mhee Teej My main issue would be the marketing aspect of this process. How do you market these type of products? How can you market this product to a large audience? Is the marketing strictly word of mouth? How drastically would the sales increase if more people knew about this product? (Which can be solved by a large company) Point being, not only do you want to sell your product to your fan base but you want to expand your fan base, so that the next sell will top your last. utuxia bittorrent is and will be the new distribution channel — time to embrace it and move it from underground into the mainstream. MaverickAshley Lenartson I love reading about what it takes to make money but just a little bit of money is all one really needs to be HAPPY…a little goes a long way to making you the kind of person you know how to be in your heart of hearts…6 cameras following Louis CK around on a stage and in the audience is enough to bring up the production costs of filming one nite and more…Hmmm! Hmmm! & the key thing to learn hear is that the product was given away for FREE but FREE is the most overused word in the FREE WORLD & then some…the point: it takes money to make money and you must have boundaries with it as IF YOU DON’T be prepared to be a Victim your whole life…one must be taught the value of a wooden nickle and MORE! The Ultimate Solution? Just because you think you are going to make money doesn’t mean you are going to make any money…the older one becomes the more they begin to let go of everything and be the person they have always wanted to be: THE TRUE SELF W/O THE EGO THROWN IN! Easier Said Than Done! PEACE & LAUGHTER ALL THE TIME! iamaveryfunnyartist blogspot com on blogspot/Google! BUY THE BOOK NOW! P.S. Review it…give it a scathing review…however, IF the book makes you laugh let me know you laughed your a** off!!! | Mid | [
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Interleukin-6 and soluble interleukin-2 receptor in juvenile chronic arthritis: correlations with clinical and laboratory parameters. We sought to determine whether levels of interleukin-6 and soluble interleukin-2 receptor were correlated with clinical parameters including functional capacity indices such as Steinbrocker's class and the Juvenile Arthritis Functional Assessment Report (JAFAR) score, with tests for inflammation, and/or with immunological parameters in 24 patients with active polyarticular or pauciarticular juvenile chronic arthritis. Levels of interleukin-6 and soluble interleukin-2 receptor were significantly higher in juvenile chronic arthritis patients than in healthy controls (p < 0.005 and p < 0.00005, respectively). Interleukin-6 levels were correlated with the following parameters: number of painful joints (p < 0.025); Ritchie's index (p < 0.025); visual analog scale pain score (p < 0.025); Steinbrocker's class (p < 0.025); JAFAR score determined by patients (p < 0.05); JAFAR score determined by parents (p < 0.05); erythrocyte sedimentation rate (p < 0.0002); and serum levels of C-reactive protein (p < 0.0003), hemoglobin (p < 0.05), albumin (p < 0.025), and alpha 2-globulins (p < 0.025). Levels of soluble interleukin-2 receptor did not correlate with any of the parameters studied. Levels of interleukin-6 and soluble interleukin-2 receptor were not correlated with each other. Abnormal levels of interleukin-6 or soluble interleukin-2 receptor were not significantly associated with the presence of antinuclear antibodies, IgM-rheumatoid factor, IgA rheumatoid factor or anticardiolipin antibodies. Our findings suggest that interleukin-6 is a useful parameter for assessing juvenile chronic arthritis and that the potential clinical value of elevated levels of soluble interleukin-2 receptor in this disease needs to be further evaluated in longitudinal studies. | High | [
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Noel Quiñones Noel Quiñones (born Noel A. Quiñones Motta; July 20, 1959) is a Puerto Rican screenwriter, film director, producer, entrepreneur and philanthropist who divides his time between filmmaking and advocating for improvements in public education in countries around the world, such as Brazil, Puerto Rico, Chile, Colombia, Peru, Costa Rica, Argentina, Spain, Mexico and the United States of America. He won an Emmy for his work and currently does motivational speaking now that he is in a wheelchair due to a spinal-chord disease. Early life Quiñones was born in Aguadilla, Puerto Rico, the son of Santiago Quiñones Elías, a lawyer and Miriam Motta Ferrer, a homemaker. He attended primary school and secondary school in Puerto Rico and, at the age of 18, he left Puerto Rico to study cinematography and film-making at Columbia College and UCLA in Hollywood, California. He graduated at age 21. Career While still in high school, Quiñones completed his first film, a thirty-minute piece called Seniors, which was shot entirely on 16mm film and featured his classmates. After he produced a film for his high school's talent show, Quiñones's decided to pursue a career as a filmmaker. Upon completion of his education in California, Quiñones returned to his Puerto Rico, and established a production company that produced television commercials for international clients. Profits from his commercial work allowed Quiñones to produce his first feature film, Columbus' Legacy (original title: Raíces Eternas) on the history and evolution of Puerto Rican culture. The film was played in Old San Juan in 2019 during the 500th anniversary of San Juan, Puerto Rico commemoration. In 1985, he produced Columbus' Legacy, which was narrated in its English version by Oscar-winning Puerto Rican actor José Ferrer. In 1986, the film won a Silver Award in the Houston International Film Festival. In 1989, he produced The Bell and San Juan