bluuebunny/crossref_metadata_2025 huggingface dataset:
An editor for the generation and customization of geometry restraints
Authors: Moriarty Nigel W. , Draizen Eli J. , Adams Paul D.
Published: February 2017

Chemical restraints for use in macromolecular structure refinement are produced by a variety of methods, including a number of programs that use chemical information to generate the required bond, angle, dihedral, chiral and planar restraints. These programs help to automate the process and therefore minimize the errors that could otherwise occur if it were performed manually. Furthermore, restraint-dictionary generation programs can incorporate chemical and other prior knowledge to provide reasonable choices of types and values. However, the use of restraints to define the geometry of a molecule is an approximation introduced with efficiency in mind. The representation of a bond as a parabolic function is a convenience and does not reflect the true variability in even the simplest of molecules. Another complicating factor is the interplay of the molecule with other parts of the macromolecular model. Finally, difficult situations arise from molecules with rare or unusual moieties that may not have their conformational space fully explored. These factors give rise to the need for an interactive editor for WYSIWYG interactions with the restraints and molecule.Restraints Editor, Especially Ligands(REEL) is a graphical user interface for simple and error-free editing along with additional features to provide greater control of the restraint dictionaries in macromolecular refinement.
Ligand fitting withCCP4
Authors: Nicholls Robert A.
Published: February 2017

Crystal structures of protein–ligand complexes are often used to infer biology and inform structure-based drug discovery. Hence, it is important to build accurate, reliable models of ligands that give confidence in the interpretation of the respective protein–ligand complex. This paper discusses key stages in the ligand-fitting process, including ligand binding-site identification, ligand description and conformer generation, ligand fitting, refinement and subsequent validation. TheCCP4 suite contains a number of software tools that facilitate this task:AceDRGfor the creation of ligand descriptions and conformers,LidiaandJLigandfor two-dimensional and three-dimensional ligand editing and visual analysis,Cootfor density interpretation, ligand fitting, analysis and validation, andREFMAC5 for macromolecular refinement. In addition to recent advancements in automatic carbohydrate building inCoot(LO/Carb) and ligand-validation tools (FLEV), the release of theCCP4i2 GUI provides an integrated solution that streamlines the ligand-fitting workflow, seamlessly passing results from one program to the next. The ligand-fitting process is illustrated using instructive practical examples, including problematic cases such as post-translational modifications, highlighting the need for careful analysis and rigorous validation.
Guidelines for the successful generation of protein–ligand complex crystals
Authors: Müller Ilka
Published: February 2017

With continuous technical improvements at synchrotron facilities, data-collection rates have increased dramatically. This makes it possible to collect diffraction data for hundreds of protein–ligand complexes within a day, provided that a suitable crystal system is at hand. However, developing a suitable crystal system can prove challenging, exceeding the timescale of data collection by several orders of magnitude. Firstly, a useful crystallization construct of the protein of interest needs to be chosen and its expression and purification optimized, before screening for suitable crystallization and soaking conditions can start. This article reviews recent publications analysing large data sets of crystallization trials, with the aim of identifying factors that do or do not make agoodcrystallization construct, and gives guidance in the design of an expression construct. It provides an overview of common protein-expression systems, addresses how ligand binding can be both help and hindrance for protein purification, and describes ligand co-crystallization and soaking, with an emphasis on troubleshooting.
Between Autonomy and Paternalism: Crisis Managers’ Constructions of Citizens’ Responsibilities in the Context of Crises and Contingencies
Authors: Hobbins Jennifer
Published: February 2017

Public discussions about the division of responsibilities between state and citizen in crises have led to reformulated policies. These are interpreted and put into practice by crisis managers. Hence, their understandings of citizens’ responsibilities are central for actions and resource allocation. This qualitative study focuses on Swedish crisis managers’ understandings of citizens’ (moral) responsibilities and practices of ‘doing’ responsibilities. Three overarching forms of ‘doing responsibilities’ were found as follows: assignment, assessment and differentiation. These ways of constructing responsibilities were permeated by two diverging rationales: the autonomy rationale and the paternalism rationale. The two rationales add up to a partly contradictory complexity that may explain individuals’ differing responsibility taking. Further, not recognizing this contradiction may negatively affect citizen's willingness to take responsibility when desired.
Leadership Ideals as Barriers for Efficient Collaboration During Emergencies and Disasters
Authors: Uhr Christian
Published: February 2017

