Introduction:
 CA-4948 is a novel small molecule oral inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). IRAK4 kinase plays an essential role in toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways These pathways are frequently dysregulated in Non-Hodgkin Lymphomas (NHL) and AML/MDS. [1] Oncogenic IRAK4-L, which is driven by spliceosome mutation (including SF3B1 and U2AF1), is preferentially expressed in >50% of AML/MDS patients [2,3]. Recently, activated IRAK4 has been identified as a driver of adaptive resistance in AML and other tumors [4]. CA-4948 not only strongly inhibits IRAK4, but also FLT3-ITD AML in vitro and in-vivo models. It has shown safety and activity in patients with relapsed or refractory NHL and will now be evaluated in patients with high-risk MDS and AML.
 Study Design and Methods:
 This is a multicenter, open-label, single arm Phase 1 dose escalation study of orally administered CA-4948 monotherapy in adult patients with AML or high risk MDS (NCT04278768). This study will be conducted in 2 parts: an initial dose escalation and dose expansion phase. The starting dose level is 200 mg BID which was determined to be safe, capable of achieving relevant levels of drug exposure and has demonstrated signs of biologic activity and clinical efficacy in an ongoing NHL study CA-4948-101. Three patients with AML or MDS will be enrolled at the starting dose. If none of the first 3 patients experience a DLT during the first cycle, patients may be enrolled into the next higher dose level of 300 mg BID.
 Dose escalation is expected to enroll approximately 18 patients to establish the initial RP2D. The safety population will include all patients in the study who received any dose of CA-4948, and the efficacy population will include patients who have a valid baseline and post-baseline disease assessment and received at least one dose of the study drug. Each treatment cycle of CA-4948 will be 28 days in length and repeated in the absence of unacceptable toxicity or disease progression.
 The major study inclusion and exclusion criteria are as follows: Relapsed or refractory AML (primary or secondary, including treatment-related) after at least one standard treatment (including chemotherapy, re-induction therapy or stem cell transplantation) based on the assessment of the investigator or high/very high risk relapsed/refractory MDS (IPSS-R criteria), following at least 6 cycles of hypomethylating agents [HMA] or evidence of early progression. Patients diagnosed with acute promyelocytic leukemia (APL, M3), blast phase of CML, allogeneic hematopoietic stem cell transplant (Allo-HSCT) within 60 days of the first dose of CA-4948, or clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to start of CA-4948 are excluded.
 The primary objective is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for CA-4948 based on the safety and tolerability, DLTs and PK/PD findings. Secondary objective is characterization of the pharmacokinetic (PK) parameters and preliminary efficacy. Exploratory objective (1)is to assess the potential association between target-related biomarkers (including IRAK4-L and downstream signaling parameters), selected genetic mutations (including spliceosome mutations), gene expression signatures, cell of origin, or other molecular classification subtypes and anti-leukemic activity (including central morphology review), and (2) to assess the pharmacodynamic effects of CA-4948 on selected biomarkers in peripheral blood and bone marrow.
 As of 03 August 2020, the trial has enrolled 3 patients in Cohort 1. Clinical updates will be later reported. After the RP2D has been determined, it may be subsequently amended including patient selection and combination therapy in a controlled design.
 References:Rhyasen, GW, Starczynowski DT, 2015. Brit J Cancer 112, 232-Smith MA. et al., 2019 Nat Cell Biol. 21(5): 640-650Choudhary G et al.2019. Blood 134 (Suppl 1): 4224.Booher R. et al.: 2019: EHA Annual Meeting, Abstr. PS991Melgar, K. et al., 2019. Sci Transl Med, 11: eaaw8828

 Garcia-Manero: Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; H3 Biomedicine: Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Merck: Research Funding; Jazz Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amphivena Therapeutics: Research Funding; AbbVie: Honoraria, Research Funding; Onconova: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Novartis: Research Funding. Platzbecker:Amgen: Honoraria, Research Funding; Geron: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Talati:Jazz: Speakers Bureau; BMS: Honoraria; Astellas: Speakers Bureau; Pfizer: Honoraria; AbbVie: Honoraria. Götze:Celgene: Research Funding.


The three-dimensional (3D) nuclear magnetic resonance (NMR) spectroscopy constitutes an important and powerful tool in analyzing chemical and biological systems. However, the abundant 3D information arrives at the expense of long acquisition times lasting hours or even days. Therefore, there has been a continuous interest in developing techniques to accelerate recordings of 3D NMR spectra, among which the ultrafast spatiotemporal encoding technique supplies impressive acquisition speed by compressing a multidimensional spectrum in a single scan. However, it tends to suffer from tradeoffs among spectral widths in different dimensions, which deteriorates in cases of NMR spectroscopy with more dimensions. In this study, the discrete decoding is proposed to liberate the ultrafast technique from tradeoffs among spectral widths in different dimensions by focusing decoding on signal-bearing sites. For verifying its feasibility and effectiveness, we utilized the method to generate two different types of 3D spectra. The proposed method is also applicable to cases with more than three dimensions, which, based on the experimental results, may widen applications of the ultrafast technique.


Author(s): Consiglio, Santina Michelle | Advisor(s): Turner, Jean L | Abstract: Super star clusters (SSCs) are important sources of energy, ionizing photons, and metals in galaxies. With masses of 100,000-1,000,000 M⊙, SSCs have the mass necessary to create O and B stars as well as to form globular clusters. Despite their overall importance, little is known about how SSCs form, evolve, and affect their environments. In my thesis, I use submillimeter tracers of gas and its kinematics from the newly commissioned Atacama Large (Sub)Millimeter Array (ALMA) as well as the Submillimeter Array (SMA) to study SSCs, their associated gas and dust and feedback from young stars in two local dwarf galaxies, NGC 5253 and II Zw 40. In II Zw 40, we find a low gas-to-dust ratio (GTD) of ~70 in a cloud near a SSC, whereas we find GTDg270 in an isolated cloud with no associated star formation l200 pc to the east, as expected in this low metallicity galaxy. We propose that the SSC has polluted its natal cloud with dust and metals. In NGC 5253, we find gas filaments that appear to be connected to the well-known HI filaments surrounding this galaxy. Infalling filaments could fuel the star formation, leading to the creation of SSCs. In NGC 5253 we also detect unusual optically thin 12CO(3–2) emission in two clouds with the embedded SSCs; we propose that the gas is thin because it is hot. Thus, we conclude that 12CO(3–2) emission alone is a poor tracer of gas mass; instead clouds could appear bright because they are hot. A comparison between older, visible star clusters and our CO(3–2) observations of young, dense, star-forming gas clumps in NGC 5253 suggest a new generation of star formation in this well-known starburst galaxy. We find that over all, the star-forming clumps emitting CO(3–2) do not correspond to known clusters, which is probably an age effect. In NGC 5253, we also find low GTDs in the central Cloud D region, particularly in Cloud D1, the cloud associated with the supernebula. We suggest that the massive clusters have locally polluted their environment. Cloud D1 has a narrow CO linewidth and no evidence of a cluster-scale outflow, we suggest that the dust pollution from the massive stars has stalled the cluster wind. Further investigation is needed as the dust fluxes are highly uncertain. Both II Zw 40 and NGC 5253 show evidence of star- forming filaments that separate into dense clumps, suggesting a common filamentary formation process for SSCs. Combined, the results from my thesis offer new insights into the importance of environments for the formation of SSCs – in the effects of SSCs polluting their local environments with dust, as well as the possibility that they may preferentially be formed by the process of cold stream accretion.


This report introduced the types of drilling equipment and their operation mechanisms. The state of the art technologies of the Top-hammer drill equipment were investigated and the technology level of Korean drill industry was compared to that of the advanced country. Based on the investigation, the necessity of fusion research and development in the Korean drilling technology and industry was discussed, and the future strategy to catch up with the advanced technology was suggested.


By reference to edible oil using process as well as hogwash oil refining technology, a method is presented to determine the contents of the sodium and chloride in hogwash oil based on ion chromatography. The molar ratio of the sodium and chloride was analyzed in order to determine whether the sample contained hogwash oil. A hogwash oil sample was extracted by deionized water before analysis. The ion chromatographic separation of the chloride was carried out on an AS19 column (250 mm x4 mm) at 30 degrees C, using 20 nmol/L KOH solution as mobile phase at a flow rate of 1 mL/min and suppressor current of 112 mA. The ion chromatographic separation of the sodium was carried out on a CS12 column (250 mm x 4 mm) at 30 degrees C, using 20 nmol/L methanesulfonic acid (MSA) as mobile phase at a flow rate of 1 mL/min and suppressor current of 59 mA. The injection volume was 25 microL and the detector was an electron capture detector (ECD). The external standard method was used to quantify chloride and sodium. The detection limits of this method were 0.005 mg/L for chloride and 0.001 mg/L for sodium. The linear range was from 0 to 5 mg/L with r2 = 0.999988 for chloride and r2 = 0.999926 for sodium. The average recoveries and relative standard deviations were 94.2% and 2.4% for chloride and 92.5% and 2.7% for sodium, respectively. The molar ratio of sodium and chloride in edible oil was approximately 1, while that in hogwash oil was more than 4. The determination of the contents and molar ratio of the chloride and sodium in hogwash oil can be used as an important basis for the judgment of hogwash oil.


To explore agents for differentiation therapy of leukemias, various combinations of cytokines and low-molecular-weight inducers were examined for differentiation-inducing activity toward three kinds of human leukemia-derived cell lines. The strongest differentiation inducing activity on promyelocytic HL60 cells and histiocytic U937 cells was obtained by combining recombinant tumor necrosis factor (rTNF), interferon-gamma (IFN-gamma), retinoic acid (RA), and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). For myeloblastic ML1 cells, the combination of rTNF, IFN-gamma, and RA had the strongest differentiation-inducing activity.


