Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of a Constitutively Active Hypoxia-Inducible Factor-1&agr; Transgene as a Therapeutic Strategy in No-Option Critical Limb Ischemia Patients: Phase I Dose-Escalation Experience

Background— Critical limb ischemia, a manifestation of severe peripheral atherosclerosis and compromised lower-extremity blood flow, results in a high rate of limb loss. We hypothesized that adenoviral delivery of a constitutively active form of the transcription factor hypoxia-inducible factor-1&agr; (ie, Ad2/HIF-1&agr;/VP16 or HIF-1&agr;) into the lower extremity of patients with critical limb ischemia would be safe and might result in a durable clinical response. Methods and Results— This phase I dose-escalation program included 2 studies: a randomized, double-blind, placebo-controlled study and an open-label extension study. In total, 34 no-option patients with critical limb ischemia received HIF-1&agr; at doses of 1×108 to 2×1011 viral particles. No serious adverse events were attributable to study treatment. Five deaths occurred: 3 in HIF-1&agr; and 2 in placebo patients. In the first (randomized) study, 7 of 21 HIF-1&agr; patients met treatment failure criteria and had major amputations. Three of the 7 placebo patients rolled over to receive HIF-1&agr; in the extension study. No amputations occurred in the 2 highest-dose groups of Ad2/HIF-1&agr;/VP16 (1×1011 and 2×1011 viral particles). The most common adverse events included peripheral edema, disease progression, and peripheral ischemia. At 1 year, limb status observations in HIF-1&agr; patients included complete rest pain resolution in 14 of 32 patients and complete ulcer healing in 5 of 18 patients. Conclusions— HIF-1&agr; therapy in patients with critical limb ischemia was well tolerated, supporting further, larger, randomized efficacy trials.
Paget’s disease of bone: a review of epidemiology, pathophysiology and management

Paget’s disease of bone is a common disorder which may affect one or many bones. Although many patients are asymptomatic, a variety of symptoms and complications may occur. Fortunately, effective pharmacologic therapy, primarily with potent bisphosphonates, is now available to treat patients with complications or symptoms. This review of Paget’s disease of bone will include epidemiology and pathophysiology, complications and clinical findings, indications for treatment, and the drugs currently available to treat this condition.
Robustness of System Equivalent Reduction Expansion Process on Spacecraft Structure Model Validation

Test-analysis models are used in the validation of the nite element models of spacecraft structures. Here, a probabilistic approach is used to assess the robustness of a system equivalent reduction expansion process based testanalysis model when experimental and analytical modes contain different levels of inaccuracy. The approach is applied to three spacecraft models, and Monte Carlo simulations were used to determine the sensitivity of the normalized cross-orthogonality check to the system equivalent reduction expansion process reduced matrix. The effect of parameters used in this reduction and the amount of inaccuracies that can be tolerated in the modes before failing the normalized cross-orthogonality check were also determined. The results show that the probability to pass the normalized cross-orthogonality check is highly determined by the number of modes used in the reduction. The relation between capability of the nite element models to predict the frequency-response function and the quality of the model validation determined using normalized cross-orthogonality check is also investigated, and it is observed that the quantities are not always correlated. This study also shows that the sensor locations can be optimally chosen using the system equivalent reduction expansion process reduced mass matrix, and this can increase the probability to pass the normalized cross-orthogonality check.
Rapid creation of BAC-based human artifical chromosome vectors by transposition with synthetic alpha-satellite arrays