Story, and worked with artists such as writer/director Jacobo Morales, and actresses Cordelia González and Rosanna DeSoto. These films garnered Quiñones fourteen awards in local and international festivals. In 1994, he collaborated with Tom Musca and playwright Mark Kemble to produce Flight of Fancy (2000), which was the winner of Best Film with a Latin theme at the Hollywood International Film Festival and Best Film at The Renaissance City Film Festival in Rhode Island, both in 2001. Quinõnes' film work also includes 17 (original title: Los 17), a documentary about educational transformation in Puerto Rico, which was the winner of Best Short Documentary at the Rincón International Film Festival in Rincón, Puerto Rico in 2012. He also produced 100,000, a documentary about the problem of stray dogs in Puerto Rico. He produced the documentary "One on One" (original title: "Uno a Uno"), which examines the cycle of poverty and crime for students that drop out of school, and presents his mentorship program that works to keep students in school. Speaking career In addition to filmmaking, Quiñones works as a motivational speaker to advocate for quality in public education. In December 2011, he was one of eleven speakers invited to the first TEDx SanJuan symposium in Puerto Rico. He spoke about how public education can be transformed by an integrated program to motivate and prepare students for the academic rigors they must address in order to succeed. Philanthropic activities While touring schools that were screening his film, Flight of Fancy, Quiñones and his wife observed the run-down condition of the classrooms, the dearth of technology, and the lack of dscplinary structure present at these schools. In 2005, after four years of interviewing students, teachers, administrators and parents, he established the philanthropic organization Operation Éxito to improve the quality of Puerto Rico's public education system. Operation Éxito's goal is to use technology and motivational strategies to develop skills and inquisitive attitudes among students towards learning science and mathematics. Since its inception, Operation Éxito has evolved beyond Puerto Rican to other Spanish-speaking countries, as well as the United States of America. Quiñones observed that students who drop out of school prematurely frequently begin a family and financially support themselves with multiple minimum wage jobs or crime. In 2012, he developed the One on One (original title: Uno a Uno) program to increase graduation rates and improve the future quality of life for students who were performing poorly in school. One on One matches certified mentors recruited from successful community and business leaders with at-risk students to improve their academic performance. The program was initiated in a school in Aguadilla, Puerto Rico where graduation rates were as low as 49%, and almost 100% of the participants graduated from high school. In 2017, the US Conference of Mayors presented the city of Aguadilla with its High Achievement Livability award for cities with 100,000 inhabitants or less for the implementation and results of the One On One program. Quiñones's philanthropic efforts are also directed at the Sor Isolina Ferré Center and its dedication to the transformation of communities and society in general through education. He also supports the Miami Project to Cure Paralysis. Filmography Personal life Quiñones has been paraplegic from the age of sixteen due to a hemorrhage of a tumor in his spinal cord. He is married to Soraya Sesto and together the couple has a daughter. Quiñones is a licensed pilot. See also List of Puerto Rican films References External links Category:1959 births Category:Living people Category:People from Aguadilla, Puerto Rico Category:Puerto Rican film directors Category:University of California, Los Angeles alumni | Mid | [
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You know guys my little cheeky going to be TWO in early of this June. So I'm being hectic planning his party menu and getting everything ready for his big day to be a perfection and the other reason is I clicked myself to complete one of my resolution.This are the reason makes me absent from blogging. Although,I spare time today to share a simple yet too delicious spicy prawn biryani. Biryani is always comes first as our favorite one pot comfort dish.Chicken or mutton are mostly I used for briyani.Therefore mutton base briyani is very famous between entire family-s of mine.But sometime we do end up makes with seafood.The taste too different and so scrumptious if you serve with few drops of lemon or lime juice on top it before you indulge yourself along with chilled raita.yummy 4.Then add the prawns,coconut milk,hot water and seasoned with salt,give a quick stir.Then stir the rice in. Place a tight-fitting lid on the pan and bring to a boil, then lower the heat to a minimum and cook the rice for another 5-10mins. 5.Turn off the heat and leave for 10 minutes.Stir well, mixing through the coriander and cashew.Serve warm with relish or raita. Thank You for stumble upon on my blog and Have A Good Day Everyone...... Thursday, 12 May 2011 I’ve been longing to make this Cheesecake Brownie for awhile now but couldn't find a reason to make this lovely gooey brownie while I'm strictly on a mission,Although, my heart always pulling towards it since I saw the soul mesmerising picture of the post at LOVE2COOK.It indeed caught my eyes. At last,I merrily made the brownies for someone's birthday(my little nephew) who is turn 6 this year.My little cousins totally indulged themselves.The small treat brought a distiction on their face made me happy.Thus,their's very encouraging praise gave me more enthusiasm to spoil them.Thank you so much sis for the lovely recipe and A big applaud