The compressive strength of single human osteons has been investigated in specially prepared samples using a microtesting machine equipped with a microwave micrometer. The main conclusions which can be drawn from our results are: (1) In agreement with Gebhardt's theories the ultimate compressive strength is greatest for osteons having transversally oriented fiber bundles, lowest for osteons having longitudinally oriented fiber bundles, and intermediate for osteons whose fiber bundles change direction in successive lamellae through an angle of about 90°. (2) The modulus of elasticity is greatest in osteons with transversally oriented fiber bundles. (3) With all three types of osteon the stress‐strain curves for fully calcified osteons are markedly different from those for osteons with low calcium content, the modulus of elasticity being much lower in osteons of the latter type. (4) Age seems to have no measurable influence on the compressive properties of osteons. (5) The comparison of compressive properties in single osteons and in macroscopic bone samples seems to support the view that the osteon is actually the mechanical unit of compact bone. (6) Fracture in osteon samples starts with microscopic fissures induced by shearing. (7) In every case these fissures form an angle of roughly 30°–35° with the axis of the osteon and do not appear to vary with the microscopic osteon structures. (8) Electron microscopy reveals distortion of bone crystals and breaking of collagen fibrils at the edges of the fissures.


Most of the gases detecting metal oxide semiconductors are operated at temperatures above 250oC. It is not energy efficient for MOS gas sensors to operate at such high temperature. To solve this problem, research and investigations are trying to obtain new MOS sensing materials that can operate at ambient temperature. In this study, gas sensing materials consisting of MOS and carbon nanotubes (CNTs) are developed for detecting gases at lower temperature. The hybrid system, MWCNTs/TiO2, demonstrates the possibility of detecting the gases at ambient temperature with high energy efficiency.


In 1969, a series of geophysical tracks was run across the Catoche Tongue, a major re-entrant into the Campeche Slope, Gulf of Mexico. Seismic reflection profiles within the tongue reveal no significant structural differences between the scarp bordering this feature and the main Campeche Scarp. Magnetic data, however, show a 200-gamma anomaly associated with the Campeche Scarp, but the scarp within the tongue has little or no anomaly. A knoll at the mouth of the tongue shows a 250-gamma anomaly. This knoll may be a remnant of the scarp base upon which the bordering reef grew. The nontectonic theory of origin proposed for the Catoche Tongue is supported by these new geophysical data.


Background: Breast cancer (BC) among young women is an emerging public health issue in Mexico, as the proportion of incident cases and deaths has been reported to be greater in women aged Methods: This study included all consecutive patients with BC diagnosed at the National Cancer Institute in Mexico in the year 2007. A panel of ER, PR, and HER2 was used as a means of classifying BC into three molecular subtypes: (a) Hormone-receptor (HR) positive and HER2-negative, (b) Triple-negative, and (c) HER2-positive. The Chi-square test was used to compare the distribution of baseline characteristics among groups according to age (≤40 years vs. >40 years). Cox proportional hazard analysis was applied to assess the association of clinical and pathological factors with recurrence free survival with follow-up through 2013. Results: Of the 696 analyzed patients, 134 (19.3%) were ≤40 years. For the whole group, locally advanced BC accounted for the majority of the cases (61%), and there was no difference regarding clinical stage of presentation between age subgroups. The BC subtype distribution differed among age subgroups (HR-pos/HER2-neg: 42% vs. 52%, triple-negative: 30% vs. 21%, HER2-pos: 24% vs. 23%, for young vs. non-young respectively). After a median follow-up of 74.6 months, 48% of young patients experienced a recurrence compared to 39% of women >40 years. After subtype and clinical stage stratification, young age remained a significant independent predictor of recurrence in patients with HR-pos/HER2-neg tumors (hazard ratio 1.71; 95% CI:1.09-2.69; P = 0.019), but was not found to be a predictor of recurrence for patients with HER2-pos and triple negative subtypes. Conclusions: The results of our present study suggest that the poor survival associated with young age is not only driven by a high proportion of triple-negative BC, but also by poor prognosis in the most prevalent HR-pos/HER2-neg subgroups. Possible explanations for this finding are a greater proportion of Luminal B BC subtype and/or tamoxifen resistance in the young age group. Further characterization of HR-pos BC should be pursued and aggressive therapeutic strategies must be considered for treatment of young women with high-risk features. It is critical to note the extremely high prevalence of BC among young women in our Institution, which comprised 19% of the total population. To address this unmet, growing burden, we adopt the model of a specialized program for the care of young women with BC, the first in Latin America, at the National Cancer Institute in Mexico. The goals of our program include optimizing complex clinical care and supporting needs for young women and their families; promoting medical, biomedical, and social research; and educating women and health professionals to promote early cancer detection and improved multidisciplinary management. Citation Format: Cynthia Villarreal-Garza, Nancy Reynoso-Noveron, Claudia Arce-Salinas, Fernando Lara-Medina, Enrique Bargallo, Leticia Mendoza-Galindo, Federico Lasa, Maria Teresa Ramirez, Alejandro Mohar. High triple-negative breast cancer prevalence and poor outcome of hormone receptor positive breast cancer among young Mexican women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-55.


Recommender systems have been playing an important role in providing personalized information to users. However, there is always a trade-off between accuracy and novelty in recommender systems. Usually, many users are suffering from redundant or inaccurate recommendation results. To this end, in this article, we put efforts into exploring the hidden knowledge of observed ratings to alleviate this recommendation dilemma. Specifically, we utilize some basic concepts to define a concept, Serendipity, which is characterized by high-satisfaction and low-initial-interest. Based on this concept, we propose a two-phase recommendation problem which aims to strike a balance between accuracy and novelty achieved by serendipity prediction and personalized recommendation. Along this line, a Neural Serendipity Recommendation (NSR) method is first developed by combining Muti-Layer Percetron and Matrix Factorization for serendipity prediction. Then, a weighted candidate filtering method is designed for personalized recommendation. Finally, extensive experiments on real-world data demonstrate that NSR can achieve a superior serendipity by a 12% improvement in average while maintaining stable accuracy compared with state-of-the-art methods.


Plantar plate tears are a common cause of forefoot pain and digital deformity. Repair of the plantar plate has been described from both a dorsal and plantar approach, each with its own benefits and drawbacks. Many of the approaches use costly devices. Our innovative repair method uses low-cost materials available in most operating room settings. We undertook a retrospective case series study to evaluate outcomes in patients who had undergone plantar plate repair with our method of repair. A review was performed to identify patients with plantar plate disruptions treated with this approach by a single surgeon. Clinical position and patient satisfaction of the involved joints were evaluated. Six patients (9 joints) underwent plantar plate repair using this innovative method and were evaluated at a median follow-up time of 19 (range 19 to 39) months. The mean visual analog scale pain score at final follow up was 0.8 ± 2.0. The median sagittal plane position of the toe was 2 mm (range 0 to 6) from the plantar skin of the digit to the ground. Five of the 6 patients (83%) stated that they would have the procedure again. We were able to obtain satisfactory outcomes with good alignment by repairing the plantar plate with this innovative method. Our data suggest that the described method of plantar plate repair can be used as an effective way to treat metatarsal phalangeal joint instability.


Significant quantities of petroleum occur in stratigraphic traps of Devonian, Mississippian, and Pennsylvanian ages in the Paradox basin. Devonian reservoirs are isolated marine sandstone bodies, but the Mississippian and Pennsylvanian traps are biohermal carbonates. Exploration has proven the reservoirs to be elusive and relatively unpredictable, but new realization that these subtle traps are localized on paleostructures has simplified exploration and led to several recent discoveries. The tectonic framework of the Paradox basin was set by the end of the Precambrian, but rejuvenation through the Paleozoic caused repeated vertical movements along basement fractures, sufficient to alter sedimentary facies during Cambrian, Devonian, and Mississippian times. Subsurface data indicate that both major and minor structures at the surface today existed in Middle Pennsylvanian time, and grew throughout Permian time. These elements served to localize Paleozoic reservoir facies by creating shoaling conditions on the paleoseafloor that produced Devonian offshore sandbars, Mississippian crinoid banks, and Middle Pennsylvanian algal bioherms. Erosion and salt movement affected much of the potential for continuous reservoir facies, and today's reservoirs are considered to be randomly distributed stratigraphic traps. However, there is ample evidence to indicate that the sedimentary growth of bioherms was localized over gentle, basement-controlled paleostructures. Whereas the reservoirs are too thin for modern seismic detection, isopach thins of underlying evaporites are evident, indicating paleostructure and the development of algal mounds along the crests and flanks of positive structures. Thus, the mapping of paleostructure, not Laramide structure, is the key to further exploration in this basin.


Large heat-input welding is increasingly employed because of its high productivity. For this welding, titanium and boron (Ti-B) bearing welding materials are suitable in acquiring high toughness at low temperatures. However, their properties at high temperatures have not been known. Preferable ductility at high temperatures is required when they are applied to the welding of fire-resistant steels. The present study examines the mechanical properties of Ti-B bearing welding materials for fire-resistant steels in large heat-input welding. Submerged arc welding with two electrodes in tandem was conducted with the heat-input of 13 kJ/mm. The mechanical and metallurgical investigation were v-notch Charpy tests, weld metal tensile tests, chemical analyses, and metallographic observation on ruptured surfaces. It was found that the addition of titanium and/or boron lowers the high temperature elongation. This reduction was caused by grain boundary fracture at the prior-austenite grain boundaries of the weld metal with titanium and boron. However, the high temperature properties were recovered in the weld metal with titanium as low as 30 ppm and nil boron, and this weld metal fractured in an intragranular mode with enough toughness.


A simple household level natural water purification system to purify water to meat small family requirement. It disused with
six important components including Storage, Sedimentation, Biological treatment, and Filtering, Disinfection and Drinking
water storage. During the treatment process Electrical conductivity and Total Dissolved Solids values is not changed but pH
is slightly increased in the bio treatment compartment due to excretion of ammonia form by the fish. A Significant change
of Coli form bacterial count between UV treatment together with sand and Charcoal filter with comparing drinking water
tank It is 90.95% reduction comparing with raw water E coli count is completely removed from this treatment process.


