bluuebunny/crossref_metadata_2025 huggingface dataset:
Enterocytozoon bieneusi Genotypes in Children in Northeast China and Assessment of Risk of Zoonotic Transmission
Authors: Yang Jinping , Song Mingxin , Wan Qiang , Li Yijing , Lu Yixin , Jiang Yanxue , Tao Wei , Li Wei
Published: October 2014

The prevalence (7.5%, 19/255) and genotypes of
Enterocytozoon bieneusi
in children of various age categories and clinical presentations were determined herein. The co-occurrence of the known genotypes (CS-4, EbpC, and Henan-IV) in children and pigs in the same study area, the phylogenetic characterization of novel genotypes (NEC1 to NEC5), and the assessment of potential risk factors associated with zoonotic transmission robustly suggested that pigs could be a significant source of human
E. bieneusi
infections in northeast China.
Rapid and Direct Detection of Herpes Simplex Virus in Cerebrospinal Fluid by Use of a Commercial Real-Time PCR Assay
Authors: Binnicker Matthew J. , Espy Mark J. , Irish Cole L.
Published: October 2014

Central nervous system infection due to herpes simplex virus (HSV) is a medical emergency and requires rapid diagnosis and initiation of therapy. In this study, we compared a routine real-time PCR assay for HSV types 1 (HSV-1) and 2 (HSV-2) to a recently FDA-approved direct PCR assay (Simplexa HSV-1/2 Direct; Focus Diagnostics, Cypress, CA) using cerebrospinal fluid samples (
n
= 100). The Simplexa HSV-1/2 assays demonstrated a combined sensitivity and specificity of 96.2% (50/52) and 97.9% (47/48), respectively. In addition, the Simplexa assay does not require nucleic acid extraction, and the results are available in 60 min.
Kaposi's Sarcoma-Associated Herpesvirus Downregulates Transforming Growth Factor β2 To Promote Enhanced Stability of Capillary-Like Tube Formation
Authors: DiMaio Terri A. , Gutierrez Kimberley D. , Lagunoff Michael
Published: October 2014

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), the most common tumor of AIDS patients worldwide. A key characteristic of KS tumors is extremely high levels of vascular slits and extravasated red blood cells, making neoangiogenesis a key component of the tumor. The main KS tumor cell is the spindle cell, a cell of endothelial origin that maintains KSHV predominantly in the latent state. In cultured endothelial cells, latent KSHV infection induces angiogenic phenotypes, including longer-term stabilization of capillary-like tube formation in Matrigel, a basement membrane matrix. The present studies show that KSHV infection of endothelial cells strongly downregulates transforming growth factor β2 (TGF-β2). This downregulation allows the stabilization of capillary-like tube formation during latent infection, as the addition of exogenous TGF-β2 inhibits the KSHV-induced stability of these structures. While two KSHV microRNAs are sufficient to downregulate TGF-β2 in endothelial cells, they are not required during KSHV infection. However, activation of the gp130 cell surface receptor is both necessary and sufficient for downregulation of TGF-β2 in KSHV-infected cells.

IMPORTANCE
Kaposi's sarcoma is a highly vascularized, endothelial cell-based tumor supporting large amounts of angiogenesis. There is evidence that KSHV, the etiologic agent of KS, induces aberrant angiogenesis. For example, KSHV induces stabilization of capillary-like tube formation in cultured endothelial cells. A clearer understanding of how KSHV regulates angiogenesis could provide potential therapeutic targets for KS. We found that KSHV downregulates TGF-β2, a cytokine related to TGF-β1 that is known to inhibit angiogenesis. The downregulation of this inhibitor promotes the stability of capillary-like tube formation insofar as adding back TGF-β2 to infected cells blocks KSHV-induced long-term tubule stability. Therefore, KSHV downregulation of TGF-β2 may increase aberrant vascularization in KS tumors through increased capillary formation and thereby aid in KS tumor promotion.
Viral Reprogramming of the Daxx Histone H3.3 Chaperone during Early Epstein-Barr Virus Infection
Authors: Tsai Kevin , Chan Lilian , Gibeault Rebecca , Conn Kristen , Dheekollu Jayaraju , Domsic John , Marmorstein Ronen , Schang Luis M. , Lieberman Paul M.
Published: October 2014

Host chromatin assembly can function as a barrier to viral infection. Epstein-Barr virus (EBV) establishes latent infection as chromatin-assembled episomes in which all but a few viral genes are transcriptionally silent. The factors that control chromatin assembly and guide transcription regulation during the establishment of latency are not well understood. Here, we demonstrate that the EBV tegument protein BNRF1 binds the histone H3.3 chaperone Daxx to modulate histone mobility and chromatin assembly on the EBV genome during the early stages of primary infection. We demonstrate that BNRF1 substitutes for the repressive cochaperone ATRX to form a ternary complex of BNRF1-Daxx-H3.3-H4, using coimmunoprecipitation and size-exclusion chromatography with highly purified components. FRAP (fluorescence recovery after photobleaching) assays were used to demonstrate that BNRF1 promotes global mobilization of cellular histone H3.3. Mutation of putative nucleotide binding motifs on BNRF1 attenuates the displacement of ATRX from Daxx. We also show by immunofluorescence combined with fluorescence
in situ
hybridization that BNRF1 is important for the dissociation of ATRX and Daxx from nuclear bodies during
de novo
infection of primary B lymphocytes. Virion-delivered BNRF1 suppresses Daxx-ATRX-mediated H3.3 loading on viral chromatin as measured by chromatin immunoprecipitation assays and enhances viral gene expression during early infection. We propose that EBV tegument protein BNRF1 replaces ATRX to reprogram Daxx-mediated H3.3 loading, in turn generating chromatin suitable for latent gene expression.