In an emergency or disaster situation, it is likely that a conglomerate of societal resources will respond to various needs. In such a multi‐organizational setting, collaboration becomes necessary. Empirical findings suggest that collaboration can be very problematical and this paper argues that a possible explanation can be found in intra‐organizational leadership ideals, dysfunctional in a collaborative context. In order to facilitate a principal discussion, an analytical framework for discussing leadership and collaboration is suggested. Moreover, literature findings suggesting individual qualities facilitating collaboration are presented. Three leadership archetypes are used to problematize intra‐organizational ideals in inter‐organizational settings. It is suggested that more attention must be paid to qualities enabling individuals to operate simultaneously in different, and partly conflicting, management contexts.
What Factors Drive Organizational Learning From Crisis? Insights From the Dutch Food Safety Services’ Response to Four Veterinary Crises
Authors: Broekema Wout , van Kleef Daphne , Steen Trui
Published: February 2017

Although organizational learning has been studied extensively, empirical studies in relation to crises and theory building have remained scarce. This study explored what factors affect the learning process from crises of a public sector organization. We studied the responses of the Dutch food safety services (NVWA) to the veterinary crises classical swine fever (1997–1998), foot‐and‐mouth disease (2001), avian influenza (2003) and Q fever (2007–2010). Data from in‐depth interviews with key experts in the organization and from crisis management documents pointed to political–economic context, social–emotional understanding, organizational structure, organizational culture, crisis management stage and organizational forgetting as key factors. Remarkably, postcrisis evaluation reports, leadership and a shared sense‐making of what lessons to learn were not found to play a central role.
Measuring site fidelity and spatial segregation within animal societies
Authors: Richardson Thomas O. , Giuggioli Luca , Franks Nigel R. , Sendova‐Franks Ana B.
Published: February 2017

Animals often display a marked tendency to return to previously visited locations that contain important resources, such as water, food, or developing brood that must be provisioned. A considerable body of work has demonstrated that this tendency is strongly expressed in ants, which exhibit fidelity to particular sites both inside and outside the nest. However, thus far many studies of this phenomena have taken the approach of reducing an animal's trajectory to a summary statistic, such as the area it covers.

Using both simulations of biased random walks, and empirical trajectories from individual rock ants, Temnothorax albipennis, we demonstrate that this reductive approach suffers from an unacceptably high rate of false negatives.

To overcome this, we describe a site‐centric approach which, in combination with a spatially‐explicit null model, allows the identification of the important sites towards which individuals exhibit statistically significant biases.

Using the ant trajectories, we illustrate how the site‐centric approach can be combined with social network analysis tools to detect groups of individuals whose members display similar space‐use patterns.

We also address the mechanistic origin of individual site fidelity; by examining the sequence of visits to each site, we detect a statistical signature associated with a self‐attracting walk – a non‐Markovian movement model that has been suggested as a possible mechanism for generating individual site fidelity.
Whole transcriptome sequencing identifies increased CXCR2 expression in PNH granulocytes
Authors: Hosokawa Kohei , Kajigaya Sachiko , Keyvanfar Keyvan , Qiao Wangmin , Xie Yanling , Biancotto Angelique , Townsley Danielle M. , Feng Xingmin , Young Neal S.
Published: February 2017

The aetiology of paroxysmal nocturnal haemoglobinuria (PNH) is a somatic mutation in the X‐linked phosphatidylinositol glycan class A gene (PIGA), resulting in global deficiency of glycosyl phosphatidylinositol–anchored proteins (GPI‐APs). This study applied RNA‐sequencing to examine functional effects of the PIGA mutation in human granulocytes. CXCR2 expression was increased in GPI‐AP‐ compared to GPI‐AP+ granulocytes. Macrophage migration inhibitory factor, a CXCR2 agonist, was significantly higher in plasma of PNH patients. Nuclear factor‐κB phosphorylation was upregulated in GPI‐AP− compared with GPI‐AP+ granulocytes. Our data suggest novel mechanisms in PNH, not obviously predicted by decreased production of the GPI moiety.
Perennial warm‐season grasses for producing biofuel and enhancing soil properties: an alternative to corn residue removal
Authors: Blanco‐Canqui Humberto , Mitchell Robert B. , Jin Virginia L. , Schmer Marty R. , Eskridge Kent M.
Published: February 2017