The electrical properties of copper tracks printed by laser-induced-forward-transfer (LIFT) are typically inferior to the bulk values. Several limiting factors have been indicated such as oxidation, droplet boundaries and grain boundaries. However, the relative contribution of each of these factors has not been determined. To improve the electrical properties of LIFT printed structures, an analysis of various factors is essential. Here, we concentrate on the effect of post-printing thermal treatment on LIFT printed copper structures. A reduction in electrical resistivity by a factor of ~3 is obtained resulting in a value lower than 3 times the bulk copper value (1.68 µΩ · cm). Real time resistance measurements indicate that an efficient thermal annealing can be achieved at 200 °C–300 °C within a couple of minutes. The morphological changes associated with such thermal treatment were analyzed using HR-SEM and XRD and highlight the role of stress relief, grain growth and formation of new grains primarily at the inter-droplet interfaces.


In this revision of the 25 French Protonemura, two new taxa are described : P. zhiltzovae sp. n. and P. ausonia padana ssp. n. Moreover, P. spinulosa (Navas 1921) is restored to the species level. Affinities, etymology, ecology and distribution are commented on for each species. Identification keys and drawings are given for males and females. Finally, Protonemura distributions within the main French mountainous massifs are discussed.


Parenting can impact young people's justice system involvement but there is a scarcity of research that examines how parenting practices, specifically mothering, are influenced by labelling processes. Accordingly, this article considers how the labelling of young people from forced migration backgrounds as criminals impacted mothering and maternal efficacy during a 'law and order crisis' in Melbourne, Australia. Drawing on interviews and focus groups with mothers and young people of South Sudanese heritage, we illustrate how this hostile social climate generated secondary stigma, and amplified anxieties and concerns about inclusivity and belonging. The research advances our theoretical understanding of parental control and parental efficacy in the post-settlement context by bringing the gendered experiences of mothers as providers of supervision and support into focus. It suggests labelling may undermine maternal efficacy and exacerbate intercultural and intergenerational tensions, but that community involvement may support parents and mitigate the risk of deviance amplification.


Consumption is an important macroeconomic aggregate, being about 70% of GNP. Finding sub-optimal behavior in consumption decisions casts a serious doubt on whether optimizing behavior is applicable on an economy-wide scale, which, in turn, challenge whether it is applicable at all. This paper has several contributions to the literature on consumption optimality. First, we provide a new result on the basic rule-of-thumb regression, showing that it is observational equivalent to the one obtained in a well known optimizing real-business-cycle model. Second, for rule-of-thumb tests based on the Asset-Pricing Equation, we show that the omission of the higher-order term in the log-linear approximation yields inconsistent estimates when lagged observables are used as instruments. However, these are exactly the instruments that have been traditionally used in this literature. Third, we show that nonlinear estimation of a system of N Asset-Pricing Equations can be done efficiently even if the number of asset returns (N) is high vis-a-vis the number of time-series observations (T). We argue that efficiency can be restored by aggregating returns into a single measure that fully captures intertemporal substitution. Indeed, we show that there is no reason why return aggregation cannot be performed in the nonlinear setting of the Pricing Equation, since the latter is a linear function of individual returns. This forms the basis of a new test of rule-of-thumb behavior, which can be viewed as testing for the importance of rule-of-thumb consumers when the optimizing agent holds an equally-weighted portfolio or a weighted portfolio of traded assets. Using our setup, we find no signs of either rule-of-thumb behavior for U.S. consumers or of habit-formation in consumption decisions in econometric tests. Indeed, we show that the simple representative agent model with a CRRA utility is able to explain the time series data on consumption and aggregate returns. There, the intertemporal discount factor is significant and ranges from 0.956 to 0.969 while the relative risk-aversion coefficient is precisely estimated ranging from 0.829 to 1.126. There is no evidence of rejection in over-identifying-restriction tests.


I read with interest the letter-to-the-editor from Juliette Madrigal-Dersch, M.D., in the October AAP News . I feel compelled to confront her opinion, mistakenly represented as fact. As many of our politicians do, she demonizes our youth as being responsible for the majority of crime when her references, as well as many others, do not support this view. The proliferation of firearms in the U.S. is both a national disgrace and public health emergency. "The latest hysterical outcry against guns," as Dr. Madrigal-Dersch puts it, is well-founded based upon the nearly 35,000 Americans killed yearly by firearm violence. An additional 20,000 persons are paralyzed by bullets every year. Most pediatricians would agree that addressing the issue of gun violence — and the nearly 5,000 children and adolescents killed every year — is not "outside the pale of pediatric practice."


U.S. courts frequently analyze new technology under copyright law. Over the years, the courts have applied copyright law to photographic cameras, computer programs, digital video recorders, and much more. However, a recent breakthrough in the neuroscience community may force judges to apply copyright standards in an unorthodox fashion. A group of researchers at UC Berkeley devised a process that reconstructs video sequences from the human brain, essentially creating a movie from the person's mind. As this neurotechnology develops, it is uncertain how judges will apply copyright law to content taken directly from the brain. Nevertheless, this Article argues that such content meets the originality standard under U.S. copyright law. Specifically, videos taken from the brain are original to the author based on the author's unique visual experiences and unique mental processes. TABLE OF CONTENTS


The optical Bloch equations, which give the time evolution of the elements of the density matrix of an atomic system subject to radiation, are generalized so that they can be applied when transitions between pairs of states can proceed by more than one stimulated route. The case considered is that for which the time scale of interest in the problem is long compared with that set by the differences in detuning of the radiation fields stimulating via the different routes. It is shown that the Bloch equations then reduce to the standard form of linear differential equations with constant coefficients. The theory is applied to a two-state system driven by two lasers with different intensities and frequencies and to a three-state Λ-system with one laser driving one transition and two driving the second. It is also shown that the theory reproduces well the observed response of a cold 40Ca+ ion when subject to a single laser frequency driving the 4S1/2–4P1/2 transition and a laser with two strong sidebands driving 3D3/2–4P1/2.


Selective angiocardiography with the exposure of multiple films in rapid sequence in two planes offers many advantages over simple venous angiocardiography. Not only by itself is it a more accurate technique, but, since it depends completely upon the placement of a catheter, the combination of this procedure and cardiac catheterization complement each other and can be performed as one study. In this way, either of the two component parts of the study can be eliminated, if necessary, or augmented and varied in accordance with the particular needs of the particular patient; for example, in a patient suspected of having a valvular pulmonic stenosis, if the withdrawal curve from pulmonary artery to right ventricle is adequate on cardiac catheterization, the angiocardiogram may be eliminated. If, on the other hand, it is impossible to enter the pulmonary artery with the catheter, a selective angiocardiogram will show the thickened valve and make the


The aim of this article is to clearly show linear and non-linear earthquake behaviour of a concrete-faced rockfill (CFR) dam. For this purpose, a typical CFR dam model is considered with its reservoir water. Reservoir water is modelled by using fluid finite elements based on the Lagrangian approach. Free-field surface motions recorded during earthquakes are deconvolved to the base of the foundation from the soil layers for earthquake analysis. Geometrically and materially non-linear behaviours of the dam are considered in the finite element analysis. The Drucker–Prager model is used for concrete slab, and the multi-linear kinematic hardening model is used for rockfill and foundation rock in the materially non-linear analysis. Non-linear behaviour of the rockfill is obtained by the uniaxial stress–strain relation. Stress–strain curve of the rockfill is obtained using the shear modulus–shear strain relation produced for the gravels. Various joints in the CFR dam are modelled considering welded and friction contacts. In this study, one-dimensional surface-to-surface contact–target element pair based on the Coulomb's friction law provides friction. According to this study, maximum displacements appear when the friction is considered in the joints. In addition, hydrodynamic pressure increases the horizontal displacements of the dam. The horizontal displacements also increase by the effect of the non-linear behaviour of the rockfill and concrete slab.


The aim of this thesis is to study how social remittance have impacted gender roles in household structures in Kosovo. By studying the ideas, norms, practices and social capitals sent from the migrant families to the residing families in the country of origin, I will examine if this has led to a change in Kosovar household structure.
By conducting a field study, both surveys and interviews were carried out within the Kosovo Albanian households. The main focus of the analysis will be shed on the 33 interviews conducted that were carried out in seven different locations around Kosovo. This gives vital information regarding Kosovars perception of how the household structure has changed.
The theoretical framework of the thesis consists of a nexus of theories with Peggy Levitt's theory on Social remittance, Amartya Sen's capabilities approach and New Economic of Labour migration theory. Together they create an understanding of the transmitting of ideas, how these ideas contribute to the capabilities of humans and shows how the migration pattern is connected to family based decisions.
The thesis is concluded by pointing out the interviewees perception of an on-going change in gender roles in Kosovar household structures. The interviewees argue that the change is occurring due to three factors – a raising awareness among the population through globalisation, improved illiteracy and better access to education and finally, the impact of the ideas from the diaspora. In the final part of the analysis, we look at how social remittance can act as a catalyst for female empowerment in household structures.


