bluuebunny/crossref_metadata_2025_split huggingface dataset:
Creation of a Long-Acting Nanoformulated 2′,3′-Dideoxy-3′-Thiacytidine
Authors: Guo Dongwei , Zhou Tian , Araínga Mariluz , Palandri Diana , Gautam Nagsen , Bronich Tatiana , Alnouti Yazen , McMillan JoEllyn , Edagwa Benson , Gendelman Howard E. 
Published: August 2016

Background:
Antiretroviral drug discovery and formulation design will facilitate viral clearance in infectious reservoirs. Although progress has been realized for selected hydrophobic integrase and nonnucleoside reverse transcriptase inhibitors, limited success has been seen to date with hydrophilic nucleosides. To overcome these limitations, hydrophobic long-acting drug nanoparticles were created for the commonly used nucleoside reverse transcriptase inhibitor, lamivudine (2′,3′-dideoxy-3′-thiacytidine, 3TC).

Methods:
A 2-step synthesis created a slow-release long-acting hydrophobic 3TC. Conjugation of 3TC to a fatty acid created a myristoylated prodrug which was encased into a folate-decorated poloxamer 407. Both in vitro antiretroviral efficacy in human monocyte-derived macrophages and pharmacokinetic profiles in mice were evaluated for the decorated nanoformulated drug.

Results:
A stable drug formulation was produced by poloxamer encasement that improved monocyte–macrophage uptake, antiretroviral activities, and drug pharmacokinetic profiles over native drug formulations.

Conclusions:
Sustained release of long-acting antiretroviral therapy is a new therapeutic frontier for HIV/AIDS. 3TC depot formation in monocyte-derived macrophages can be facilitated through stable subcellular internalization and slow drug release.
Estimating time to the common ancestor for a beneficial allele
Authors: Smith Joel , Coop Graham , Stephens Matthew , Novembre John 
Published: August 2016

AbstractThe haplotypes of a beneficial allele carry information about its history that can shed light on its age and putative cause for its increase in frequency. Specifically, the signature of an allele’s age is contained in the pattern of local ancestry that mutation and recombination impose on its haplotypic background. We provide a method to exploit this pattern and infer the time to the common ancestor of a positively selected allele following a rapid increase in frequency. We do so using a hidden Markov model which leverages the length distribution of the shared ancestral haplotype, the accumulation of derived mutations on the ancestral background, and the surrounding background haplotype diversity. Using simulations, we demonstrate how the inclusion of information from both mutation and recombination events increases accuracy relative to approaches that only consider a single type of event. We also show the behavior of the estimator in cases where data do not conform to model assumptions, and provide some diagnostics for assessing and improving inference. Using the method, we analyze population-specific patterns in the 1000 Genomes Project data to provide a global perspective on the timing of adaptation for several variants which show evidence of recent selection and functional relevance to diet, skin pigmentation, and morphology in humans.
Unlocked capacity of proteins to attack membranes characteristic of aggregation: the evil for diseases and aging from Pandora’s box
Authors: Lim Liangzhong , Lu Yimei , Song Jianxing 
Published: August 2016

AbstractAggregation of specific proteins is characteristic of a large spectrum of human diseases including all neurodegenerative diseases, while aggregation of non-specific proteins has been now identified to be a biomarker for cellular aging down toEscherichia coli. Previously, as facilitated with our discovery in 2005 that “completely insoluble” proteins could be all solubilized in unsalted water [Song (2009)FEBS Lett. 583: 953], we found that the TDP-43 prion-like domain in fact contains an intrinsic membrane-interacting subdomain [Lim et al. [2016]PLoS Biol.14, e1002338]. We decrypted that ALS-causing mutations/cofactor-depletion act to render the wellstructured folds of cytosolic VAPB-MSP domain and SOD1 into highly disordered states, thus becoming buffer-insoluble. Most surprisingly, this also unlocks the amphiphilic/hydrophobic regions universally exiting in proteins, which thus acquire a novel capacity in abnormally interacting with membranes [Qin et al. (2013)F1000Res2-221.v2; Lim (2016)BBA-Biomembranes.1858: 2223]. Here we aimed extend our discovery to address two fundamental questions: 1) why manyE. coliproteins become aggregated in aging; and 2) whether aggregation-prone proteins can also acquire a novel capacity in interacting with membranes; by dissecting the 557-residue S1 ribosomal protein into 7 fragments to disrupt its 6 S1 folds, followed by extensive CD and NMR characterizations. The results reveal that we have successfully eliminated all 6 S1 folds and fragment 4 becomes highly disordered and thus buffer-insoluble. Most strikingly, F4 does acquire a capacity in transforming into a helical conformation in membrane environments. Here, for the first time, our study deciphers that like ALScausing mutants, the disruption of a well-foldedE. colicytosolic protein also unlocks its amphiphilic/hydrophobic regions which are capable of abnormally interacting with membranes. Therefore, proteins, the most important functional players for all forms of life, can transform into membrane-toxic forms triggering diseases and aging, if their hydrophobic/amphiphilic regions are unlocked by genetic, pathological or/and environmental factors, which is characteristic of severe aggregation.
Micro-C XL: assaying chromosome conformation at length scales from the nucleosome to the entire genome
Authors: Hsieh Tsung-Han S. , Fudenberg Geoffrey , Goloborodko Anton , Rando Oliver J. 
Published: August 2016