Removal of corn (Zea mays L.) residues at high rates for biofuel and other off‐farm uses may negatively impact soil and the environment in the long term. Biomass removal from perennial warm‐season grasses (WSGs) grown in marginally productive lands could be an alternative to corn residue removal as biofuel feedstocks while controlling water and wind erosion, sequestering carbon (C), cycling water and nutrients, and enhancing other soil ecosystem services. We compared wind and water erosion potential, soil compaction, soil hydraulic properties, soil organic C (SOC), and soil fertility between biomass removal from WSGs and corn residue removal from rainfed no‐till continuous corn on a marginally productive site on a silty clay loam in eastern Nebraska after 2 and 3 years of management. The field‐scale treatments were as follows: (i) switchgrass (Panicum virgatum L.), (ii) big bluestem (Andropogon gerardii Vitman), and (iii) low‐diversity grass mixture [big bluestem, indiangrass (Sorghastrum nutans (L.) Nash), and sideoats grama (Bouteloua curtipendula (Michx.) Torr.)], and (iv) 50% corn residue removal with three replications. Across years, corn residue removal increased wind‐erodible fraction from 41% to 86% and reduced wet aggregate stability from 1.70 to 1.15 mm compared with WSGs in the upper 7.5 cm soil depth. Corn residue removal also reduced water retention by 15% between −33 and −300 kPa potentials and plant‐available water by 25% in the upper 7.5 cm soil depth. However, corn residue removal did not affect final water infiltration, SOC concentration, soil fertility, and other properties. Overall, corn residue removal increases erosion potential and reduces water retention shortly after removal, suggesting that biomass removal from perennial WSGs is a desirable alternative to corn residue removal for biofuel production and maintenance of soil ecosystem services.
Cytochrome 2B6 polymorphism and efavirenz‐induced central nervous system symptoms : a substudy of the ANRS ALIZE trial
Authors: Gallien S , Journot V , Loriot M‐A , Sauvageon H , Morlat P , Reynes J , Reliquet V , Chêne G , Molina J‐M ,   the ANRS 099 ALIZE trial study group
Published: February 2017

Objectives

Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the relationship of CYP2B6 polymorphisms with the occurrence of efavirenz‐induced central nervous system (CNS) symptoms are limited.

Methods

We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP‐binding cassette, sub‐family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV‐infected adults virologically suppressed on a protease inhibitor‐based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial. Kaplan−Meier methods and Cox regression analysis were used to investigate their association with efavirenz plasma levels and CNS events up to 48 months after switching.

Results

In total, 191 patients with a median age of 41 years, who were 87% male and 85% Caucasian, were enrolled in the study. Variant allelic frequencies were 0.49, 0.93, 0.59 and 0.63 for CYP2B6 516, CYP3A5 392, ABCB1 2677 and ABCB1 3435, respectively. The median efavirenz plasma concentration (MEPC) was 2.2 mg/L [interquartile range (IQR) 1.7–2.8 mg/L] and was significantly higher in patients with the deficient CYP2B6 516T. Overall, 242 CNS events were reported in 104 individuals (54%). No correlation was found between MEPC and CNS events. The occurrence of a first CNS event was lower in patients with the CYP2B6 516 G/G genotype vs. CYP2B6 516 T genotypes [50% (IQR: 40–60%) vs. 66% (IQR: 56–75%), respectively; P = 0.02]. In an adjusted Cox regression model, there was a tendency towards a higher risk of a first CNS event among carriers of the variant CYP2B6 516 T allele (relative risk 1.4 [95% CI, 0.99–2.1]; P?=?.06), compared with noncarriers.

Conclusions

The deficient CYP2B6 516 T allele is associated with higher efavirenz plasma drug levels and more frequent CNS‐related symptoms.
Spontaneous mediastinal myeloid sarcoma in a common marmoset (Callithrix jacchus) and review of the veterinary literature
Authors: Morosco Danielle T. , Cline Curtis R. , Owston Michael A. , Kumar Shyamesh , Dick Edward J.
Published: February 2017

Background

Myeloid sarcoma is a rare manifestation of myeloproliferative disorder defined as an extramedullary mass composed of myeloid precursor cells. A 9‐month old, female, common marmoset (Callithrix jacchus) had increased respiratory effort.

Methods

A complete necropsy with histology and immunohistochemistry was performed.

Results

The thymus was replaced by a firm, gray‐tan mass with a faint green tint, filling over 50% of the thoracic cavity. Sheets of granulocytes, lymphoid cells, nucleated erythrocytes, megakaryocytes, and hematopoietic precursors of indeterminate cell lineage replaced the thymus, perithymic connective tissue, mediastinal adipose tissues, epicardium, and much of the myocardium. The cells demonstrated diffuse strong cytoplasmic immunoreactivity for lysozyme, and strong, multifocal membranous immunoreactivity for CD117.

Conclusion

We report the first case of a myeloid sarcoma in a common marmoset (C. jacchus), similar to reported human cases of mediastinal myeloid sarcoma, and present a review of myeloproliferative diseases from the veterinary literature.
Neuroprotection and endocytosis: erythropoietin receptors in insect nervous systems
Authors: Miljus Natasa , Massih Bita , Weis Marissa A. , Rison Jan Vincent , Bonnas Christel B. , Sillaber Inge , Ehrenreich Hannelore , Geurten Bart R. H. , Heinrich Ralf
Published: February 2017

