bluuebunny/crossref_metadata_2025_split huggingface dataset:
TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus
Authors: Shi Bingjie , Li Juan , Shi Xuanling , Jia Wenxu , Wen Yi , Hu Xiongbing , Zhuang Fengfeng , Xi Jianzhong , Zhang Linqi 
Published: October 2016

Abstract:
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity, and low cytotoxicity. We report here systematic design and characterization of 28 novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity, and lower cytotoxicity compared with zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials. Sequence analysis of target cell line GHOST-CCR5-CXCR4 and human primary CD4+ T cells showed that the double-strand breaks at the TALEN targeted sites resulted in truncated or nonfunctional CCR5 proteins thereby conferring protection against HIV-1 infection in vitro. None of the CCR5-TALENs had detectable levels of off-target nuclease activity against the homologous region in CCR2 although substantial level was identified for CCR5-ZFN in the primary CD4+ T cells. Our results suggest that the CCR5-TALENs identified here are highly functional nucleases that produce protective genetic alterations to human CCR5. Application of these TALENs directly to the primary CD4+ T cells and CD34+ hematopoietic stem cells (HSCs) of infected individuals could help to create an immune system resistant to HIV-1 infection, recapitulating the success of “Berlin patient” and serving as an essential first step towards a “functional” cure of AIDS.
Sequencing of small RNAs of the fern Pleopeltis minima (Polypodiaceae) offers insight into the evolution of the microRNA repertoire in land plants
Authors: Berruezo Florencia , de Souza Flavio S. J. , Picca Pablo I. , Nemirovsky Sergio I. , Martinez-Tosar Leandro , Rivero Mercedes , Mentaberry Alejandro N , Zelada Alicia M. 
Published: October 2016

AbstractMicroRNAs (miRNAs) are short, single stranded RNA molecules that regulate the stability and translation of messenger RNAs in diverse eukaryotic groups. Several miRNA genes are of ancient origin and have been maintained in the genomes of animal and plant taxa for hundreds of millions of years, and functional studies indicate that ancient miRNAs play key roles in development and physiology. In the last decade, genome and small RNA (sRNA) sequencing of several plant species have helped unveil the evolutionary history of land plant miRNAs. Land plants are divided into bryophytes (liverworts, mosses), lycopods (clubmosses and spikemosses), monilophytes (ferns and horsetails), gymnosperms (cycads, conifers and allies) and angiosperms (flowering plants). Among these, the fern group occupies a key phylogenetic position, since it represents the closest extant cousin taxon of seed plants, i.e. gymno- and angiosperms. However, in spite of their evolutionary, economic and ecological importance, no fern genome has been sequenced yet and few genomic resources are available for this group. Here, we sequenced the small RNA fraction of an epiphytic South American fern, Pleopeltis minima (Polypodiaceae), and compared it to plant miRNA databases, allowing for the identification of miRNA families that are shared by all land plants, shared by all vascular plants (tracheophytes) or shared by euphyllophytes (ferns and seed plants) only. Using the recently described transcriptome of another fern, Lygodium japonicum, we also estimated the degree of conservation of fern miRNA targets in relation to other plant groups. Our results pinpoint the origin of several miRNA families in the land plant evolutionary tree with more precision and are a resource for future genomic and functional studies of fern miRNAs.
Recovery of hand function after stroke: separable systems for finger strength and control
Authors: Xu Jing , Ejaz Naveed , Hertler Benjamin , Branscheidt Meret , Widmer Mario , Faria Andreia V. , Harran Michelle , Cortes Juan C. , Kim Nathan , Celnik Pablo A. , Kitago Tomoko , Luft Andreas R. , Krakauer John W. , Diedrichsen Jörn 
Published: October 2016