IMPORTANCE
Epstein-Barr Virus (EBV) is a human herpesvirus that efficiently establishes latent infection in primary B lymphocytes. Cellular chromatin assembly plays an important role in regulating the establishment of EBV latency. We show that the EBV tegument protein BNRF1 functions to regulate chromatin assembly on the viral genome during early infection. BNRF1 alters the host cellular chromatin assembly to prevent antiviral repressive chromatin and establish chromatin structure permissive for viral gene expression and the establishment of latent infection.
Vaccine-Induced CD107a+CD4+T Cells Are Resistant to Depletion following AIDS Virus Infection
Authors: Terahara Kazutaka , Ishii Hiroshi , Nomura Takushi , Takahashi Naofumi , Takeda Akiko , Shiino Teiichiro , Tsunetsugu-Yokota Yasuko , Matano Tetsuro
Published: October 2014

CD4+T-cell responses are crucial for effective antibody and CD8+T-cell induction following virus infection. However, virus-specific CD4+T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4+T-cell induction by vaccination may thus result in enhancement of virus replication following infection. In the present study, we show that vaccine-elicited CD4+T cells expressing CD107a are relatively resistant to depletion in a macaque AIDS model. Comparison of virus-specific CD107a, macrophage inflammatory protein-1β, gamma interferon, tumor necrosis factor alpha, and interleukin-2 responses in CD4+T cells of vaccinated macaques prechallenge and 1 week postchallenge showed a significant reduction in the CD107a−but not the CD107a+subset after virus exposure. Those vaccinees that failed to control viremia showed a more marked reduction and exhibited significantly higher viral loads at week 1 than unvaccinated animals. Our results indicate that vaccine-induced CD107a−CD4+T cells are depleted following virus infection, suggesting a rationale for avoiding virus-specific CD107a−CD4+T-cell induction in HIV vaccine design.

IMPORTANCEInduction of effective antibody and/or CD8+T-cell responses is a principal vaccine strategy against human immunodeficiency virus (HIV) infection. CD4+T-cell responses are crucial for effective antibody and CD8+T-cell induction. However, virus-specific CD4+T cells can be preferential targets for HIV infection. Here, we show that vaccine-induced virus-specific CD107a−CD4+T cells are largely depleted following infection in a macaque AIDS model. While CD4+T-cell responses are important in viral control, our results indicate that virus-specific CD107a−CD4+T-cell induction by vaccination may not lead to efficient CD4+T-cell responses following infection but rather be detrimental and accelerate viral replication in the acute phase. This suggests that HIV vaccine design should avoid virus-specific CD107a−CD4+T-cell induction. Conversely, this study found that vaccine-induced CD107a+CD4+T cells are relatively resistant to depletion following virus challenge, implying that induction of these cells may be an alternative approach toward HIV control.
HIV-1 Envelope Glycan Moieties Modulate HIV-1 Transmission
Authors: Shen Ruizhong , Raska Milan , Bimczok Diane , Novak Jan , Smith Phillip D.
Published: October 2014

The HIV-1 envelope protein (Env) is heavily glycosylated, with approximately 50% of the Env molecular mass being contributed by
N
-glycans. HIV-1 Env
N
-glycans shield the protein backbone and have been shown to play key roles in determining Env structure, surface exposure, and, consequently, antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. Also, the role of Env glycan moieties on HIV-1 transmission has not been systematically defined. Using viruses with modified Env glycan content and heterogeneity, we examined the effects of Env glycan moieties on the major events of HIV-1 transmission. Compared to viruses with less oligomannose and more complex Env glycans, viruses with more oligomannose and less complex glycans more efficiently (i) transcytosed across an epithelial cell monolayer, (ii) attached to monocyte-derived macrophages (MDMs), (iii) bound monocyte-derived dendritic cells (MoDCs), and (iv)
trans
-infected primary lymphocytes via MoDCs. However, viruses with more oligomannose and less complex glycans displayed impaired infectivity in TZMbl cells, MDMs, primary lymphocytes, and fresh human intestinal tissue. Thus,
N
-linked Env glycans display discordant effects on the major events of HIV-1 transmission, with mature oligosaccharide structures on Env playing a crucial role in HIV-1 infection. Env glycosylation should be taken into consideration in the development of vaccine strategies to interdict HIV-1 transmission.

