Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemagglutinin-Neuraminidase Balance Influences the Virulence Phenotype of a Recombinant H5N3 Influenza A Virus Possessing a Polybasic HA0 Cleavage Site

ABSTRACT Although a polybasic HA0 cleavage site is considered the dominant virulence determinant for highly pathogenic avian influenza (HPAI) H5 and H7 viruses, naturally occurring virus isolates possessing a polybasic HA0 cleavage site have been identified that are low pathogenic in chickens. In this study, we generated a reassortant H5N3 virus that possessed the hemagglutinin (HA) gene from H5N1 HPAI A/swan/Germany/R65/2006 and the remaining gene segments from low pathogenic A/chicken/British Columbia/CN0006/2004 (H7N3). Despite possessing the HA0 cleavage site GERRRKKR/GLF, this rH5N3 virus exhibited a low pathogenic phenotype in chickens. Although rH5N3-inoculated birds replicated and shed virus and seroconverted, transmission to naive contacts did not occur. To determine whether this virus could evolve into a HPAI form, it underwent six serial passages in chickens. A progressive increase in virulence was observed with the virus from passage number six being highly transmissible. Whole-genome sequencing demonstrated the fixation of 12 nonsynonymous mutations involving all eight gene segments during passaging. One of these involved the catalytic site of the neuraminidase (NA; R293K) and is associated with decreased neuraminidase activity and resistance to oseltamivir. Although introducing the R293K mutation into the original low-pathogenicity rH5N3 increased its virulence, transmission to naive contact birds was inefficient, suggesting that one or more of the remaining changes that had accumulated in the passage number six virus also play an important role in transmissibility. Our findings show that the functional linkage and balance between HA and NA proteins contributes to expression of the HPAI phenotype. IMPORTANCE To date, the contribution that hemagglutinin-neuraminidase balance can have on the expression of a highly pathogenic avian influenza virus phenotype has not been thoroughly examined. Reassortment, which can result in new hemagglutinin-neuraminidase combinations, may have unpredictable effects on virulence and transmission characteristics of a virus. Our data show the importance of the neuraminidase in complementing a polybasic HA0 cleavage site. Furthermore, it demonstrates that adaptive changes selected for during the course of virus evolution can result in unexpected traits such as antiviral drug resistance.
Assessing Teachers Needs for Environmental Education Services

Acknowledgments: The authors thank several anonymous reviewers and the graduate students of FOR 6934: Steven Bostick, Daniel Carl, Marina D’Abreau, Christopher Demers, Jennifer Hale, Katie Lynch, and Rachel Tyler. Authors Alison Bowers and Gabriella Scollo were also part of this class. This research was supported by the Florida Agricultural Experiment Station and by a grant from the Crown Region Environmental Education Service Project, and approved for publication as Journal Series No. R-08146.
The TMPRSS2–ERG Gene Fusion Blocks XRCC4-Mediated Nonhomologous End-Joining Repair and Radiosensitizes Prostate Cancer Cells to PARP Inhibition

Exposure to genotoxic agents, such as ionizing radiation (IR), produces DNA damage, leading to DNA double-strand breaks (DSB); IR toxicity is augmented when the DNA repair is impaired. We reported that radiosensitization by a PARP inhibitor (PARPi) was highly prominent in prostate cancer cells expressing the TMPRSS2–ERG gene fusion protein. Here, we show that TMPRSS2–ERG blocks nonhomologous end-joining (NHEJ) DNA repair by inhibiting DNA-PKcs. VCaP cells, which harbor TMPRSS2–ERG and PC3 cells that stably express it, displayed γH2AX and 53BP1 foci constitutively, indicating persistent DNA damage that was absent if TMPRSS2–ERG was depleted by siRNA in VCaP cells. The extent of DNA damage was enhanced and associated with TMPRSS2–ERG's ability to inhibit DNA-PKcs function, as indicated by its own phosphorylation (Thr2609, Ser2056) and that of its substrate, Ser1778-53BP1. DNA-PKcs deficiency caused by TMPRSS2–ERG destabilized critical NHEJ components on chromatin. Thus, XRCC4 was not recruited to chromatin, with retention of other NHEJ core factors being reduced. DNA-PKcs autophosphorylation was restored to the level of parental cells when TMPRSS2–ERG was depleted by siRNA. Following IR, TMPRSS2–ERG-expressing PC3 cells had elevated Rad51 foci and homologous recombination (HR) activity, indicating that HR compensated for defective NHEJ in these cells, hence addressing why TMPRSS2–ERG alone did not lead to radiosensitization. However, the presence of TMPRSS2–ERG, by inhibiting NHEJ DNA repair, enhanced PARPi-mediated radiosensitization. IR in combination with PARPi resulted in enhanced DNA damage in TMPRSS2–ERG-expressing cells. Therefore, by inhibiting NHEJ, TMPRSS2–ERG provides a synthetic lethal interaction with PARPi in prostate cancer patients expressing TMPRSS2–ERG. Mol Cancer Ther; 14(8); 1896–906. ©2015 AACR.
Multimerin: a bench-to-bedside chronology of a unique platelet and endothelial cell protein--from discovery to function to abnormalities in disease.