ABSTRACTStructural analysis of chromosome folding in vivo has been revolutionized by Chromosome Conformation Capture (3C) and related methods, which use proximity ligation to identify chromosomal loci in physical contact. We recently described a variant 3C technique, Micro-C, in which chromatin is fragmented to mononucleosomes using micrococcal nuclease, enabling nucleosome-resolution folding maps of the genome. Here, we describe an improved Micro-C protocol using long crosslinkers, termed Micro-C XL, which exhibits greatly increased signal to noise, and provides further insight into the folding of the yeast genome. We also find that signal to noise is much improved in Micro-C XL libraries generated from relatively insoluble chromatin as opposed to soluble material, providing a simple method to physically enrich for bona-fide long-range interactions. Micro-C XL maps of the budding and fission yeast genomes reveal both short-range chromosome fiber features such as chromosomally-interacting domains (CIDs), as well as higher-order features such as clustering of centromeres and telomeres, thereby addressing the primary discrepancy between prior Micro-C data and reported 3C and Hi-C analyses. Interestingly, comparison of chromosome folding maps ofS. cerevisiaeandS. pomberevealed widespread qualitative similarities, yet quantitative differences, between these distantly-related species. Micro-C XL thus provides a single assay suitable for interrogation of chromosome folding at length scales from the nucleosome to the full genome.
Robust nonparametric descriptors for clustering quantification in single-molecule localization microscopy
Authors: Jiang Shenghang , Challapalli Sai Divya , Wang Yong 
Published: August 2016

ABSTRACTWe report a robust nonparametric descriptor,J′(r), for quantifying the spatial organization of molecules in singlemolecule localization microscopy.J′(r), based on nearest neighbor distribution functions, does not require any parameter as an input for analyzing point patterns. We show thatJ′(r) displays a valley shape in the presence of clusters of molecules, and the characteristics of the valley reliably report the clustering features in the data. More importantly, the position of theJ′(r) valley (rJ′m) depends exclusively on the density of clustering molecules (ρc). Therefore, it is ideal for direct measurements of clustering density of molecules in single-molecule localization microscopy.
Numerical Analysis of the Immersed Boundary Method for Cell-Based Simulation
Authors: Cooper Fergus R. , Baker Ruth E. , Fletcher Alexander G. 
Published: August 2016

AbstractMathematical modelling provides a useful framework within which to investigate the organization of biological tissues. With advances in experimental biology leading to increasingly detailed descriptions of cellular behaviour, models that consider cells as individual objects are becoming a common tool to study how processes at the single-cell level affect collective dynamics and determine tissue size, shape and function. However, there often remains no comprehensive account of these models, their method of solution, computational implementation or analysis of parameter scaling, hindering our ability to utilise and accurately compare different models. Here we present an effcient, open-source implementation of the immersed boundary method (IBM), tailored to simulate the dynamics of cell populations. This approach considers the dynamics of elastic membranes, representing cell boundaries, immersed in a viscous Newtonian fluid. The IBM enables complex and emergent cell shape dynamics, spatially heterogeneous cell properties and precise control of growth mechanisms. We solve the model numerically using an established algorithm, based on the fast Fourier transform, providing full details of all technical aspects of our implementation. The implementation is undertaken within Chaste, an open-source C++ library that allows one to easily change constitutive assumptions. Our implementation scales linearly with time step, and subquadratically with mesh spacing and immersed boundary node spacing. We identify the relationship between the immersed boundary node spacing and fluid mesh spacing required to ensure fluid volume conservation within immersed boundaries, and the scaling of cell membrane stiffness and cell-cell interaction strength required when refining the immersed boundary discretization. This study provides a recipe allowing consistent parametrisation of IBM models.
International trade and food security: conceptual discussion, WTO and the case of China
Authors: Zhu Yu 
Published: August 2016

Purpose
The purpose of this paper is to discuss the concept and measurements of food security under the framework of The Food and Agriculture Organization of the United Nations, explores the link between international trade and food security with an empirical investigation into the case of China, and draw policy implications in the context of WTO.