Background: In 2015, commercial pediatric digoxin injection 0.05 mg/mL was discontinued, leaving only one adult concentration (0.25 mg/mL) for injection on the Canadian market. No published studies have documented the chemical stability over a long period of time of a diluted solution of digoxin for injection. Objective: The aim of this study was to assess the chemical stability of 2 digoxin injection formulations 0.05 mg/mL diluted in 2 vehicles stored at 5°C or a 25°C. Methods: The compounded solution of digoxin 0.05 mg/mL for injection was prepared with digoxin 0.25 mg/mL after dilution in 2 different vehicles, normal saline, and a compounding of the commercial vehicle. Half of the compounding products were stored in 2 mL transparent glass vials at 25°C and the other half at 5°C. Chemical stability was evaluated by HPLC–UV analysis on days 0, 14, 30, 60, 90, 120, 150, 180 for each temperature conditions. In addition, samples were tested for organoleptic change, presence of particular matter as well as sterility. Results: For all tested preparations, the concentration of digoxin remained above 90.0% of the initial concentration throughout the 180-day study. Furthermore, no organoleptic change was observed; particulate matter assessment was in acceptable range; and sterility specifications were met. Conclusions: Digoxin 0.05 mg/mL obtained with a dilution of digoxin 0.25 mg/mL by normal saline or a copy of the commercial vehicle remained stable for at least 180 days at 5°C and 25°C.


Background: Plinabulin is a vascular disrupting agent (VDA) that binds ‐ tubulin, destabilizing tumor vascular endothelial cytoskeletal architecture and leading to selective collapse of established tumor vasculature. With a structure differing from other ‐tubulin binding VDAs, preclinical studies suggested improvements in toxicology and efficacy leading to clinical assessment of plinabulin. VDAs have been of particular interest given indications of significant activity in NSCLC, as well as potential differentiation from other agents in terms of utility in certain patient subsets such as those with squamous cell carcinoma (SCC) or at risk for bleeding events. Plinabulin was seen to act synergistically with docetaxel in murine models of NSCLC, resulting in the initiation of this clinical trial (the ADVANCE study). Methods: Patients with advanced NSCLC having received prior chemotherapy were enrolled (patients with other malignancies could be enrolled during the Phase 1 portion). Patients were permitted to have been previously treated with bevacizumab, as well as VEGFR or EGFR targeted agents. Docetaxel (75 mg/m2) was given on Day 1 and plinabulin on Days 1 & 8 in 21‐day cycles. During Phase 1, the dose of plinabulin was escalated from the single agent biologic effect dose (BED) of 13.5 mg/m2 to determine a Recommended Phase 2 Dose (RP2D) in combination with docetaxel. During Phase 2, 154 patients are randomized to receive docetaxel with or without plinabulin at the RP2D, with overall survival compared as the primary outcome. Results: 13 patients were enrolled into the Phase 1 portion, of which 10 had NSCLC. The dose of plinabulin was escalated to 30 mg/m2, thus 30 mg/m2 of plinabulin with 75 mg/m2 docetaxel was selected as the RP2D. Toxicites were as expected with either agent alone. Nausea, vomiting, fatigue, fever, tumor pain, and diarrhea were most frequently seen, with one DLT of nausea, vomiting, dehydration and neutropenia observed at 30 mg/m2. Changes in expected pharmacokinetics of the 2 drugs in combination were not seen, and the best response in patients with evaluable NSCLC was higher with the combination than expected with docetaxel alone, with 6/8 having reductions in tumor measurements and 2/8 reaching partial response (>30% reduction). Based on these outcomes the Phase 2 portion of the study was initiated. Enrollment is half complete, with 77 patients having been enrolled. Patients with all histologies of NSCLC, including SCC are being enrolled. Interim data from these patients will be analyzed in October 2009 and presented. Conclusions: In this Phase 1/2 evaluation of plinabulin in combination with docetaxel, during the Phase 1 portion PK and safety data did not demonstrate an unexpected toxicities or an adverse drug‐drug interaction, and activity was encouraging relative to the 5–10% response rate reported with docetaxel alone in this population. Efficacy and safety are now being compared in the Phase 2 portion with a 1:1 randomization into 2 arms [docetaxel (75 mg/m2) +/− plinabulin (30 mg/m2)]. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C30.


Mice severely deficient in coagulation Factor (F)VII that survive to adulthood have been developed, thus allowing the study of spontaneous bleeding and inflammatory phenotypes under conditions of a deficiency of extrinsic coagulation, especially in organs e.g., the heart, that continually undergo normal mechanical challenge. Mice genetically modified to produce very low levels (∼1% of wild-type) of coagulation FVII (FVIItTA/tTA) spontaneously developed heart abnormalities that were revealed by echocardiography. There were no significant differences between groups at baseline for the hemodynamic and respiratory parameters: temperature and heart rate (HR). The end-systolic functions of FVIItTA/tTA mice heart were comparable to wild-type (WT) controls. However, there were significant changes in the end-diastolic parameters of FVIItTA/tTA hearts. The diameter at end-diastole in FVIItTA/tTA mice was smaller compared to WT mice, which was due to the stiffness of the interventricular wall. When viewed from the parasternal short-axis, these mice had evidence of hypokinesis, indicating alteration of the elastic properties of the left ventricular (LV) wall. Correspondingly, the stroke volume, ejection fraction, fractional shortening, and cardiac output were lower in FVIItTA/tTA mice, compared to WT mice. Mitral valve inflow was compromised in FVIItTA/tTA mice, as demonstrated by the reduced early/late (E/A) filling ratio. We found that the spontaneous impaired cardiac function in FVIItTA/tTA mice was associated with an increased ratio of heart weight to body weight. Decreases in ventricular size, accompanied by reductions in systolic and diastolic functions, suggest a restrictive cardiomyopathy, consistent with an infiltrative myopathic process. Microscopic analysis of mouse hearts showed severe patchy fibrosis in FVIItTA/tTA mice. Hemosiderin deposition in hearts of these mice, along with large increases in inflammatory cells, ultimately resulting in widespread collagen deposition, were found. Significant increases in mRNA levels of TGF-beta, TNF-alpha, and a variety of matrix metalloproteinases, beginning at early ages in FVIItTA/tTA mice, supported the fibrotic pathology. The results of this study demonstrated that hemorrhagic and inflammatory responses to a severe FVII deficiency resulted in the development of cardiac fibrosis, manifest echocardiographically as a restrictive cardiomyopathy, with significantly compromised ventricular diastolic and systolic functions. These data also suggest that a FVII deficiency differentially regulates the expression level of inflammation and extracellular matrix proteins, which result in compromised cardiac function.


In this letter, we present a novel approach for spectral-spatial classification in hyperspectral imagery. To this end, after applying principal component analysis (PCA) for dimensionality reduction, we extract the spectral-spatial information by first reorganizing the local image patch with the first d principal components(PCs) into a vector representation, followed by a sorting scheme to make it invariant to local image rotation.. Since no additional operation except sorting the pixels is required, this step is performed efficiently. Afterwards, the resulting feature descriptors are embedded into a linear support vector machine (SVM) for classification. To evaluate the proposed method, experiments were preformed on two hyperspectral images with high spatial resolution. The experimental results confirmed that the proposed method outperforms the existing algorithms on classification accuracy.


Industrial businesses face increased pressure to drive operational excellence, and that includes keeping people safe and managing costs. Legal compliance is a requirement, and budget constraints are a reality. This paper examines how connected technology can help streamline safety processes and improve worksite efficiency. We discuss how data and real-time analytics from digitally connected devices using the Industrial Internet of Things (IIOT) can improve organizational productivity, compliance and safety performance including, most crucially, response time to life-threatening incidents.
 On the ground studies with clients show an incident is resolved in the shortest period of time when using connected technology. Using traditional methods, we found an incident response can take up to 3 and a half hours which, when dealing with toxic gas exposure for example, only leads to the recovery of a body. With connected technology, the worker can be rescued in less than five minutes and their life saved. Connected technology also supports organizational environmental, social and governance (ESG) efforts by protecting people and communities with capabilities that allow for plume dispersion modeling that prevent downstream impact and location technology to easily find and retrieve lost devices.
 Overall, our research determined that a more digital environment means enhanced competitiveness, compliance and performance by delivering:
 Higher quality and faster decisions Increased transparency, collaboration and efficiency Better outcomes, including driving to net zero and saving lives.


Fluoride in spray pyrolysis precursor solutions for silicon-doped zinc oxide (SiZO) transparent conductor thin films significantly improves their electrical conductivity by enhancing silicon doping efficiency and not, as previously assumed, by fluoride doping. Containing only earth-abundant elements, SiZO thus prepared rivals the best solution-processed indium-doped ZnO in performance.


: The report contains the results of faunistic study of parasitic cestodes occurring in fishes in the S. Dvina, Mezen' and Pechora river basins. 26 cestode species have been recorded in the region explored. The cestode fauna in the first basin is represented by 19 species, in the second basin--14, in the third basin--18.


Five dimensional Einstein gravity vacuum solutions in general fall into two classes of black rings with horizon topology S2 × S1, and black holes with horizon topology S3. These solutions are specified by their mass and two spins. There are "overlapping" regions of this parameter space where one has extremal rings and holes of the same spins. We show that for such regions the hole has generically a larger entropy than the ring, and likewise, the central charge of the proposed chiral 2d CFT dual to the hole is larger than that of the ring. For special places of this overlapping region where one of the spins tends to zero, the entropies of the extremal ring and hole also tend to zero and essentially become equal. In this case we are dealing with Extremal Vanishing Horizon (EVH) black holes or rings. The near horizon geometry of the near-EVH hole and rings both contain locally AdS3 throats, providing a basis for the EVH/CFT proposal, a 2d CFT description of the low energy excitations of EVH hole or ring. We argue how the near-EVH hole and near-EVH ring can be distinguished from this dual 2d CFT viewpoint: The hole is a thermal state with zero temperature in the left sector and finite temperature in the right, while the ring is a generic state in the ground state (of the CFT on the plane) in the left sector and a thermal state in the right. The latter is part of the Hilbert space of the 2d CFT obtained in the Discrete Light Cone Quantization (DLCQ). firstname.lastname@example.com email@example.com firstname.lastname@example.com


The election of Barak Hussein Obama as the 44th president of the United States suggests that conventional notions of blackness are being disaggregated. The old hypo-descent rule has lost its power to define who is black and who is not. Today conventional racial designations may be less important than factors like skin tone, especially when combined with traditional tropes of high status whiteness like elite education, stable family structure, high socio-economic status and "command of spoken English." Further, empirical research suggests that most skin tone bias – colorism – is implicit or unconscious and impacts not only darker-skinned black Americans, but all individuals with darker skin tones, even whites (although to different degrees). Since twentieth century anti-discrimination laws presume that discrimination is explicit and intentional, these laws are ill-equipped to determine when implicitly biased decisions based on skin tone are actionable. This chapter explores whether skin tone, rather than racial classification or racial self- identification, will, in the near future, determine who gets better access to quality education, jobs and real power in America. In other words, whether color, more than old racial classification schemes, matter in the "post-racial" Obama era and, if so, the legal implications of this development.