Efficient construction of BAC-based human artificial chromosomes (HACs) requires optimization of each key functional unit as well as development of techniques for the rapid and reliable manipulation of high-molecular weight BAC vectors. Here, we have created synthetic chromosome 17-derived alpha-satellite arrays, based on the 16-monomer repeat length typical of natural D17Z1 arrays, in which the consensus CENP-B box elements are either completely absent (0/16 monomers) or increased in density (16/16 monomers) compared to D17Z1 alpha-satellite (5/16 monomers). Using these vectors, we show that the presence of CENP-B box elements is a requirement for efficient de novo centromere formation and that increasing the density of CENP-B box elements may enhance the efficiency of de novo centromere formation. Furthermore, we have developed a novel, high-throughput methodology that permits the rapid conversion of any genomic BAC target into a HAC vector by transposon-mediated modification with synthetic alpha-satellite arrays and other key functional units. Taken together, these approaches offer the potential to significantly advance the utility of BAC-based HACs for functional annotation of the genome and for applications in gene transfer.
Queen Victoria: First Media Monarch

1905. “Killing home rule with kindness” was the backhanded description of their varying mix of land and other reforms, as well as local government restructuring. These policies were marked by a determination to use government power to control the disturbances that were characteristic of Ireland. Hudson, a lecturer and academic adviser at Texas A&M University, contends that these policies not only produced economic improvement and beneficial social change but also went far in achieving their underlying goal-winning Irish hearts and minds, and reconciling the Irish people to the Union. Hudson’s approach is in the tradition of a “life and times” analysis of the Balfour brothers and George Wyndham. Hudson is careful to distinguish their particular ideas and approaches to the making of Irish policy. He praises Gerald Balfour for his skill in promoting substantial and far-reaching land reform acts and is especially critical of the hubristic Wyndham’s failure to engage with detail and 10 control the Dublin Castle bureaucracy. It is Wyndham who receives much of the responsibility for the policy’s failure in this narrative account, which culminates with the near-total nieltdown and discrediting of Constructive Unionism in 1904-05, as a consequence of the Earl of Dunraven and undersecretary Antony MacDonnell’s ill-advised devolutionary schemes. Although Hudson does attempt, in two introductory chapters, to place the policy of Constructive Unionism in perspective, this work is best seen as an attempt to undermine historiographical orthodoxies. Hudson is critical of most takes on the period, in particular Catherine B. Shannon’s Arthur J. Balfour and Ireland (2002) and Andrew Gailey ’s Ireland iind the Death of Kindness (1987). for their deterministic assumptions about the inevitability of the triumph of Irish nationalism. This attempt to return contingency and agency to historical events and actors is ;always useful. Hudson’s argument can be t‘aulted for some of the same underlying weaknesses that characterized the policies he ;malyzes: an underappreciation of how deeply ingrained Irish bitterness or Unionist hostility and the genuine popularity of Irish nationalism which went beyond grievances arising out of land tenure, influenced events. However, The Ireland that We Made does add to our understanding of how Constructive Unionism was made and unmade as ideology and practical policy.
Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth Published, JLR Papers in Press, September 16, 2006.

Eicosanoids participate in the regulation of cellular proliferation. Thus, we observed that prostaglandin E2 interaction with membrane receptors is involved in the control of 3T6 fibroblast growth induced by serum. However, our results suggested that another arachidonic acid pathway might be implicated in these events. Our results show that 3T6 fibroblasts synthesized hydroxyeicosatetraenoic acids (HETEs) such as 12-HETE through the cytochrome P-450 (CYP450) pathway. However, 3T6 fibroblasts did not produce leukotriene B4 (LTB4), and lipoxygenase inhibitors and LT antagonists failed to inhibit 3T6 fibroblast growth induced by FBS. In contrast, we observed that CYP450 inhibitors such as SKF-525A, 17-octadecynoic acid, 1-aminobenzotriazole, and 6-(2-propargyloxyphenyl)hexanoic acid reduced 12(S)-HETE levels, 3T6 fibroblast growth, and DNA synthesis induced by FBS. The impairment of DNA synthesis and 3T6 fibroblast growth induced by SKF-525A were reversed by exogenous addition of HETEs. Moreover, we report that 5-HETE, 12(S)-HETE, and 15(S)-HETE are mitogenic on 3T6 fibroblast in the absence of another growth factor, and this effect was dependent on the activation of the phosphatidylinositol-3-kinase pathway. In conclusion, our results show that HETEs, probably produced by CYP450, are involved in the control of 3T6 fibroblast growth.
Fully Implicit Discrete-Adjoint Methods for Rotorcraft Applications