At slow stepwise insertion of the glass micro-electrode into the cell of Nitellopsis obtusa and Nitella translucens four potential jumps were recorded which corresponded to the penetration of the micro-electrode across the cell wall, the plasmalemma, the supposed chlorolemma and the tonoplast, respectively. The photo-electric depolarization appeared after the third jump only, which was supposed to be the penetration of a membrane layer between the plasmalemma and the streaming part of the cytoplasm. The vibration of this chlorolemma, caused probably by the protoplasmic streaming, resulted in large (up to 100 mV) hyperpolarizing and depolarizing potential fluctuations when the micro-electrode tip was near to this membrane. During cell excitation the potential difference (p.d.) had changed also across the chlorolemma. It was shown that the potential changes across the chlorolemma, caused by local illumination on the isolated part of the cell, were measurable also at a considerable distance (more than 1-4 cm) from the illuminated and isolated sequence. The lightand electron microphotographs obtained showed that the chloroplasts might really form a very compact layer with tight connections between the neighbouring chloroplasts and that there existed at least one continuous membrane layer which separated the immobile chloroplasts from the streaming cytoplasm. It was concluded that the p.d. measured between the streaming cytoplasm and the external medium was the sum of the p.d.s across the cell wall, the plasmalemma and the chlorolemma, respectively.


The majority of existing gesture recognition games consist of gesture recognition and scoring, thus providing game content and interaction. This paper uses Leap Motion gesture recognition to present a game model that reflects gesture-dependent impact levels and the physical characteristics of players. A game was implemented in which gestures are recognised through the Leap Motion that accompanies a player's gesture by providing a gesture-specific weight, thereby considering the player's physical characteristics. Leap Motion is used as the interface with which to implement a natural punch-style for gesture generation and to stimulate a player's interest and immersion experience.


Introduction: Paragangliomas are tumors originated from the chromaffin cells of the neural crest. They can be observed from the base of the skull to the bladder or along the sympathetic ganglionar chain. Retroperitoneal paragangliomas can represent a true surgical challenge due to their tight relation to large size vessels. Presentation of the case: Woman, of 40 years of age, who, three years before admittance, had presented paroxysmal crises of severe arterial hypertension. The abdominal TC scan revealed the presence of an inter-aorto-cava retroperitoneal mass of 4 cm in diameter compatible with a paraganglioma. The patient was subjected to surgery after having been prepared with calcium channel blockers during two weeks. Surgery confirmed the presence of the inter-aortocava paranganglioma of 5 cm in diameter that displaced the cava vein to the front; the tumor was successfully resected. The patient required intensive care and was discharged on the 7 th day after surgery without complications. At 24 months, her blood pressure is normal and without recurrence. Conclusion: Retroperitoneal paragangliomas are not frequent tumors, their surgical treatment is difficult. A multidisciplinary specialized team and close monitoring during the perioperative period are required.


Laminar mixing in SMX static mixers and the effect of geometry on mixing are studied using computational fluid dynamics. A frame-indifferent parameter is used to classify the flow types in the SMX mixer. All three typical flows (simple shear, pure elongation, and squeezing) appear within the flow field of the SMX mixer. The strain rate distribution in the SMX mixer is observed to be very nonuniform. A mixing element with 10 crossbars shows the best mixing quality, followed closely by the standard SMX mixing element with eight crossbars. The improved designs of the mixing element increase the average and peak strain rate, and provide a more uniform strain rate distribution and faster mixing rate compared to those of the standard SMX mixer. © 2005 American Institute of Chemical Engineers AIChE J, 2006


Collaborative filtering has become one of the most effective recommender system techniques for generating predictions. However, these systems typically overlook the privacy of individuals as they collect plain preferences of users. Privacy-preserving collaborative filtering systems propose ways of offering predictions without violating the confidentiality of users. Disguising user preferences reduces the accuracy as the data disguising process causes a level of distortion in the preferences. In this study, a genetic algorithm-based approach is proposed to maintain more accurate predictions based on disguised user data. Similarity calculation is improved compared to traditional privacy- preserving collaborative filtering by implementation of genetic algorithm onto a model-based scheme. Experimental outcomes obtained on a real-world data set confirm that the improved genetic algorithm-based scheme significantly outperforms traditional methods in terms of accuracy.


This thesis is concerned with a study of the fragmentations of some small ions produced by photoionization. The study of unimolecular reactions of this kind is of fundamental interest, providing a much clearer insight into the processes occurring than do conventional kinetic studies where results are complicated by collisions between molecules. Such studies are also of interest in connection with the mechanisms and energetics of the ion dissociation processes responsible for the fragmentation patterns in mass spectroscopy. A general discussion is given of the processes occurring within a molecule after the absorbtion of a photon, with specific reference to the study of the energy distribution of the electrons produced in photoionization and the energetics of the fragmentation of the residual photoions. Direct and statistical theories of dissociation are considered; in particular the well established Quasi Equilibrium Theory (QET). This theory assumes that the rate of dissociation of an ion is slow relative to the rate of internal energy equilibration and describes each fragmentation pathway as a motion along a separable 'reaction coordinate'. This theory is in many ways similar to the statistical theories of unimolecular reactions. It is difficult to devise a direct and unambiguous test of the extent to which the QET is obeyed in particular cases. The release of kinetic energy in ion dissociations was first noted in relation to mass spectral appearance energies - partly accounting for the so called 'kinetic shift' of appearance energies from their thermodynamic limits. A major aim of the work presented here was to relate this release of kinetic energy to the mechanism of fragmentation. A discussion of experimental techniques is introduced by a general consideration of the types of photon source and energy analyzer which may be used. The experimental work was carried out with an analyzer built originally as a photoelectron spectrometer (with a view to various possible avenues of development). For ion kinetic energy measurements various modifications were found to be necessary, particularly to achieve satisfactory mass resolution of the various ionic fragments from their time of flight through the instrument. Initial experiments were made by pulsing the photon source but extensive investigations and modifications led to a new technique in which the ions were continuously produced and their admission to the energy analyzer was pulsed. Electronic equipment was developed to allow the recording of the data on a multi-channel analyzer. Eventually a reasonable mass resolving power was obtained and the kinetic energy resolution for ions improved to approximately 15 meV. Much consideration was given to the interpretation of the ion energy distribution data obtained. A detailed investigation of the fragmentation of the O 2 + ion was employed to test these methods as this dissociation is fairly well understood from spectroscopic information. Equations were developed to enable the observed energy distributions to be related to the kinetic energy releases occurring in centre of mass coordinates and computer programs written to handle the data. For the O 2 + ion it was found that the observed shape of the O + fragment energy distribution could be completely accounted for on the basis of the known potential energy curves for the O 2 + ion. An experimental study was then made of a group of fluorine compounds; for some of these the investigations required an initial study of their photoelectron spectra in order to obtain information about the excited states of the ions. For CCl 3 F, CCl 2 F 2 and CClF 3 the photoelectron spectra and their assignments are in broad agreement with results published elsewhere after this work was completed. In the case of CClF 3 a band not reported elsewhere was observed. The photoelectron spectrum of C 2 F 6 was also obtained; it does not appear to have been previously reported. The energy distribution of fragment ions produced in the photoionization of all these compounds as well as those of CF 4 and SF 6 were recorded and analyzed using both the helium and neon resonance lines (21.22 eV and 16.85 eV respectively). Little evidence was found to support the idea that the pattern of ionic decomposition is necessarily determined by the bonding character of the electron lost in ionization. A high reverse activation energy appears to apply to processes in which fluroine is lost from these molecules. The loss of a chlorine atom however seems to be a less rapid process with little kinetic energy release. In an investigation of the fragmentation of NO 2 + the ions NO + , O + and N + were observed. Consideration of the predissociations of the various states of NO 2 + showed that dissociation from the 1 A 2 state of the ion could only be via a spin-forbidden process. High kinetic energy releases were observed in many cases, reflecting the large excess energies possessed by the ions over their dissociation limits. In general the experimental energy distributions were shown to be consistent with the excess energies involved. In the case of the O + fragment there appears to be structure in the distribution of energy release which may reflect the vibrational levels of the parent molecule ion.


Modern petrophysical software has broad capabilities for the display and manipulation of subsurface digital log data and for its integration with core data. Color and scale are two of the most important display attributes that can be used to enhance the visualization and interpretation of rock properties. The gamma-ray (GR) log, the most important log used in subsurface interpretation, is conventionally displayed on a linear scale of American Petroleum Institute (API) units. This makes it difficult to interpret in very clean lithologies with low API values or where the range of values is very large. We determine how displaying GR values on a logarithmic scale enhances the recognition of cyclicity in lithofacies with low GR values concurrently with rocks with very high API values. We further enhance the GR curve with a color-fill pattern that is intuitive and suggests the lithofacies. We calibrate the core-derived lithofacies data to the color-fill pattern, interactively "tuning" it to match lithofacies boundaries, further increasing the value of the methodology. Because of the many factors that cause variation in recorded API values, we normalized the GR curves, either by bulk shifts or statistical means, so that they display the same colors for equivalent lithologies in all wells in a cross section. We have developed two integrated studies demonstrating techniques to improve the display and interpretation of borehole logs, specifically those of Mesozoic carbonates and evaporites of the Middle East and Cenozoic siliciclastic fluvial and marginal marine systems of the Llanos Foothills of Colombia. Many examples of custom color-fill patterns for petrophysical logs could be suggested, the possibilities being limited only by the data available and the interpretation being presented.