Erythropoietin (Epo) plays a dual role as an erythropoiesis‐stimulating hormone and a locally produced cytoprotectant in various vertebrate tissues. Splice variants and engineered derivatives of Epo that mediate neuroprotection but do not stimulate erythropoiesis suggest that alternative receptors, different from the ‘classical’ homodimeric receptor involved in haematopoiesis, mediate neuroprotective Epo functions. Previous studies on grasshoppers demonstrated neuroprotective and neuroregenerative effects of Epo that involved similar transduction pathways as in mammals. To advance the characterization of yet unidentified neuroprotective Epo receptors, we studied the neuroprotective potency of the human non‐erythropoietic Epo splice variant EV‐3 in primary cultured locust brain neurons. We demonstrate that EV‐3, like Epo, protects locust neurons from hypoxia‐induced apoptotic death through activation of the Janus kinase/signal transducer and activator of transcription transduction pathway. Using the fluorescent dye FM1–43 to quantify endocytotic activity we show that both Epo and EV‐3 increase the number of fluorescently labelled endocytotic vesicles. This reveals that binding of Epo to its neuroprotective receptor induces endocytosis, as it has been described for the mammalian homodimeric Epo‐receptor expressed by erythroid progenitors. Reduction in Epo‐stimulated endocytotic activity following pre‐exposure to EV‐3 indicated that both Epo and its splice variant bind to the same receptor on locust neurons. The shared neuroprotective potency of Epo and EV‐3 in insect and mammalian neurons, in the absence of erythropoietic effects of EV‐3 in mammals, suggests a greater similarity of the unidentified nervous Epo receptors (or receptor complexes) across phyla than between mammalian haematopoietic and neuroprotective receptors. Insects may serve as suitable models to evaluate the specific protective mechanisms mediated by Epo and its variants in non‐erythropoietic mammalian tissues.

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Emotional and sensory profiling by children and teenagers: A case study of the check‐all‐that‐apply method on biscuits
Authors: Schouteten Joachim J. , De Steur Hans , Lagast Sofie , De Pelsmaeker Sara , Gellynck Xavier
Published: February 2017

Sensory and emotional profiling by consumers is gathering interest among scientists and companies as it could help to better understand the motives for food choice. Although children and teenagers are important food consumer groups, they are underrepresented in sensory research and little is known on how children and teenagers perform on these tasks. Therefore, this study investigates the emotional and sensory profiling of a traditional biscuit product among 122 children and teenagers (10–14 years old). The check‐all‐that‐apply (CATA) approach has been applied for conducting the emotional and sensory profiling task using an age‐appropriate protocol. Children and teenagers evaluated four different samples (market leader, store brand, small producer, and local bakery) and assessed their overall liking under three conditions: blind, expected (brand logo) and informed. Overall liking differed significantly among the samples and brand information influenced the informed liking scores. Samples were associated with different emotional profiles and sensory attributes by the children and teenagers.

Practical applications

This study illustrates the potential of using CATA questions for obtaining emotional connotations and sensory attributes of food products with children and teenagers. Together with the insights regarding their attitudes toward traditional food products and store brands, this could help producers when developing promotion initiatives to bring their traditional food products to a potential market of young consumers. Including both sensory and emotional measurements yield interesting insights for the product development if companies want to produce products in alignment with the brand message. Further, this study shows that branding influences not only the overall liking but also the sensory perception of the food products. Therefore, this study adds to the discussion on the need and importance of a more realistic product presentation during sensory testing.
Effects of distance from models on the fitness of floral mimics
Authors: Duffy K. J. , Johnson S. D.
Published: February 2017

Rewardless plants can attract pollinators by mimicking floral traits of rewarding heterospecific plants. This should result in the pollination success of floral mimics being dependent on the relative abundance of their models, as pollinator abundance and conditioning on model signals should be higher in the vicinity of the models. However, the attraction of pollinators to signals of the models may be partially innate, such that spatial isolation of mimics from model species may not strongly affect pollination success of mimics.

We tested whether pollination rates and fruit set of the rewardless orchid Disa pulchra were influenced by proximity and abundance of its rewarding model species, Watsonia lepida.

Pollination success of the orchid increased with proximity to the model species, while fruit set of the orchid increased with local abundance of the model species. Orchids that were experimentally translocated outside the model population experienced reduced pollinaria removal and increased pollinator‐mediated self‐pollination.

These results confirm predictions that the pollination success of floral mimics should be dependent on the proximity and abundance of model taxa, and thus highlight the importance of ecological facilitation among species involved in mimicry systems.
Cold acclimation in warmer extended autumns impairs freezing tolerance of perennial ryegrass (Lolium perenne) and timothy (Phleum pratense)
Authors: Dalmannsdottir Sigridur , Jørgensen Marit , Rapacz Marcin , Østrem Liv , Larsen Arild , Rødven Rolf , Rognli Odd Arne
Published: February 2017