AbstractLoss of hand function after stroke is a major cause of long-term disability. Hand function can be partitioned into strength and independent control of fingers (individuation). Here we developed a novel paradigm, which independently quantifies these two aspects of hand function, to track hand recovery in 54 patients with hemiparesis over the first year after their stroke. Most recovery of both strength and individuation occurred in the first three months after stroke. Improvement in strength and individuation were tightly correlated up to a strength level of approximately 60% of the unaffected side. Beyond this threshold, further gains in strength were not accompanied by improvements in individuation. Any observed improvements in individuation beyond the 60% threshold were attributable instead to a second independent stable factor. Lesion analysis revealed that damage to the hand area in motor cortex and the corticospinal tract (CST) correlated more with individuation than with strength. CST involvement correlated with individuation even after factoring out the strength-individuation correlation. The most parsimonious explanation for these behavioral and lesion-based findings is that most strength recovery, along with some individuation, can be attributed to descending systems other than the CST, whereas further recovery of individuation is CST dependent.
Analysis of primary modulation based x‐ray scatter correction methods
Authors: Horváth Áron , Hadházi Dániel , Horváth Gábor 
Published: October 2016

PurposeThe purpose of this study is to provide an overview of primary modulation based scatter estimation techniques and evaluate their performance as well as to propose improvements. There have been published two distinct approaches to estimate scatter with primary modulators; however they have not been compared, so far. This work seeks to quantify their performance (focusing on how accurately they can estimate a smooth scatter from primary modulated images with real textures and signal to noise ratios) along with that of proposed improved variants. The influence of the parameters of the described algorithms on the estimation error is also investigated.MethodsSimulations were carried out using primary components derived from real chest DTS projections. After modulation, artificial scatter distributions were added to these projections, and the difference between the estimated and the artificial scatter distributions was quantified. Two existing and four proposed methods were assessed. The performance of the scatter estimators was examined under noisy and noiseless circumstances and with scatter distributions of different bandwidths. The proposed methods (SSE, SSENP, ADASE) solve the problem of varying effective transmission factors in the case of cell‐image based methods, and they include an improved gradient based method (LSGSE) as well, which estimates scatter distribution more accurately.ResultsIt was found that the gradient based algorithms outperformed the cell‐image based algorithms under noiseless conditions, while the cell‐image based solutions proved to be insensitive to noise. The proposed improved methods reached considerably lower scatter estimation errors than the existing ones. Modulator cell sampling windows of different sizes and shapes were examined. Although much lower effective transmission factors (higher contrast between the attenuated and unattenuated cells) can be achieved using narrow windows, in our case the best estimation results are provided by windows that cover about half of the pixels of a modulator cell. The effect of detector backscatter on scatter estimation was also studied, and a solution was proposed to incorporate this type of scatter into the primary modulation framework.ConclusionsConsidering all the above results, the authors suggest the use of LSGE for scatter estimation with primary modulation.
Physiological Adaptations following Resistance Training in Youth Athletes—A Narrative Review
Authors: Legerlotz Kirsten , Marzilger Robert , Bohm Sebastian , Arampatzis Adamantios 
Published: October 2016

Purpose:To understand the mechanisms for the effects of resistance training on functional parameters, and to assess the injury risk of the involved tissues, it is necessary to examine the underlying morphological and structural changes of the respective tissues.Methods:The presented information on physiological adaptations have been deduced from cross-sectional studies comparing youth athletes with controls and children with adults as well as from longitudinal studies examining the effects of resistance training in untrained children and adolescents and in youth athletes.Results:The evidence indicates, that training induced changes in motor performance rely partly on enhanced neuromuscular control, and partly on morphological adaptation of muscles and tendons, such as changes in muscle, muscle fiber and tendon cross-sectional area, muscle composition, and tendon material properties, with the bone also adapting by increasing bone mineral content and cortical area.Conclusion:Although the training induced adaptations of the investigated tissues follows similar principles in children as in adults, the magnitude of the adaptive response appears to be more subtle. As studies investigating physiological adaptation in youth athletes are sparse, more research in this area is warranted to elucidate the specific physiological stimulus-response relationship necessary for effective training programs and injury prevention.
Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner
Authors: Mullarkey Caitlin E. , Bailey Mark J. , Golubeva Diana A. , Tan Gene S. , Nachbagauer Raffael , He Wenqian , Novakowski Kyle E. , Bowdish Dawn M. , Miller Matthew S. , Palese Peter 
Published: October 2016