Design/methodology/approach
This paper elaborates the theoretical interconnection between food security and international trade and then utilize an autoregressive distributed lag model to investigate how/whether trade affects food security in China from two dimensions.

Findings
The authors find that international trade indeed leads China to increase its dependence on food imports, namely, it negatively affects the food security in China. Owing to the importance of food security under multilateral trade system, this paper then briefly analyzes two relevant topics of Doha Round negotiation, i.e. public stockholding for food security and special safeguard measures. It is proposed that WTO members should support the food self-sufficiency endeavors of developing countries and appropriately exempt them from rigid discipline of domestic support and market access.

Originality/value
This paper discusses the interaction of international trade and food security in various aspects. Empirical study shows that increasing dependence on food imports will negatively impact the food security of China. It is concluded that WTO members should support the food self-sufficiency endeavors of developing countries and appropriately exempt them from rigid discipline of domestic support and market access.
Recognizing voice: the child with autism spectrum disorder
Authors: Ni Chuileann Susan Jennifer , Quigley Jean 
Published: August 2016

Purpose
This paper assesses the ability of the minimally verbal child with autism to recognise their own voice. The rationale for this study rests in recent advances in technology aimed at making the voice of speech generating devices (SGDs) sound more like the child using them (van Santen and Black, 2009). The purpose of this paper is to investigate the child’s ability to actually recognise the sound of their own voice in a series of short experiments using computer-based methodology.

Design/methodology/approach
Using a voice-face matching computerised paradigm, the performance of 33 children with autism was compared to that of 27 children with developmental delay (DD), and 33 typically developing (TD) children. The children were matched for verbal and non-verbal ability and a training period was conducted prior to the main test to ensure children’s understanding of what was expected of them.

Findings
The findings of this study suggest that the child with autism recognise the sound of their own voice at test, but with much greater difficulty than age-and-ability matched comparison groups. The implications of this finding are useful for researchers in the field of speech mimicry technology and manufacturers of SGD software packages. The paper also provides empirical insights about how the child with autism may process voice in their everyday social interactions.

Research limitations/implications
Some limitations to this study exist, for instance, there were only a small number of presentations involving self-voice in this task. This may have over simplified the process for the young TD children and the children with DD. Nevertheless, it is striking that despite being matched for non-verbal mental age, the children with autism performed significantly less well than either of the other two groups of children. However, future studies would benefit from adjusting the number of presentations of voice and face accordingly. It is also important to note that for some children with autism the simultaneous presentation of faces and voices may act more as an interference effect (Cook and Wilding, 1997; Joassin et al., 2004) than a facilitation effect (Molholm et al., 2002). Future studies may wish to test a subgroup on voice recognition without the aid of visual prompts.

Practical implications
The paper includes implications for the type of voice children with autism may prefer to use when communicating via a SGD. The authors suggest that if the child does not recognise or prefer the sound of their own natural voice on such devices, partial or complete abandonment of the SGD may occur.

Originality/value
This paper fulfils an identified need to research how children’s abilities and preferences can be taken into account at the point of decision making for particular communication tools.
Indoor navigation with smart phone IMU for the visually impaired in university buildings
Authors: Zegarra Flores Jesus Victor , Rasseneur Laurence , Galani Rodrigue , Rakitic Fabienne , Farcy René 
Published: August 2016

Purpose
The purpose of this paper is to design and test effective indoor navigation solutions for visually impaired people in situations where GPS, bluetooth or Wi-Fi signals are unavailable. The authors use the inertial measurement units (IMU), the compass and the barometer of a smart phone.

Design/methodology/approach
The authors have used commercial Android smart phones with IMU, compass and barometer to record a path and to give navigation instructions in an adapted way using a mobility-specific vocabulary. The method proposed is to save paths taking into account different indoor waypoints such as the stairs (change from one floor to another) and the change of direction of the trajectory of the path (e.g. one-fourth turn right or left), recording data from the IMU sensor’s, compass and barometer of the smart phone. Having this information and the characteristics of the each segment (distance, azimuth to the north and pressure) of the path, it is possible to provide functional navigation guidance to the visually impaired subject. Three different visually impaired people (one partially sighted and two fully blind) and three sighted people have tested the paths. The efficiency of the navigation is analyzed in terms of distance and time using the comparison between blind and sighted people.