IMPORTANCE
HIV-1 Env
N
-glycans shield the protein backbone and play key roles in determining Env structure and surface exposure, thereby impacting Env antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. In the study described in this report, we investigated systematically the role of Env glycan moieties on HIV-1 transmission. We show that
N
-linked Env glycans display discordant effects on the major events of HIV-1 transmission. These data indicate that Env glycan moieties impact HIV-1 transmission and that modulation of Env glycan moieties offers a potential strategy for the development of therapeutic or prophylactic vaccines against HIV-1.
Role of Mason-Pfizer Monkey Virus CA-NC Spacer Peptide-Like Domain in Assembly of Immature Particles
Authors: Strohalmová-Bohmová Karolína , Spiwok Vojtěch , Lepšík Martin , Hadravová Romana , Křížová Ivana , Ulbrich Pavel , Pichová Iva , Bednárová Lucie , Ruml Tomáš , Rumlová Michaela
Published: October 2014

The hexameric lattice of an immature retroviral particle consists of Gag polyprotein, which is the precursor of all viral structural proteins. Lentiviral and alpharetroviral Gag proteins contain a peptide sequence called the spacer peptide (SP), which is localized between the capsid (CA) and nucleocapsid (NC) domains. SP plays a critical role in intermolecular interactions during the assembly of immature particles of several retroviruses. Published models of supramolecular structures of immature particles suggest that in lentiviruses and alpharetroviruses, SP adopts a rod-like six-helix bundle organization. In contrast, Mason-Pfizer monkey virus (M-PMV), a betaretrovirus that assembles in the cytoplasm, does not contain a distinct SP sequence, and the CA-NC connecting region is not organized into a clear rod-like structure. Nevertheless, the CA-NC junction comprises a sequence critical for assembly of immature M-PMV particles. In the present work, we characterized this region, called the SP-like domain, in detail. We provide biochemical data confirming the critical role of the M-PMV SP-like domain in immature particle assembly, release, processing, and infectivity. Circular dichroism spectroscopy revealed that, in contrast to the SP regions of other retroviruses, a short SP-like domain-derived peptide (SPLP) does not form a purely helical structure in aqueous or helix-promoting solution. Using 8-Å cryo-electron microscopy density maps of immature M-PMV particles, we prepared computational models of the SP-like domain and indicate the structural features required for M-PMV immature particle assembly.

IMPORTANCE
Retroviruses such as HIV-1 are of great medical importance. Using Mason-Pfizer monkey virus (M-PMV) as a model retrovirus, we provide biochemical and structural data confirming the general relevance of a short segment of the structural polyprotein Gag for retrovirus assembly and infectivity. Although this segment is critical for assembly of immature particles of lentiviruses, alpharetroviruses, and betaretroviruses, the organization of this domain is strikingly different. A previously published electron microscopic structure of an immature M-PMV particle allowed us to model this important region into the electron density map. The data presented here help explain the different packing of the Gag segments of various retroviruses, such as HIV, Rous sarcoma virus (RSV), and M-PMV. Such knowledge contributes to understanding the importance of this region and its structural flexibility among retroviral species. The region might play a key role in Gag-Gag interactions, leading to different morphological pathways of immature particle assembly.
Determinants of Efficient Degradation of APOBEC3 Restriction Factors by HIV-1 Vif
Authors: Baig Tayyba T. , Feng Yuqing , Chelico Linda
Published: October 2014

The APOBEC3 deoxycytidine deaminases can restrict the replication of HIV-1 in cell culture to differing degrees. The effects of APOBEC3 enzymes are largely suppressed by HIV-1 Vif that interacts with host proteins to form a Cullin5-Ring E3 ubiquitin ligase that induces
48
K-linked polyubiquitination (poly-Ub) and proteasomal degradation of APOBEC3 enzymes. Vif variants have differing abilities to induce degradation of APOBEC3 enzymes and the underlying biochemical mechanisms for these differences is not fully understood. We hypothesized that by characterizing the interaction of multiple APOBEC3 enzymes and Vif variants we could identify common features that resulted in Vif-mediated degradation and further define the determinants required for efficient Vif-mediated degradation of APOBEC3 enzymes. We used Vifs from HIV-1 NL4-3 (IIIB) and HXB2 to characterize their induced degradation of and interaction with APOBEC3G, APOBEC3G D128K, APOBEC3H, and APOBEC3B in 293T cells. We quantified the APOBEC3G-Vif and APOBEC3H-Vif interaction strengths
in vitro
using rotational anisotropy. Our biochemical and cellular analyses of the interactions support a model in which the degradation efficiency of Vif
IIIB
and Vif
HXB2
correlated with both the binding strength of the APOBEC3-Vif interaction and the APOBEC3-Vif interface, which differs for APOBEC3G and APOBEC3H. Notably, Vif bound to APOBEC3H and APOBEC3B in the natural absence of Vif-induced degradation and the interaction resulted in
63
K-linked poly-Ub of APOBEC3H and APOBEC3B, demonstrating additional functionality of the APOBEC3-Vif interaction apart from induction of proteasomal degradation.