This paper presents the development of a fully implicit, low-memory discrete-adjoint method by means of automatic source-code differentiation applied to the Helicopter Multi-Block computational fluid dynamics solver. The method is suitable for applications in flight mechanics, as well as shape optimization, and is demonstrated in this paper for popular flow cases reported in the literature. In particular, adjoint computational fluid dynamics computations were undertaken for airfoils, wings, and rotor-blade cases, and the obtained results were found to agree well with published solutions and with finite differences of flow derivatives. The method has been demonstrated for inviscid and viscous cases, and the results suggest that the current implementation is robust and efficient. The cost of the adjoint computations is relatively low due to the employed source-code differentiation, and most of the time, it is no more than the cost of a steady-state flow solution.
UC Office of the President Recent Work Title Current Approaches for Investigating and Predicting Cytochrome P 450 3 A 4-Ligand Interactions Permalink

Cytochrome P450 3A4 (CYP3A4) is the major and most important drug-metabolizing enzyme in humans that oxidizes and clears over a half of all administered pharmaceuticals. This is possible because CYP3A4 is promiscuous with respect to substrate binding and has the ability to catalyze diverse oxidative chemistries in addition to traditional hydroxylation reactions. Furthermore, CYP3A4 binds and oxidizes a number of substrates in a cooperative manner and can be both induced and inactivated by drugs. In vivo, CYP3A4 inhibition could lead to undesired drug-drug interactions and drug toxicity, a major reason for late-stage clinical failures and withdrawal of marketed pharmaceuticals. Owing to its central role in drug metabolism, many aspects of CYP3A4 catalysis have been extensively studied by various techniques. Here, we give an overview of experimental and theoretical methods currently used for investigation and prediction of CYP3A4ligand interactions, a defining factor in drug metabolism, with an emphasis on the problems addressed and conclusions derived from the studies.
Seamless handover scheme for proxy mobile IPv6 using smart buffering

PMIPv6 is proposed as a new network-based mobility protocol and it does not require MN's involving in mobility signaling. PMIPv6 can handover relatively faster than MIPv6 because of using link layer attachment information and micro mobility characteristic. However, current PMIPv6 cannot prevent packet loss in disruption period. We proposed in this paper, Smart Buffering scheme for supporting seamless handover in PMIPv6. Smart Buffering scheme prevents packet loss totally by buffering lost candidate packets in a current serving MAG and forwarding it to a new MAG, after an MN successfully connected. Smart Buffering also performs redundant packet removing in a previous MAG and packet reordering in a new MAG to maximize performance of seamless handover. All these procedures between a previous MAG and a new MAG are processed using simple message exchanges without requiring any involving of an MN. We verified the effectiveness of the Smart Buffering by simulation with various parameters. Simulation results prove that proposed scheme prevent packet loss in the handover and handle buffered packets very efficiently. As a result, we conclude that Smart Buffering is very useful for supporting seamless handover in PMIPv6.
AVOCADO: Visualization of Workflow–Derived Data Provenance for Reproducible Biomedical Research

A major challenge of data-driven biomedical research lies in the collection and representation of data provenance information to ensure reproducibility of findings. In order to communicate and reproduce multi-step analysis workflows executed on datasets that contain data for dozens or hundreds of samples, it is crucial to be able to visualize the provenance graph at different levels of aggregation. Most existing approaches are based on node-link diagrams, which do not scale to the complexity of typical data provenance graphs. In our proposed approach we reduce the complexity of the graph using hierarchical and motif-based aggregation. Based on user action and graph attributes a modular degree-of-interest (DoI) function is applied to expand parts of the graph that are relevant to the user. This interest-driven adaptive provenance visualization approach allows users to review and communicate complex multi-step analyses, which can be based on hundreds of files that are processed by numerous workflows. We integrate our approach into an analysis platform that captures extensive data provenance information and demonstrate its effectiveness by means of a biomedical usage scenario.
Prevention of hepatocellular carcinoma in the Asia–Pacific region: Consensus statements