Findings
The main finding is that it is possible to guide visually impaired people some hundreds of meters just using the sensors of a smart phone under certain conditions: the visually impaired person has to understand the guidance instructions and respect some strategies (e.g. not to walk diagonally across vast spaces). Additionally it is observed that the visually impaired participants walked distances, which are not much different to the optimal values. On the other hand; because of their hesitations using their white cane to find free paths, they take in some cases 50 percent more time to arrive (for a few minutes path, this time is not critical and even more efficient than looking for a guide). One thing to highlight is that even with this hesitation, the subjects arrived to the final destination.

Originality/value
This paper demonstrates how an IMU coupled to a compass and a barometer from a Smart Phone employing a spoken mobility language (e.g. next corridor to the left; at the end of the stairs turn right, turn left, etc.) can guide visually impaired people inside buildings.
Cyber victimization and psychological adjustment difficulties among adolescents
Authors: Wright Michelle F. 
Published: August 2016

PurposeThe purpose of this paper is to investigate the buffering effect of the mediation of technology use and social support from school resource officers on the associations between cyber victimization and psychosocial adjustment difficulties (i.e. depression, anxiety, loneliness) over three years (wave-one=sixth grade; wave-two=seventh grade; wave-three=eighth grade).Design/methodology/approachParticipants were 867 eighth graders from the Midwestern USA (ages range from 13 to 15 years old; 51 percent female).FindingsThe findings revealed that high levels of wave-two perceived social support from school resource officers and the mediation of technology use made the relationship between wave-one cyber victimization and wave-three depression more negative, while lower levels of this support and less mediation of technology use made the association more positive. These patterns were not found for anxiety and loneliness.Originality/valueImplications for prevention and intervention programs and the role of school resource officers in such programs are also discussed.
The continued marginalization of campus police
Authors: Patten Ryan , Alward Lucas , Thomas Matthew , Wada James 
Published: August 2016

Purpose
The purpose of this paper is to examine a campus community’s knowledge and acceptance of their campus police as “real” police.

Design/methodology/approach
Using the liminality theoretical framework, this study surveyed students, faculty, staff, and administrators (n=1,484). Students were surveyed in-person, while staff, faculty, and administrators participated through an e-mail link to an online survey.

Findings
Results indicate that campus police are stuck in a liminal state. While 80 percent of the sample thought campus police should be armed, almost two-thirds (64 percent) did not know or were unsure of campus police officer tasks and three-quarters (75 percent) did not know or were unsure of campus police training requirements.

Research limitations/implications
The participants come from one university campus, so the generalizability of the sample is limited.

Originality/value
This study provides more evidence of the marginalization of campus police. Specifically, this study highlights that a majority of participants could not or were unable to identify campus police officers’ training and duties. Instead of using small qualitative samples, this study utilized over 1,400 participants on one campus, which provides more explanatory power about the perception problems of the campus police. This study also continues to advance and expand liminal theory.
Reducing school violence
Authors: Crawford Charles , Burns Ronald 
Published: August 2016

Purpose
Recent highly publicized acts of violence and shootings on school campuses have prompted numerous crime prevention responses. The purpose of this paper is to assess the impact of protective measures such as law enforcement, security policies, and school/neighborhood characteristics on school violence within the context of the racial composition of the school and grade level.

Design/methodology/approach
The data used in this study were part of the School Survey on Crime and Safety collected in 2006. The dependent measures of school violence include reports of serious violence, physical attacks/fights, gun or knife possession, and threats and attacks with a weapon. The sample was divided by racial composition of the school (predominately white, and predominately minority schools) and by grade level (high schools, and all other grades). A negative binomial regression was conducted due the count-based dependent variables.

Findings
Findings revealed that minority schools often face higher levels of reported violence and had a heavier law enforcement presence, which often had mixed or counterproductive results for reducing school violence. School characteristics, such as reports of bullying, location, gang activity, and security measures yielded numerous statistically significant results.

Research limitations/implications
Officials proposing school violence prevention efforts should strongly consider the importance of school and community characteristics, most notably grade level, and the unique context of a predominately white or minority school as there were different statistically significant results. Furthermore, officials should be cautious about relying on simple efforts such as more security personnel to address school violence. Violence and crime on school grounds should not be viewed as being isolated from violence and other forms of crime in the community. Policy recommendations and suggestions for future research are provided.

Originality/value
This study differs from much of the previous literature, which typically examines student and administrator attitudes about victimization and crime prevention. The current study examines detailed information on the effects of school violence prevention efforts and moves beyond most other works as it considers school safety approaches within the context of racial composition of the school and by different grade levels.