IMPORTANCE
APOBEC3 enzymes can potently restrict the replication of HIV-1 in the absence of HIV-1 Vif. Vif suppresses APOBEC3 action by inducing their degradation through a direct interaction with APOBEC3 enzymes and other host proteins. Vif variants from different HIV-1 strains have different effects on APOBEC3 enzymes. We used differing Vif degradation capacities of two Vif variants and various APOBEC3 enzymes with differential sensitivities to Vif to delineate determinants of the APOBEC3-Vif interaction that are required for inducing efficient degradation. Using a combined biochemical and cellular approach we identified that the strength of the APOBEC3-Vif binding interaction and the APOBEC3-Vif interface are determinants for degradation efficiency. Our results highlight the importance of using Vif variants with different degradation potential when delineating mechanisms of Vif-induced APOBEC3 degradation and identify features important for consideration in the development of HIV-1 therapies that disrupt the APOBEC3-Vif interaction.
The Human Cytomegalovirus UL26 Protein Antagonizes NF-κB Activation
Authors: Mathers Chun , Schafer Xenia , Martínez-Sobrido Luis , Munger Joshua
Published: October 2014

Viral infection frequently triggers activation of host innate immune pathways that attempt to limit viral spread. The NF-κB pathway is a critical component that governs this response. We have found that the human cytomegalovirus (HCMV) UL26 protein antagonizes NF-κB activation. Upon infection, an HCMV strain lacking the UL26 gene (ΔUL26) induced the nuclear translocation of the NF-κB RelB subunit and activated expression and secretion of interleukin-6 (IL-6), an NF-κB target gene. The ΔUL26 mutant was also more sensitive to challenge with tumor necrosis factor alpha (TNF-α), a canonical NF-κB inducer. Further, expression of UL26 in the absence of other viral proteins blocked NF-κB activation induced by either TNF-α treatment or infection with Sendai virus (SeV). Our results indicate that UL26 expression is sufficient to block TNF-α-induced NF-κB nuclear translocation and IκB degradation. Last, UL26 blocks TNF-α-induced IκB-kinase (IKK) phosphorylation, a key step in NF-κB activation. Combined, our results indicate that UL26 is part of a viral program to antagonize innate immunity through modulation of NF-κB signaling.

IMPORTANCEThe NF-κB signaling pathway regulates innate immunity, an integral host process that limits viral pathogenesis. Viruses have evolved mechanisms to modulate NF-κB signaling to ensure their replication. HCMV is a major cause of birth defects and disease in immunosuppressed populations. HCMV is known to actively target the NF-κB pathway, which is important for HCMV infection. Our results indicate that the HCMV UL26 gene is a key modulator of NF-κB pathway activity. We find the UL26 gene is both necessary and sufficient to block NF-κB activation upon challenge with antiviral cytokines. Further, UL26 attenuates the phosphorylation and activation of a key NF-κB activating kinase complex, IKK. Our study provides new insight into how HCMV targets the NF-κB pathway. Given its importance to viral infection, the mechanisms through which viruses target the NF-κB pathway highlight areas of vulnerability that could be therapeutically targeted to attenuate viral replication.
Protocol for an exploration of knowledge sharing for improved discharge from a mental health ward
Authors: Rowley Emma , Wright Nicola , Waring Justin , Gregoriou Kyri , Chopra Arun
Published: October 2014

Introduction

Strategies to reduce hospital admissions for mental health service users have received vast amounts of attention, yet the transfer of care from hospital to the community has been ignored. The discharge process is complex, messy, disjointed and inefficient, relying on cross-agency and organisational working. Focusing on one acute mental health admission ward, we will investigate whether the discharge process for people with severe mental health problems can be enhanced through the creation, implementation and utilisation of a knowledge sharing proforma that is used on their admission to the ward.

Methods and analysis

The project uses qualitative interviews to understand the complex processes associated with being admitted and discharged from inpatient mental health wards. Practitioners will be asked to identify and map the relevant stakeholders involved in admission and discharge, and discuss any problems with the process. The study team will work with clinicians to develop a knowledge collection proforma, which will be piloted for 2 months. Qualitative interviews will be carried out to collect reflections on the experiences of using the tool, with data used for further refinement of the intervention. Baseline and repeat quantitative measures will be taken to illustrate any changes to length of stay and readmission rates achieved as a result of the study.

Ethics and dissemination

A key issue is that participants are able to comment frankly on something that is a core part of their work, without fear or reprise. It is equally important that all participants are offered the opportunity to develop and coproduce the knowledge collection proforma, in order that the intervention produced is fit for purpose and usable in the real world, away from a research environment. The study has received ethical approval from Nottingham University Business School ethics committee, and has all appropriate National Health Service research governance clearances.
Clinical trial: free fatty acid suppositories compared with enema as bowel preparation for flexible sigmoidoscopy
Authors: Ormarsson Orri Thor , Asgrimsdottir Gudrun Marta , Loftsson Thorsteinn , Stefansson Einar , Kristinsson Jon Orvar , Lund Sigrun Helga , Bjornsson Einar Stefan
Published: October 2014

Objectives

The purpose of this trial was to evaluate the efficacy and safety of recently developed suppositories containing free fatty acids as a bowel-cleansing agent prior to flexible sigmoidoscopy and compare them with Klyx (docusate sodium/sorbitol).