The evolution of antimicrobial resistance (AMR) has mainly been studied in planktonic bacteria exposed to sub-inhibitory antimicrobial (AM) concentrations. However, in a number of infections that are treated with AMs the bacteria are located in biofilms where they tolerate high doses of AM. In the present study, we continuously exposed biofilm residing E. coli at body temperature to high ciprofloxacin (CIP) concentrations increasing from 4 to 130 times the minimal inhibitory concentration (MIC), i.e., from 0.06 to 2.0 mg/L. After 1 week, the biofilms were full of CIP resistant bacteria. The evolutionary trajectory observed was the same as described in the literature for planktonic bacteria, i.e., starting with a single mutation in the target gene gyrA followed by mutations in parC, gyrB, and parE, as well as in genes for regulation of multidrug efflux pump systems and outer membrane porins. Strains with higher numbers of these mutations also displayed higher MIC values. Furthermore, the evolution of CIP resistance was more rapid, and resulted in strains with higher MIC values, when the bacteria were biofilm residing than when they were in a planktonic suspension. These results may indicate that extensive clinical AM treatment of biofilm-residing bacteria may not only fail to eradicate the infection but also pose an increased risk of AMR development.


Additive manufacturing (AM) is a novel fabrication technique which enables production of very complex designs that are not feasible through conventional manufacturing techniques. However, one major barrier against broader adoption of additive manufacturing processes is concerned with the quality of the final products, which can be measured as presence of internal defects, such as pores and cracks, affecting the mechanical properties of the fabricated parts. In this paper, a data-driven methodology is proposed to predict the size and location of porosities based on in-situ process signatures, i.e. thermal history. Size as well as location of pores highly affect the resulted fatigue life where near-surface and large pores, compared to inner or small pores, significantly reduces the fatigue life. Therefore, building a model to predict the porosity size and location will pave the way toward building an in-situ prediction model for fatigue life which would drastically influence the additive manufacturing community. The proposed model consists of two phases: in Phase I, a model is established to predict the occurrence and location of small and large pores based on the thermal history; and subsequently, a fatigue model is trained in Phase II to predict the fatigue life based on porosity features predicted from Phase I. The model proposed in Phase I is validated using a thin wall fabricated by a direct laser deposition process and the Phase II model is validated based on fatigue life simulations. Both models provide promising results that can be further studied for functional outcomes.


Poverty alleviation is the principle pre-condition for economic development of a developing country. In Bangladesh each village has about 355 households below the poverty line and the average income of these households is below Tk 3,500/-per month [1]. Rapid population growth and extreme scarcity of agricultural land require development of alternative sources of employment and income. Although the rural economy of Bangladesh is going through diversification, the pace of the progress can be significantly enhanced through human resource development and creation of alternative investment opportunities. In this paper, we argue that introduction of PV Home system could work as a catalyst in the process of transforming rural economy of Bangladesh. The PV Home system is likely to create opportunities home based income generating activities as well as better educational attainment for household members. Therefore, the PV Home system would have both short term and long term impacts on economic growth and diversification of rural economy. Index Terms : PV home system; rural households; annual flow; forward and backward linkage; solar radiation. J. Elec. Engg., Instn. Engrs., Bangladesh, 36(II), December 2009: 39-42


In this paper we explore the possibilities of having an algorithm that can protect Zigbee wireless sensor networks from intrusion; this is done from the Internet of Things paradigm. This algorithm is then realised as part of an intrusion detection system for Zigbee sensors used in wireless networks. The paper describes the algorithm used, the programming process, and the architecture of the system developed as well as the results achieved.


Abstract Gastrointestinal (GI) malignant neoplasms have a high global incidence and a huge impact on cancer-associated mortality. In the past years, excitement was growing among oncologists and patients alike for the use of immunotherapy, specifically immune checkpoint inhibitors. The approval of several PD-1/PD-L1 and CTLA-4 inhibitors radically changed the treatment landscape in many cancer types and established immune-oncology as a new treatment strategy against cancer. Despite major breakthrough reports, shortcomings of immune checkpoint inhibitors (ICI) have been observed, including primary and acquired treatment resistance, especially in patients receiving ICIs as a single treatment. Several immunotherapies for the treatment of GI tumors have recently emerged; however, checkpoint inhibition has not yet shown similar success in GI malignancies compared to other solid tumors. Various phase I–III trials focusing on immunotherapies for GI tumors have found only moderate to unsatisfactory objective response rates (ORR), ranging between 10 % and 25 %. In particular, negative studies have been reported in gastric and pancreatic cancer. Nevertheless, small subsets of cancers, such as DNA mismatch repair deficient (dMMR)/microsatellite instable (MSI) cancers, among others, seem to benefit from treatment with immune checkpoint inhibition. Routine testing for the rare molecular features that can predict response should be implemented in clinical routine for all GI tumors, and large scale clinical trials to identify predictive biomarkers are needed. This article will address the current use and evidence for immunotherapy in GI malignancies and future trends in this area for clinical practice.


Summary
A strain of yellow fever virus of jungle origin was easily maintained by alternate passage through a species of marmoset (Callithrix aurita) and Aedes aegypti mosquitoes. Nine cycles have been completed.
Yellow fever virus, also of jungle origin, was similarly passed through cebus monkeys (Cebus versutus) and Aedes aegypti. Five cycles were completed when the series was voluntarily interrupted.
Using Haemagogus equinus as vector in conjunction with the marmoset as host, three cycles were completed before the series was interrupted for lack of fresh mosquitoes.
The implication of these observations in relation to the epidemiology of South American jungle yellow fever is briefly discussed.


Protein-catalyzed aminoacylation of the 3′-overhang of tRNA by an aminoacyl-adenylate could not have taken place prior to the advent of genetically coded peptide synthesis, and yet the latter process has an absolute requirement for aminoacyl-tRNA. There must therefore have been an earlier nonprotein-catalyzed means of generating aminoacyl-tRNA. Here, we demonstrate efficient interstrand aminoacyl transfer from an aminoacyl phosphate mixed anhydride at the 5′-terminus of a tRNA acceptor stem mimic to the 2′,3′-diol terminus of a short 3′-overhang. With certain five-base 3′-overhangs, the transfer of an alanyl residue is highly stereoselective with the l-enantiomer being favored to the extent of ∼10:1 over the d-enantiomer and is much more efficient than the transfer of a glycyl residue. N-Acyl-aminoacyl residues are similarly transferred from a mixed anhydride with the 5′-phosphate to the 2′,3′-diol but with a different dependence of efficiency and stereoselectivity on the 3′-overhang length and sequence. Given a prebiotically plausible and compatible synthesis of aminoacyl phosphate mixed anhydrides, these results suggest that RNA molecules with acceptor stem termini resembling modern tRNAs could have been spontaneously aminoacylated, in a stereoselective and chemoselective manner, at their 2′,3′-diol termini prior to the onset of protein-catalyzed aminoacylation.


What is already known about this subject The prevalence of child obesity in the U.S. is higher among Hispanic and black than white children. Racial/ethnic disparities have widened with the development of the child‐obesity epidemic. Obese minority children are at greater risk of being obese also as adults.


Background A difficult birth at term (DBAT) may manifest as fetal acidosis and low Apgar scores and is often referred to as "perinatal asphyxia," especially when infants show signs of neonatal encephalopathy (NE). In contrast to DBAT resulting in moderate-to-severe NE, which is associated with neurodevelopmental disorders, little is known about the prognosis of less severe forms of DBAT, with or without NE. Objective The purpose of this study was to evaluate the International Classification of Functioning, Disability and Health, Children & Youth Version activity "mobility" and other neurodevelopmental sequelae in infants with DBAT at age 6 years. Methods The index cohort (n=62; 35 boys, 27 girls) consisted of consecutive term infants with DBAT based on clinical criteria in a Dutch nonacademic hospital from 1999 to 2005. Neonatal encephalopathy was assessed according to the Sarnat grading system and excluded infants with severe NE. The matched reference cohort (n=81; 49 boys, 32 girls) consisted of healthy term infants. The primary outcome at 6 years was limited mobility (Movement Assessment Battery for Children score ≤15th percentile). Secondary outcomes included learning and behavioral problems and the presence of minor neurological dysfunction. Results Three children developed cerebral palsy and were excluded from analyses. Children with DBAT more often had limited mobility than children without DBAT (risk ratio [RR]=2.44; 95% confidence interval [95% CI]=1.16, 5.14). The risk of limited mobility rose with increasing severity of NE (mild NE: RR=3.38; 95% CI=1.40, 8.16; moderate NE: RR=4.00; 95% CI=1.54, 10.40), and manual abilities especially were affected (RR=4.12; 95% CI=1.40, 12.14). Learning problems, need for physical therapy, and complex minor neurological dysfunction were more common in children with DBAT than in children without DBAT. Conclusions Term infants who develop mild or moderate NE following DBAT are at increased risk for limited mobility at age 6 years. Routine monitoring of neuromotor development in these children is warranted.


ABSTRACT FROM: Eley TC, McAdams TA, Rijsdijk FV, et al . The Intergenerational Transmission of Anxiety: A Children-of-Twins Study. Am J Psychiatry 2015;172:630–7.

Anxiety disorders can run in families and both genetic and environmental influences have been implicated in this association. Although paediatric twin studies are able to ascertain the proportion of variance in child/adolescent phenotypes due to genetic and environmental influences, to date, they have not been able to specify the extent to which genes and the environment contribute to the transmission of anxiety between parents and their children, that is, whether similarities in the amount of anxiety experienced by parents and their offspring are accounted for by sharing genes, living together or both. For this, other genetically sensitive designs are needed. The children-of twins model is one such design and involves adult twin pairs and their offspring.1

The …


This study, which is a part of a larger project on learner corpora, used a corpus linguistic approach to analyzing ESL writing produced by freshmen college students from five private schools in Metro Manila, Philippines, in their first week of classes. The data for the study includes (1) essay scores used to classify texts by levels of proficiency, (2) computer tagging results, and (3) MANOVA, ANOVA, and regression analyses. The analyses revealed that most of the general text characteristics (e.g. fluency, unique words, word per sentence, number of sentence, number of paragraphs) and lexical (except conjuncts), clause-level, and grammatical features all have a steady increase across proficiency levels. This implies that the (1) writers of high score essays (level 2 and 3) are likely to employ more of these structures, and (2) The employment of these structures impact the raters' assignment of scores on the essays. The findings of the present study lead to tentative conclusions and implications for curricular enhancement and research.