to you to made my day remarkable. Muaks Earlier I do made a kid's friendly chocolate brownie using some simple ingredients and these one is my second.But Sadly:-(,I had only one piece to taste the outcome.Frankly,I felt overwhelming desire to have another one but I stick to NO NO. Why you waiting for?Go experiment it right now.Put things together give a good stir (splash, splosh) and bake.Indulge yourself. Sunday, 8 May 2011 A Blissful Happy Mother's Day to all mothers in the world.Hope you all have a lovely relaxing day and get pampered and spoiled by your loved one.Have a happy Weekend. Today I'm going to share a salad version of mine.A very creamy potato salad with a hint of mustard, a worthy side dish to the magnificent Parmesan garlic chicken drumsticks.A simple and very filling potato salad were easy to cook, while the mayonnaise and mustard provided the sharp and creamy flavors.One of the salad mostly I prepare every time when we grilled meats or fish. We had this scrumptious combo for our picnic last couple of weeks ago at Greenwich Park where the Greenwich Meridian (0° longitude) and Greenwich Mean Time is situated.Generally the place a loaded with foreigners.Apparently its ours best choice park,where we hang around most of free time in summer time and the last picnic we had were blasted with fun and joy.Seems our cutie pie love the picnic indeed. Well come to the the Parmesan garlic chicken drumsticks.Is new choice of flavor which recently I experimented.Its another simple drumstick using a minimal ingredients garlic,basil ,parmesan cheese and seasoned with salt and pepper bring together to get a succulent and juicy PGC.I used chicken wings on my first batch which is really yummy and fully binded with the flavor.For the second batch I used drumstick but honestly I not really keen on this drumstick,its certainly pale in taste and the flavor not really absorbed I thought. Creamy Mustardy Potato Salad Ingredients: 600g Potato 70g Cooked ham-cut into cubes 200g Cucumber 1 small Red onion-sliced 1stalk Spring onion-chopped thinly 1Boiled egg-cut into small pieces 1/4cup Mayonnaise 1/2tbsp English mustard Salt and Pepper-to taste Method: 1.Peel the skin and cut the potato into big chunk and place them with 1/2 tablespoons of salt in a large pot of water.Bring the water to a boil, then lower the heat and simmer for 10 minutes, or until the potatoes are tender when pierced with a knife. Drain the potatoes in a colander.Keep aside. 2.Meanwhile,Cut the cucumber lengthwise, scoop out the seeds and soaked in salted water for 5 minute.Drain and gently squeeze out the excess water. In a small bowl, whisk together the mayonnaise,English mustard.Keep aside. 3.Place the boiled potatoes in a large bowl.Using the back of a fork, crush the potatoes coarsely (do not mash them, just break them up).Pour enough mayo mix over them to moisten. Add the cucumber, red onion, chopped spring onion, egg, ham and seasoned with salt and pepper. 4.Toss well, cover, and refrigerate for a few hours to allow the flavors to blend. Serve cold or at room temperature. Search This Blog Featured On About Me Welcome to My Cookingdom. This blog is simply a peek at my thoughts of foods I love,how I get around & a taste of the expat life & i humble to sharing my passion on food and you will definitely indulge with tempting flavor. | Low | [
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WASHINGTON ― The Pentagon plans to invest more than $20 billion in munitions in its next budget. But whether the industrial base will be there to support such massive buys in the future is up in the air — at a time when America is expending munitions at increasingly intense rates. The annual Industrial Capabilities report, put out by the Pentagon’s Office of Manufacturing and Industrial Base Policy, has concluded that the industrial base of the munitions sector is particularly strained, something the report blames on the start-and-stop nature of munitions procurement over the last 20 years, as well as the lack of new designs being internally developed. Some suppliers have dropped out entirely, leaving no option for replacing vital materials. Other key suppliers are foreign-owned, with no indigenous capability to produce vital parts and materials ― setting up the risk that a conflict with China could rely on Chinese-made parts. And the military’s desire to tinker with existing designs rather than create band-new weapons has left the industrial base with a lack of design experience, which means “design skills for critical components within the missile sector industrial base are at risk,” the authors write. All this is happening as the U.S. is expending munitions at a rapid rate. For instance, the Special Inspector General for Afghanistan Reconstruction concluded that 1,186 munitions were dropped in that country during the first quarter of 2018 ― the highest number recorded for the first three months of the year since tracking began in 2013; that number is also more than two and a half times the amount dropped in the first quarter of 2017. Mackenzie Eaglen, a defense expert with the American Enterprise Institute, said figures in the report line up with worries from senior military leaders over the last two years. “This report puts a bunch of solid facts and figures, and real companies and impact, behind the anecdotal concerns of leadership,” Eaglen said, who added that the overall facts show “munitions production is then at risk.” × Fear of missing out? Sign up for the Early Bird Brief, the defense industry's most comprehensive news and information, straight to your inbox. Thanks for signing up. By giving us your email, you are opting in to the Early Bird Brief. America’s critical minerals problem has gone from bad to worse Without access to such minerals, our precision-guided