Among approximately 650 000 people who die from hepatocellular carcinoma (HCC) each year, at least two‐thirds live in Asia. Efforts to improve early diagnosis and treatment have not yet impacted mortality. An Asia–Pacific Working Party convened in Hong Kong in June 2008 to consider ways to prevent HCC in this region. Separate reviews have summarized epidemiology of HCC, preventive approaches related to hepatitis B virus (HBV), hepatitis C virus (HCV) and non‐viral liver diseases, and the role of surveillance to detect HCC at a curative stage. We now present Consensus Statements from these deliberations and reviews. As chronic hepatitis B is the most common cause of HCC in Asia, effective hepatitis B vaccination programs are the most important strategy to reduce HCC incidence. Prevention of HCV by screening blood donors, universal precautions against blood contamination in health‐care settings and reducing HCV transmission from injection drug use are also vital. There is strong evidence that effective antiviral therapy to control HBV infection or eradicate HCV substantially reduces (but does not abolish) HCC risk. With hemochromatosis, family screening, early diagnosis and correcting iron overload to prevent liver fibrosis prevents HCC. There is currently insufficient evidence to give firm recommendations on alcohol, obesity/metabolic risk factors and other liver diseases. HCC surveillance for high‐risk groups is recommended in individual cases but cost‐effectiveness is not as high as infant hepatitis B vaccination and screening blood for HCV. Widespread application of HCC surveillance in Asia–Pacific countries depends on economic factors and health‐care priorities.
Outcomes of inpatients with and without sickle cell disease after high‐volume surgical procedures

In this study, we examined differences in inpatient costs, length of stay, and in‐hospital mortality between hospitalizations for patients with and without sickle cell disease (SCD) undergoing high‐volume surgical procedures. We used Clinical Classification Software (CCS) codes to identify discharges in the 2002–2005 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project for patients who had undergone either cholecystectomy or hip replacement. We limited the non‐SCD cohort to hospitals where patients with SCD had undergone the same procedure. We compared inpatient outcomes using summary statistics and generalized linear regression analysis to adjust for patient, hospital, and procedural characteristics. Overall, the median age of surgical patients with SCD was more than three decades less than the median age of patients without SCD undergoing the same procedure. In recognition of the age disparity, we limited the analyses to patients aged 18 to 64 years. Nonetheless, patients with SCD undergoing cholecystectomy or hip replacement were 12.1 and 14.4 years younger, had inpatient stays that were 73% and 82% longer, and incurred costs that were 46% and 40% higher per discharge than patients without SCD, respectively. Inpatient mortality for these procedures was low, ∼0.6% for cholecystectomy and 0.2% for hip replacement and did not differ significantly between patients with and without SCD. Multivariable regression analyses revealed that higher inpatient costs among patients with SCD were primarily attributable to longer hospital stays. Patients with SCD who underwent cholecystectomy or hip replacement required more health care resources than patients without SCD. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Food Waste Bins: Bridging Infrastructures and Practices

Recent years have seen an increasing number of councils begin separate food waste collections from domestic premises, a change that has resulted in householders having to sort food waste and keep it in separate bins until collection. Yet bins – of any kind – have been subject to little investigation, despite being a central element of the waste infrastructure. This paper attends to this omission by examining food bins. First of all, it explores the ways that bins have agency through an exploration of how their presence has affected waste practices. We find that their agency is three-fold: it is symbolic, relational and, importantly, material – an aspect which has been overlooked all too often in analyses of material culture and consumption. Secondly, we show how this material agency can be troubling: we explore how this agency is managed by households through practices of accommodation and resistance. Examining the food bin's agency and how it is consumed gives an insight into the implementation of, and engagement with, waste policy ‘on the ground’. This allows us to make some suggestions for how to improve the implementation of this policy. This paper also opens up two new areas of study: first, a more sustained and developed exploration of bins, giving some pointers as to other possible issues. Secondly, and more broadly, the paper examines the extent to which the objects that materialize policy can be useful in the implementation of that policy, especially if the policy seeks ‘behaviour change’.
YouTube everywhere: impact of device and infrastructure synergies on user experience