Finishing refers to all the procedures associated with shaping, contouring, and polishing. Polishing immediately after restoration composite resin placement is most clinicians performance. Polishing time can effect strength of composite resin restoration. Immediate polishing may increase on both the surface roughness and the water sorption compared to delayed polishing for 24 hours and may lead to color change of composite resin restoration. The objectives of this study was to evaluate the effect of polishing time on color stability of composite resin nano particle after immersion in mouthwash. This research is experimental laboratory design. Total specimen were 20 and divided in two group. The first group was polished immediately and the second group was polished after 24 hours (n=10). Polishing was done by using Enhance (aluminium oxide) with low speed handspiece 15,000 rpm for 15 second. The specimens were immersed in 20 ml herbal mouthwash for 360 minutes. Color measurement of specimen before and after immersion was obtained by stereomicroscope modified with camera digital and used Adobe Photoshop 7.0 program for evaluate L, a, and b value. The L, a, and b value were input in CIELab (Commission Internationale de l'Eclairage L, a, b) formula with ∆E parameter. Data were analyzed using Independent T-test at a significance level of 0,05. Analysis result of Independent T-test showed that there is significant difference of color change value of composite resin polished immediately is higher than delayed polish for 24 hours. Immediately and delayed for 24 hours can effect on color stability of composite resin nano particle. ∆E value in this research was about 0-2 (∆E<3,7), so color change after immersion in herbal mouthwash was not visual perceptible.


52-year-old Indian builder initially presented to his General Practitioner with exertional breathlessness but no angina. His medical history included previous tuberculosis infection, Type 2 Diabetes Mellitus and hypothyroidism. He was referred to the cardiologist to exclude coronary artery disease.
 Stress testing found T-wave inversion in the inferior electrocardiogram leads and transthoracic echocardiogram showed reduced right ventricular (RV) function with basal wall hypokinesia. Cardiac Magnetic Resonance Imaging (MRI) revealed a 5cm x 2.5cm pericardial cyst (Figure 1a). As imaging suggested minimal RV compression and no venous obstruction, the patient was investigated for other causes of breathlessness.
 Repeat computed tomography (CT) two years later demonstrated enlargement of the cyst (6cm x 3.6cm) with contrast reflux into the inferior vena cava (IVC) (Figure 1b). Due to worsening breathlessness, surgical excision was offered.
 Surgery was attempted through a lower hemi-sternotomy. However, due to limited access to the cyst and thickened pericardium, median sternotomy was performed. The cyst measured 10cm x 7cm and was heavily adherent to the RV wall, right atrium and IVC preventing complete excision. The cyst was therefore unroofed, releasing cheese-like material suspicious of a tuberculous cyst (Figure 2). Adhesiolysis was undertaken to remove remaining cyst wall. Prior to closure, inflamed pericardial tissue was excised.
 Histopathology revealed a chronically inflamed pseudocyst with necrotising and non-necrotising granulomatous inflammation. Ziehl-Neelsen, Grocott, Gram and periodic acid-Schiff-diastase stains were negative. Intraoperative and histological findings and history of tuberculosis suggested a diagnosis of tuberculous pericardial cyst.
 The patient recovered uneventfully with significant symptomatic improvement at 2-month follow-up.


Big data sources provide a significant opportunity for governments and development stakeholders to sense and identify in near real time, economic impacts of shocks on populations at high spatial and temporal resolutions. In this study, we assess the potential of transaction and location based measures obtained from automatic teller machine (ATM) terminals, belonging to a major private sector bank in Indonesia, to sense in near real time, the impacts of shocks across income groups. For each customer and separately for years 2014 and 2015, we model the relationship between aggregate measures of cash withdrawals for each year, total inter-terminal distance traversed by the customer for the specific year and reported customer income group. Results reveal that the model was able to predict the corresponding income groups with 80% accuracy, with high precision and recall values in comparison to the baseline model, across both the years. Shapley values suggest that the total inter-terminal distance traversed by a customer in each year differed significantly between customer income groups. Kruskal-Wallis test further showed that customers in the lower-middle class income group, have significantly high median values of inter-terminal distances traversed (7.21 Kms for 2014 and 2015) in comparison to high (2.55 Kms and 0.66 Kms for years 2014 and 2015), and low (6.47 Kms for 2014 and 2015) income groups. Although no major shocks were noted in 2014 and 2015, our results show that lower-middle class income group customers, exhibit relatively high mobility in comparison to customers in low and high income groups. Additional work is needed to leverage the sensing capabilities of this data to provide insights on, who, where and by how much is the population impacted by a shock to facilitate targeted responses.


A numerical model is presented for the evaluation of the dielectric permittivity tensor changes as induced by guided modes during the formation of holographic gratings in arbitrary photorefractive graded-index planar waveguides. Comparisons among lithium niobate waveguides with different cuts and technology are shown.


Vaccination trials against Mycoplasma mycoides subsp. mycoides in suckling and weaned kids are described. A formalin-killed vaccine with adjuvant was used. Challenge to the vaccinated suckling kids was by ingestion of dam's infected milk and by subcutaneous inoculation of 10(6) organisms, and to the vaccinated weaned kids, by subcutaneous inoculation alone. The weaned 6-week-old kids were vaccinated, given a booster 3 weeks later and challenged 1 month after that. Serological monitoring was by enzyme-linked-immunosorbent assay (ELISA). The six control kids remained serologically negative and after challenge were pyrexic and mycoplasmaemic. All died or were killed in extremis, with a characteristic cellulitis at the site of inoculation, arthritis and swollen spleen. In contrast, the vaccinated kids remained healthy. There was a modest antibody response to the initial vaccination and a further steep rise after the booster. After challenge the organism was recovered only from the lymph nodes proximal to the site of challenge in some animals, and from the liver and kidney in two animals. All the vaccinated suckling kids were unaffected by ingestion of their dam's infected milk. The kids that received only one vaccine inoculation on the day of birth, and one control kid, succumbed to subcutaneous challenge, whereas the kids that were given a booster, except for one, remained healthy.


Opportunistic scheduling has been known as one of the possible ways of exploiting multi-user diversity, which comes from the time-varying propagation characteristics and broadcast nature of wireless radios, to improve communication efficiency and reliability. Multi-channel multi-radio technology has offered great opportunity in designing wireless network MAC protocol to utilize all kinds of resource diversities. Other than multi-user diversity, we identify the unique multi-radio diversity which can be exploited in multi-radio wireless network to improve network throughput performance. The proposed opportunistic multi-radio MAC (OMMAC) takes advantage of multi-radio diversity to increase the spectrum usage as much as possible. Extensive NS2 simulation results demonstrate that OMMAC significantly improves the network throughput in both single and multi-hop wireless networks.


Most breeds of sheep are "seasonal breeders", meaning that ovulation only occurs during certain times of the year. There are some methods for estrus synchronization in Sheep. The methods of estrus synchronization can be classified as natural (ram effect) and pharmacological methods. The "ram effect" (RE) is an inexpensive technique than pharmacological methods. Pheromones in the wool, wax and urine of a ram stimulate to be nervously and hormonal ewes on reproductive activity. Ram or male effect involves the introduction of rams to ewe, which has been previously isolated from males for 4- 6 weeks. If anestrous ewes are preconditioned by a period of isolation, the introduction of rams induces changes in their reproductive physiology: Luteinizing Hormone (LH) pulsatility is increased, and ovulation is induced in many of the ewes. Ram effect is a necessary technique for lambing in the out of season in the breeding condition due to its applicable of the using is cheaper and easier than others.


In this work we consider piecewise linear vector quantizer of two-dimensional memoryless Laplacian source. Linearization method of the compression function is analyzed, then the effects of this linearization methods of the compression function on total distortion (granular and overload) are presented an this method is also compared with nonlinear method. The vector space is partitioned using rectangular cells. Ill. 3, bibl. 5 (in English; summaries in English, Russian and Lithuanian).


Teleological behaviorism (TEB) is a behavioral identity theory that denies what seems to be the intuitively obvious notion that our minds are contained in our bodies—more specifically, in our brains. TEB holds, instead, that our minds are identical with abstract, temporally, and socially extended patterns in our overt behavior. TEB depends not on efficient causes but on a wide (or inclusive) version of final causes. This article illustrates how TEB accounts for mental acts and defends it against other theories of mind such as neural identity theory and double-aspect theories.


The explosive growth of the World Wide Web (WWW) has resulted in intricate Web sites, demanding for tools and methods to complement user skills in the task of searching for the desired information. In this context Web usage mining techniques have been developed for the discovery and analysis of frequent navigation patterns from Web server logs, which can be used as input for recommendation engines. Web usage mining techniques have been associated with Web content mining approaches in order to increase the accuracy of recommendation mechanisms. Existing approaches represent Web pages' content essentially by means of keywords, N-grams or ontologies of concepts, being, therefore, incapable of capturing the semantic information and the relationships among pages at the semantic level. Herein, we propose a method that combines usage patterns extracted from server logs with detailed semantic data that characterizes the content of the corresponding pages. Thus, a method to extract and analyze frequent semantic navigation patterns which are fed into a recommendation engine is proposed. We argue that by integrating usage and Web pages' detailed semantic information in the personalization process we will be able to increase the recommendation accuracy. The proposed method is an example of semantic Web mining that combines two fast developing research areas; Semantic Web and Web Usage Mining. We conducted an extensive experimental evaluation that provides strong evidence that the recommendation accuracy increases with the integration of semantic and usage data. The results show that the proposed method is able to achieve 15-17% better accuracy than a usage based model, 5-7% better than a N-gram based model and 4-6% better than a ontology based model. Also the proposed method is able to address the new item problem of solely usage based techniques by augmenting navigation patterns with newly added pages in a Web site.