Design

A controlled, non-inferiority, single-blind, randomised study on outpatients undergoing flexible sigmoidoscopy.

Setting

Department of Gastroenterology, Landspitali-University Hospital and endoscopic clinic.

Patients

53 outpatients undergoing flexible sigmoidoscopy.

Intervention

Participants were randomised to receive either free fatty acid suppositories (28) or a standard bowel preparation with Klyx enema (25). In the study group, two suppositories were administered the evening before as well as 2 h prior to the sigmoidoscopy. In the control group, Klyx enema (120 mL) was administered the evening before and repeated 2 h prior to the procedure.

Main outcome measurements

Quality of the bowel cleansing, height of scope insertion and safety.

Results

The mean height of scope insertion and bowel cleansing was 43 cm (SD=13.4) in the study group and 48 cm (SD=10.4) in the control group (NS). The investigating physicians were less satisfied with the bowel preparation in the study group compared with the control group with a difference of 20% (p<0.016). The amount of faeces noted in the rectum was similar in both groups with no significant difference (p<0.56). No serious side effects, toxic reaction or irritation were observed.

Conclusions

The suppositories are well tolerated with no significant side effects. The suppositories had distinct bowel emptying effect and as effective as Klyx in rectal cleansing. Although physician's satisfaction was slightly lower, the height of scope insertion was similar.

Trial registration number

EudraCT nr.: 2010-018761-35.
Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements
Authors: Putterman Chaim , Furie Richard , Ramsey-Goldman Rosalind , Askanase Anca , Buyon Jill , Kalunian Kenneth , Chatham W Winn , Massarotti Elena , Kirou Kyriakos , Jordan Nicole , Blanco Irene , Weinstein Arthur , Chitkara Puja , Manzi Susan , Ahearn Joseph , O'Malley Tyler , Conklin John , Ibarra Claudia , Barken Derren , Dervieux Thierry
Published: October 2014

Objective

To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE).

Methods

The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity.

Results

AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03).

Conclusions

CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.
Energy intake over 2 days is unaffected by acute sprint interval exercise despite increased appetite and energy expenditure
Authors: Beaulieu Kristine , Olver T. Dylan , Abbott Kolten C. , Lemon Peter W.R.
Published: October 2014

A cumulative effect of reduced energy intake, increased oxygen consumption, and/or increased lipid oxidation could explain the fat loss associated with sprint interval exercise training (SIT). This study assessed the effects of acute sprint interval exercise (SIE) on energy intake, subjective appetite, appetite-related peptides, oxygen consumption, and respiratory exchange ratio over 2 days. Eight men (25 ± 3 years, 79.6 ± 9.7 kg, body fat 13% ± 6%; mean ± SD) completed 2 experimental treatments: SIE and recovery (SIEx) and nonexercise control. Each 34-h treatment consisted of 2 consecutive 10-h test days. Between 0800–1800 h, participants remained in the laboratory for 8 breath-by-breath gas collections, 3 buffet-type meals, 14 appetite ratings, and 4 blood samples for appetite-related peptides. Treatment comparisons were made using 2-way repeated measures ANOVA or t tests. An immediate, albeit short-lived (<1 h), postexercise suppression of appetite and increase in peptide YY (PYY) were observed (P < 0.001). However, overall hunger and motivation to eat were greater during SIEx (P < 0.02) without affecting energy intake. Total 34-h oxygen consumption was greater during SIEx (P = 0.04), elicited by the 1491-kJ (22%) greater energy expenditure over the first 24 h (P = 0.01). Despite its effects on oxygen consumption, appetite, and PYY, acute SIE did not affect energy intake. Consequently, if these dietary responses to SIE are sustained with regular SIT, augmentations in oxygen consumption and/or a substrate shift toward increased fat use postexercise are most likely responsible for the observed body fat loss with this type of exercise training.
Fault reconstructions using aeromagnetic data in the Great Bear magmatic zone, Northwest Territories, Canada
Authors: Hayward Nathan , Corriveau Louise
Published: October 2014