Speaking skill pedagogy has always remained as a huge enigma for English as a Second Language (ESL) educators. Despite the challenge, the need to master the skills prevail in academia. The undergraduates especially those from the technical division seem to grapple with the ability to perform well in their studies and market products upon employment due to the inability to communicate well in English. Nowadays, there are numerous platforms available for ESL learners to improve their speaking proficiency. Thus, this paper intended to study the effectiveness of using Skype activities via online approach to help students enhance their confidence in speaking in English. Reflective journals were collected from 100 undergraduates who enrolled in an English course in a public university. Besides, 10 undergraduates were randomly selected to participate in a semi-structured interview. Thematic analysis was conducted using Transana software where four main themes emerged: account possession; familiarity; challenges; and features. It was found that many participants were aware of Skype but did not have the account prior to the study. Majority of the participants admitted that Skype activities helped them to converse better which enhanced their motivation to speak in English more confidently and fluently.


We examine the set of formula-to-formula valid inferences of Classical Logic, where the premise and the conclusion share at least a propositional variable in common. We review the fact, already proved in the literature, that such a system is identical to the first-degree entailment fragment of R. Epstein's Relatedness Logic, and that it is a non-transitive logic of the sort investigated by S. Frankowski and others. Furthermore, we provide a semantics and a calculus for this logic. The semantics is defined in terms of a p-matrix built on top of a 5-valued extension of the 3-element weak Kleene algebra, whereas the calculus is defined in terms of a Gentzen-style sequent system where the left and right negation rules are subject to linguistic constraints.


EXECUTIVE SUMMARY. The work of the 2021-2022 AACP Research and Graduate Affairs Committee (RGAC) focused on barriers to graduate education and research-related careers in pharmacy education. AACP President Stuart Haines charged the RGAC with identifying the critical barriers that hinder current PharmD students/recent graduates as well as under-represented groups (e.g., Black and Latino) from pursuing advanced degrees and research-related career paths in the pharmaceutical, social & behavioral, and clinical sciences and recommending changes that might address these barriers — this may include recommendations to change the fundamental structure of graduate education. The committee began its work with a literature review to survey current perspectives on these barriers and assess the supporting evidence for effective solutions and programs, including their relevance to pharmacy education. Based on the review, the committee was able to identify numerous obstacles to entry into and progression through research training, for both underrepresented learners and student pharmacists. Obstacles are individual, e.g., lack of exposure to and self-efficacy in research, financial constraints, structural, e.g., lengthy training time, programmatic rigidity, and institutional, e.g., implicit and explicit bias. The committee found evidence of effective approaches and programs to address these barriers that could be applied in pharmacy schools. These approaches include improvements to existing practices in recruitment, admissions and hiring practices as well as creation of new programs and structural changes to existing programs to increase accessibility to learners. The committee also recognized a need for more research and development of additional approaches to address these barriers. The committee makes a series of recommendations that AACP develop resource guides and programs to address key issues in the recruitment and retention of underrepresented students and student pharmacists into graduate education and research careers, including as faculty. The committee also proposes new AACP policies to support innovative graduate programs and early, longitudinal engagement of learners from elementary school onward to increase access to graduate education and to support environments and cultures of commitment to accessibility, diversity, equity, inclusiveness, antiracism in pharmacy education.


The principal applications of the current locus of single-phase induction motors are the predetermination of the performance of a projected motor on the basis of its constants, and the determination of the performance and constants of an existing motor on the basis of a few simple tests. The first question is particularly attractive to a mathematically trained mind, because, with constants considered as known, it is simply a problem of mathematics; a great amount of work has been done to find and perfect its solution. The second problem is, perhaps, more difficult than the first. Its thorough treatment requires not only the knowledge of the solution of the first problem, but also the ability to make use of more or less complicated combinations of constants given by tests instead of the constants themselves; moreover, the exact solution usually cannot be obtained, and one is obliged to make certain incorrect assumptions, drawing upon the practical experience to to set proper limits to these inaccuracies; for this reason, perhaps, the second problem has always been less popular with investigators than the first, and the available results still leave room for improvement, especially in connection with the ''tilted'' diagram. In what follows this problem is treated by a method which is believed to combine the accuracy with comparative simplicity of the final results-the latter, at least, to the extent which can reasonably be expected when dealing with an apparatus of such inherent complexity as the single-phase induction motor.


BACKGROUND
The prosthetic screw fixes the prostheses to the implants. Upon osteointegration, the untightening of the prosthetic screw is the most common problem in oral rehabilitation with implants.

OBJECTIVE
To study the deformation of the implant retaining hexagonal screw head.

METHODS
This investigation used two methods for evaluating the screw head's area of deformation (mm2 ): a stereoscopic microscopy and micro computed tomography (microCT). For stereoscopic microscopy, 16 titanium alloy (T) and 16 titanium gold-plated alloy (G) screws of the Zimmer Biomet™ brand were used, divided into eight groups: group 0 (control group), groups T1 and G1 (screws tightened 10 times to 20 Ncm), the groups T2 and G2 (screws tightened 20 times to 20 Ncm) and the groups T3 and G3 (screws tightened 10 times to 30 Ncm). In the study with microCT, one screw was randomly chosen from each of the groups described above to perform the scanning by microCT.

RESULTS
When comparing the type of screw material using stereoscopic microscopy, no statistically significant differences were found (p > 0.05). Contrarily, different number of successive grips and different torque value showed statistically significant differences in the head section of the retaining screws (p < 0.05). The observation by microCT showed the torque applied is crucial to the head deformation in titanium screws. In gold-plated screws the successive tightening appears to be pivotal.

CONCLUSION
Titanium and gold screws tend to behave similarly. By increasing the tightening cycles and the torque values of protocols greater levels of deformations can be expected. In general, microCT data showed better results for gold-plated titanium alloy.

CLINICAL SIGNIFICANCE
To control severe screw head deformation and the impossibility of untightening the implant's restoration, clinicians should avoid extreme torque values and prevent surpassing 10 tightening cycles.


Medicine and law no longer accurately represent a complete definition of professional status. Today the term has come to refer to a worker more than an autonomous, skilled individual providing services to clients. Ambiguities regarding what constitutes a profession have created an opening for other groups to claim this status. Using teachers as an example, this paper explores the contemporary profession. It is contended that maintaining the service user's trust has become an integral part of professional status. There are expectations as to standards of service, especially where advice is given. And yet, employing the service user's perspective also reveals limitations particularly how the law's technical analysis of tort liability may dash these expectations. Profession may give rise to obligations in favour of employers of professionals but the term is not necessarily as effective when service-users seek to enforce expectations.


Due to its many advantages, demand for natural gas has increased considerably and many models for predicting natural gas consumption are developed. The aim of this paper is to present an overview and systematic analysis of the latest research papers that deal with predictions of natural gas consumption for residential and commercial use from the year 2002 to 2017. Literature overview analysis was conducted using the two most relevant scientific databases Web of Science Core Collection and Scopus. The results indicate neural networks as the most common method used for predictions of natural gas consumption, while most accurate methods are genetic algorithms, support vector machines and ANFIS. Most used input variables are past natural gas consumption data and weather data, and prediction is most commonly made on daily and annual level on a country area level. Limitations of the research raise from relatively small number of analyzed papers but still research could be used for significant improving of prediction models for natural gas consumption.


Information systems are open, reactive, and often distributed systems that maintain persistent data. The Troll and omTroll languages aim at specifying information systems on a high level of abstraction, supported by tools integrated in the Tbench. The development is rooted in abstract data types, conceptual modeling, behavior modeling, specification of reactive systems, and concurrency theory. The approach taken is object-oriented. Sequential object behavior is specified using linear-time temporal logic. Specifications are composed by structuring mechanisms like inheritance, generalization and aggregation. For specifying interaction in concurrent aggregations, we suggest an extended logic called distributed temporal logic which is based on n-agent logic. Labelled event structures serve as a denotational behavior model for giving interpretation.


We develop the theory of an Andreev junction, which provides a method to probe the intrinsic topology of the Fermi sea of a two-dimensional electron gas (2DEG). An Andreev junction is a Josephson $\pi$ junction proximitizing a ballistic 2DEG, and exhibits low-energy Andreev bound states that propagate $\textit{along}$ the junction. It has been shown that measuring the nonlocal Landauer conductance due to these Andreev modes in a narrow linear junction leads to a topological Andreev rectification (TAR) effect characterized by a quantized conductance that is sensitive to the Euler characteristic $\chi_F$ of the 2DEG Fermi sea. Here we expand on that analysis and consider more realistic device geometries that go beyond the narrow linear junction and fully adiabatic limits considered earlier. Wider junctions exhibit additional Andreev modes that contribute to the transport and degrade the quantization of the conductance. Nonetheless, we show that an appropriately defined $\textit{rectified conductance}$ remains robustly quantized provided large momentum scattering is suppressed. We verify and demonstrate these predictions by performing extensive numerical simulations of realistic device geometries. We introduce a simple model system that demonstrates the robustness of the rectified conductance for wide linear junctions as well as point contacts, even when the nonlocal conductance is not quantized. Motivated by recent experimental advances, we model devices in specific materials, including InAs quantum wells, as well as monolayer and bilayer graphene. These studies indicate that for sufficiently ballistic samples observation of the TAR effect should be within experimental reach.