missiles will not hit their targets, our aircraft and submarines will sit unfinished in depots, and our war-fighters will be left without the equipment they need to complete their missions. Parts and pieces An overall issue identified by the report is a lack of diversity in the industrial base, as well as a lack of knowledge on how to develop new systems. “The loss of this design and production capability could result in costly delays, unanticipated expense, and a significant impact to many current and future missile programs, damaging the readiness of the Department [of Defense] and negatively impacting a foundational national defense priority by placing the ballistic missile production capability at risk,” according to the report. While there are a pair of new projects underway ― the Long-Range Anti-Ship Missile and the Joint Air to Ground Missile ― neither is truly a new design as much as it is modernization for existing capabilities. Neither program features “significant design work,” the authors note, adding that the DoD “remains concerned that the design engineering capabilities needed for tactical and strategic missile systems may not be readily available in the absence of a long-term demand signal.” As to diversity in the industrial base, well ― there isn’t any, with the authors concluding that Raytheon and Lockheed Martin account for about 97 percent of the DoD’s munitions and missile procurement funding. But while those two firms are doing well, there are concerns about sub-tier suppliers in the realm of “thermal batteries, SRMs [solid rocket motors], fuzes, jet engines, inertial measurement units (IMUs), GPS receivers, seekers, and warheads,” as well as how healthy that base will remain in the future. Four industrial areas stand out as “high risk” areas of concern: Solid rocket motors. A military-only technology, SRMs are basically split between Orbital ATK and AerojetRocketdyne. However, Orbital is set to take on a broader section of this production, essentially leaving the U.S. with only one producer of this vital equipment, which the authors warn “can lead to cost increases due to lack of competition, decreases in internal research and development efforts, and risk of security of supply if a catastrophic accident should occur.” A military-only technology, SRMs are basically split between Orbital ATK and AerojetRocketdyne. However, Orbital is set to take on a broader section of this production, essentially leaving the U.S. with only one producer of this vital equipment, which the authors warn “can lead to cost increases due to lack of competition, decreases in internal research and development efforts, and risk of security of supply if a catastrophic accident should occur.” Thermal batteries. Used in all DoD missiles and guided munitions, there is one (unnamed) manufacturer of these technologies who controls about 80 percent of the market. Should something happen to that company, the DoD’s munitions stock could be endangered. In addition, the near monopoly means there has been a lack of investment in improving the technology. Used in all DoD missiles and guided munitions, there is one (unnamed) manufacturer of these technologies who controls about 80 percent of the market. Should something happen to that company, the DoD’s munitions stock could be endangered. In addition, the near monopoly means there has been a lack of investment in improving the technology. Fuzes. Used on all munitions, there is actually an excess of fuze capacity in the industrial base, due in part to improvements in other areas making the fuze less important. “Excess capacity limits manufacturers from being cost competitive and limits investment in improvements to fuze technologies, including sustaining a viable design engineering cadre,” the authors write. Used on all munitions, there is actually an excess of fuze capacity in the industrial base, due in part to improvements in other areas making the fuze less important. “Excess capacity limits manufacturers from being cost competitive and limits investment in improvements to fuze technologies, including sustaining a viable design engineering cadre,” the authors write. Small turbine engines. There are currently two companies involved in this sector, but one ― Teledyne Turbine Engines ― has announced it will be leaving the business in 2018, leaving only Williams International to supply this capability. Overall, the authors found that of the 121 second-tier suppliers for munition capabilities, 98 percent of them were single/sole source. And of the 73 third-tier suppliers, 98 percent were also single/sole source. America's supply of bombs and missiles may be imperiled in the future thanks to a lack of suppliers and a reliance on Chinese companies to provide key materials. (Paul Weatherman/U.S. Navy) Material readiness? There are also concerns about materials used in the systems. For example, the department is facing rising costs for ammonium perchlorate, used in almost all DoD missile programs. The sole producer, American Pacific, is only operating at 10-15 percent of capacity due to limited demand; as a result, there have been large increases in cost per round of chemical compound, a trend likely to continue into the 2020s. Another example: Dechlorane Plus 25, a component in the insulation of weapons. “There is no domestic supplier for this material; the sole source is Occidental Chemical in Belgium,” the authors write. “Even more concerning is that the pre-cursor to make Dechlorane came from China. The Chinese source can no longer produce that pre-cursor and so there is now no source for Dechlorane in the world.” And the sole producer of dimeryl diisocyanate, a key propellant ingredient used in systems like the AIM-9X and AMRAAM missiles, has informed the Pentagon it will be leaving the business shortly, leaving the DoD with “no qualified source” of the material. The Pentagon is left to scramble to find potential replacements for these materials, which the authors optimistically conclude could be “the beginning of what could serve as a model for mitigating material obsolescence in the future.” But Eaglen thinks the issue of foreign suppliers needs to be dealt with quickly, or risk getting out of hand. “It’s worrisome enough for a capability that is essential in hostilities that policymakers will likely want to start considering special protections and/or subsidies when needed,” she said. “I’m not sure the bell can be un-rung in the case of Chinese suppliers. | Mid | [