Syringomyelia is characterized by progressive abnormal cerebrospinal fluid (CSF) accumulation in the spinal cord. It causes dissociated suspended anesthesia that affects pain and temperature sensation, predominantly in the upper limbs. Etiology is unclear, although a number of theories have been proposed. The accepted consensus, however, is that syringomyelia is a manifestation of an underlying pathology rather than a disease itself. Treatment of the primary cause often leads to regression of the syrinx.


The importance of total body fat and distribution has been stressed as a major risk factor for both adults and children. There is paucity of information concerning total and abdominal obesity among university students in South Africa. The purpose of this study was to screen for total and abdominal obesity among university of Venda health sciences students, using the proxy measures of body mass index (BMI) and waist-to-height ratio (WHtR). A stratified random sample of 389 (199 males and 199 females) university students aged 19-24 years, participated in the study. Height, weight, waist and hip circumferences were measured using standard techniques. Body mass index was calculated by dividing body mass by stature in meters squared. The WHO criteria were used to determine BMI categories, while WHtR was calculated by dividing waist circumference (in cm) by stature (in cm). A WHtR ≤ 0.50 was used to determine abdominal obesity. The mean age, BMI and WHtR of the participants were 20.8±2.1, 23.8±4.6 and 0.54±0.1, respectively. Overall, 7.5%, 21.4% and 11.1% of the students were underweight, overweight and obese, respectively. The percentage of students who were overweight was higher in females (11.7%) than males (9.7%), whereas obesity occurred more among the males (6.2%) compared with the females (4.9%). Underweight was 4.4% and 3.1% for females and males, respectively. A total of 102 students (19.2%) had central obesity as determined by WHtR. The proportion of males with a WHtR ≥ 0.5 was 59 (11.1%), while females were 43 (8.1%), with the males having statistically significant (p=0.001) WHtR compared to females. The prevalence of total and abdominal obesity is high among the University of Venda students; which is worrisome, given the health consequences of excessive body fat. Intervention measures should be instituted to address the rising trend of overweight and obesity in the students.


Abstract:
 Plestiodon kishinouyei is the largest skink in Japan and is endemic to Miyako and Yaeyama Islands, located in the southern part of the Ryukyu Archipelago, Japan. It is considered to be heliothermic and thus exclusively diurnal. However, I observed this species to be active on Iriomote-jima Island several times at night. Nocturnal activity was recorded mostly on rainy nights and exclusively in fall, whereas most daytime activity was observed on days without rain and in the summer. These field observations suggest that P. kishinouyei is occasionally active at night. To better understand its thermal ecology, further studies of the nocturnal habits of P. kishinouyei should be performed.


The Amazonian rainforest is critical to our shared human future. Therefore, we need to understand the structure and function of their forests and soils are a critical part of that investigation. Towards that end, soil samples were taken in eight different forests, both non-flooded (terra firme-low forests, terra firme-high forests, white sand-varillal forests, white sand-chamizal forests and palm forests) and flooded by black-water (high restinga, low restinga and tahaumpa forests), at two locations in Loreto Province, Peru and analyzed for soil pH, soil organic matter, and soil nitrogen (N), phosphorus (P), and potassium (K). Results showed that: (1) soil pH of the non-flooded forests was very similar to flooded forests, but flooded forests became more basic as flooding increased in duration; (2) soil organic matter was lowest in the two non-flooded terra firme forests and increased as flooding increased in duration; (3) N was lowest in the palm forest, P was lowest in terra firme-low terrace forest and K was lowest in the terra firme-high terrace forest; (4) N decreased sharply as flooding duration increased, both P and K increased while (5) for some non-flooded forests there was a correspondence between soil fertility and floristic similarity. In conclusion, while flooding decreases pH and N, it increases soil organic matter, P and K.

 Key words: Palm forest, restinga, tahuampa, terra firme, white sand forest.


Fragmented sleep is a common and troubling symptom in ageing and Alzheimer's disease; however, its neurobiological basis in many patients is unknown. In rodents, lesions of the hypothalamic ventrolateral preoptic nucleus cause fragmented sleep. We previously proposed that the intermediate nucleus in the human hypothalamus, which has a similar location and neurotransmitter profile, is the homologue of the ventrolateral preoptic nucleus, but physiological data in humans were lacking. We hypothesized that if the intermediate nucleus is important for human sleep, then intermediate nucleus cell loss may contribute to fragmentation and loss of sleep in ageing and Alzheimer's disease. We studied 45 older adults (mean age at death 89.2 years; 71% female; 12 with Alzheimer's disease) from the Rush Memory and Aging Project, a community-based study of ageing and dementia, who had at least 1 week of wrist actigraphy proximate to death. Upon death a median of 15.5 months later, we used immunohistochemistry and stereology to quantify the number of galanin-immunoreactive intermediate nucleus neurons in each individual, and related this to ante-mortem sleep fragmentation. Individuals with Alzheimer's disease had fewer galaninergic intermediate nucleus neurons than those without (estimate -2872, standard error = 829, P = 0.001). Individuals with more galanin-immunoreactive intermediate nucleus neurons had less fragmented sleep, after adjusting for age and sex, and this association was strongest in those for whom the lag between actigraphy and death was <1 year (estimate -0.0013, standard error = 0.0005, P = 0.023). This association did not differ between individuals with and without Alzheimer's disease, and similar associations were not seen for two other cell populations near the intermediate nucleus. These data are consistent with the intermediate nucleus being the human homologue of the ventrolateral preoptic nucleus. Moreover, they demonstrate that a paucity of galanin-immunoreactive intermediate nucleus neurons is accompanied by sleep fragmentation in older adults with and without Alzheimer's disease.


This paper proposes an innovative ultrasonic time of flight (TOF) measurement method with narrow-band transducers. By introducing the received ultrasonic wave peak time sequences (PTSs) of two slightly different frequencies, the relative TOF can be accurately identified with a much better resolution than a wave period. The new PTS TOF measurement is achieved in two steps. First, a PTS is built for receiving the ultrasound signal of each frequency according to the arrival time of the wave peaks by calculating the mean value of the adjacent crossover time. Second, the arrival time of the wave front is rebuilt by estimating the common initiation time of the PTSs for the received waves of slightly different frequencies. A mathematical model is derived to describe the signal reception, from which the TOF estimation algorithm was derived. A simulation model describing the characteristics of the ultrasonic transducer and the ultrasonic wave propagation physics was developed to verify the feasibility of the new algorithm. Finally, an experimental system for measuring the relative TOF over the known distance of 550-1450 mm was implemented to confirm feasibility and to demonstrate that a subwavelength resolution of 0.015 times of the wavelength was indeed achievable in measuring distances over meters.


In this article we follow an approach of Oosterlink and Weidenmeier to explore the reaction of financial markets to the Expedition of the Thousands, a fundamental event for unification of Italy which occured in 1860. We provide evidence of a collapse of quotations of bonds of Kingdom of the Two Sicilies, in particular focusing on daily quotation from early May to the end of October. We show how markets reacted to the victory of Garibaldi and provide an interesting insight into economic history of our country.


The silver-mediated one-pot synthesis of 3-trifluoromethylpyrazoles using a traceless directing group was investigated by density functional theory (DFT) calculations. In this paper, we studied computationally the two putative reaction mechanisms and origins of high regioselectivity to elucidate the principal features of this transformation. The calculated results reveal (1) the pathway involving silver-mediated cycloaddition is more kinetically favored; (2) the origin of high regioselectivity for the reaction; (3) silver(I) and nitro group can effectively improve the reaction activity and reduce the overall barrier of the reaction to 22.9 kcal mol−1.


Cascade defects generated by ion irradiation in Bi2212 single crystal were investigated by transmission electron microscopy (TEM). The irradiation was performed by 18 MeV Fe 8+ ions at 1x10 12 ions/cm 2 . The size and distribution of cascade defects were quantitatively measured by using an image analysis method. TRIM cord was applied to theoretical calculation compared with the results obtained from quantitative measurement results. The calculation results were consistent with experimental. Meanwhile, the differences of magnetization before and after irradiation were detected by SQUID measurements. The size and distribution of the cascade defects were found to be much influential for enhancement of critical current density. The relationship between irradiation condition and cascade defect can be used to form a model sample for controlling flux pinning centers with optimum size. In addition, the critical current density and cascade defects induced by 18, 14, and 10 MeV Fe ion irradiation along c-axis were also studied. The critical current density of this sample was compared with that of 18 MeV Fe 8+ ion irradiation sample in same fluence.


The United Nations Human Rights Council has established several international commissions of inquiry to investigate situations of concern, make findings as to the existence of violations and offer recommendations for follow-up action. Many commissions have gone beyond the realm of human rights, also finding that international humanitarian law was violated and international crimes were committed. While scholars have extensively explored human rights bodies' engagement with international humanitarian law, the migration of international criminal law (ICL) into human rights fact-finding has received less attention. In light of commissions' bourgeoning engagement with ICL, the time is ripe to critically examine the evolution and possible consequences of 'dejudicialised' international criminal law. Possible jurisdictional bases for this normative migration are explored. After laying the jurisdictional foundations, the article examines how commissions have utilised ICL norms in practice. The article cautions against normative distortions that may arise from the translocation of ICL norms into non-judicial settings. Recognising that differentiated treatment of international legal norms might in principle be possible in different institutional contexts, the article explores how normative coherence in ICL could be promoted in the non-judicial setting of international commissions of inquiry.


A spectral-domain analysis is performed on three multi-layer parallel-coupled lines. The self and mutual capacitances of the structure, the per-unit-length capacitance matrix elements, and the three quasi-TEM mode per-unit-length capacitances are derived explicitly for the first time in terms of capacitances corresponding to arbitrary excitations. The mode impedances of the lines are found to be unequal for lines of equal width unlike previously reported.


