bluuebunny/crossref_metadata_2025 huggingface dataset:
Zika Virus Testing Considerations: Lessons Learned from the First 80 Real-Time Reverse Transcription-PCR-Positive Cases Diagnosed in New York State
Authors: St. George Kirsten , Sohi Inderbir S. , Dufort Elizabeth M. , Dean Amy B. , White Jennifer L. , Limberger Ronald , Sommer Jamie N. , Ostrowski Stephanie , Wong Susan J. , Backenson P. Bryon , Kuhles Daniel , Blog Debra , Taylor Jill , Hutton Brad , Zucker Howard A.
Published: December 2016

The performance and interpretation of laboratory tests for Zika virus (ZKV) continue to be evaluated. Serology is cross-reactive, laborious, and frequently difficult to interpret, and serum was initially solely recommended for molecular diagnosis. ZKV testing was initiated in January 2016 in New York State for symptomatic patients, pregnant women, their infants, and patients with Guillain-Barré syndrome who had traveled to areas with ZKV transmission. Subsequently, eligibility was expanded to pregnant women with sexual partners with similar travel histories. Serum and urine collected within 4 weeks of symptom onset or within 6 weeks of travel were tested with real-time reverse transcription-PCR (RT-PCR) assays targeting the ZKV envelope and NS2B genes. In this review of lessons learned from the first 80 positive cases in NYS, ZKV RNA was detected in urine only in 50 patients, in serum only in 19 patients, and in both samples concurrently in 11 patients, with average viral loads in urine a log higher than those in serum. Among 93 positive samples from the 80 patients, 41 were positive on both gene assays, 52 were positive on the envelope only, and none were positive on the NS2B only. Of the 80 infected patients, test results for 74 (93%) would have defined their infection status as not detected or equivocal if the requirement for positive results from two assay targets (two-target-positive requirement) in the initial federal guidance to public health laboratories was enforced, if urine was not tested, or if the extended eligibility time for molecular testing was not implemented. These changes facilitated more extensive molecular diagnosis of ZKV, reducing reliance on time-consuming and potentially inconclusive serology.
Emergence of
mmpT5
Variants during Bedaquiline Treatment of Mycobacterium intracellulare Lung Disease
Authors: Alexander David C. , Vasireddy Ravikiran , Vasireddy Sruthi , Philley Julie V. , Brown-Elliott Barbara A. , Perry Benjamin J. , Griffith David E. , Benwill Jeana L. , Cameron Andrew D. S. , Wallace Richard J.
Published: December 2016

Bedaquiline (BDQ), a diarylquinoline antibiotic that targets ATP synthase, is effective for the treatment of
Mycobacterium tuberculosis
infections that no longer respond to conventional drugs. While investigating the off-label use of BDQ as salvage therapy, seven of 13 patients with
Mycobacterium intracellulare
lung disease had an initial microbiological response and then relapsed. Whole-genome comparison of pretreatment and relapse isolates of
M. intracellulare
uncovered mutations in a previously uncharacterized locus,
mmpT5
. Preliminary analysis suggested similarities between
mmpT5
and the
mmpR5
locus, which is associated with low-level BDQ resistance in
M. tuberculosis
. Both genes encode transcriptional regulators and are adjacent to orthologs of the
mmpS5-mmpL5
drug efflux operon. However, MmpT5 belongs to the TetR superfamily, whereas MmpR5 is a MarR family protein. Targeted sequencing uncovered nonsynonymous
mmpT5
mutations in isolates from all seven relapse cases, including two pretreatment isolates. In contrast, only two relapse patient isolates had nonsynonymous changes in ATP synthase subunit c (
atpE
), the primary target of BDQ. Susceptibility testing indicated that
mmpT5
mutations are associated with modest 2- to 8-fold increases in MICs for BDQ and clofazimine, whereas one
atpE
mutant exhibited a 50-fold increase in MIC for BDQ. Bedaquiline shows potential for the treatment of
M. intracellulare
lung disease, but optimization of treatment regimens is required to prevent the emergence of
mmpT5
variants and microbiological relapse.
Mice Expressing Minimally Humanized CD81 and Occludin Genes Support Hepatitis C Virus Uptake
In Vivo
Authors: Ding Qiang , von Schaewen Markus , Hrebikova Gabriela , Heller Brigitte , Sandmann Lisa , Plaas Mario , Ploss Alexander
Published: December 2016

Hepatitis C virus (HCV) causes chronic infections in at least 150 million individuals worldwide. HCV has a narrow host range and robustly infects only humans and chimpanzees. The underlying mechanisms for this narrow host range are incompletely understood. At the level of entry, differences in the amino acid sequences between the human and mouse orthologues of two essential host factors, the tetraspanin CD81 and the tight junction protein occludin (OCLN), explain, at least in part, HCV's limited ability to enter mouse hepatocytes. We have previously shown that adenoviral or transgenic overexpression of human CD81 and OCLN facilitates HCV uptake into mouse hepatocytes
in vitro
and
in vivo
. In efforts to refine these models, we constructed knock-in mice in which the second extracellular loops of CD81 and OCLN were replaced with the respective human sequences, which contain the determinants that are critical for HCV uptake. We demonstrate that the humanized CD81 and OCLN were expressed at physiological levels in a tissue-appropriate fashion. Mice bearing the humanized alleles formed normal tight junctions and did not exhibit any immunologic abnormalities, indicating that interactions with their physiological ligands were intact. HCV entry factor knock-in mice take up HCV with an efficiency similar to that in mice expressing HCV entry factors transgenically or adenovirally, demonstrating the utility of this model for studying HCV infection
in vivo
.