0.611510791366906,
31.875,
20.25
] |
Association of increased prostaglandin E2 content in bronchoalveolar lavage fluid and intrathoracic malignancy. Prostaglandin E2 (PGE2), a metabolite of arachidonic acid, plays an important role in immunoregulation. We have previously reported an increased PGE2 content in bronchoalveolar lavage fluid (BALF) in 18 patients who had primary lung cancer as compared with 6 patients who had benign lung diseases and 10 normal smokers. In this article, we report our further observation, including additional 73 patients with primary lung cancer, 11 patients who had carcinoma other than lung cancer with and without lung metastases, and 24 patients with various benign lung diseases. Prostaglandin E2 content of BALF in patients with primary lung cancer and patients with extrathoracic cancer with lung metastases was markedly increased to 283.7 +/- 423.8 and 278.3 +/- 303.4 pg/ml, respectively. In contrast, patients who had extrathoracic cancer without lung metastases and patients with benign lung diseases had PGE2 content in BALF of 22.6 +/- 6.6 and 27.2 +/- 12.4 pg/ml, respectively. Values between the subgroups of patients with lung cancer (primary and metastatic) and patients with benign diseases or extrathoracic cancer without lung metastasis were significantly different (p < .001). Follow up of eight patients who successfully underwent surgical resection of cancer showed decreased levels of PGE2 in all but two patients. Although the exact cause and mechanism of the observed increase of PGE2 in BALF of patients with lung cancer are not clear at this point, current study together with our previous observations clearly indicates that the presence of lung cancer, both primary and metastatic, is associated with an elevated PGE2 content of BALF. The clinical significance of this observation is not known. However, an increased amount of PGE2 in BALF might adversely affect the course of lung cancer, because PGE2 is a down regulator of immune response against infection and neoplasm. Further investigations into the mechanism(s) and the role of PGE2 in BALF are warranted. | High | [
0.723514211886304,
35,
13.375
] |
Multielectrode cochlear implantation in children: the Quebec experience. The Quebec Cochlear Implant Research Program has implanted three children since August 1987. This paper reports the results obtained with these children. All of them improved their auditory abilities with cochlear implantation and training. However, the abilities which spontaneously recovered following implantation, the speed of improvement, and the overall level of performance are different from one child to the other. Our data suggest that the age at onset of hearing loss, and possibly the number of years of deafness, may be related to the differences in performance. | High | [
0.694581280788177,
35.25,
15.5
] |
(CNN) Drivers from South to North are warned to expect icy roads on Monday. Light freezing rain is forecast to cause dangerous, slick conditions over a swath of the Southeast into the afternoon. Atlanta, getting ready for the college football national championship game between Georgia and Alabama and a visit from President Donald Trump, should be rid of the icy rain hours before kickoff at 8:17 p.m. Knoxville seeing the ice now. https://t.co/zceT66boBv — Brian Smith WTVC (@StormTrackBrian) January 8, 2018 Sleet and freezing rain are forecast for late afternoon along the Northeast Corridor and those nasty, icy elements are expected bedevil motorists and inconvenience commuters in New York, New Jersey and other points in the mid-Atlantic and New England. Because much of the East has had to deal with "persistent arctic air," the National Weather Service said, it will be tough to "completely scour its presence out." On Monday morning, winter weather advisories covering 70 million people were in place for more than a dozen states and many more cities. Read More | Mid | [
0.61214953271028,
32.75,
20.75
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Q: I guess, pull-up/down resistors fried. What can i do? Arduino Mega ADK is working well but it is not working circuit in which pull-up/down resistors. It is generating wrong results. I guess, pull-up/down resistors fried. What can i do? A: If you want internal pullup or pulldown resistors on input pins, you can use external ones to do the same job as internal ones if you wish to. Generally, if you use say 100 k Ohms from a pin to V+ or ground then it will act as a pullup or pull down respectively on an input pin, but have much effect on an output pin - which is what you want to happen. However, it is unlikely that 'fried internal resistors is the reason for code not working and, if this is the case, there is probably unknown and unknowable other damage as well. Pull up/down resistors are usually not actually resistors. They are FETs with high Rds_on values that look resistor like when on. Anything that "fries" them has a reasonable prospect of doing other damage as well. | Mid | [
0.591687041564792,
30.25,
20.875
] |