BACKGROUND
Completely video-assisted thoracoscopic lobectomy is a reasonable treatment for early-stage non-small-cell lung cancer (NSCLC). At present, the indication for this procedure is stage Ia and Ib peripheral lung cancer (≤ 5 cm); however, for larger tumors, it remains controversial whether this surgical technique is comparable to open lobectomy. This study aimed to evaluate the safety, completeness, and efficacy of thoracoscopic lobectomy, and to compare this technique with open lobectomy for the treatment of non-small-cell lung cancer when the tumor's diameter was greater than 5 cm.

METHODS
From May 2001 to April 2011, 802 patients underwent a lobectomy for treatment of non-small-cell lung cancer at our center. In 133 patients, the tumor was > 5 cm. There were 98 men and 35 women, median age 63 years (range: 29 - 81 years). We divided the patients into two groups, group V (completely video-assisted thoracoscopic surgery), and group T (open lobectomy), and evaluated the two groups for age, gender, tumor size, pathological type, location, duration of surgery, blood loss, lymph node dissection, pathological stage, time of drainage, hospitalization, complications, overall survival and recurrence.

RESULTS
There were 46 cases in group V and 87 cases in group T. Age, gender, tumor size, location, pathological type and stage were similar between the two groups. Group V had shorter operative duration ((186.5 ± 62.8) minutes vs. (256.7 ± 67.5) minutes, P < 0.001) and reduced bleeding ((218.5 ± 174.6) ml vs. (556.9 ± 187.2) ml, P < 0.001). There were no significant differences between the two groups in complications, lymph node dissection, time of drainage and hospitalization. The recurrence between the two groups was equivalent (2.4% vs. 3.8%, P = 0.670). The overall survival at 1, 2 and 3 years was 95.1%, 81.6% and 69.6% for group V and 88.3%, 78.8% and 64.0% for group T. Kaplan-Meier survival curves showed that there was no significant differences between the two groups (P = 0.129).

CONCLUSIONS
Completely video-assisted thoracoscopic lobectomy was similar to open lobectomy in safety, completeness, and efficacy, but had a shorter operative duration, and reduced bleeding. This is a minimally invasive procedure that is feasible for a subset of non-small-cell lung cancer patients with tumor size > 5 cm.


Corrugated horn antennas are frequently used as the feed elements in reflector antennas for satellite and deep space communications. A particular application is the multifrequency feed horns for the reflector antennas of the JPL/NASA Deep Space Network (DSN). In this application, it is desirable to design a horn that has a nearly perfect circularly symmetric pattern (i.e., identical E- and H-plane patterns), with zero or low cross-polarization, a specified beam width, and a low return loss at the design frequency range. A parametric study of the corrugated horns, however, shows that the objective function relating the pattern shape, beam width and return loss is a nonlinear function of the corrugation dimensions with many local optima. As a result one has to resort to global optimization techniques, such as evolutionary algorithms, for successful design of such antennas. Here, an evolutionary programming (EP) algorithm is used to optimize the pattern of a corrugated circular horn subject to various constraints on return loss, antenna beam width, pattern circularity, and low cross-polarization. Examples of design synthesis for a few corrugated horns are presented. The results show excellent and efficient optimization of the desired horn parameters.


Like most animals, the survival of fish depends crucially on navigation in space. This capacity has been documented in numerous behavioral studies that have revealed navigation strategies and the sensory modalities used for navigation. However, virtually nothing is known about how freely swimming fish represent space and locomotion in the brain to enable successful navigation. Using a novel wireless neural recording system, we measured the activity of single neurons in the goldfish lateral pallium, a brain region known to be involved in spatial memory and navigation, while the fish swam freely in a two-dimensional water tank. Four cell types were identified: border cells, head direction cells, speed cells and conjunction head direction with speed. Border cells were active when the fish was near the boundary of the environment. Head direction cells were shown to encode head direction. Speed cells only encoded the absolute speed independent of direction suggestive of an odometry signal. Finally, the conjunction of head direction with speed cells represented the velocity of the fish. This study thus sheds light on how information related to navigation is represented in the brain of swimming fish, and addresses the fundamental question of the neural basis of navigation in this diverse group of vertebrates. The similarities between our observations in fish and earlier findings in mammals may indicate that the networks controlling navigation in vertebrate originate from an ancient circuit common across vertebrates. Summary Navigation is a fundamental behavioral capacity facilitating survival in many animal species. Fish is one lineage where navigation has been explored behaviorally, but it remains unclear how freely swimming fish represent space and locomotion in the brain. This is a key open question in our understanding of navigation in fish and more generally in understanding the evolutionary origin of the brain's navigation system. To address this issue, we recorded neuronal signals from the brain of freely swimming goldfish and successfully identified representations of border and swimming kinematics in a brain region known to be associated with navigation. Our findings thus provide a glimpse into the building blocks of the neural representation underlying fish navigation. The similarity of the representation in fish with that of mammals may be key evidence supporting a preserved ancient mechanism across brain evolution.


In the last decade, the increasing popularity of neuroscience has involved architecture. Both neuroscientists and architects have endeavoured to understand how the experience of architecture works from the standpoint of cognitive functioning. This has been possible thanks to the neuroimaging techniques such as fMRI and discoveries like mirror neurons. These researches, despite their outstanding quality, are difficult to implement for what concerns the practice of architectural design. However, there is a common ground where architectural theory, phenomenology and neuroscience intersect, represented by empathy, embodiment, and emotion. They are the frame of the awareness of space and the counterpart of the visual perception. The main goal of design is to make the living space but to take a meaning, it has to be the "negative" of the human body. This process comes into existence through "old" tools, i.e. the mentioned empathy, embodiment, and emotion. Still, they can get a new meaning if their traditional hermeneutic is blended with the latest knowledge provided by neurosciences.


This paper proposes a method to obtain the optimal placement of wind turbines (WTs) in an offshore wind farm (WF). The optimization objective is to minimize the levelized average cost per net electric power generated by a WF with a fixed number of WTs while the distance between WTs is not less than the allowed minimal distance in the far wake region. The WT wake losses have been taken into account, with the Frandsen–Gaussian (F-G) wake model and the optimization problem is subsequently solved by the hybrid grey wolf optimization (HGWO) algorithm. Synthesis methods that contain a special WT ranking strategy for multiple WTs are described in detail. Both the F-G model and Jensen's model are applied in the offshore WF optimization simulation platform for comparison. Simulation results demonstrate that the F-G model is more consistent with real wakes and thus the optimization result is more accurate than the commonly used Jensen's model.


The Forest Vegetation Simulator (FVS) is a national system of forest growth models maintained by the USDA Forest Service. It is the official tool for stand growth projection on National Forest lands, but it is also used widely on other ownerships. Model extensions and post-processors permit FVS users to perform a broad range of functions, including silvicultural manipulations, wildlife habitat analyses, and fuel treatment evaluations. Because FIA data were made available in FVS-ready format through the FIA Mapmaker interface, an increasing number of users have been using FVS as their tool of choice for compilation of FIA data at the plot level. With the transition from Mapmaker to FIDO, users who have built analysis systems around this data availability have lost access to new data. Due to the need to update FIA-FVS data translation, there is an opportunity to re-design the system to eliminate prior limitations and take advantage of recent developments in FIA and FVS. Select capabilities of FVS, and potential modifications and enhancements to the FIA-FVS linkage are discussed.


The purposes of this study were to analyze the kinematics and electromyographic variables of the upper extremity for the backhand clear motion according to the type of hitting in badminton. Seven elite male university players were selected as the subjects. Four digital video cameras and Noraxon Telemyo 2400 were used to collect the 3D kinematics and electromyographic data. The results were as follows: 1) in the phase of impact, the time of motion for the overhead backhand clear was the longest, 2) in the event of impact, the distance of step toward X direction was the longest and the distance of step toward Y direction was the shortest for the overhead backhand clear, 3) in the event of backswing, the rotation angles of shoulder and pelvis and the flexion angle of shoulder for the overhead backhand clear were the biggest, 4) the maximum flexion angular velocity of shoulder and the maximum extension angular velocity of elbow for the overhead backhand clear were the biggest, and 5) in the phase of impact, mean EMG of the wrist flexor, triceps, and trapezius muscle for the overhead backhand clear was bigger than that for the underhand stroke and in the phase of follow-through, mean EMG of the wrist flexor and extensor, biceps, triceps, and trapezius muscle for the overhead backhand clear was the biggest.


Preoperative and postoperative cognitive and memory functions, psychiatric outcome, and EEGs were evaluated in 32 epileptic patients who underwent temporal lobe surgery. The presence and location of preoperative slow wave focus in routine EEG predicted memory functions of the non-resected side after surgery. Neuropsychological tests of the function of the frontal lobes also showed improvement. Moreover, psychiatric ratings showed that seizure free patients had significantly less affective symptoms postoperatively than those who were still exhibiting seizures. After temporal lobectomies, successful outcome in postoperative memory functions can be achieved in patients with unilateral slow wave activity in preoperative EEGs. This study suggests a new role for routine EEG in preoperative evaluation of patients with temporal lobe epilepsy.


The EU's October Summit was dominated by three main issues: migration, international trade and relations with Russia, with EU leaders being eager to display a certain degree of unity and normality. The Summit was a rather unspectacular meeting in terms of actual results. But it did not pass unnoticed, given that it was overshadowed by the veto of Wallonia to CETA, which questions the Union's credibility as in international trade actor. With respect to migration, the focus was once again on the security aspects and on fire-fighting rather than on the remaining structural deficiencies. The debate on relations with Russia showed major divisions between national capitals. However, the fact that President Putin seems ready to do whatever it takes to re-establish Moscow as a global power increases the chances that the EU front will remain united. In more general terms, the inability to reach concrete decisions and the divides between member states on many core policy issues displayed at the October Summit indicate that the road from Bratislava to Rome, where EU leaders want to give the public a "vision of an attractive EU", will be a bumpy road. This is a worrisome perspective given that what is at stake is much more than the EU itself: it is the danger of the emergence of a regressive and illiberal Europe – a Europe in which key values, orientations, norms and principles are being increasingly undermined.