Sediment binding crusts of Lithocodium aggregatum and associated Bacinella irregularis abound in a shallow water limestone layer, in South-East France. The sudden appearance of these crusts denotes a local, conspicuous change in the otherwise balanced, open marine depositional environment. Based on regional correlations, the layer is Lower Hauterivian, Ligatus Zone, directly dated by an assemblage of orbitolinids, and indirectly by a specimen of ammonite. It is older than the Faraoni OAE (latest Hauterivian, Angulicostata auct. Zone), and presumably not linked with a global climate change. Two facies are recognized: (1) Lithocodium bindstone, with Bacinella, other microencrusters, and fluorescent automicrite of microbial origin; (2) floatstones containing numerous fragments of Lithocodium and accompanying biota. Coarse rhomboedral dolomite is locally present. Two modern analogues of microbial mediation are put forward to explain the Lithocodium event: (a) Lagoa Vermelha, in Brazil, along with anoxic, marginal marine conditions; (b) Highborne Cay, in the Bahamas, along with oxic, open marine conditions. A stack of four, Upper Hauterivian parasequences is described: Parasequence 1 ends with oolitic deposits; the somewhat deeper water Parasequence 2 occurs only in the south-eastern part of the study area, towards the direction of the Subalpine depotcenter; Parasequence 3 matches the layer with Lithocodium and Bacinella, with wide thickness variations (0.8 m - 11 m), resulting from a syn-sedimentary tectonic activity in the area of a major feature, the Vuache fault system. Parasequence 4 finally corresponds to the resumption of the normal, Urgonian carbonate factory.


For earthquake prediction, we should strategically link several methods, exchange and share earthquake-related information. The hydrological method has been recently developed and not yet had a suitable theory which can adequately explain hydrological precursors to earthquakes. Therefore it is important to clarify the mechanism of earthquake-related hydrological changes and turn the hydrological information into the information which can be easily understood by seismologists. From this point of view, we propose four roles of hydrological methods for earthquake prediction; (1) providing crustal deformation data estimated from hydrological changes, which is usually useful for the short-term prediction, (2) providing the information related to displacements of ground surface caused by groundwater level changes, which will enable us to eliminate some non-tectonic deformations of ground surface and contribute to improving S/N ratio in the geodetic measurement such as GPS observations, which will be useful for the mid-term or long-term prediction, (3) providing the information related to temporal changes in permeability in and around active fault zones, which contributes much to understanding the earthquake-cycle in the active faults and the long-term prediction, and (4) providing the information of pore-pressure changes in the focal region. At present, only the first role can be applied to the practical short-term prediction. Therefore detecting more reliable hydrological precursors to earthquakes depends on how they are connected to preseismic crustal deformation. The `strain model' attributes groundwater changes to volumetric strain changes, and is the only model that can quantitatively explain the precursors at present although it needs more improvement. For the improvement, comparing groundwater level changes with crustal deformation is effective.


Background: Low back pain (LBP) is a common cause of morbidity in health care workers. Low back pain will impose occupational and problem in personal life and also problem in health care system. Nurses are among the occupational groups that are vulnerable to LBP. Low back pain can occur from manual lifting (patients in particular). This study aimed to investigate ergonomic intervention to reduce of LBP and fatigue among nurses at Prof Dr. WZ Yohanes Hospital, Kupang. Subjects and Method: This was a quasi-experiment with one group pre test post test conducted at Prof Dr. WZ Yohanes Hospital, Kupang, East Nusa Tenggara. Total of 20 nurses with LBP were selected randomly for this study. The dependent variables were LBP and fatigue. The independent variable was stretching intervention conducted for 30 to 45 minutes by simple stretching. Pain level was measured by Oswestry instrument. The data was analyzed by paired t-test. Results: Level of LBP after stretching (Mean= 9.45; SD=3.76) was lower than before (Mean= 11.77; SD= 3.95) or it decreased by 19.74% and it was statistically significant (p<0.001). Fatigue score after stretching (Mean= 373.72; SD= 39.54) was lower than before (Mean= 421.52; SD= 50.46) or it decreased by 11.33% and it was statistically significant (p<0.001). Conclusion: Strecthing intervention is effective for reducing LBP and fatigue among nurses.


The assembly and release of retroviruses from the host cells requires a coordinated series of interactions between viral structural proteins and cellular trafficking pathways. Although a number of cellular factors involved in retrovirus assembly have been identified, it is likely that retroviruses utilize additional trafficking factors to expedite their assembly and budding that have not yet been defined. We performed a screen using an siRNA library targeting host membrane trafficking genes in order to identify new host factors that contribute to retrovirus assembly or release. We utilized two retroviruses that follow very distinct assembly pathways, HIV-1 and Mason-Pfizer monkey virus (M-PMV) in order to identify host pathways that are generally applicable in retrovirus assembly versus those that are unique to HIV or M-PMV. Here we report the identification of 24 host proteins identified in the screen and subsequently validated in follow-up experiments as contributors to the assembly or release of both viruses. In addition to identifying a number of previously unsuspected individual trafficking factors, we noted multiple hits among proteins involved in modulation of the actin cytoskeleton, clathrin-mediated transport pathways, and phosphoinositide metabolism. Our study shows that distant genera of retroviruses share a number of common interaction strategies with host cell trafficking machinery, and identifies new cellular factors involved in the late stages of retroviral replication.


In non-relativistic mechanics the center of mass of an isolated system is easily separated out from the relative variables. For a N-body system these latter are usually described by a set of Jacobi normal coordinates, based on the clustering of the centers of mass of sub-clusters. The Jacobi variables are then the starting point for separating orientational variables, connected with the angular momentum constants of motion, from shape (or vibrational) variables. Jacobi variables, however, cannot be extended to special relativity. We show by group-theoretical methods that two new sets of relative variables can be defined in terms of a clustering of the angular momenta of sub-clusters and directly related to the so-called dynamical body frames and canonical spin bases. The underlying group-theoretical structure allows a direct extension of such notions from a nonrelativistic to a special-relativistic context if one exploits the rest-frame instant form of dynamics. The various known definitions of relativistic center of mass are recovered. The separation of suitable relative variables from the so-called canonical internal center of mass leads to the correct kinematical framework for the relativistic theory of the orbits for a N-body system with action-ata-distance interactions. The rest-frame instant form is also shown to be the correct kinematical framework for introducing the Dixon multi-poles for closed and open N-body systems, as well as for continuous systems, exemplified here by the configurations of the Klein-Gordon field that are compatible with the previous notions of center of mass. Invited contribution for the book Atomic and Molecular Clusters: New Research (Nova Science).


A parameterised wideband equivalent circuit model capturing the per-unit-length (p.u.l.) frequency-dependent resistance and inductance of on-chip coplanar waveguides (CPWs) is presented. The parameterised model for on-chip CPWs is suitable for various process nodes and over a large geometry range with signal line width-to-thickness ratios w s / t between 1 and 15 and spacing-to-thickness ratios s / t between 0.25 and 15. The model has been validated by both EM simulation and measurements of fabricated test chips. The model is accurate to within 10% over the normalised geometry range. The model can easily be implemented into standard circuit simulators.


In recent decades, handling of bio-hazardous dyes such as crystal violet in various discharges is a growing concern which can affect the global aquatic scenario. A low-cost environment-friendly nanocomposite was synthesized for the removal of crystal violet dye from industrial effluent solution. The efficacy of plant(Azadirachta indica)-mediated synthesized silver nano soil composite as an adsorbent was evaluated in a batch reactor. A composite model system was introduced linear and non-linear responsiveness towards the kinetics of adsorption of crystal violet onto Ag-nano soil composite during batch experimental study. The equilibrium kinetics was analysed using pseudo-second-order kinetic model system. The coefficient of determination and chi-square tests were implemented to explore the best fit of the equation. The experimental data were better represented by non-linear model system than that of linear model system.


GaN-based light emitting diode (LED) structure (n-GaN/quantum wells/p-GaN) was grown by molecular beam epitaxy (MBE) on a GaN-on-Si template substrate grown by metal organic chemical vapor deposition (MOCVD). The GaN crystal grew continuously on the template and surface of the GaN film was flat. We fabricated very thin comb-shaped electrodes on the GaN film as semi-transparent metal contacts. Blue light emission was observed from the semi-transparent electrode region on p-GaN crystal at peak wavelength of 410nm at room temperature. On the other hand, we propose a light distribution variable device which changes the light direction emitted from LEDs by integration of GaN-based LEDs and Si micromachining technology. To demonstrate the light distribution variable device, we fabricated micro stage from the template substrate as preliminary experiment for the light distribution variable device. The device was successfully fabricated and we observed that the stage moved about 40 μm at the voltage of 100 V. These values are almost same as calculated values. Photoluminescence (PL) was also observed in this device. The electric wiring has not been completed, these results demonstrate the usefulness of monolithic fabrication of GaN-Si hybrid MEMS.


Abstract  An increasing number of patients with previous minimally invasive thoracic procedures for anterior mediastinal tumors are now requiring cardiac surgery. This paper highlights the potential damage that can occur when standard sternal splitting techniques are used in these patients.


Ripe fruits of Barbados cherry Malpighia glabra L. proceeding from the fruit-growing section of Iguatemi Experimental Farm of Universidade Estadual de Maringa (PR), were triturated in a liquefier and hulled in a stainless steel sieve with 25 mesh. The bagasse (seeds and hull) was discarded and the vitamin C content was immediately determined, which was 1.79 g by 100 g of pulp. After that, the integral pulp was packed in glass flasks and submitted to the exhaustion and pasteurization processes and then hermetically closed. After the heat treatment the vitamin C content was 1.54 g by 100 g of pulp. The sealed flasks of Barbados cherry pulp, with and without the aluminum foil protection, were stored for 40 days. The first portion was kept at room temperature, the second in a refrigerator (1 degree C), and the third in a freezer (-18 degrees C). The vitamin C content analysis were realized on the 5th, 10th, 15th, 20th, 30th and 40th day. For the flasks stored without the aluminum foil protection, there was a loss of 22.08%, 7.79% and 1.30% and with aluminum foil the loss was of 10.40%, 3.90% and 1.30% for the storage at room, refrigeration and freezing temperatures, respectively. The results show that freezing method is the best form of vitamin C preservation.