South Florida's skyline is crammed with the telltale signs of a condominium bust. A huge construction boom led to a condo market that peaked two years ago. Since then sales have stalled and prices have been in a freefall while the construction continues -- creating headaches for sellers but an unlikely opportunity for a handful of realtors who call themselves "Condo Vultures." Real estate agent Peter Zalewski established his company early this year and named it for the buzzards that descend...Full Story | Low | [
0.49484536082474206,
30,
30.625
] |
If you start working with the Google maps API, one of the first things you might want to do is to add a marker or custom icon to the map at a specific location. This is easy enough to do and you can have a look at this example on how to do it. But what if you want to add text or a label to one of your markers that always shows up on the map, not only when you hover over the marker? Strangely enough, this isn’t as easy as you would think… Luckily Marc Ridey wrote a very helpful article with example code (for API V3) on how to easily add labels to the markers on your Google map. You might need to customize it a bit to suite your specific needs, but it will surely save you loads of time. Hi Simão! Thanks for your comment. I’m sure Google will continue to develop the APIs for the different map applications and hopefully in the near future we would be able to add labels very easily and with nice customization options too! I’m glad you found the post helpful. :) Man, you just saved me a hundred hours! This works perfectly. Instead of appending a span to the div, I am appending a div to the div so that I can style it with an image of the place I’m marking and 3 pieces of text data about the place. Took me about 5 minutes to adjust your code. Thank you so much!! | High | [
0.705248990578734,
32.75,
13.6875
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Barack Obama @BarackObama Barack Hussein Obama II (Listeni/bəˈrɑːk huːˈseɪn oʊˈbɑːmə/; born August 4, 1961) is the 44th and current President of the United States. He is the first African American to hold the office. Obama served as a U.S. Senator representing the state of Illinois from January 2005 to November 2008, when he resigned following his victory in the 2008 presidential election. Born in Honolulu, Hawaii, Obama is a graduate of Columbia University and Harvard Law School, where he was the president of the Harvard Law Review. He was a community organizer in Chicago before earning his law degree. He worked as a civil rights attorney in Chicago and taught constitutional law at the University of Chicago Law School from 1992 to 2004. He served three terms representing the 13th District in the Illinois Senate from 1997 to 2004. One minute you're in a Beverly Hills mansion ... the next you're in some dude's garage -- at least, that's how it went for President Obama today when he stopped by Marc Maron's house to be on MM's… READ MORE > President Barack Obama is finally weighing in on the international FIFA scandal -- saying it's important for the U.S. to make sure the sport is clean ... because the Americans are good at it… READ MORE > | Mid | [
0.610576923076923,
31.75,
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Generally, in the semiconductor industry the most difficulty and/or problems occur with the formation of external electrical connections and with interconnections to different components on a single substrate. Semiconductor devices are typically fabricated on a planar substrate by sequentially growing or depositing several different layers of material and then patterning or etching one or more of the layers to expose a lower surface. Metal is then deposited on the exposed surfaces for interconnections or external connections. One problem in this process is that the etching requires masking which adds several complicated steps to the process and, consequently, a large amount of labor and cost. Also, the metal contacts require a relatively large amount of real estate and, consequently, many semiconductor devices are limited in size by the ability to provide external connections to them. Accordingly, it would be highly advantageous to provide semiconductor devices and methods of manufacture which do not include additional etching steps for the formation of interconnections and external connections. It is a purpose of the present invention to provide novel ultra-small semiconductor devices and methods of fabrication and connection. It is another purpose of the present invention to provide novel ultra-small semiconductor devices and methods of fabrication and connection in which at least some of the interconnections are formed automatically during the formation of the various layers. It is still another purpose of the present invention to provide novel ultra-small semiconductor devices and methods of fabrication and connection in which external terminals and interconnections are formed without requiring additional masking and etching steps. It is a further purpose of the present invention to provide novel ultra-small semiconductor devices which are smaller than previously possible with standard external terminals. It is still a further purpose of the present invention to provide novel ultra-small semiconductor devices using simplified methods of fabrication and connection. | High | [
0.700265251989389,
33,
14.125
] |
Q: how to find out the current NODE_ENV the express app is running under? I was just wondering if i can find out what is the current value of NODE_ENV (i.e. either development or production) in a express code (so i can't use app.configure('production' function(){})). A: Try process.env.NODE_ENV It should do the trick. A: Within your express script, app.settings.env should house that value. | Mid | [
0.582978723404255,
34.25,
24.5