IMPORTANCE
At least 150 million individuals are chronically infected with hepatitis C virus (HCV). Chronic hepatitis C can result in progressive liver disease and liver cancer. New antiviral treatments can cure HCV in the majority of patients, but a vaccine remains elusive. To gain a better understanding of the processes culminating in liver failure and cancer and to prioritize vaccine candidates more efficiently, small-animal models are needed. Here, we describe the characterization of a new mouse model in which the parts of two host factors that are essential for HCV uptake, CD81 and occludin (OCLN), which differ between mice and humans, were humanized. We demonstrate that such minimally humanized mice develop normally, express the modified genes at physiological levels, and support HCV uptake. This model is of considerable utility for studying viral entry in the three-dimensional context of the liver and to test approaches aimed at preventing HCV entry.
Lassa Virus Cell Entry Reveals New Aspects of Virus-Host Cell Interaction
Authors: Torriani Giulia , Galan-Navarro Clara , Kunz Stefan
Published: December 2016

Viral entry represents the first step of every viral infection and is a determinant for the host range and disease potential of a virus. Here, we review the latest developments on cell entry of the highly pathogenic Old World arenavirus Lassa virus, providing novel insights into the complex virus-host cell interaction of this important human pathogen. We will cover new discoveries on the molecular mechanisms of receptor recognition, endocytosis, and the use of late endosomal entry factors.
Promising Role of Toll-Like Receptor 8 Agonist in Concert with Prostratin for Activation of Silent HIV
Authors: Rochat M. A. , Schlaepfer E. , Speck R. F.
Published: December 2016

The persistence of latently HIV-infected cells in patients under combined antiretroviral treatment (cART) remains the major hurdle for HIV eradication. Thus far, individual compounds have not been sufficiently potent to reactivate latent virus and guarantee its eliminationin vivo. Thus, we hypothesized that transcriptional enhancers, in concert with compounds triggering the innate immune system, are more efficient in reversing latency by creating a Th1 supportive milieu that acts against latently HIV-infected cells at various levels. To test our hypothesis, we screened six compounds on a coculture of latently infected cells (J-lat) and monocyte-derived dendritic cells (MDDCs). The protein kinase C (PKC) agonist prostratin, with a Toll-like receptor 8 (TLR8) agonist, resulted in greater reversion of HIV latency than any single compound. This combinatorial approach led to a drastic phenotypic and functional maturation of the MDDCs. Tumor necrosis factor (TNF) and cell-cell interactions were crucial for the greater reversion observed. Similarly, we found a greater potency of the combination of prostratin and TLR8 agonist in reversing HIV latency when applying it to primary cells of HIV-infected patients. Thus, we demonstrate here the synergistic interplay between TLR8-matured MDDCs and compounds acting directly on latently HIV-infected cells, targeting different mechanisms of latency, by triggering various signaling pathways. Moreover, TLR8 triggering may reverse exhaustion of HIV-specific cytotoxic T lymphocytes that might be essential for killing or constraining the latently infected cells.IMPORTANCECuring HIV is the Holy Grail. The so-called “shock and kill” strategy relies on drug-mediated reversion of HIV latency and the subsequent death of those cells under combined antiretroviral treatment. So far, no compound achieves efficient reversal of latency or eliminates this latent reservoir. The compounds may not target all of the latency mechanisms in all latently infected cells. Moreover, HIV-associated exhaustion of the immune system hinders the efficient elimination of the reactivated cells. In this study, we demonstrated synergistic latency reversion by combining agonists for protein kinase C and Toll-like receptor 8 in a coculture of latently infected cells with myeloid dendritic cells. The drug prostratin stimulates directly the transcriptional machinery of latently infected cells, and the TLR8 agonist acts indirectly by maturing dendritic cells. These findings highlight the importance of the immune system and its activation, in combination with direct-acting compounds, to reverse latency.
Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins
Authors: Zoubchenok Daria , Veillette Maxime , Prévost Jérémie , Sanders-Buell Eric , Wagh Kshitij , Korber Bette , Chenine Agnès L. , Finzi Andrés
Published: December 2016