AbstractAim:To investigate the effect and mechanism of morphine on purine nucleotide catabolism.Methods:The rat model of morphine dependence and withdrawal and rat C6 glioma cells in culture were used. Concentrations of uric acid in the plasma were measured by the uricase-rap method, adenosine deaminase (ADA) and xanthine oxidase (XO) in the plasma and tissues were measured by the ADA and XO test kit. RT-PCR and RT-PCR-Southern blotting were used to examine the relative amount of ADA and XO gene transcripts in tissues and C6 cells.Results:(i) the concentration of plasma uric acid in the morphine-administered group was significantly higher (P<0.05) than the control group; (ii) during morphine administration and withdrawal periods, the ADA and XO concentrations in the plasma increased significantly (P<0.05); (iii) the amount of ADA and XO in the parietal lobe, liver, small intestine, and skeletal muscles of the morphine-administered groups increased, while the level of ADA and XO in those tissues of the withdrawal groups decreased; (iv) the transcripts of the ADA and XO genes in the parietal lobe, liver, small intestine, and skeletal muscles were higher in the morphine-administered group. The expression of the ADA and XO genes in those tissues returned to the control level during morphine withdrawal, with the exception of the skeletal muscles; and (v) the upregulation of the expression of the ADA and XO genes induced by morphine treatment could be reversed by naloxone.Conclusion:The effects of morphine on purine nucleotide metabolism might be an important, new biochemical pharmacological mechanism of morphine action.


One of the most popular strategies of optimization of drug properties in pharmaceutical industry appears to be a solid form change into a cocrystalline. A number of virtual screening approaches have been previously developed to allow a selection of the most promising cocrystal formers (coformers) for an experimental follow-up. A significant drawback of those methods is related to the lack of accounting for the crystallinity contribution to cocrystal formation. To address this issue, we propose in this study two virtual coformer screening approaches based on a modern cloud-computing crystal structure prediction (CSP) technology at a dispersion-corrected density functional theory (DFT-D) level. The CSP-based methods were for the first time validated on challenging cases of indomethacin and paracetamol cocrystallization, in respect of which the previously developed approaches provided poor predictions. The calculations demonstrated a dramatic improvement of the virtual coformer screening performance relative to the other methods. It is demonstrated that the crystallinity contribution to the formation of paracetamol and indomethacin cocrystals is a dominant one, and therefore should not be ignored in the virtual screening calculations. Our results encourage a broad utilization of the proposed CSP-based technology in pharmaceutical industry, as the only virtual coformer screening method, which directly accounts for the crystallinity contribution.


Based on some experience of smokers, smoking habit can be stopped in some time. However, not all that successful in stopping the habitin a long period of time. Still a little research to see how the experience of the former smokers who successfully stopped smoking habit. This research aims to explore in depth the psychological experience of former smokers in stopping smoking habit. This research uses qualitative research methods with the phenomenology of approach. Data obtained with the in-depth interview against 5 persons participating which have variation in the length of time it has managed to stop smoking. Research results get some major aspect of the successful. Response smokers in quitting smoking; the obstacles they face, the mechanism of motivation and koping used in stop smoking habit, and the changes to be felt after quitting. This research managed to identify some important aspects such as the strategies used and the underlying motivation to stop smoking. Expected results of this research can be an input for smokers or health workers in providing support so that smokers can quit their habits for long periods of time or permanently.


— Publications on the field of alkali-activated binders, state that this new material is likely to have high potential to become an alternative to Portland cement. Classical alkali-activated cements could be made more eco-efficient if the use of sodium silicate is avoided. Besides, most alkali-activated cements suffer from severe efflorescence originated by the fact that alkaline and/or soluble silicates that are added during processing cannot be totally consumed. This paper presents experimental results on hybrid alkaline cements. Compressive strength results and efflorescence's observations show that the new mixes already analyzed are promising. SEM results show that no traditional porous ITZ was detected in these binders.


BACKGROUND AND OBJECTIVES
Clinics licensed to provide pharmacotherapy for opiate dependence disorder are required to perform random urine drug screen (RUDS) tests. The results provide the empirical basis of individual treatment and programmatic effectiveness, and public health policy. Patients consent to witnessed testing but most tests are unwitnessed. The purpose of the present study was to compare treatment effectiveness estimates derived from witnessed versus unwitnessed urine samples.

METHODS
We adopted a policy requiring visually witnessed urine drug screens (WUDS) and studied its impact (a single group, pretest-posttest design) on the RUDS test results in 115 male veterans enrolled in the St. Louis VA Opioid Treatment Program.

RESULTS
The percentage of opioid-positive urine samples increased significantly following implementation of WUDS (25% vs. 41%, χ(2) = 66.5, p < .001).

CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE
Results of this preliminary study suggest that random testing alone does not ensure the integrity of UDS testing. Outcome calculations based on random unwitnessed tests may overestimate the effectiveness of opioid dependence disorder treatment.


The growth of a bradytrophic mutant isolated from the methanol-utilizing yeast Hansenula polymorpha was found to be stimulated by both tyrosine and phenylalanine. The mutant contained about half as much chorismate mutase activity as the wild-type strain. When grown in a medium containing 2% mehtanol as the major carbon and energy source, the bradytroph excreted a low but significant level (28 mg/liter) of L-tryptophan.


A simplified exponential (SEXP) approximation, combining the exponential approximation and the first-order mean spherical approximation, is proposed to improve the equation of state for the Lennard-Jones (LJ) fluid. The SEXP approximation, which can be implemented in an analytical manner, yields better radial distribution functions of the LJ fluid. Extensive comparisons with two typical perturbation theories show that the SEXP approximation is more appropriate to describe the behaviors of the LJ fluid. The latest 33-parameter modified Benedict-Webb-Rubin equation, also calculated, is inadequate in the region of phase coexistence. The SEXP approximation is applied to the calculation of methane properties with much better results than the Peng-Robinson equation of state for saturated liquid densities and second virial coefficients.


We consider the problem of designing optimal stabilizing decentralized controllers subject to arbitrary subspace constraints. Recent work considered structural constraints, where each part of the controller has access to some measurements but not others, and developed a parametrization of the stabilizing structured controllers such that the objective is a convex function of the parameter, with the parameter subject to a single quadratic equality constraint. Here we further show that other types of controller constraints arising in decentralized control and other areas of constrained control can be simultaneously encapsulated in this framework with one additional quadratic equality constraint.


The study asserts that conflicting sacrificial rules were the motive of the schism in Judean society, in the last period of the Second Temple. The study substantiates the thesis by a meticulous examination and comparison of the rabbinic and Qumran exegetical methods, and an exhaustive scrutiny of biblical sacrificial rules, demonstrating their deficiencies, the cause of the exegetical dissensions among the different groups. It is a short record of historical struggles, due to cult issues, and a scrutiny of Qumran literature, corroborating the utmost significance of the Temple cult in that group, complement the study. The study is useful for a comprehension of Qumran literature and particularly of the system of thought of its authors and their approach to the biblical writings.


Colposcopy of the vagina is a part of the colposcopic examination which is often omitted. It is an extremely serious mistake that makes the colposcopic examination less valuable. The instrumentarium, technique of the examination and distinctive features of colposcopic images showing vaginal changes have been presented in detail.


The objective of this study is to develop a neuro controlled active suspension for the ride quality improvement. The performance index of the optimal control is represented as the frequency-shaped using Parseval's theorem. The incorporation of frequencydependent weighting matrices allow one to emphasize the specific variables related to the vibrations of the specific bands of frequencies. Once the active control law is obtained. we use the artificial neural networks to train the neuro controller to learn the relation of road input and controlforce.
From the numerical results. we found that back propagation learning does good pattern matching and the neuro controlled suspension may reduce the vertical acceleration of the driver's seat and sprung mass motions significantly at desired bands of frequencies.


Because virus infections elicit various cellular responses that inhibit viral replication and growth, viruses must intervene to attenuate antiviral measures in order to thrive. The genome guardian p53 plays a central part not only in DNA damage responses, inducing cell cycle arrest or apoptosis, but also in the innate host immune control of viral infections by orchestrating diverse signaling pathways originating from many different cellular receptors and sensors. Many viruses have acquired sophisticated mechanisms to regulate p53 functions by deploying subversive proteins and modulating its post‐transcriptional status. In this review, we overview the mechanisms by which DNA and RNA viruses manage p53 signaling in favor of their continued survival. Copyright © 2012 John Wiley & Sons, Ltd.


An evaluation of the risk to the Calvert Cliffs Unit 1 nuclear power plant due to pressurized thermal shock (PTS) has been completed by Oak Ridge National Laboratory (ORNL) with the assistance of several other organizations. This evaluation was part of a Nuclear Regulatory Commission program designed to study the PTS risk to three nuclear plants, the other two plants being Oconee Unit 1 and H.B. Robinson Unit 2. The specific objectives of the program were to (1) provide a best estimate of the frequency of a through-the-wall crack in the pressure vessel at each of the three plants, together with the uncertainty in the estimated frequency and its sensitivity to the variables used in the evaluation; (2) determine the dominant overcooling sequences contributing to the estimated frequency and the associated failures in the plant systems or in operator actions; and (3) evaluate the effectiveness of potential corrective measures.