ABSTRACT

Broadly neutralizing antibodies that recognize the conserved hemagglutinin (HA) stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of the mechanisms by which stalk-specific antibodies achieve protection is rapidly evolving. It has recently been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies require Fc-Fcγ receptor (FcγR) interactions for optimal protection
in vivo
. Here we examine the neutrophil effector functions induced by stalk-specific antibodies. As the most abundant subset of blood leukocytes, neutrophils represent a critical innate effector cell population and serve an instrumental role in orchestrating downstream adaptive responses to influenza virus infection. Yet, the interplay of HA stalk-specific IgG, Fc-FcγR engagement, and neutrophils has remained largely uncharacterized. Using an
in vitro
assay to detect the production of reactive oxygen species (ROS), we show that human and mouse monoclonal HA stalk-specific IgG antibodies are able to induce the production of ROS by neutrophils, while HA head-specific antibodies do not. Furthermore, our results indicate that the production of ROS is dependent on Fc receptor (FcR) engagement and phagocytosis. We went on to assess the ability of monoclonal HA stalk-specific IgA antibodies to induce ROS. Consistent with our findings for monoclonal IgGs, only HA stalk-specific IgA antibodies elicited ROS production by neutrophils. This induction is dependent on the engagement of FcαR1. Taken together, our findings describe a novel FcR-dependent effector function induced by HA stalk-specific IgG and IgA antibodies, and importantly, our studies shed light on the mechanisms by which HA stalk-specific antibodies achieve protection.

IMPORTANCE
The present study provides evidence that broadly neutralizing HA stalk-specific antibodies induce downstream Fc-mediated neutrophil effector functions. In addition to their ability to neutralize, this class of antibodies has been shown to rely on Fc-Fc receptor interactions for optimal protection
in vivo
. Curiously, neutralizing antibodies that bind the HA head domain do not require such interactions. Our findings build on these previous observations and provide a more complete picture of the relationship between stalk-specific antibodies and cells of the innate immune compartment. Furthermore, our data suggest that the ability of HA stalk-specific antibodies to mediate Fc-Fc receptor engagement is epitope dependent. Overall, this work will inform the rational design of improved influenza virus vaccines and therapeutics.
Development and Validation of an Automatic Segmentation Algorithm for Quantification of Intracerebral Hemorrhage
Authors: Scherer Moritz , Cordes Jonas , Younsi Alexander , Sahin Yasemin-Aylin , Götz Michael , Möhlenbruch Markus , Stock Christian , Bösel Julian , Unterberg Andreas , Maier-Hein Klaus , Orakcioglu Berk 
Published: October 2016

Background and Purpose—
ABC/2 is still widely accepted for volume estimations in spontaneous intracerebral hemorrhage (ICH) despite known limitations, which potentially accounts for controversial outcome-study results. The aim of this study was to establish and validate an automatic segmentation algorithm, allowing for quick and accurate quantification of ICH.

Methods—
A segmentation algorithm implementing first- and second-order statistics, texture, and threshold features was trained on manual segmentations with a random-forest methodology. Quantitative data of the algorithm, manual segmentations, and ABC/2 were evaluated for agreement in a study sample (n=28) and validated in an independent sample not used for algorithm training (n=30).

Results—

ABC/2 volumes were significantly larger compared with either manual or algorithm values, whereas no significant differences were found between the latter (
P
<0.0001; Friedman+Dunn’s multiple comparison). Algorithm agreement with the manual reference was strong (concordance correlation coefficient 0.95 [lower 95% confidence interval 0.91]) and superior to ABC/2 (concordance correlation coefficient 0.77 [95% confidence interval 0.64]). Validation confirmed agreement in an independent sample (algorithm concordance correlation coefficient 0.99 [95% confidence interval 0.98], ABC/2 concordance correlation coefficient 0.82 [95% confidence interval 0.72]). The algorithm was closer to respective manual segmentations than ABC/2 in 52/58 cases (89.7%).