The effect of variable autumn temperatures in combination with decreasing irradiance and daylength on photosynthesis, growth cessation and freezing tolerance was investigated in northern‐ and southern‐adapted populations of perennial ryegrass (Lolium perenne) and timothy (Phleum pratense) intended for use in regions at northern high latitudes. Plants were subjected to three different acclimation temperatures; 12, 6 and 9/3°C (day/night) for 4 weeks, followed by 1 week of cold acclimation at 2°C under natural light conditions. This experimental setup was repeated at three different periods during autumn with decreasing sums of irradiance and daylengths. Photoacclimation, leaf elongation and freezing tolerance were studied. The results showed that plants cold acclimated during the period with lowest irradiance and shortest day had lowest freezing tolerance, lowest photosynthetic activity, longest leaves and least biomass production. Higher acclimation temperature (12°C) resulted in lower freezing tolerance, lower photosynthetic activity, faster leaf elongation rate and higher biomass compared with the other temperatures. Photochemical mechanisms were predominant in photoacclimation. The northern‐adapted populations had a better freezing tolerance than the southern‐adapted except when grown during the late autumn period and at the highest temperature; then there were no differences between the populations. Our results indicate that the projected climate change in the north may reduce freezing tolerance in grasses as acclimation will take place at higher temperatures and shorter daylengths with lower irradiance.
Use of locking compression plates in ulnar fractures of 18 horses*
Authors: Jacobs Carrie C. , Levine David G. , Richardson Dean W.
Published: February 2017

Objectives

To describe the outcome, clinical findings, and complications associated with the use of the locking compression plate (LCP) for various types of ulnar fractures in horses.

Study Design

Retrospective case series.

Sample Population

Client owned horses (n = 18).

Methods

Medical records, radiographs, and follow‐up for horses having an ulnar fracture repaired using at least 1 LCP were reviewed. Fifteen of 18 horses had fractures of the ulna only, and 3 horses had fractures of the ulna and proximal radius.

Results

All 18 horses were discharged from the hospital. Complications occurred in 5 horses; incisional infection (n = 4, 22%), implant‐associated infection (n = 2, 11%), and colic (n = 1, 6%). Follow‐up was available for all horses at a range of 13‐120 months and 15 horses (83%) were sound for their intended purpose and 3 horses (17%) were euthanatized. One horse was euthanatized for complications associated with original injury and surgery.

Conclusions

The LCP is a viable method of internal fixation for various types of ulnar fractures, with most horses in this series returning to soundness.
Urbanisation and Food Security: An Overview
Authors: Azizan Muhammad Uzair , Mohd Raid Maryanti , Hussin Khadijah
Published: February 2017

Urbanisation has given significant impact to various sectors, particularly in agriculture. Essentially, agricultural production activities depend heavily on land resources. At the same time, land is also needed as vital resources for the country development. Despite of the initiative of urbanism to better the country development process, it has raised concern among the land administrator regarding the status of the national’s food security. Food security has been threatened by the needs of the physical development due to urbanisation. Therefore, this article attempts to study the impact of urbanisation on the agriculture sector and examined the role of urbanism to safeguard the land resources for food security purposes. It is hope that, this article will form an inclusive understanding regarding the idea of urbanism in pursuing the betterment of an economic progress without compromising the needs for the national food security.
Statistical Shape Modeling for Cavopulmonary Assist Device Development: Variability of Vascular Graft Geometry and Implications for Hemodynamics
Authors: Bruse Jan L. , Giusti Giuliano , Baker Catriona , Cervi Elena , Hsia Tain-Yen , Taylor Andrew M. , Schievano Silvia
Published: February 2017

Patients born with a single functional ventricle typically undergo three-staged surgical palliation in the first years of life, with the last stage realizing a cross-like total cavopulmonary connection (TCPC) of superior and inferior vena cavas (SVC and IVC) with both left and right pulmonary arteries (LPA and RPA), allowing all deoxygenated blood to flow passively back to the lungs (Fontan circulation). Even though within the past decades more patients survive into adulthood, the connection comes at the prize of deficiencies such as chronic systemic venous hypertension and low cardiac output (CO), which ultimately may lead to Fontan failure. Many studies have suggested that the TCPC’s inherent insufficiencies might be addressed by adding a cavopulmonary assist device (CPAD) to provide the necessary pressure boost. While many device concepts are being explored, few take into account the complex cardiac anatomy typically associated with TCPCs. In this study, we focus on the extra cardiac conduit (ECC) vascular graft connecting IVC and pulmonary arteries (PAs) as one possible landing zone for a CPAD and describe its geometric variability in a cohort of 18 patients that had their TCPC realized with a 20 mm vascular graft. We report traditional morphometric parameters and apply statistical shape modeling (SSM) to determine the main contributors of graft shape variability. Such information may prove useful when designing CPADs that are adapted to the challenging anatomical boundaries in Fontan patients. We further compute the anatomical mean 3D graft shape (template graft) as a representative of key shape features of our cohort and prove this template graft to be a significantly better approximation of population and individual patient’s hemodynamics than a commonly used simplified tube geometry. We therefore conclude that statistical shape modeling results can provide better models of geometric and hemodynamic boundary conditions associated with complex cardiac anatomy, which in turn may impact on improved cardiac device development.
Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen
Authors: Santiago-Tirado Felipe H. , Onken Michael D. , Cooper John A. , Klein Robyn S. , Doering Tamara L.
Published: February 2017

The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen
Cryptococcus neoformans
invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an
in vitro
model BBB to show that a “Trojan horse” mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged
C. neoformans
-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens.