INTRODUCTION The Hampton Roads region is located in southeastern Virginia where the Chesapeake Bay meets the Atlantic Ocean. The region includes seventeen municipal governments and has a large federal government presence with 26 federal agencies represented (See Figure 1). The region has a population that exceeds 1.7 million and is home to the deepest water harbor on the U.S. East Coast. Hampton Roads' economy is dependent on the local waterways and houses the world's largest naval facility, the sixth largest containerized cargo complex and supports a thriving shipbuilding and repair industry as well as a tourism industry. However, the region's vast coastline also contributes to its vulnerability from climate change. Hampton Roads is experiencing sea level rise at twice the global rate with regional projections in the January 2017 National Oceanic and Atmospheric Administration (NOAA) report, Global and Regional Sea Level Rise Scenarios for the United States, of 1.9 feet of sea level rise at the low end and 11.5 feet of sea level rise under the most extreme case between 2000 and 2100 (NOAA, 2017). Planning for adaptation to sea level rise requires regional partnerships and strategies, especially for watersheds that cross municipal boundaries. While many of the municipalities in the region are forward thinking in their approaches to sea level rise, there is not a regional plan for adaptation and current federal funding models do not support analysis of and planning for sea level rise impacts on a regional scale. For coastal communities to be successful in sea level rise adaptation, there has to be a national understanding that water knows no borders and only collaborative problem-solving approaches that cross municipal boundaries will move regions toward adaptation. Functional boundaries of ecosystems or watersheds need to be the focus of adaptation rather than political boundaries of local, state, and federal entities. Coordination and collaboration between entities is the only way to achieve optimal outcomes.


In this work we analyse the pollination community in a South American forest known as 'talar'. This is a vegetal woody community that inhabits fossil coastal banks characterized by seasonal temperate weather and calcareous soil, at the coast of the Rio de la Plata, in the province of Buenos Aires, Argentina. We obtained data of the interactions between anthophylous insects and entomophylous flowering plants over an extensive period of time. We showed that pollination system parameters, such as partners' identity, system size, and connectance, fluctuated among months, when sampled year-long. Maximal network size occurred in early spring and early autumn, when both the number of mutualistic species and the number of interactions peaked, and this was also when network asymmetry was higher than average. Monthly connectance of the plant-flower visitor matrix decreased to its lowest values at these peaks. Available data suggest that cumulative traditional connectance (i.e. the connectance calculated as the whole number of interactions registered in the community divided by the full size system) underestimates actual connectance values by a factor of c. 3 ×. Monthly values of connectance decreased exponentially as system size increased, and the distribution of interactions per species followed power-law regimes for animals, and truncated power-law regimes for plants, in accordance with patterns previously deduced from among-network cumulative communities studies. We think that either within or and among pollination networks, systems that are organized as power-law regimes may be a basic property of these webs, and provide examples of the fact. Both seasonal changes and interactions between mutualists like competition, and some degree of facilitation, may be very important to understand the performance of the system as a whole, and the role and importance of different species in the community. We suggest that communities of plant – pollinators that exhibit extended activity, such as temperate or tropical seasonal ones, should be studied through consecutive plant-pollinator webs rather than cumulative ones. The partition of the system into smaller serial parts allows us to obtain outstanding information of every short period. This information is flattened by the average effect when we considered the combined analysis of the whole data.


This research examines how consumers feel when they use counterfeits, and how these feelings affect purchase intentions toward counterfeits and genuine brands. We find that counterfeit users experience mixed emotions, stemming from concerns about the signals the counterfeit might send to others. Accordingly, mixed emotions are stronger in public versus private settings, and among consumers chronically concerned about social signaling (i.e., consumers high in social-adjustive motives). Because mixed emotions can be unpleasant, counterfeit users subsequently gravitate away from counterfeits and toward genuine brands (which communicate largely positive social signals and thus elicit no mixed emotions). In this manner, counterfeit consumption may drive demand for genuine brands. A final experiment tests implications for reducing counterfeit consumption. As predicted, consumers exposed to anti-counterfeiting advertisements designed to elicit mixed emotions are willing to pay a higher price premium for genuine over counterfeit products. Collectively, these findings identify the emotional consequences of counterfeit consumption and highlight that an effective way to understand and reduce counterfeit consumption is to focus on the social context in which many counterfeits are used.


The increasing attention to climate changes have led national Governments to design environmental tax policies able to face environmental problems and their associated economic consequences as a negative change of GDP. The environmental taxation in particular is considered a powerful instrument of pollution control. More important, it provides public revenue that can be recycled both at State level and Local level in order to attain the reduction of greenhouse gas emissions and the regional double dividend. In this respect, we use a Computable General Equilibrium (CGE) model with imperfect labour market, to assess the regional effects of an environmental fiscal reform designed with the aim of reducing the CO2 emissions in a fiscal federalism setting. In particular, we introduce a local green tax on commodities output with a progressive structure. The tax burden depends on the commodity polluting power and the tax revenue is collected by the Local Government. According to the fiscal federalism principles the Central Government reduces the transfers to the Local Government by the same amount of the tax revenue and compensates the transfer reduction with a cut in Households income tax. The application is done on a bi-regional Social Accounting Matrix for Italy and the results highlights the distributional effects of the reform on macroeconomic variables into the bi-regional income circular flow.


The corrosion inhibition behaviour of Sabic iron in the absence and in presence of some azo compounds derived from 2, 3-and 2, 7-dihydroxynaphthalene was investigated using weight loss, thermometry and galvanostatic polarizations techniques. It was found that, the inhibition efficiency of these compounds depends on their concentration and chemical structure. The inhibitive action of these azo compounds was discussed in terms of blocking the electrode surface by adsorption of the azo dye molecules through the active centres in their structure. The adsorption process follows Temkin isotherm. The effect of temperature on the rate of corrosion was considered and some activated thermodynamic functions were computed and discussed. Quantum chemical calculations and molecular simulations were further applied to reveal the adsorption structure and explain the experimental results.


Background: Today, medical tourism is a growing phenomenon in the healthcare industry, especially among developing countries. Objectives: The purpose of this study was to compare the Iranian medical tourism industry with selected countries. Methods: This comparative study was conducted in 2020. Data were gathered from databases, including PubMed, Web of Knowledge, Scopus, Magiran, SID, and websites of the World Tourism Association, the Ministry of Tourism, and the Ministry of Health of the selected countries from 2000 to 2020. A researcher-made checklist was used to collect data. Selected countries were compared in terms of the status of tourism and travel competitiveness, governance and policy-making status, the status of the medical tourism industry, and medical tourism infrastructure Results: The main difference between the selected countries and Iran lies in the organizational structure of the main stakeholders of the tourism industry. In other countries, this industry is organized and supervised by specific coordination bodies. In terms of tourism and travel competitiveness, Singapore, with a global rank of 17, was better than other countries. Based on the status of the medical tourism industry, Costa Rica ranked 7th in the world, and Singapore, the UAE (Dubai), Turkey, UAE (Abu Dhabi), Jordan, and Iran ranked 15, 22, 27, 31 35, and 41, respectively. In Iran, all indicators of medical tourism infrastructure were lower than those of other countries except for competitive prices. Conclusions: Considering a low rank of Iran in all the studied components, the organizational integration structure of the medical tourism industry and increasing competitiveness can help the development of this industry in Iran.


This study surveys the external morphology of the mouthparts in the guild of spore-feeders among the coleopterous superfamily Staphylinoidea, evaluating the influence of different phylogenetic and ecological starting points on the formation of their mouthparts. Our emphasis is on a scanning electron microscope analysis (SEM) of the involved trophic structures in spore-feeding larvae and adults of the Ptiliidae, Leiodidae and Staphylinidae, describing the fine structure of their main functional elements. Functionally, mouthpart structures resemble brushes, brooms, combs, rakes, rasps, excavators, knives, thorns, cram-brushes, bristle troughs, blocks and differently structured grinding surfaces. Their different involvement in the various aspects of the feeding process (i.e. food gathering, transporting, channelling and grinding) is deduced from our SEM analyses plus direct video observations. We infer five different patterns of food transport and processing, discriminating adults of ptiliids, leiodids plus staphylinids (excluding some aleocharines), several aleocharine staphylinids, and the larvae of leiodids and staphylinids. The structural diversity of the mouthparts increases in the order from (1) Ptiliidae, (2) Leiodidae towards (3) Staphylinidae, reflecting the increasing systematic and ecological diversity of these groups. Comparisons with non-spore-feeders show that among major lineages of staphylinoids, shifts from general microphagy to sporophagy are not necessarily constrained by, nor strongly reflected in, mouthpart morphology. Nevertheless, in several of these lineages the organs of food intake and grinding have experienced particular fine-structural modifications, which have undergone convergent evolution, probably in response to specialized mycophagy such as spore-feeding. These modifications involve advanced galeal rakes, galeal or lacinial 'spore brushes' with arrays of stout bristles, reinforced obliquely ventrad orientated prosthecal lobes and the differentiations of the molar grinding surfaces into stout teeth or tubercles. In addition, several staphylinids of the tachyporine and oxyteline groups with reduced mandibular molae have evolved secondary trituration surfaces, which in some aleocharines are paralleled by considerable re-constructions of the labium–hypopharynx.


Today, Cloud computing become an emerging technology which will has a significant impact on IT Infrastructure. Still, Cloud computing is infancy. In the current cloud computing environment there is numerous of application, consist of millions of module, these application serve from large quantity of users and the user request becomes dynamic. So there must be provision that all resources are dynamically made available to satisfy the needs of requesting users. The resource provisioning was done by considering Service Level Agreements (SLA) and with the help of parallel processing using different types of scheduling heuristic. In this paper we realize such various policies for resource provisioning and issues related to them in current cloud computing environment.