The Great Bear magmatic zone, located in Wopmay orogen, is a 1.875–1.84 Ga belt, 450 km long by 100 km wide of volcanic and allied plutonic rocks interpreted as a Paleoproterozoic magmatic arc. The belt, which contains economically important mineralization, was folded and subsequently cut by a swarm of northeast-striking transcurrent faults, which are part of a regional conjugate fault system interpreted to result from terminal collision of the Nahanni – Fort Simpson terrane. Fault reconstructions based on the interpretation of aeromagnetic data and geological maps provide first-order models of deformation mechanisms associated with, and the configuration of the Great Bear magmatic zone prior to, its dissection by northeast-striking transcurrent faults. The models show that vertical axis block rotation (plane strain) of ∼4.5° can explain fault offsets in the south, but that greater rotation is required to explain many of the displacements in the north. However, offsets on transcurrent faults that border the Camsell River district are greater than can be explained by vertical axis block rotation model alone and may include a component of Mesoproterozoic contractional deformation associated with the Racklan–Forward orogeny. Following reconstruction, iron oxide alkali alteration and associated mineralization, which pre-date transcurrent faulting, form a pair of northerly trending zones on the east and west margins of the belt. We suggest that these zones, whose exposure is related to broad synclinal folding of some of the oldest rocks in the Great Bear magmatic zone, are where iron oxide copper–gold (IOCG)-targeted exploration efforts should be focused on these areas in both outcrop and subcrop.
Detection of a surrogate biological agent with a portable surface plasmon resonance sensor onboard an unmanned aircraft system
Authors: Palframan Mark C. , Gruszewski Hope A. , Schmale David G. , Woolsey Craig A.
Published: October 2014

A system was developed to perform near real-time biological threat agent (BTA) detection with a small autonomous unmanned aircraft system (UAS). Biological sensors recently reached a level of miniaturization and sensitivity that have made UAS integration a feasible task. A surface plasmon resonance (SPR) biosensor was integrated into a small UAS platform for the first time, providing the UAS with the capability to collect and then quantify the concentration of a surrogate biological agent in near realtime. The sensor operator ran the SPR unit through a ground-station laptop, viewing the sensor data in real time during flight. An aerial sampling mechanism was also developed for use with the SPR sensor. The sampling system utilized a custom impinger setup to collect and concentrate aerosolized particles. The SPR and sampling system's feasibility was demonstrated using an aerosolized sucrose solution as a mock BTA. Three field experiments were carried out to test and validate the biological sampling system. In the first field experiment, the collection system was tested by flying the UAS through a ground-based plume of water-soluble blue dye. In the second field experiment, a sucrose solution was autonomously aerosolized, collected, and then detected by the combined sampling and SPR sensor subsystems onboard the UAS. In the third field experiment, a dye was released from one UAS (the leader) and captured by another UAS (the follower). Together, these field experiments illustrate the capability of the UAS to detect and quantify the concentration of a BTA released at altitude. Our integrated SPR system sets the stage for future work to detect and track BTAs in the atmosphere and assist in localizing their sources.
Cosmic structure
Authors: Davis Marc
Published: October 2014

The history of cosmic structure goes back to the time of Einstein's youth, although few scientists actually thought of the problem of galaxy and cluster formation. The data and ideas were collected slowly as astronomers slowly realized the nature of the problem of large-scale structure. This paper will review several of the key episodes in the history of the field. Starting with the discovery of dark matter in the 30s, the CMBR discovery in the 1960s to the idea of an early episode of inflation in the 1980s, the field has had an acceleration of discovery. In the 80s it was realized that the initial conditions of the universe were specified by the cold dark matter (CDM). Now initial conditions for the formation of structure could be specified for any type of dark matter. With the advent of computing resources, highly nonlinear phases of galaxy formation could be simulated and scientists could ask whether cold dark matter was the correct theory, even on the scale of dwarf spheroidal galaxies, or do the properties of the dwarfs require a different type of dark matter? In an idiosyncratic list, we review several of the key events of the history of cosmic structure, including the first measurements of ξ(r), then the remarkable success of Λ CDM explanations of the large-scale universe. We next turn to velocity fields, the large-scale flow problem, a field which was so promising 20 years ago, and to the baryon acoustic oscillations, a field of remarkable promise today. We review the problem of dwarf galaxies and Lyman-α absorption systems, asking whether the evidence is pointing toward a major switch in our understanding of the nature of dark matter. Finally, we discuss flux anomalies in multiply-lensed systems, which set constraints on the number of dwarf galaxies associated with the lensing galaxy, a topic that is now very interesting since simulations have indicated there should be hundreds of dwarfs orbiting the Milky Way, rather than the 10 that are known. It is quite remarkable that many of the today's results are dependent on techniques first used by Einstein.
General dissipative coefficient in warm intermediate inflation in Loop Quantum Cosmology in light of Planck and BICEP2
Authors: Herrera Ramón , Olivares Marco , Videla Nelson
Published: October 2014

In this paper, we study a warm intermediate inflationary model with a general form for the dissipative coefficient Γ(T, ϕ) = CϕTm/ϕm-1 in the context of Loop Quantum Cosmology (LQC). We examine this model in the weak and strong dissipative regimes. In general, we discuss in great detail the characteristics of this model in the slow-roll approximation. Also, we assume that the modifications to perturbation equations result exclusively from Hubble rate. In this approach, we use recent astronomical observations from Planck and BICEP2 experiments to restrict the parameters in our model.
Motion Editing Tool to Create Dancing Motions of Humanoid Robot
Authors: Lim Dae-Young , Kwak Hyun-Jin , Ryoo Young-Jae
Published: October 2014