In studies conducted about 8 years ago, the author and her colleagues raised a monoclonal antibody that recognized an uncharacterized human platelet protein with a reduced molecular mass of 155 kDa. Investigations of this protein's nonreduced structure yielded surprising findings: in its native state, it exists as massive disulfide-linked multimers millions of daltons in size, making it one of the largest proteins found in the human body. This feature led the author to designate this protein "multimerin. " Multimerin is found in endothelial cells as well as in platelets. It originates from a single subunit protein, promultimerin, that undergoes extensive N-glycosylation, proteolytic processing and polymerization during biosynthesis. Recent data from the cloning and sequencing of its complementary DNA indicate that multimerin is a unique protein. Like von Willebrand factor, it has a massive repeating structure, but these proteins are unrelated. Multimerin's sequence contains the adhesive motif Arg-Gly-Asp-Ser, central coiled-coil sequences, several epidermal growth-factor-like motifs, and a globular domain that is similar to a protein-binding domain found in complement C1q and in collagens type VIII and X. Investigations of multimerin's function indicate that it binds the coagulation protein factor V and its activated form, factor Va. In platelets, but not in plasma, all of the biologically active factor V is complexed with multimerin. Multimerin may also have functions as an extracellular matrix or adhesive protein. Recently, members of 2 Canadian families with puzzling autosomal-dominant bleeding disorders were found to have a deficiency of platelet multimerin. Studies of these patients may provide a unique opportunity to evaluate the functions of multimerin.
LENSVIEW : software for modelling resolved gravitational lens images

We have developed a new software tool, lensview, for modelling resolved gravitational lens images. Based on the lensmem algorithm, the software finds the best-fitting lens mass model and source brightness distribution using a maximum entropy constraint. The method can be used with any point spread function or lens model. We review the algorithm and introduce some significant improvements. We also investigate and discuss issues associated with the statistical uncertainties of models and model parameters and the issues of source plane size and source pixel size. We test the software on simulated optical and radio data to evaluate how well lens models can be recovered and with what accuracy. For optical data, lens model parameters can typically be recovered with better than 1 per cent accuracy, and the degeneracy between mass ellipticity and power law is reduced. For radio data, we find that systematic errors associated with using processed radio maps, rather than the visibilities, are of similar magnitude to the random errors. Hence analysing radio data in image space is still useful and meaningful. The software is applied to the optical arc HST J15433+5352 and the radio ring MG1549+3047 using a simple elliptical isothermal lens model. For HST J15433+5352, the Einstein radius is 0.525 ± 0.015 arcsec which probably includes a substantial convergence contribution from a neighbouring galaxy. For MG1549+3047, the model has Einstein radius 1.105 ± 0.005 arcsec and core radius 0.16 ± 0.03 arcsec. The total mass enclosed in the critical radius is 7.06 × 1010 M⊙ for our best model. We finish by discussing issues relating to modelling of resolved lens images for this method and some alternatives.
A Two-Way Street: Green Big Data Processing for a Greener Smart Grid