As e-learning environments become more popular, many studies have been proposed to provide adaptive environments offering learners and educators customized courses for more effective learning and course construction. Some solutions are aimed at helping learners, while others are aimed at helping educators and course designers/developers. However, a serious lack of conceptual clarity of definitions and uses of learning objects, could have resulted in design and usability problems in current elearning systems. The paper proposes ReLOAMS, a Reusable Learning Objects Authoring and Management System, being implemented to address the problem of usability and reusability of learning objects in elearning systems. The paper describes the design rationale, systems architecture, and development concluding with a discussion on the impact of the design of e-learning systems. Educational technology is essentially the use of technology to help improve learning (Jolliffe et al. 2001). Ong and Wong (2004) defined supporting tools as gadgets that are technology-enabled and provided by the environment for teachers to track the profile and various competencies levels of the students. New approaches and innovative methods of teaching have been adopted to foster better learning, both classroom-based and electronically mediated. Learning with technology has brought about many new expressions. Many educational institutions are using educational tools in the form of e-learning in course delivery. With rapid advancement in the technology, e-learning becomes pervasive in the education industry.


Hysteresis loops of melt-spun were measured at different temperatures between 4.2 K and 250 K. The loops were analysed on the basis of the micromagnetism using the finite element technique. By fitting the calculated with the experiment, the value of the exchange constant across the inter-grain boundary was estimated to be about 90% of that across the inner-grain boundary. increases to a maximum at the spin reorientation temperature and then decreases with increasing temperature. With decrease of the exchange interaction across the grain boundary, decreases below and increases above , and the Stoner-Wohlfarth model provides the theoretical lower and upper limits of below and above , respectively. The calculations reproduce the hysteresis loops fairly well. The magnetization proceeds by non-coherent rotation, and the spin distribution becomes quite non-uniform in some grains when H decreases to near .


The power to assess potential outcomes and intervention strategies is critical for epidemic preparedness. But emerging and mutated pathogens always challenge our current knowledge, pleading for fresh approaches to explore their epidemic potentials up front. This paper coupled a within-host viral dynamics model and a between-host network model of Ebola virus (EBOV) infection showing that its transmission characteristics can be faithfully recapitulated. Based on this multiscale model, EBOV's incubation period is predicted in the range from 2.6 to 12.4 days, while infected subjects can remain infectious until day 17. The predicted basic reproductive number (R0) differs by age-groups: the overall is 1.4 and the highest is 4.7 for the 10-14 years old. Random vaccination strategies can reduce R0 and case-fatality rate, eliminate the possibility of large outbreaks, but the effect depends on timing and coverage. A random vaccination program can reduce R0 below one if 85% coverage is achieved, and if it was conducted during the period from five months before to one week after the start of an epidemic. A vaccination coverage of 33% can reduce the epidemic size by ten to hundred times compared to a non-intervention scenario. Altogether, infection characteristics and epidemic mitigation approaches could be assessed using experimental data. An early, age-group specific, and high coverage vaccination program is the most beneficial.


Forty-five patients with chronic obstructive pulmonary disease were studied to compare the acute effects of ipratropium bromide (60 J..L g), salbutamol (300 J..L g) and placebo (3 puffs) on the forced expiratory volume in 1 sec (FEV 1) and forced vital capacity (PVC). Ipratropium bromide produced a significantly greater improvement than salbutamol in both FEV1 and FVC at 15,60 and 180 minutes after drug administration. It may therefore be concluded that in patients with chronic obstructive pulmonary disease, ipratropium bromide has greater potency and a longer duration of action than salbutamoL


In order for all to be included according to their needs and specificities, the objectives proposed by school education must be directed to the recognition and problematization of differences. The objective of this study was to analyze the implementation of programs and actions proposed in the scope of the National Policy of Special Education from the perspective of Inclusive Education (BRASIL, 2008), in a school located in a small municipality in the west of São Paulo. The methodology consisted of formative intervention on public educational policies, programs and actions in an inclusive perspective, and participant observation to follow the actions developed by the school management team, based on a qualitative approach. The programs and actions of the Ministry of Education are effective, since they aim to contribute and help with the guarantee, not only of access, but also of the permanence with the quality of students in the school context.


Anti-amphiphysin antibodies are uncommonly detected in paraneoplastic neurologic syndromes (PNS). If this happens, it is likely to present as a stiff-person syndrome (SPS). Here, we report the �rst case of PNS with pruritus as the �rst complaint,whose serum examination showed anti-amphiphysin antibodies IG+++, and the lung puncture con�rmed small-cell lung cancer (SCLC). During the progression of the disease, the patient developed dysphagia and anxiety. With chemotherapy and paroxetine 20mg/d, his symptoms signi�cantly improved. This case report emphasizes that clinicians should consider diagnoses other than anxiety states or esophageal cancer in a patient with pruritus and dysphagia, such as PNS.


PurposeAs an emerging measurement technique with the merit of easy alignment and high sensitivity, laser self-mixing interferometry (SMI) has wide applications in the detection of physical quantities. Considering that the characteristics of lasers have a determining influence on sensors' performance, the authors have established an open cavity solid-state laser (SSL) with more adjustment flexibility to act as a laser source.Design/methodology/approachThe fundamental structure of a SSL has been presented with an Nd:YAG rod severing as an active material and a birefringent filter inserted in the resonator as a mode selecting element. The power stability has been tested by a power meter, while the mode pattern has been inspected with a scanning Fabry–Perot interferometer, and the linewidth has been observed through a wavelength meter. A loudspeaker driven by a function generator is located in the extracavity to introduce phase modulation for SMI signal observation.FindingsThe established Nd:YAG SSL operates in a single longitudinal mode with the power stability of 0.2 mW and the linewidth less than 10 MHz. The SMI phenomenon occurs in the SSL, and the SMI signal obtained shows a fine signal-to-noise ratio of about 30 dB.Originality/valueTo the authors knowledge, SMI sensors using SSLs, especially in open cavity type, have rarely been reported, and they can find significant applications in designing high performance SMI sensors and instruments.


We propose a Model-Based Reinforcement Learning (MBRL) algorithm named VF-MC-PILCO, specifically designed for application to mechanical systems where velocities cannot be directly measured. This circumstance, if not adequately considered, can compromise the success of MBRL approaches. To cope with this problem, we define a velocity-free state formulation which consists of the collection of past positions and inputs. Then, VF-MC-PILCO uses Gaussian Process Regression to model the dynamics of the velocity-free state and optimizes the control policy through a particle-based policy gradient approach. We compare VF-MC-PILCO with our previous MBRL algorithm, MC-PILCO4PMS, which handles the lack of direct velocity measurements by modeling the presence of velocity estimators. Results on both simulated (cart-pole and UR5 robot) and real mechanical systems (Furuta pendulum and a ball-and-plate rig) show that the two algorithms achieve similar results. Conveniently, VF-MC-PILCO does not require the design and implementation of state estimators, which can be a challenging and time-consuming activity to be performed by an expert user.


Queer musical phenomenology refers to the practice of disorientation away from established music theories, including one's own. In Lewin's "Phenomenology" article, queering can be understood as his intentional, self-critical, conceptual disorientations—first departing from Schenkerian theory, and then moving toward and finally away from the perception-model. Through a close reading of Lewin in combination with Sara Ahmed's Queer Phenomenology, which offers a theory of embodied lives marginalized by pathways of normativity, I examine the generalizable application of theories such as queer phenomenology to another domain beyond gender and sexual embodiment: music theory at large. Lewin's practice models a form of music theory that I regard as phenomenologically queer.


Incorporation of 14C-p-hydroxybenzoate and 2-14C-mevalonate into ubiquinone in vivo and in vitro was distinctly increased in regenerating rat liver lobes within 1st and 2nd day after partial hepatectomy, whereas incorporation of 2-14C-mevalonate into sterols was unaltered. The stimulation observed was partially due to an increase in the rate of biosynthesis of the enzymes, catalysing the incorporation of the label into the ubiquinone. Preliminary administration of cholesterol or cholesterol with bile into rats caused an inhibition of the multistep biosynthesis of sterols at several sites and stimulated the ubiquinone synthesis. Intravenous administration of ubiquinone-9 emulsion was accompanied by more than 3-fold increase in concentration of the substance in regenerating liver tissue and did not cause any effect on the rate of incorporation of 14C-p-hydroxybenzoate and 14-C-methyl methionine into slices, obtained from this tissue.


Space-time adaptive processing (STAP) techniques have been motivated as a key enabling technology for advanced airborne radar applications. In this paper, a slow-time code design is considered for the STAP technique in airborne radar, and the principle for improving signal-to-clutter and noise ratio (SCNR) based on slow-time coding is given. We present two algorithms for the optimization of transmitted codes under the energy constraint on a predefined area of spatial-frequency and Doppler-frequency plane. The proposed algorithms are constructed based on convex optimization (CVX) and alternating direction (AD), respectively. Several criteria regarding parameter selection are also given for the optimization process. Numerical examples show the feasibility and effectiveness of the proposed methods.


We report crystallographic and electrical properties of ErBa2Cu3Oy/SrTiO3 (Er123/STO) films which were fabricated by the pulsed-laser-deposition (PLD) method in the temperature range of 720∼780°C, and dramatic enhancement of critical current density (Jc) by an oxygen post-annealing process. The PLD Er123/STO films were found to be crystallographically excellent in the deposition temperature region below 770°C from the intensity of diffraction peaks of 00l, the pole-figure of a reciprocal (102) plane and microstructures of the surface and the cross-section. Interestingly, in this temperature region, Jc values were clearly increased to the order of 1010 Am-2 by oxygen post-annealing in comparison with those of the as-grown films (0.3∼0.6×1010 Am-2). Enhancement of Jc was accomplished in a wide annealing temperature range of 350∼500°C, which is corresponding with an annealing temperature range where the critical temperature shows over 90 K on a polycrystalline sample. On the other hand, Irreversibility fields were almost independent of the annealing temperature. These results indicated that insufficient carrier-doped region was partly existed even in a non-equilibrium process such as the PLD method. Therefore, homogenization of oxygen contents in a whole part of the Er123 film is crucially important for enhancement of critical current properties, which strongly suggests that the oxygen annealing is effective for improvement of functionality of devices in PLD-REBa2Cu3Oy (RE: rare earth elements) thin films.