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Q: Lighttpd caching shell_exec() output? I have a PHP script which runs an external process. The external process outputs a JSON string with data from the system which changes every now and then. When I run the external process I can clearly see that the JSON string is different every time I run it. However, when I call my PHP script using AJAX from a web browser the JSON string is not updated after the first call to the PHP script. The only time the JSON string gets updated is if I refresh the page or run the external process manually while I'm inside the website. Why is this happening? Does LIGHTTPD cache the output? EDIT: Here's my LIGHTTPD config file content: server.modules = ( "mod_access", "mod_cgi", "mod_alias", "mod_compress", "mod_redirect", # "mod_rewrite", ) server.document-root = "/var/www" server.upload-dirs = ( "/var/cache/lighttpd/uploads" ) server.errorlog = "/var/log/lighttpd/error.log" server.pid-file = "/var/run/lighttpd.pid" server.username = "www-data" server.groupname = "www-data" server.port = 80 index-file.names = ( "index.php", "index.html", "index.lighttpd.html" ) url.access-deny = ( "~", ".inc" ) static-file.exclude-extensions = ( ".php", ".pl", ".fcgi" ) compress.cache-dir = "/var/cache/lighttpd/compress/" compress.filetype = ( "application/javascript", "text/css", "text/html", "text/plain" ) # default listening port for IPv6 falls back to the IPv4 port include_shell "/usr/share/lighttpd/use-ipv6.pl " + server.port include_shell "/usr/share/lighttpd/create-mime.assign.pl" include_shell "/usr/share/lighttpd/include-conf-enabled.pl" $HTTP["url"] =~ "/cgi-bin/" { cgi.assign = ( "" => "" ) } cgi.assign = ( ".cgi" => "" ) EDIT According to the following Google Product thread a person called johnjbarton mentions the following: Ok I spoke with a Chrome cache expert. The problem in my case is very likely described on this bug: Bug 30862 - Dynamically inserted subresources aren't revalidated even when the containing document is reloaded https://bugs.webkit.org/show_bug.cgi?id=30862 The force-refresh only forces resource loaded in the outer page. It does not force refresh on XHR loaded resources. Which is pretty much all of the resources in a dojo app. When I look at the console of chrome under the Network section it says that all of the requests that my website is making are of type XHR. Can this be somehow related? EDIT The headers of my request are Accept */* Content-Type application/x-www-form-urlencoded VERY IMPORTANT EDIT I edited my PHP script so that it appends the results of the process it executes in to a log file. It turns out that the output of the process always is the same. However when I run the process manually it constantly changes as expected. It seems to me as if LIGHTTPD is caching the output of the process that it executes. EDIT This is what my PHP script looks like: <?php session_start(); if(!isset($_SESSION['user'])){ header("Location: /"); } else { header('Content-type: application/json'); $output = shell_exec('/home/debian/myProcess/myProcess'); file_put_contents("/var/log/lighttpd/access.log", $output, FILE_APPEND | LOCK_EX); echo $output; } ?> A: Ok, so I found the cause of the problem. The process I am executing which I call myProcess runs a process itself called iwlist. iwlist seems to require to be run as root. Since my PHP script executes ANY process as the LIGHTTPD server user called www-data, the process myProcess will be executed as www-data which in turn tries to execute iwlist as www-data as well, and that is where it all failed. My solution was to run myProcess through a daemon which dumps the output of myProcess to a file which my PHP script can read. This works perfectly. ` | Low | [
0.515662650602409,
26.75,
25.125
] |
Q: Take random ids, then store those random ids into the db so I'm working on a code snippet that essentially takes out 35 random ids from the table List. What I would like to do to find the ids that got randomly generated, store them into a database called Status. The purpose is to avoid duplication the next time I get a new 35 random ids from the List. So I never get the same random id twice. Here's what I've tried, but been unsuccessful to get working. @schedule = current_user.schedules.new if @schedule.save @user = User.find(params[:id]) Resque.enqueue(ScheduleTweets, @user.token) @schedule.update_attribute(:trial, true) flash[:notice] = "success" redirect_to :back else flash[:alert] = "Try again." redirect_to :back end and the worker: def self.perform(user_token) list = List.first(6) @status = list.statuses.create list.each do |list| Status.create(list_id: "#{list}") if list.avatar.present? client.create_update(body: {text: "#{list.text}", profile_ids: profile_ids, media: { 'thumbnail' => 'http://png-1.findicons.com/files/icons/85/kids/128/thumbnail.png', 'photo' => 'http://png-1.findicons.com/files/icons/85/kids/128/thumbnail.png' } }) end end end however the Status.create(list_id: #list) doesn't work. Does anybody have any idea what is going on, and how I can make the list_ids get saved successfully to Status? It's also associated: list has many statuses, and status belongs to list A: The following line of code is wrong: Status.create(list_id: "#{list}") # WRONG In your case the list variable is a List instance. And you're passing its string version to list_id which expects an integer. Do this: Status.create(list_id: list.id) Or this: list.statuses.create I think the following will also work: Status.create(list: list) | Mid | [
0.567198177676537,
31.125,
23.75
] |
.app-page { position: absolute; height: 100%; width: 100%; min-height: 600px; } | Low | [
0.31804281345565705,
13,
27.875
] |
Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes. To quantify adverse events (AEs) associated with the use of metformin (MET), sulphonylureas (SUs) and thiazolidinediones (TZDs) in a usual care setting, and to assess the relationship of AEs to treatment patterns and glycaemic response in patients with type 2 diabetes. An electronic medical record database was used to identify patients with type 2 diabetes age >or=18 years from 1996 to 2005. Patients naïve to oral antidiabetic therapy were followed for 395 days postinitiation of MET, SU or TZD treatment. AEs related to study drugs were evaluated during the follow-up period. Baseline and follow-up A1C levels were compared by drug regimen. Associations between the change in A1C, drug regimen changes and AEs were evaluated. A total of 14,512 patients (mean age 60.8 years, 52.9% female) were identified. During the follow-up period, 12.7% of patients experienced an AE (8.6% MET, 15.9% SU and 19.8% TZD patients). SU and TZD patients were more likely to experience an AE than MET (p < 0.001) patients. AEs did not significantly influence A1C outcomes, although MET and SU patients experiencing an AE were more likely to add-on therapy (odds ratio (OR) = 1.34 and OR = 1.37, respectively; p < 0.05) than those without an AE. MET patients with AEs were more likely to switch therapy (OR = 1.91; p < 0.05) than those without an AE. The occurrence of AEs did not significantly impact glycaemic response to therapy. However, AEs may lead to greater treatment switches for patients receiving MET and add-on therapy for MET-treated and SU-treated patients. | High | [
0.6875,
35.75,
16.25
] |
Q: Power button listener - blackberry 10 So, i'm developing a blackberry 10 application (c++ native) and i need some sort of listener for the power button that will work inside and outside of the application. If i press the power button 2 times while outside, i need it to do something and while inside the app to do something else. For inside the app, i'm planning to use cascade key listener, but have no idea what to use for outside of the app. A: Found out the solution to this problem. Basically, i don't check for the power button press, but i check for when the screen locks/unlocks with onLockStateChanged. | Low | [
0.534606205250596,
28,
24.375
] |
Q: Intellij diagnosing crash problem Sometimes Intellij IDEA crashes for no obvious reason. First, it becomes quite slow, CTRL + N (class search) often takes a bit longer than usual time to respond when you type something into it, jumping between files takes more time. And then it crashes.. What is the usual route to diagnose Intellij crash? I've been monitoring memory on the status bar when it crashed and it had about 100MB (out of 512MB) left at that time. Are there any useful logs that would point in the direction of the problem? [UPDATE] 3 crashes in total. 1 instance: A fatal error has been detected by the Java Runtime Environment: EXCEPTION_ACCESS_VIOLATION (0xc0000005) at pc=0x6d93acab, pid=3120, tid=5588 JRE version: 6.0_24-b07 Java VM: Java HotSpot(TM) Client VM (19.1-b02 mixed mode windows-x86 ) Problematic frame: V [jvm.dll+0x9acab] 2 instances: A fatal error has been detected by the Java Runtime Environment: java.lang.OutOfMemoryError: requested 32756 bytes for ChunkPool::allocate. Out of swap space? Internal Error (allocation.cpp:166), pid=2484, tid=5568 Error: ChunkPool::allocate Memory configuration: -Xss2m -Xms32m -Xmx512m Increased the memory to -Xmx768, hopefully that will delay the out of memory error by a bit. Increasing the memory to -Xmx1024 caused weird address mapping problems after running IDEA for a while (integer overflow?). The machine has 3GB of RAM. A: Intellij wouldnt start up i.e. flashes IntelliJ and crashes. Fix: Set -Xmx to default 512MB in idea.exe.vmoptions file located in folder C:\Program Files (x86)\JetBrains\IntelliJ IDEA Community Edition 14.1.4\bin How I landed on this issue: I was having Xmx set to 2048MB earlier and it crashed hitting GC limit. Then on IntelliJ wouldn't start. A: Please define "crashes". If the window just disappears, it usually means the JVM bug and there will be hs_err_pidXXX.log files in the IDEA working directory (usually IDEA_HOME/bin). In some cases updating JDK to the new version or changing Garbage Collector strategy (via vmoptions file) can workaround such issues. If the IDE stops responding completely, you need to provide thread dumps. If it behaves weird, then you need to check idea.log for exceptions. In some cases it can be caused by OutOfMemory issues. Increasing heap size in idea.vmoptions should help. Check the FAQ for IDEA files locations. If IDEA is becoming very slow on certain operations, you need to provide CPU snapshot. | Mid | [
0.574468085106383,
30.375,
22.5
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Influence of lactose concentration of milk and yogurt on growth rate of rats. Growth rates of rats fed lyophilized diets of yogurt, milk, 100% lactose-hydrolyzed milk, and 100% lactose-hydrolyzed yogurt were compared. No differences were significant in weight gains between the animals fed lactose-hydrolyzed diets over 3 wk. Further more, rats fed the lactose-hydrolyzed diets had significantly larger weight gains during the 1st wk than those fed unhydrolyzed diets. This may have been from the deleterious effect of lactose, which was in concentrations of 43% in milk and 36% in yogurt. However, by the 2nd wk, rats fed yogurt had growth rates similar to those fed lactose-hydrolyzed diets, and by the 3rd wk, no differences of growth rates were significant. Continued consumption of high concentrations of lactose improved digestion of lactose. Yogurt fermentation produced growth benefit as compared to the milk from which it was made by reducing the lactose content and by supplying microbial lactase activity. | Mid | [
0.622222222222222,
31.5,
19.125
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