Conclusions—
An automatic segmentation algorithm for volumetric analysis of spontaneous ICH was developed and validated in this study. Algorithm measurements showed strong agreement with manual segmentations, whereas ABC/2 exhibited its limitations, yielding inaccurate overestimations of ICH volume. The refined, yet time-efficient, quantification of ICH by the algorithm may facilitate evaluation of clot volume as an outcome predictor and trigger for surgical interventions in the clinical setting.
The Threefold Root of Whiteheadian Temporality
Authors: Weber Michel 
Published: October 2016

The author argues that all temporal (epi-)phenomena are grounded in the fact of a “creative advance into novelty,” which includes (1) thatgenuinenovelty appears in the world, (2) that past events do not completely vanish (their ontological status is changed,lowered, so to speak), and (3) that there is an upward trend in terms of the “intensity” or “value” of experience.Five steps structure this paper: a short introduction to Whitehead’s blend of process thought; a contrasted specification of Whiteheadian creative advance and its three characters—creativity, efficacy, and vision; and, in conclusion, a meditation on the question of common sense.
The Secret of Long Tenure: A Study of Zheng Gangzhong’s Letters to Qin Gui’s Associates
Authors: Chu Ming-kin 
Published: October 2016

This article offers a case study of the relationship between early Southern Song literati and the chief councilor Qin Gui (1090-1155) through an analysis of Zheng Gangzhong’s (1088-1154) epistolary network. It shows how Zheng, deputy pacification commissioner of Sichuan between 1142 and 1147, attempted to build good rapport with the councilor’s associates through correspondence. As suggested, it was essential for heads of regional governments like Zheng Gangzhong, who was vulnerable to accusations of abuse of authority, to ingratiate themselves with senior officials surrounding Qin Gui if they wished to enjoy a stable career. This group of senior officials, despite being constantly in flux because of Qin Gui’s efforts to protect his leadership, facilitated Qin’s prolonged dominance by linking him to high-ranking officials like Zheng Gangzhong without exposing him to the charge of promoting factionalism. Cet article propose une étude de cas sur les relations entre les lettrés du début des Song du Sud et le premier ministre Qin Gui (1090-1155) basée sur l’analyse du réseau épistolaire de Zheng Gangzhong (1088-1154). Il montre comment Zheng, vice-commissaire à la pacification au Sichuan de 1142 à 1147, s’efforçait d’établir par correspondance de bonnes relations avec les associés du premier ministre. Ainsi qu’il est suggéré, il était essentiel pour un chef de gouvernement régional comme Zheng, qui prêtait le flanc aux accusations d’abus d’autorité, d’être dans les bonnes grâces des fonctionnaires de haut rang entourant Qin Gui s’il voulait s’assurer une carrière stable. Bien qu’en renouvellement constant en raison des efforts de Qin Gui pour protéger son leadership, ce groupe de personnalités haut placées a aidé Qin à rester au pouvoir pendant de longues années en le liant à des hauts fonctionnaires comme Zheng Gangzhong, sans pour autant l’exposer à être dénoncé pour factionnalisme.
Rising Waters, Rising Threats: The Human Trafficking of Indigenous Women in the Circumpolar Region of the United States and Canada
Authors: Sweet Victoria 
Published: October 2016

Among indigenous people around the world, human trafficking is taking a tremendous toll. While trafficking is not an exclusively indigenous issue, disproportionately large numbers of indigenous people, particularly women, are modern trafficking victims. In Canada, several groups concerned about human trafficking have conducted studies primarily focused on the sex trade because many sex workers are actually trafficking victims under both domestic and international legal standards. These studies found that First Nations women and youth represent between 70 and 90% of the visible sex trade in areas where the Aboriginal population is less than 10%. Very few comparable studies have been conducted in the United States, but studies in both Minnesota and Alaska found similar statistics among U.S. indigenous women.
With the current interest in resource extraction, and other opportunities in the warming Arctic, people from outside regions are traveling north in growing numbers. This rise in outside interactions increases the risk that the indigenous women may be trafficked. Recent crime reports from areas that have had an influx of outsiders such as Williston, North Dakota, U.S. and Fort McMurray, Alberta, Canada, both part of the new oil boom, demonstrate the potential risks that any group faces when people with no community accountability enter an area. The combination of development in rural locations, the demographic shift of outsiders moving to the north, and the lack of close monitoring in this circumpolar area is a potential recipe for disaster for indigenous women in the region. This paper suggests that in order to protect indigenous women, countries and indigenous nations must acknowledge this risk and plan for ways to mitigate risk factors.
LA PARTICULE WŌ ET WŎ EN CANTONAIS
Authors: RICAUD Philippe 
Published: October 2016