In this paper we present a complete measurement study that compares YouTube traffic generated by mobile devices (smart-phones,tablets) with traffic generated by common PCs (desktops, notebooks, netbooks). We investigate the users' behavior and correlate it with the system performance. Our measurements are performed using unique data sets which are collected from vantage points in nation-wide ISPs and University campuses from two countries in Europe and the U.S. Our results show that the user access patterns are similar across a wide range of user locations, access technologies and user devices. Users stick with default player configurations, e.g., not changing video resolution or rarely enabling full screen playback. Furthermore it is very common that users abort video playback, with 60% of videos watched for no more than 20% of their duration. We show that the YouTube system is highly optimized for PC access and leverages aggressive buffering policies to guarantee excellent video playback. This however causes 25%-39% of data to be unnecessarily transferred, since users abort the playback very early. This waste of data transferred is even higher when mobile devices are considered. The limited storage offered by those devices makes the video download more complicated and overall less efficient, so that clients typically download more data than the actual video size. Overall, this result calls for better system optimization for both, PC and mobile accesses.
America's Asia

University Press. All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or information storage and retrieval) without permission in writing from the publisher, except for reading and browsing via the World Wide Web. Users are not permitted to mount this file on any network servers.
English Verbs in Hungarian / English Codeswitching

This study examines the integration of English verbs in Hungarian-English language contact. While previous research indicates that codeswitching (CS) of verbs does not occur as readily as that of nouns, the conditioning factors that determine by what means and in what forms verbs can be incorporated into another language are not yet fully understood (e.g. Muysken 2000, Myers-Scotton 2002). The aim of this paper is to address two questions. First, I investigate why Hungarian employs a strategy of morphological integration in verb borrowing. Drawing on a corpus of adult bilinguals’ naturalistic CS (Bolonyai 1997) and examples published in the literature (e.g. Kontra 1995), this paper specifically explores why English verbs need to be adapted with a derivational, denominal verbalizer (VBZ) suffix –l (-ol, -el, -öl) in Hungarian, as in (1). The second question concerns the status of the verbalizer in the grammar of the bilingual child. At issue is whether English verbs occur with the Hungarian verbalizer from early on in child bilingual speech, or if it takes time and exposure before adult-like integration of verbs appears in child CS. The investigation is based on the analysis of longitudinal CS data from an English-dominant bilingual child.
Low Virulence and Lack of Airborne Transmission of the Dutch Highly Pathogenic Avian Influenza Virus H5N8 in Ferrets

Highly pathogenic avian influenza (HPAI) H5N8 viruses that emerged in poultry in East Asia spread to Europe and North America by late 2014. Here we show that the European HPAI H5N8 viruses differ from the Korean and Japanese HPAI H5N8 viruses by several amino acids and that a Dutch HPAI H5N8 virus had low virulence and was not transmitted via the airborne route in ferrets. The virus did not cross-react with sera raised against pre-pandemic H5 vaccine strains. This data is useful for public health risk assessments.
Occupational Factors and Sick Leave in Australian Employees

Objectives: To investigate occupational factors associated with sick leave over a 4-year period in Australian employees. Methods: Longitudinal data (self-report) from 2861 Australian full-time employees (69.4% male) were used. Occupational factors and relevant covariates were assessed at baseline with sick leave assessed yearly over a 4-year period. The data were analyzed using multinomial logistic regression models. Results: Job strain and longer commuting time were associated with long sick leave, whereas long work hours were inversely associated with long sick leave. Conclusions: These results provide further evidence that certain aspects of work are associated with sick leave, whereas other work aspects such as long work hours are inversely associated with sick leave. Organizations need to understand and address these factors to improve the well-being of employees and increase workplace productivity.