Integrating renewables into the mainstream energy market is pivotal for the green revolution promised by the smart grid. The real power behind realization of the smart grid goals lies in the volume, variety, velocity of the big data generated by a variety of sources. Nevertheless, the smart grid needs data centers to digest the big data for its profound green revolution. However, big data processing is the radix for data centers to be seen as energy black holes. Unless data centers are transformed into energy-efficient enterprises, big data are going to be responsible for superfluous energy burn, potentially reversing the smart grid genesis with regard to green environmental impact. This paper describes the role of the big data enterprise in envisioning the smart grid. We dissect the big data enterprise into six vital planes impacting the energy footprints of data centers. We present a survey of key strategies to make these six vital planes greener. Moreover, we present open challenges and directions in this context. We assert that a cross-plane approach toward a greener optimization is crucial. In this vein, we present a green orchestrator that is capable of incorporating different planes in an integrated fashion to boost energy profile of the big data enterprise.
A framework for multi-vehicle navigation using feedback-based motion primitives

We present a hybrid control framework for solving a motion planning problem among a collection of heterogenous agents. The proposed approach utilizes a finite set of low-level motion primitives, each based on a piecewise affine feedback control, to generate complex motions in a gridded workspace. The constraints on allowable sequences of successive motion primitives are formalized through a maneuver automaton. At the higher level, a control policy generated by a shortest path non-deterministic algorithm determines which motion primitive is executed in each box of the gridded workspace. The overall framework yields a highly robust control design on both the low and high levels. We experimentally demonstrate the efficacy and robustness of this framework for multiple quadrocopters maneuvering in a 2D or 3D workspace.
A 93.7% peak efficiency DC-DC buck converter with all-pass network based passive level shifter in 55 nm CMOS

This paper proposes a DC-DC buck converter with all-pass network based passive level shifter in 55nm standard CMOS process, for battery powered portable applications. In order to handle high battery voltages in this advanced standard CMOS process, a passive level shifter based on all-pass network is applied for gate oxide protection. Drain extension is proposed to obtain high breakdown voltage of active region. The proposed buck converter with the passive level shifter works in DCM operation as its load current varies from 0.1–10mA. The buck converter achieves a peak efficiency of 93.7% and 83.8% at 10mA load current, with a supply voltage of 1.8V and 3.7V, respectively.
State Commission of Inquiry into the Events of October 2000: A Retrospective: Introduced by Elie Rekhess

EOR YEARS, THERE WERE THOSE who contested the very notion of addressing the issue of Arabs in Israel through the tools of historical research. The host of reasons offered claimed that such practice was "premature," or pointed to the lack of a "sufficient perspective. " Indeed, anyone reviewing the books, articles and research papers on the Arab population published thirty or even twenty years ago, is impressed by the paucity of research materials.
Decomposition techniques for parallel resolution of constraint satisfaction problems in shared memory: a comparative study

This paper provides both a formal and an empirical study of decomposition techniques for parallel resolution of Constraint Satisfaction Problems (CSP) in shared memory. The main contribution of this study is to bring together decomposition techniques with Backtrack search to solve CSP on parallel architectures in shared memory. Another contribution is to demonstrate how to obtain good scalability up to hundreds of processors in shared memory for CSP resolution and more generally for Irregular Applications.
Parent Report as a Means of Administering the Prescreening Developmental Questionnaire: An Evaluation Study

The increasing emphasis on screening the pediatric population for developmental delays requires that rapid and efficient screening tests be developed and evaluated. This study assessed the ability of three rapid screening procedures to predict full Denver Developmental Screening Test (DDST) results. Ninety children were randomly assigned to one of three prescreening groups. The first group was prescreened with the Prescreening Developmental Questionnaire (PDQ), administered in the “standard” fashion, i.e., mother reads and answers 10 questions about her child's development. The second group was prescreened using a modified means of administering the PDQ (PDQ-M); a health care professional read each PDQ question to the mother. The third group was prescreened with the Alpern-Boll Developmental Profile II, a relatively lengthy procedure utilizing parent report information. All of the children were then tested with the DDST. Each of the prescreening procedures was highly predictive of performance on the DDST. The Alpern-Boll profile, as anticipated, demonstrated greater validity than the PDQ and PDQ-M on six of seven indices of prescreening test validity, generated from a four-group referral matrix. The PDQ-M was more similar to the Alpern-Boll on four indices, while the PDQ was more similar on three. It was judged that the two PDQ procedures were equivalent in their validity characteristics. The PDQ-M appears to be an acceptable means of rapidly screening preschool children for developmental delays.
Hemorrhagic Transformation (HT) and Symptomatic Intracerebral Hemorrhage (sICH) Risk Prediction Models for Postthrombolytic Hemorrhage in the Stroke Belt