This paper attempts to establish a general methodology for interpreting Chinese final particles. This analysis divides the intrinsic value of final particles into denotative and discursive. This methodology is applied to the Cantonese wō and wŏ to show that:
1°) wō and wŏ are two variants of the same unit;
2°) the particle wó-wŏ refers to an act of enunciation;
3°) if it is the act of enunciation of the speaker's or the listener's utterance, the variant is wŏ;
4°) if it is the act of enunciation of another utterance, the variant is wŏ.
Other examples, taken from Cantonese (t'im) and Taiwanese (kong), supply further evidence for this analysis.
Getting the right balance: insole design alters the static balance of people with diabetes and neuropathy
Authors: Paton Joanne , Glasser Sam , Collings Richard , Marsden Jon 
Published: October 2016

AbstractBackgroundOver 1 in 3 older people with diabetes sustain a fall each year. Postural instability has been identified as independent risk factor for falls within people with Diabetic Peripheral Neuropathy (DPN). People with DPN, at increased risk of falls, are routinely required to wear offloading insoles, yet the impact of these insoles on postural stability and postural control is unknown. The aim of this study was to evaluate the effect of a standard offloading insole and its constituent parts on the balance in people with DPN.MethodsA random sample of 50 patients with DPN were observed standing for 3 × 30 s, and stepping in response to a light, under five conditions presented in a random order; as defined by a computer program; 1) no insole, 2) standard diabetic: a standard offloading insole made from EVA/poron®, and three other insoles with one design component systematically altered 3) flat: diabetic offloading insole with arch fill removed, 4) low resilient memory: diabetic offloading insole with the cover substituted with low resilience memory V9, 5) textured: diabetic offloading insole with a textured PVC surface added (Algeos Ltd). After each condition participants self‐rated perceived steadiness.ResultsInsole design effected static balance and balance perception, but not stepping reaction time in people with DPN. The diabetic and memory shaped insoles (with arch fill) significantly increased centre of pressure velocity (14 %, P = 0.006), (13 %, P = 0.001), and path length (14 %, P = 0.006), (13 %, P = 001), when compared to the no insole condition. The textured shaped and flat soft insole had no effect on static balance when compared to the no insole condition (P > 0.05).ConclusionInsoles have an effect on static balance but not stepping reaction time. This effect is independent of neuropathy severity. The addition of a textured cover seems to counter the negative effect of an arch fill, even in participants with severe sensation loss. Static balance is unaffected by material softness or resilience. Current best practice of providing offloading insoles, with arch fill, to increase contact area and reduce peak pressure could be making people more unstable. Whilst flat, soft insoles maybe the preferable design option for those with poor balance. There is a need to develop an offloading insole that can reduce diabetic foot ulcer risk, without compromising balance.
Methods of Assessment of Competence Level of Public Employees and Its Impact on the Results of Their Professional Activity
Authors: Столярова  , Stolyarova V. , Вашаломидзе  , Vashalomidze E. 
Published: October 2016

The article analyzes the applied methods for assessing the level of competence of civil servants at all stages of their career and gives suggestions for their
improvement. The recommendations of formation mechanisms more closely related indicators of the level of competence of civil servants with the indicators
of the results of their professional activity are justified. The basic directions of improvement of motivation and stimulation of civil servants working for the final
results of the federal ministries and other federal agencies in the economic crisis are offered.