IMPORTANCE
The fungal pathogen
Cryptococcus neoformans
invades the brain, causing a meningoencephalitis that kills hundreds of thousands of people each year. One route that has been proposed for this brain entry is a Trojan horse mechanism, whereby the fungus crosses the blood-brain barrier (BBB) as a passenger inside host phagocytes. Although indirect experimental evidence supports this intriguing mechanism, it has never been directly visualized. Here we directly image Trojan horse transit and show that it is regulated independently of free fungal entry, contributes to cryptococcal BBB crossing, and allows mutant fungi that cannot enter alone to invade the brain.
In Situ
Tagged nsp15 Reveals Interactions with Coronavirus Replication/Transcription Complex-Associated Proteins
Authors: Athmer Jeremiah , Fehr Anthony R. , Grunewald Matthew , Smith Everett Clinton , Denison Mark R. , Perlman Stanley
Published: February 2017

Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown. To begin to address these questions, we created an
in situ
tagged form of nsp15 using the prototypic CoV, mouse hepatitis virus (MHV). In MHV, nsp15 contains the genomic RNA packaging signal (P/S), a 95-bp RNA stem-loop structure that is not required for viral replication or nsp15 function. Utilizing this knowledge, we constructed an internal hemagglutinin (HA) tag that replaced the P/S. We found that nsp15-HA was localized to discrete perinuclear puncta and strongly colocalized with nsp8 and nsp12, both well-defined members of the RTC, but not the membrane (M) protein, involved in virus assembly. Finally, we found that nsp15 interacted with RTC-associated proteins nsp8 and nsp12 during infection, and this interaction was RNA independent. From this, we conclude that nsp15 localizes and interacts with CoV proteins in the RTC, suggesting it plays a direct or indirect role in virus replication. Furthermore, the use of
in situ
epitope tags could be used to determine novel nsp-nsp interactions in coronaviruses.

IMPORTANCE
Despite structural and biochemical data demonstrating that the coronavirus nsp15 protein contains an endoribonuclease domain, its precise function during coronavirus infection remains unknown. In this work, we created a novel
in situ
tagged form of nsp15 to study interactions and localization during infection. This
in situ
tag was tolerated by MHV and did not affect viral replication. Utilizing this tag, we established that nsp15 localized to sites of replication but not sites of assembly throughout infection. Furthermore, we found that nsp15 interacted with the putative viral primase nsp8 and polymerase nsp12 during CoV infection. The strong association of nsp15 with replication complexes and interactions with replicative CoV enzymes suggest nsp15 is involved in CoV replication. These data and tools developed in this study help elucidate the function of nsp15 during infection and may be used to uncover other novel viral protein interactions.
Modulation of amyloid assembly by glycosaminoglycans: from mechanism to biological significance
Authors: Quittot Noé , Sebastiao Mathew , Bourgault Steve
Published: February 2017

Glycosaminoglycans (GAGs) are long and unbranched polysaccharides that are abundant in the extracellular matrix and basement membrane of multicellular organisms. These linear polyanionic macromolecules are involved in many physiological functions from cell adhesion to cellular signaling. Interestingly, amyloid fibrils extracted from patients afflicted with protein misfolding diseases are virtually always associated with GAGs. Amyloid fibrils are highly organized nanostructures that have been historically associated with pathological states, such as Alzheimer’s disease and systemic amyloidoses. However, recent studies have identified functional amyloids that accomplish crucial physiological roles in almost all living organisms, from bacteria to insects and mammals. Over the last 2 decades, numerous reports have revealed that sulfated GAGs accelerate and (or) promote the self-assembly of a large diversity of proteins, both inherently amyloidogenic and non-aggregation prone. Despite the fact that many studies have investigated the molecular mechanism(s) by which GAGs induce amyloid assembly, the mechanistic elucidation of GAG-mediated amyloidogenesis still remains the subject of active research. In this review, we expose the contribution of GAGs in amyloid assembly, and we discuss the pathophysiological and functional significance of GAG-mediated fibrillization. Finally, we propose mechanistic models of the unique and potent ability of sulfated GAGs to hasten amyloid fibril formation.
A decomposition of equivariant K-theory in twisted equivariant K-theories
Authors: Gómez José Manuel , Uribe Bernardo
Published: February 2017