Background Symptomatic intracerebral hemorrhage (sICH) remains the most feared complication of intravenous tissue plasminogen activator (IV tPA) treatment. We aimed to investigate how previously validated scoring methodologies would perform in treated patients in two US Stroke Belt states. Methods and Results We retrospectively reviewed consecutive patients from two centers in two Stroke Belt states who received IV tPA (2008–2011). We assessed the ability of three models to predict sICH. sICH was defined as a type 2 parenchymal hemorrhage with deterioration in National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or death. Among 457 IV tPA-treated patients, 19 (4.2%) had sICH (mean age 68, 26.3% Black, 63.2% female). The Cucchiara model was most predictive of sICH in the entire cohort (AUC: 0.6528) and most predictive of sICH among Blacks (OR = 6.03, 95% CI 1.07–34.1, P = 0.0422) when patients were dichotomized by score. Conclusions In our small sample from the racially heterogeneous US Stroke Belt, the Cucchiara model outperformed the other models at predicting sICH. While predictive models should not be used to justify nontreatment with thrombolytics, those interested in understanding contributors to sICH may choose to use the Cucchiara model until a Stroke Belt model is developed for this region.
A pilot study of orthopaedic resident self-assessment using a milestones’ survey just prior to milestones implementation

Objectives To pilot test if Orthopaedic Surgery residents could self-assess their performance using newly created milestones, as defined by the Accreditation Council on Graduate Medical Education. Methods In June 2012, an email was sent to Program Directors and administrative coordinators of the154 accredited Orthopaedic Surgery Programs, asking them to send their residents a link to an online survey. The survey was adapted from the Orthopaedic Surgery Milestone Project. Completed surveys were aggregated in an anonymous, confidential database. SAS 9.3 was used to perform the analyses. Results Responses from 71 residents were analyzed. First and second year residents indicated through self-assessment that they had substantially achieved Level 1 and Level 2 milestones. Third year residents reported they had substantially achieved 30/41, and fourth year residents, all Level 3 milestones. Fifth year, graduating residents, reported they had substantially achieved 17 Level 4 milestones, and were extremely close on another 15. No milestone was rated at Level 5, the maximum possible. Earlier in training, Patient Care and Medical Knowledge milestones were rated lower than the milestones reflecting the other four competencies of Practice Based Learning and Improvement, Systems Based Practice, Professionalism, and Interpersonal Communication. The gap was closed by the fourth year. Conclusions Residents were able to successfully self-assess using the 41 Orthopaedic Surgery milestones. Respondents’ rate improved proficiency over time. Graduating residents report they have substantially, or close to substantially, achieved all Level 4 milestones. Milestone self-assessment may be a useful tool as one component of a program’s overall performance assessment strategy.
A novel public key crypto system based on semi-modules over quotient semi-rings

2 Faculty of Science, Department of Mathematics, Guilan University, Rasht, Iran ebrahimi@guilan.ac. ir Abstract: In A generalization of the original Diffie-Hellman key exchange in (Z/pZ)* found a new depth when Miller and Koblitz suggested that such a protocol could be used with the group over an elliptic curve. Maze, Monico and Rosenthal extend such a generalization to the setting of a Semi-group action on a finite set, more precisely, linear actions of abelian semi-rings on semimodules. In this paper, we extend such a generalization to the linear actions of quotient semi-rings on semi-modules. In fact, we show how the action of quotient semi-rings on a semi-module gives rise to a generalized Diffie-Hellman and ElGamal protocol. This leads naturally to a cryptographic protocol whose difficulty is based on the hardness of a particular control problem, namely the problem of steering the state of some dynamical system from an initial vector to some final location.
The cytoskeletal arrangements necessary to neurogenesis