A series of alpha-Mo2C/gamma-Al2O3 catalysts with different Mo loadings were prepared by temperature-programmed reaction and characterized by X-ray diffraction, BET specific surface area determination, and NH3 temperature-programmed desorption. Their ability to decompose hydrazine was tested using a thruster and a microreactor. The catalytic activity for hydrazine decomposition of the fresh alpha-Mo2C/gamma-Al2O3 catalyst is higher than that of the passivated alpha-Mo2C/gamma-Al2O3 catalyst. The catalytic activity also decreased with the reaction time at 303 K, and the deactivation is mainly due to strongly adsorbed NHx species. Flushing with N-2 at 773 K recovers the activity of the catalyst. It was shown that hydrazine decomposes to NH3 and N-2 at low temperatures, and the produced NH3 dissociates into N-2 and H-2 at elevated temperatures.


A number of previous studies have examined both the overall level of belief expressed by young people in the paranormal and the major demographic predictors of such belief. Building on this research tradition, the present study examines how one specific paranormal belief concerning contact with the spirits of the dead integrates with the wider teenage worldview. Data provided by 33,982 pupils age 13 to 15 years throughout England and Wales demonstrated that almost one in three young people (31%) believed that it is possible to contact the spirits of the dead. Compared with young people who did not share this belief, the young people who believed in the possibility of contacting the spirits of the dead displayed lower psychological wellbeing, higher anxiety, greater isolation, greater alienation, less positive social attitudes, and less socially conforming lifestyles. Overall, paranormal beliefs seem to be associated with a less healthy worldview, in both personal and social terms.


Until a century ago, the fifth-century Greek poet Bacchylides was known only by 107 nonsequential lines buried as quotations in the writings of other ancient authors. With the discovery in 1896 of a papyrus containing his work, 1,382 lines were reassembled and the poems of Bacchylides finally began to take shape for the modern reader. Slavitt argues in the Introduction to this collection that, although Bacchylides is often considered a "lesser Pindar," he is a poet who warrants consideration. "He deserves attention not because he is beetling, like Pindar, but because he is not. He relies on craftsmanship and reliably displays an attractive grace and elegance."


Although there is considerable evidence that carbohydrate metabolism plays an important part in the process of cell division (see Bullough, 1952), conclusions have differed regarding the relative importance of glycolysis and catabolism involving respiration. In the adult mouse epidermis Bullough & Johnson (1951) found that cell division was dependent upon the respiratory oxidation of pyruvate by the tricarboxylic acid cycle. On the other hand, Pomerat & Willmer (1939) showed that, in tissue culture, agents that inhibited respiration had little immediate effect on cell division, while Laser (1933) found that growth of cultured fibroblasts could continue when respiration was greatly diminished by low oxygen tensions. Further, Warburg (1930) concluded that cell growth is associated with glycolysis. A similar difference in the relationship of mitotic activity to the respiratory and glycolytic forms of carbohydrate metabolism was indicated by changes occurring in the midbrain and the red-blood cells of the chicken embryo during embryonic development.


Monkeys were trained to emit 10 responses to terminate a schedule complex consisting of a light and masking noise in the presence of which brief, intravenous injections of naloxone (0.01 mg/kg per injection), dl-cyclazocine (0.003, 0.01 mg/kg per injection), or saline were scheduled to occur over blocks of consecutive daily sessions. Completion of the fixed ratio (FR 10) response requirement terminated the schedule complex, producing a time-out of 60 s in which responses were without consequence and injections did not occur. Sessions lasted for 100 min or ended after 100 injections, whichever came first. When monkeys received an intramuscular injection of morphine (10 mg/kg) 60 min preceding each session, responding to avoid injections of naloxone or cyclazocine was well maintained, though morphine-dependent monkeys tolerated injections of saline or the vehicle in which cyclazocine was dissolved. When the morphine pretreatment regimen was discontinued, monkeys tolerated injections of naloxone and cyclazocine though, at the larger cyclazocine dose (0.01 mg/kg per injection), responding was maintained for at least 30 consecutive sessions in two postdependent animals, but not in two other monkeys treated identically. The capacity of these morphine-antagonist drugs to support responding that avoids their injection depends evidently upon whether monkeys are rendered morphine dependent or not; in the case of cyclazocine, however, an increased sensitivity to the negative-reinforcing effects of the drug appears to persist in some "postdependent" monkeys.


In this experiment, we aimed to fabricate SWCNT conjugated with tamoxifen and evaluated its anticancer potential against human breast cancer cells (MCF-7). The results showed that SWCNT was synthetized successfully using chemical vapor deposition (CVD) method. The results of Raman spectroscopy, SEM, and TEM analyses confirmed the synthesis of highly pure SWCNT. The functionalization of SWCNT was performed by oxidizing of SWCNT, attachment of polyethylene glycol (PEG) to oxidized SWCNT, and attachment of azelaic acid to the polyethylene glycol group. As a result, the SWCNT with free functional carboxylic acid and hydroxyl groups (SWCNT-PEG) was developed. The SWCNT-PEG was then conjugated with tamoxifen (SWCNT-PEG-TAM). The FT-IR together with NMR results confirmed the conjugation of tamoxifen to functionalized SWCNT (SWCNT-PEG-TAM). The cytotoxic concentrations (CC50) of SWCNT-PEG, tamoxifen, and SWCNT-PEG-TAM were >100, , and μg/ml, respectively. Linking tamoxifen to functionalized SWCNT enhanced the cytotoxic action of tamoxifen against breast cancer cells up to 2.3 times. The results of the morphological examination and caspase-3 activity confirmed the higher cytotoxic action of SWCNT-PEG-TAM as compared to free tamoxifen. The results obtained in this study indicated that this delivery system enhanced the therapeutic effects and anticancer potential of tamoxifen against human breast cancer cells.


Propofol, a commonly used intravenous anesthetic agent during surgery, has relatively widespread pharmacological actions. Previous studies have reported that propofol may act as an antitumor drug in several cancer types, such as pancreatic cancer, lung cancer and gastric cancer. However, the underlying mechanism in ovarian cancer remain unknown. Therefore, the present study investigated the pharmacological effect of propofol on microRNAs (miRNAs) in ovarian cancer treatment. Propofol (1, 5 or 10 µg/ml) was used to treat A2780 and SKOV3 ovarian cancer cells for 1, 2, 3, 4 or 5 days. The MTT assay was used to detect cell viability, while wound healing and Transwell assays were utilized to assess the invasive and migratory abilities. The bioinformatics prediction approach identified differentially expressed miRNAs (miRs) that were used in Gene Ontology, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes analyses. The expression levels of miR-125a-5p and lin-28 homolog B (LIN28B) were evaluated by reverse transcription-quantitative PCR (RT-qPCR). A luciferase assay was performed to identify the relationship between miR-125a-5p and LIN28B. Western blotting was conducted to measure the protein expression of LIN28B. It was demonstrated that propofol significantly upregulated miR-125a-5p to exert its antitumor activity. RT-qPCR results suggested that propofol could upregulate miR-125a-5p and LIN28B expression levels in ovarian cancer cell lines. Western blot analysis also indicated that propofol could enhance the expression of LIN28B in ovarian cancer cell lines. The luciferase assay identified that miR-125a-5p could directly inhibit the expression of LIN28B to suppress proliferation and metastasis in ovarian cancer. In conclusion, these results suggested that propofol inhibited ovarian cancer proliferation and metastasis by enhancing miR-125a-5p, which targets LIN28B.


Active neurokinin (NK) receptors were visualized with 5-nm colloidal gold-protein-substance P (GPSP) and -senktide (GPSenk) complexes on vascular tissues. Electron micrographs of pig coronary strips incubated with GPSP showed gold particles either bound to the plasmalemma or inside intracytoplasmic vesicles of endothelial cells. Preincubation with SP or the NK1 receptor antagonist L-703606 prevented GPSP marking. No gold particles were seen after incubation with GPSenk. On coronary strips in vitro, which had been precontracted with U46619, GPSP induced relaxations similar to those produced by equimolar concentrations of SP, both relaxations being inhibited by L-703606. Analogous to senktide, GPSenk was totally inactive on arterial strips. Incubation of rat portal veins with GPSenk showed gold particles bound to the plasmalemma or inside intracytoplasmic vesicles of smooth muscle cells. Preincubation with senktide or the NK3 receptor antagonist R-820 prevented GPSenk marking. On portal veins in vitro GPSenk induced contractions similar to those induced by equimolar concentrations of senktide or NKB; these effects were inhibited by R-820. Our results show that colloidal gold-protein complexes present biological activity and selectivity similar to those of their respective native ligand and detect the presence of active receptors; in addition, they suggest the presence of NK-receptor-mediated endocytosis in endothelial cells of coronary artery and in smooth muscle cells of the portal vein.


C2 domains are widely-spread protein signaling motifs that in classical PKCs act as Ca2+-binding modules. However, the molecular mechanisms of their targeting process at the plasma membrane remain poorly understood. Here, the crystal structure of PKCα-C2 domain in complex with Ca2+, 1,2-dihexanoyl-sn-glycero-3-[phospho-l-serine] (PtdSer), and 1,2-diayl-sn-glycero-3-[phosphoinositol-4,5-bisphosphate] [PtdIns(4,5)P2] shows that PtdSer binds specifically to the calcium-binding region, whereas PtdIns(4,5)P2 occupies the concave surface of strands β3 and β4. Strikingly, the structure reveals a PtdIns(4,5)P2-C2 domain-binding mode in which the aromatic residues Tyr-195 and Trp-245 establish direct interactions with the phosphate moieties of the inositol ring. Mutations that abrogate Tyr-195 and Trp-245 recognition of PtdIns(4,5)P2 severely impaired the ability of PKCα to localize to the plasma membrane. Notably, these residues are highly conserved among C2 domains of topology I, and a general mechanism of C2 domain-membrane docking mediated by PtdIns(4,5)P2 is presented.