For [Formula: see text] a finite group and [Formula: see text] a [Formula: see text]-space on which a normal subgroup [Formula: see text] acts trivially, we show that the [Formula: see text]-equivariant [Formula: see text]-theory of [Formula: see text] decomposes as a direct sum of twisted equivariant [Formula: see text]-theories of [Formula: see text] parametrized by the orbits of the conjugation action of [Formula: see text] on the irreducible representations of [Formula: see text]. The twists are group 2-cocycles which encode the obstruction of lifting an irreducible representation of [Formula: see text] to the subgroup of [Formula: see text] which fixes the isomorphism class of the irreducible representation.
Scene Categorization Through Using Objects Represented by Deep Features
Authors: Bai Shuang
Published: February 2017

Objects in scenes are thought to be important for scene recognition. In this paper, we propose to utilize scene-specific objects represented by deep features for scene categorization. Our approach combines benefits of deep learning and Latent Support Vector Machine (LSVM) to train a set of scene-specific object models for each scene category. Specifically, we first use deep Convolutional Neural Networks (CNNs) pre-trained on the large-scale object-centric image database ImageNet to learn rich object features and a large number of general object concepts. Then, the pre-trained CNNs is adopted to extract features from images in the target dataset, and initialize the learning of scene-specific object models for each scene category. After initialization, the scene-specific object models are obtained by alternating between searching over the most representative and discriminative regions of images in the target dataset and training linear SVM classifiers based on obtained region features. As a result, for each scene category a set of object models that are representative and discriminative can be acquired. We use them to perform scene categorization. In addition, to utilize global structure information of scenes, we use another CNNs pre-trained on the large-scale scene-centric database Places to capture structure information of scene images. By combining objects and structure information for scene categorization, we show superior performances to state-of-the-art approaches on three public datasets, i.e. MIT-indoor, UIUC-sports and SUN. Experiment results demonstrated the effectiveness of the proposed method.
A Dictionary-Based Approach for Identifying Biomedical Concepts
Authors: Gong Lejun , Yang Ronggen , Liu Quan , Dong Zhenjiang , Chen Hong , Yang Geng
Published: February 2017

In this research, we provided a dictionary-based approach for identifying biomedical concepts from the literature. The approach first crawled experimental corpus by E-utilities and built a concept dictionary. Then, we developed an algorithm called Variable-step Window Identification Algorithm (VWIA) for matching biomedical concepts based on preprocessing, POS tagging and the formation of phrase block. The approach could identify embedded biomedical concepts and new concepts, which could identify concepts more completely. The proposed approach obtain 95.0% F-measure overall for the test dataset. Thus, it is promising for the method of biomedical text mining.
Construction of Arakelov-modular lattices over totally definite quaternion algebras
Authors: Hou Xiaolu
Published: February 2017

We study ideal lattices constructed from totally definite quaternion algebras over totally real number fields, and generalize the definition of Arakelov-modular lattices over number fields. In particular, we prove for the case where the totally real number field is [Formula: see text] that for [Formula: see text] a prime integer, there always exists a totally definite quaternion algebra over [Formula: see text] from which an Arakelov-modular lattice of level [Formula: see text] can be constructed.
Trinomials defining quintic number fields
Authors: Patsolic Jesse , Rouse Jeremy
Published: February 2017

Given a quintic number field K/ℚ, we study the set of irreducible trinomials, polynomials of the form x5 + ax + b, that have a root in K. We show that there is a genus 4 curve CK whose rational points are in bijection with such trinomials. This curve CK maps to an elliptic curve defined over a number field, and using this map, we are able (in some cases) to determine all the rational points on CK using elliptic curve Chabauty.
Optimization design of bonnet inner based on pedestrian head protection and stiffness requirements
Authors: Peng Xiongqi , Thanakijkasem Purit , Zeng Xiaomin , Lu Hongsheng
Published: February 2017

Head impact with bonnet is one of the major causes for pedestrian severe injury or fatality in car accidents. This paper proposes a multidisciplinary design optimization method for bonnet inner based on pedestrian head protection along with bonnet stiffness requirement. A finite element (FE) model of a child headform impactor is developed and verified via simulation according to Global Technical Regulation No. 9 (GTR No. 9). Static stiffness analysis and headform collision simulation against one impact point for a particular bonnet are implemented. Parametric design and optimization analysis are carried out. Optimization solution significantly achieves a better head protection effect, which clearly affirms the feasibility of the proposed multidisciplinary optimization method and provides a reference approach to optimal design of engine bonnet inner.
Evaluation and Performance Modeling of a Burst Buffer Solution
Authors: Schenck Wolfram , El Sayed Salem , Foszczynski Maciej , Homberg Wilhelm , Pleiter Dirk
Published: February 2017