During the process of neurogenesis, the stem cell committed to the neuronal cell fate starts a series of molecular and morphological changes. The understanding of the physio-pathology of mechanisms controlling the molecular and morphological changes occurring during neuronal differentiation is fundamental to the development of effective therapies for many neurologic diseases. Unfortunately, our knowledge of the biological events occurring in the cell during neuronal differentiation is still poor. In this study, we focus preliminarily on the relevance of the cytoskeletal rearrangements, which earlier drive the morphology of the neuronal precursors, and later the migrating/mature neurons. In fact, neuritogenesis, neurite branching, outgrowth and retraction are seminal to the development of a fully functional nervous system. With this in mind, we highlight the importance of iPSC technology to study the processes of cytoskeletal-driven morphological changes during neuronal differentiation.
The role of local leaders in cultural transformation and development

Through cross-disciplinary and participatory processes involving key stakeholders from the Zambian education sector, as well as from the traditional leadership structure, a localized HIV/AIDS-prevention strategy, Interactive School and Community Approach (ISACA), was developed and implemented throughout one province between 2002 and 2006. The study is guided by constructivist grounded theory and explores the impact of the chiefs’ involvement in preventing the spread of HIV/AIDS through close collaboration and interaction across traditionally vertical boundaries, for example between the formal educational and traditional leadership structures. The strategy created communicative spaces for the merger of Western and indigenous knowledge. The study reveals the importance of involving the chiefs, the custodians of culture and traditions in cultural transformation and development, and shows their significant role as gate-openers and change agents, a precondition for sustainable local development.
Exploring impulse buying and variety seeking by retail shoppers: towards a common conceptual framework

Abstract Impulse buying and variety seeking are both low-effort feelings-based behaviours with similar psychological origins. However, there is little research exploring the common sociopsychological processes regulating these behaviours. This gap is addressed with a conceptual framework incorporating the discrepancy between actual and optimum stimulation levels as the driver of both the behaviours, and self-monitoring as the moderator of interpersonal influences on these. Findings from a field-survey-based study with retail shoppers show that both the behaviours are responses to exploratory urges triggered by lower stimulation levels. Moreover, high self-monitors exhibit greater impulsiveness in private and seek greater variety in public compared to low self-monitors. The paper concludes with a discussion on its conceptual and managerial contribution along with some of its limitations and directions for future research.
Proton-transfer and hydrogen-bond interactions determine fluorescence quantum yield and photochemical efficiency of bacteriophytochrome

Phytochromes are red-light photoreceptor proteins that regulate a variety of responses and cellular processes in plants, bacteria, and fungi. The phytochrome light activation mechanism involves isomerization around the C15═C16 double bond of an open-chain tetrapyrrole chromophore, resulting in a flip of its D-ring. In an important new development, bacteriophytochrome (Bph) has been engineered for use as a fluorescent marker in mammalian tissues. Here we report that an unusual Bph, RpBphP3 from Rhodopseudomonas palustris, denoted P3, is fluorescent. This Bph modulates synthesis of light-harvesting complex in combination with a second Bph exhibiting classical photochemistry, RpBphP2, denoted P2. We identify the factors that determine the fluorescence and isomerization quantum yields through the application of ultrafast spectroscopy to wild-type and mutants of P2 and P3. The excited-state lifetime of the biliverdin chromophore in P3 was significantly longer at 330–500 ps than in P2 and other classical phytochromes and accompanied by a significantly reduced isomerization quantum yield. H/D exchange reduces the rate of decay from the excited state of biliverdin by a factor of 1.4 and increases the isomerization quantum yield. Comparison of the properties of the P2 and P3 variants shows that the quantum yields of fluorescence and isomerization are determined by excited-state deprotonation of biliverdin at the pyrrole rings, in competition with hydrogen-bond rupture between the D-ring and the apoprotein. This work provides a basis for structure-based conversion of Bph into an efficient near-IR fluorescent marker.