ISSN: 2410-9649 Shadrach et al / Chemistry International 6(2) (2020) 83-90 iscientic.org. 84 www.bosaljournals/chemint/ firstname.lastname@example.com soups), as "Dodo" (fried ripe fruit), "Kpekere" (thinly sliced fried slightly ripe/unripe plantain fruit). However, the peels are mostly regarded as waste and often discarded indiscriminately in landfills, drainages and road sides; consequently posing a threat to the environment (Auta and Kumurya, 2015; Baiyeri et al., 2011). The Plantain peel which accounts for about 40 % of the total fruit weight (Gilver and Liliana, 2017) has reportedly been shown to have potential as a promising raw material which could find useful industrial applications especially in the agro-based industries. The peels have been considered for use as organic fertilizers in places like Somalia to enrich soils and enhance better crop production and yield (Eun-Hye et al., 2010; Okareh et al., 2015). Reports have shown the peels as being good potential substitute for corn starch in the diet of snails and also incorporated with other waste materials in the diet of pigs (Okareh et al., 2015; Omale and Okafor, 2008). Meanwhile, in the chemical industry, the peels have shown potential for the generation of important chemicals like ethanol and also alkali for the manufacturing of soap. As a way of ensuring a safer environment, attempts have been made to use polyphenolic resol resins from the ethanol extract of plantain peels for the adsorption of heavy metals since the peels show high retention affinity for lead, nickel and chromium (Andres et al., 2015). Also in the food industry, flour made from the peels has been reportedly used to enrich wheat flour at various percentages in producing snacks like cookies and sausages; serving as a good source of fibre, antioxidants and potentially benefiting humans in the management and prevention of life style related diseases (Gilver and Liliana, 2017; Arun et al., 2015). Several studies have reported the antifungal and antibacterial activities of different parts including the peel of plantain plant for the treatment of a large number of human ailments (Auta and Kumurya, 2015). The ethanol extracts of the peels were used against eight human pathogenic microbes; five bacteria and three fungi and they proved effective against these human pathogens which have been implicated in several human diseases (Ighodaro, 2012). Thus, the peel extracts have been suggested for use in pharmaceutical and medical formulations. Some of the main pharmacological effects of the plantain plant including the peels are; antiulcer, analgesic, wound-healing, hair growth promoter, haemostatic activity among others (Alexandre et al., 2019; Aruwa et al., 2019; Barroso et al., 2019; D'Eliseo et al., 2019; Elbadrawy and Sello, 2016; Mohamad Sukri et al., 2019; Sanjeev et al., 2012). The use of plantain peel concurrently as food and medicine has not been given much attention; as focus is drawn more to its pharmacological applications. Hence, this study comparatively investigated the nutraceutical potential of ripe and unripe plantain peels. This was done by carrying out phytochemical screening on different solvent extracts of the peels as well as determining their proximate and mineral compositions. MATERIAL AND METHODS Sample collection and preparation Fresh ripe and unripe plantain fruits were harvested from a farm inside the Federal Government Girls' College, Sagamu, Ogun state. The peels were separated from the plantain pulp, thoroughly washed and sliced into chip size (0.5 cm2) with the aid of a cutting knife and then oven-dried at 50 oC for 10 hours. The dried peels were then pulverized with the aid of a laboratory blender (Lexus MG-2053 Optima), stored separately in airtight containers and kept in a refrigerator until further use. The pulverized samples were used for phytochemical screening, mineral and proximate composition analyses. The ripe plantain peel was coded as RPP while the unripe was coded as UPP. Extraction of samples Five grams each of the ripe and unripe pulverized plantain peel samples were macerated separately in 25 mL of the three different solvents viz; ethanol, acetone and water at room temperature for 48 hours. The resulting mixture was filtered through with Whatmann No. 42 filter paper and were then subjected to phytochemical screening using standard methods. Phytochemical screening Preliminary phytochemical screening was performed to determine the presence of secondary metabolites: alkaloids, tannins, flavonoids, phenolics, steroids, cardiac glycosides, saponins, terpenoids, reducing sugar and phytosterols in ethanol, acetone and water extracts of ripe and unripe plantain peels. These assays were carried out by standard methods (Martinez and Valencia, 2003; Pawaskar and Kale, 2007; Venkatesan et al., 2009; Sivaraj et al., 2011; Teresa and Bandiola, 2018)


New non-volatile memory (e.g., phase-change memory) provides fast access, large capacity, byte-addressability, and non-volatility features. These features, fast-byte-persistency, will bring new opportunities to fault tolerance. We propose a fine-grained checkpoint based on non-volatile memory. We extend the current virtual memory manager to manage non-volatile memory, and design a persistent heap with support for fast allocation and checkpointing of persistent objects. To achieve a fine-grained checkpoint, we scatter objects across virtual pages and rely on hardware page-protection to monitor the modifications. In our system, two objects in different virtual pages may reside on the same physical page. Modifying one object would not interfere with the other object. This allows us to monitor and checkpoint objects smaller than 4096 bytes in a fine-grained way. Compared with previous page-grained based checkpoint mechanisms, our new checkpoint method can greatly reduce the data copied at checkpoint time and better leverage the limited bandwidth of non-volatile memory.


Abnormal activation of the EGF receptor (EGFR) signaling is a hallmark of lung cancer. However, the role of heparin-binding EGF-like growth factor (HB-EGF), one of EGFR ligands, in lung tumorigenesis has been unappreciated. In this study, we showed that HB-EGF was highly expressed in a subgroup of lung cancer cells, the proliferation of which was dependent on HB-EGF signaling. Members of CITED family proteins respond to various cytokine signalings, regulating cell proliferation; among them, we identified CITED4 as a downstream effecter of HB-EGF. We revealed that CITED4 was upregulated by HB-EGF through a STAT3 dependent pathway. Moreover, CITED4-silencing attenuated HB-EGF-mediated lung cancer cell proliferation. ChIP analysis and promoter reporter assay showed that STAT3 bound CITED4 promoter, enhancing CITED4 transcription. Co-immunoprecipitation analysis identified MYC as a CITED4-interacting protein. Furthermore, we found that CITED4 expression promoted MYC-mediated transcription of cyclin D1 promoter, leading to increased G1/S cell cycle transition. Thus, our findings support that HB-EGF-CITED4 signaling cascade plays a critical role in aberrant proliferation in lung cancer with potential as a biomarker for lung cancer progression. Citation Format: Cheng-Han Hsieh, Yu-Ting Chou, Cheng-Wen Wu. HB-EGF‑mediated CITED4 signaling in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 40. doi:10.1158/1538-7445.AM2015-40


Measuring the blood pressure of patients with atrial fibrillation is difficult due to the high variability of the blood pressure. To obtain a representative average, the blood pressure should be measured as often as possible. Each blood pressure measurement should be repeated at least three times in succession.


Adrenocortical carcinoma is a rare disease. Additionally, in the case of coexisting pregnancy, there are diagnostic difficulties due to associated physiological hormonal changes as well as imaging limitations. Cushing's syndrome and virilization during pregnancy is a rare entity with few cases reported in the literature. Misdiagnosis is common as the syndrome may be easily confused with preeclampsia or gestational diabetes. We present the case of a 31-year-old pregnant woman with rapidly developing symptoms related to hormonally active adrenocortical cancer.


The B cell lymphoma I.29 consists of a mixture of cells expressing membrane-bound immunoglobulin M (IgM) (lambda) and IgA (lambda) of identical idiotypes. Whereas most of the cells express either IgM or IgA alone, 1 to 5% of the cells in this tumor express IgM and IgA simultaneously within the cytoplasm and on the cell membrane (R. Sitia et al., J. Immunol. 127:1388-1394, 1981; R. Sitia, unpublished data). When IgM+ cells are purified from the lymphoma and passaged in mice or cultured, a portion of the cells convert to IgA+. These properties suggest that some cells of the I.29 lymphoma may undergo immunoglobulin heavy chain switching, although it is also possible that the mixed population was derived by a prior switching event in a clone of cells. We performed Southern blotting experiments on genomic DNAs isolated from populations of I.29 cells containing variable proportions of IgM+ and IgA+ cells and on a number of cell lines derived from the lymphoma. The results were consistent with the deletion model for heavy chain switching, as the IgM+ cells contained rearranged mu genes and alpha genes in the germ line configuration on both the expressed and nonexpressed heavy chain chromosomes, whereas the IgA+ cells had deleted both mu genes and contained one rearranged and one germ line alpha gene. In addition, segments of DNA located within the intervening sequence 5' to the mu gene, near the site of switch recombination, were deleted from both the expressed and the nonexpressed chromosomes. Although mu genes were deleted from both chromosomes in the IgA+ cells, the sites of DNA recombination differed on the two chromosomes. On the expressed chromosome, Smu sequences were recombined with S alpha sequences, whereas on the nonexpressed chromosome, Smu sequences were recombined with S gamma 3 sequences.


The popular NL-means denoising algorithm proposes to modify the intensity of each voxel of an image by a weighted sum of the intensities of similar voxels. The success of the NL-means rests on the fact that there are typically enough such similar voxels in natural, and even medical images; in other words, that there is some self-similarity/redundancy in such images. However, similarity between voxels (or rather, between patches around them) is usually only assessed in a spatial neighbourhood of the voxel under study. As the human brain exhibits approximate bilateral symmetry, one could wonder whether a voxel in a brain image could be more accurately denoised using information from both ipsi- and contralateral hemispheres. This is the idea we investigate in this paper. We define and compute a mid-sagittal plane which best superposes the brain with itself when mirrored about the plane. Then we use this plane to double the size of the neighbourhoods and hopefully find additional interesting voxels to be included in the weighted sum. We evaluate this strategy using an extensive set of experiments on both simulated and real datasets.