Hierarchical storage architectures are required to meet both, capacity and bandwidth requirements for future high-end storage architectures. In this paper we present the results of an evaluation of an emerging technology, DataDirect Networks' (DDN) Infinite Memory Engine (IME). IME allows to realize a fast buffer in front of a large capacity storage system. We collected benchmarking data with IOR and with the HPC application NEST. The IOR bandwidth results show how well network bandwidth towards such fast buffer can be exploited compared to the external storage system. The NEST benchmarks clearly demonstrate that IME can reduce I/O-induced load imbalance between MPI ranks to a minimum while speeding up I/O as a whole by a considerable factor. In addition to these direct measurements, a performance model for NEST is developed. In combination with a generic and abstract burst buffer architecture, this model generates predictions about appropriate burst buffer and I/O parameters to achieve specific performance goals for NEST on HPC clusters of varying size. Specifically, it is investigated in which parameter range burst buffers are able to counteract the widening performance gap between compute and I/O.
The Role of Plant Innate Immunity in the Legume-Rhizobium Symbiosis
Authors: Cao Yangrong , Halane Morgan K. , Gassmann Walter , Stacey Gary
Published: February 2017

A classic view of the evolution of mutualism is that it derives from a pathogenic relationship that attenuated over time to a situation in which both partners can benefit. If this is the case for rhizobia, then one might uncover features of the symbiosis that reflect this earlier pathogenic state. For example, as with plant pathogens, it is now generally assumed that rhizobia actively suppress the host immune response to allow infection and symbiosis establishment. Likewise, the host has retained mechanisms to control the nutrient supply to the symbionts and the number of nodules so that they do not become too burdensome. The open question is whether such events are strictly ancillary to the central symbiotic nodulation factor signaling pathway or are essential for rhizobial host infection. Subsequent to these early infection events, plant immune responses can also be induced inside nodules and likely play a role in, for example, nodule senescence. Thus, a balanced regulation of innate immunity is likely required throughout rhizobial infection, symbiotic establishment, and maintenance. In this review, we discuss the significance of plant immune responses in the regulation of symbiotic associations with rhizobia, as well as rhizobial evasion of the host immune system.
Bureaucracy and Service Delivery
Authors: Pepinsky Thomas B. , Pierskalla Jan H. , Sacks Audrey
Published: February 2017

This article reviews the literature on the politics of bureaucracy in the developing world, with a focus on service delivery and bureaucratic performance. We survey classic topics and themes such as the developmental state, principal–agent relations, and the efficient grease hypothesis, and we link them to new research findings in political science, sociology, and economics. We identify the concept of embeddedness as an important yet still underexplored framework that cuts across disciplines and may be used to understand bureaucratic performance and service delivery. Looking forward, we outline a framework for conceptualizing bureaucratic action by exploiting variation across time, space, task, and client, and we identify promising areas for further research on the bureaucrat–citizen encounter in developing countries.
Characteristics of the local cutaneous sensory thermoneutral zone
Authors: Filingeri Davide , Zhang Hui , Arens Edward A.
Published: February 2017

Skin temperature detection thresholds have been used to measure human cold and warm sensitivity across the temperature continuum. They exhibit a sensory zone within which neither warm nor cold sensations prevail. This zone has been widely assumed to coincide with steady-state local skin temperatures between 32 and 34°C, but its underlying neurophysiology has been rarely investigated. In this study we employ two approaches to characterize the properties of sensory thermoneutrality, testing for each whether neutrality shifts along the temperature continuum depending on adaptation to a preceding thermal state. The focus is on local spots of skin on the palm. Ten participants (age: 30.3 ± 4.8 yr) underwent two experiments. Experiment 1 established the cold-to-warm inter-detection threshold range for the palm’s glabrous skin and its shift as a function of 3 starting skin temperatures (26, 31, or 36°C). For the same conditions, experiment 2 determined a thermally neutral zone centered around a thermally neutral point in which thermoreceptors’ activity is balanced. The zone was found to be narrow (~0.98 to ~1.33°C), moving with the starting skin temperature over the temperature span 27.5–34.9°C (Pearson r = 0.94; P < 0.001). It falls within the cold-to-warm inter-threshold range (~2.25 to ~2.47°C) but is only half as wide. These findings provide the first quantitative analysis of the local sensory thermoneutral zone in humans, indicating that it does not occur only within a specific range of steady-state skin temperatures (i.e., it shifts across the temperature continuum) and that it differs from the inter-detection threshold range both quantitatively and qualitatively. These findings provide insight into thermoreception neurophysiology.

NEW & NOTEWORTHY Contrary to a widespread concept in human thermoreception, we show that local sensory thermoneutrality is achievable outside the 32–34°C skin temperature range. We propose that sensory adaption underlies a new mechanism of temperature integration. Also, we have developed from vision research a new quantitative test addressing the balance in activity of cutaneous cold and warm thermoreceptors. This could have important clinical (assessment of somatosensory abnormalities in neurological disease) and applied (design of personal comfort systems) implications.