In this paper, a motion editing tool to create dancing motions of a humanoid robot is proposed. In order to build performances or dancing of a humanoid robot, a motion editing tool to create specific motions is necessary. Especially, to generate more natural motions is required for a dancing robot. We proposed a motion editing tool and algorithm to create the natural motions. The proposed motion editing tool can create robot's motions composed of several steps which are captured from every joint while the robot plays. The motion editing tool generates the continuous motion interpolated between each steps. A humanoid robot of 50 cm tall is developed to test the proposed tool. The robot using the motion editing tool was demonstrated the natural dancing performance.
THE INFLUENCE OF FAMILY MORAL SUPPORT AND PERSONAL PROBLEMS ON FIRM PERFORMANCE: THE CASE OF KOREAN FEMALE ENTREPRENEURS
Authors: WELSH DIANNE HB , KIM GYU , MEMILI ESRA , KACIAK EUGENE
Published: October 2014

Less than one-fifth of all entrepreneurs are women in Korea (Xavier et al., 2012). We investigate the determinants of Korean women entrepreneurs' firm performance. Specifically, we examine the impact of personal problems and family support and their interaction effects on firm performance. We find empirical support for the negative effects of personal problems on firm performance and positive moderation effects of family support on this link. Implications and future studies are discussed.
Morphology, seismic characterization and sediment dynamics of the Baiyun Slide Complex on the northern South China Sea margin
Authors: Li Wei , Wu Shiguo , Völker David , Zhao Fang , Mi Lijun , Kopf Achim
Published: October 2014

A large submarine slope failure, the Baiyun Slide Complex, has been discovered in the northern South China Sea. We describe the slide complex morphology, the seismic character of its structural elements and the slide evolution based on high-quality seismic reflection and multi-beam bathymetry data. The Baiyun Slide Complex has three major slide scars that show differences in headwall and sidewall geometry, the nature of the basal shear surfaces and the internal architecture of the deposits. From these observations, we propose a four-phase emplacement model. An extrapolation of the post-slide drape thickness (60 m) gives a rough age estimate for the mass transport events of 0.3 Ma. Pore pressure models for the unfailed continental slope in the vicinity of the Baiyun Slide are based on porosity measurements at nearby Ocean Drilling Program Site 1146. They show that excess pore pressure in slope sediments is anomalously high at a depth around 93 m, most probably as a consequence of a dramatic increase in sedimentation rates over the past 1.8 Ma. This excess pore pressure is proposed to be the major preconditioning factor for the slide initiation, possibly aided by volcano-tectonic activity and gas hydrate dissociation. The unfailed slope is stable under static conditions. However, a near-field earthquake of Mw 5 would suffice to induce a slope instability at
c
. 93 m depth.
Optogenetics, the intersection between physics and neuroscience: light stimulation of neurons in physiological conditions
Authors: Deng Wei , Goldys Ewa M. , Farnham Melissa MJ , Pilowsky Paul M.
Published: October 2014

Neuronal stimulation by light is a novel approach in the emerging field of optogenetics, where genetic engineering is used to introduce light-activated channels. However, light is also capable of stimulating neurons even in the absence of genetic modifications through a range of physical and biological mechanisms. As a result, rigorous design of optogenetic experiments needs to take note of alternative and parallel effects of light illumination of neuronal tissues. Thus all matters relating to light penetration are critical to the development of studies using light-activated proteins. This paper discusses ways to quantify light, light penetration in tissue, as well as light stimulation of neurons in physiological conditions. We also describe the direct effect of light on neurons investigated at different sites.
The repeated sit-to-stand maneuver is a superior method for cardiac baroreflex assessment: a comparison with the modified Oxford method and Valsalva maneuver
Authors: Horsman H. M. , Tzeng Y. C. , Galletly D. C. , Peebles K. C.
Published: October 2014

Baroreflex assessment has diagnostic and prognostic utility in the clinical and research environments, and there is a need for a reliable, simple, noninvasive method of assessment. The repeated sit-to-stand method induces oscillatory changes in blood pressure (BP) at a desired frequency and is suitable for assessing dynamic baroreflex sensitivity (BRS). However, little is known about the reliability of this method and its ability to discern fundamental properties of the baroreflex. In this study we sought to: 1) evaluate the reliability of the sit-to-stand method for assessing BRS and compare its performance against two established methods (Oxford method and Valsalva maneuver), and 2) examine whether the frequency of the sit-to-stand method influences hysteresis. Sixteen healthy participants underwent three trials of each method. For the sit-to-stand method, which was performed at 0.1 and 0.05 Hz, BRS was quantified as an integrated response (BRSINT) and in response to falling and rising BP (BRSDOWNand BRSUP, respectively). Test retest reliability was assessed using the intraclass correlation coefficient (ICC). Irrespective of frequency, the ICC for BRSINTduring the sit-to-stand method was ≥0.88. The ICC for a rising BP evoked by phenylephrine (PEGAIN) in the Oxford method was 0.78 and ≤0.5 for the remaining measures. During the sit-to-stand method, hysteresis was apparent in all participants at 0.1 Hz but was absent at 0.05 Hz. These findings indicate the sit-to-stand method is a statistically reliable BRS assessment tool and suitable for the examination of baroreflex hysteresis. Using this approach we showed that baroreflex hysteresis is a frequency-dependent phenomenon.
Renal redox dysregulation in AKI: application for oxidative stress marker of AKI
Authors: Kasuno Kenji , Shirakawa Kiichi , Yoshida Haruyoshi , Mori Kiyoshi , Kimura Hideki , Takahashi Naoki , Nobukawa Yasunari , Shigemi Kenji , Tanabe Sawaka , Yamada Narihisa , Koshiji Takaaki , Nogaki Fumiaki , Kusano Hitoshi , Ono Takahiko , Uno Kazuko , Nakamura Hajime , Yodoi Junji , Muso Eri , Iwano Masayuki
Published: October 2014

Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemia-reperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90–0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 μg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys.
Hypoxia as a key player in the AKI-to-CKD transition
Authors: Tanaka Shinji , Tanaka Tetsuhiro , Nangaku Masaomi
Published: October 2014

Recent clinical and animal studies have shown that acute kidney injury (AKI), even if followed by complete recovery of renal function, can eventually result in chronic kidney disease (CKD). Renal hypoxia is emerging as a key player in the pathophysiology of the AKI-to-CKD transition. Capillary rarefaction after AKI episodes induces renal hypoxia, which can in turn profoundly affect tubular epithelial cells, (myo)fibroblasts, and inflammatory cells, culminating in tubulointerstitial fibrosis, i.e., progression to CKD. Damaged tubular epithelial cells that fail to redifferentiate might supply a decreased amount of vascular endothelial growth factor and contribute to capillary rarefaction, thus aggravating hypoxia and forming a vicious cycle. Mounting evidence also shows that epigenetic changes are closely related to renal hypoxia in the pathophysiology of CKD progression. Animal experiments suggest that targeting hypoxia is a promising strategy to block the transition from AKI to CKD. However, the precise mechanisms by which hypoxia induces the AKI-to-CKD transition and by which hypoxia-inducible factor activation can exert a protective effect in this context should be clarified in further studies.
Time-sensitive reorganization of the somatosensory cortex poststroke depends on interaction between Hebbian and homeoplasticity: a simulation study
Authors: Bains Amarpreet Singh , Schweighofer Nicolas
Published: October 2014

Together with Hebbian plasticity, homeoplasticity presumably plays a significant, yet unclear, role in recovery postlesion. Here, we undertake a simulation study addressing the role of homeoplasticity and rehabilitation timing poststroke. We first hypothesize that homeoplasticity is essential for recovery and second that rehabilitation training delivered too early, before homeoplasticity has compensated for activity disturbances postlesion, is less effective for recovery than training delivered after a delay. We developed a neural network model of the sensory cortex driven by muscle spindle inputs arising from a six-muscle arm. All synapses underwent Hebbian plasticity, while homeoplasticity adjusted cell excitability to maintain a desired firing distribution. After initial training, the network was lesioned, leading to areas of hyper- and hypoactivity due to the loss of lateral synaptic connections. The network was then retrained through rehabilitative arm movements. We found that network recovery was unsuccessful in the absence of homeoplasticity, as measured by reestablishment of lesion-affected inputs. We also found that a delay preceding rehabilitation led to faster network recovery during the rehabilitation training than no delay. Our simulation results thus suggest that homeoplastic restoration of prelesion activity patterns is essential to functional network recovery via Hebbian plasticity.
Influence of common synaptic input to motor neurons on the neural drive to muscle in essential tremor
Authors: Gallego Juan A. , Dideriksen Jakob L. , Holobar Ales , Ibáñez Jaime , Pons José L. , Louis Elan D. , Rocon Eduardo , Farina Dario
Published: October 2014

Tremor in essential tremor (ET) is generated by pathological oscillations at 4–12 Hz, likely originating at cerebello-thalamo-cortical pathways. However, the way in which tremor is represented in the output of the spinal cord circuitries is largely unknown because of the difficulties in identifying the behavior of individual motor units from tremulous muscles. By using novel methods for the decomposition of multichannel surface EMG, we provide a systematic analysis of the discharge properties of motor units in nine ET patients, with concurrent recordings of EEG activity. This analysis allowed us to infer the contribution of common synaptic inputs to motor neurons in ET. Motor unit short-term synchronization was significantly greater in ET patients than in healthy subjects. Furthermore, the strong association between the degree of synchronization and the peak in coherence between motor unit spike trains at the tremor frequency indicated that the high synchronization levels were generated mainly by common synaptic inputs specifically at the tremor frequency. The coherence between EEG and motor unit spike trains demonstrated the presence of common cortical input to the motor neurons at the tremor frequency. Nonetheless, the strength of this input was uncorrelated to the net common synaptic input at the tremor frequency, suggesting a contribution of spinal afferents or secondary supraspinal pathways in projecting common input at the tremor frequency. These results provide the first systematic analysis of the neural drive to the muscle in ET and elucidate some of its characteristics that determine pathological tremulous muscle activity.