The envelope glycoproteins (Envs) from human immunodeficiency virus type 1 (HIV-1) mediate viral entry. The binding of the HIV-1 gp120 glycoprotein to CD4 triggers conformational changes in gp120 that allow high-affinity binding to its coreceptors. In contrast to all other Envs from the same phylogenetic group, M, which possess a serine (S) at position 375, those from CRF01_AE strains possess a histidine (H) at this location. This residue is part of the Phe43 cavity, where residue 43 of CD4 (a phenylalanine) engages with gp120. Here we evaluated the functional consequences of replacing this residue in two CRF01_AE Envs (CM244 and 92TH023) by a serine. We observed that reversion of amino acid 375 to a serine (H375S) resulted in a loss of functionality of both CRF01_AE Envs as measured by a dramatic loss in infectivity and ability to mediate cell-to-cell fusion. While no effects on processing or trimer stability of these variants were observed, decreased functionality could be linked to a major defect in CD4 binding induced by the replacement of H375 by a serine. Importantly, mutations of residues 61 (layer 1), 105 and 108 (layer 2), and 474 to 476 (layer 3) of the CRF01_AE gp120 inner domain layers to the consensus residues present in group M restored CD4 binding and wild-type levels of infectivity and cell-to-cell fusion. These results suggest a functional coevolution between the Phe43 cavity and the gp120 inner domain layers. Altogether, our observations describe the functional importance of amino acid 375H in CRF01_AE envelopes.

IMPORTANCE
A highly conserved serine located at position 375 in group M is replaced by a histidine in CRF01_AE Envs. Here we show that H375 is required for efficient CRF01_AE Env binding to CD4. Moreover, this work suggests that specific residues of the gp120 inner domain layers have coevolved with H375 in order to maintain its ability to mediate viral entry.
Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine
Authors: Nogales Aitor , Rodriguez Laura , Chauché Caroline , Huang Kai , Reilly Emma C. , Topham David J. , Murcia Pablo R. , Parrish Colin R. , Martínez-Sobrido Luis
Published: December 2016

Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV
in vivo
and
ex vivo
. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV.

IMPORTANCE
Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.
Coordinate Regulation of Antimycin and Candicidin Biosynthesis
Authors: McLean Thomas C. , Hoskisson Paul A. , Seipke Ryan F.
Published: December 2016

Natural products produced by members of the phylum
Actinobacteria
underpin many industrially and medically important compounds; however, the majority of the ~30 biosynthetic pathways harbored by an average species are not expressed in the laboratory. Understanding the diversity of regulatory strategies controlling the expression of these pathways is therefore critical if their biosynthetic potential is to be explored for new drug leads. Our findings reveal that the candicidin cluster-situated regulator FscRI coordinately controls the biosynthesis of both candicidin and antimycin, which is the first observation of cross-regulation of disparate biosynthetic gene clusters specifying unrelated natural products. We anticipate that this will emerge as a major strategy by which members of the phylum
Actinobacteria
coordinately produce natural products, which will advance our understanding of how the expression of secondary metabolism is controlled and will aid the pursuit of “silent” biosynthetic pathway activation.
Delayed ventricular septal rupture complicating anterior wall myocardial infarction
Authors: Dulai Rajdip , Hline Aye , Javaid Mahvesh Rana , Akhtar Javed
Published: December 2016

A 59-year-old woman was admitted to our hospital with acute pulmonary oedema and cardiogenic shock 35 days after anterior ST elevation myocardial infarction. She developed a new loud pan systolic murmur. Echocardiography revealed a ventricular septal rupture with a significant left to right shunt. She was immediately transferred to the local cardiothoracic unit where she underwent a successful ventricular septal defect (VSD) repair. Ventricular septal rupture often presents within the first 24 hours of acute myocardial infarction and is rare thereafter. It carries a poor mortality (41–80%) even when recognised. Timely recognition of this life-threatening complication can help reduce the resultant morbidity and mortality. Doctors should be aware that this well-recognised complication may present unusually late as in this case.
Radical resection and improvised surgical reconstruction for a rare malignant triton tumour of intercostal nerve in a patient with neurofibromatosis type 1
Authors: Chaudhry Ikram Ulhaq , Cheema Ahsan Iqbal , Mutari Hadi , Amr Samir S
Published: December 2016

A man aged 28 years, with neurofibromatosis type 1, presented with abdominal pain and visible right lower chest swelling. He had cutaneous neurofibromas and several café-au-lait spots. CT scan of the chest and abdomen revealed a giant mass most likely originating from the right 7th intercostal nerve, extending downwards into the abdomen causing massive hepatic compression. A Trucut biopsy showed malignant peripheral nerve sheath tumour. Radical surgical resection with wide margins was performed. The chest wall and diaphragm were reconstructed with improvised surgical technique with excellent results. Final histopathology report revealed a triton tumour of the intercostal nerve.
Squamous cell carcinoma of the extrahepatic bile duct with metachronous para-aortic lymph node metastasis successfully treated with S-1 plus cisplatin
Authors: Nishiguchi Ryohei , Kim Dal Ho , Honda Masayuki , Sakamoto Tsuguo
Published: December 2016

The most common histological classification of bile duct cancer is adenocarcinoma and squamous cell carcinoma (SCC) is relatively rare. We report a case of a 78-year-old man with SCC of the extrahepatic bile duct associated with metachronous para-aortic lymph node metastasis. He had undergone subtotal stomach-preserving pancreatoduodenectomy. The pathological findings demonstrated moderately differentiated SCC of the distal extrahepatic bile duct (T1N1M0, stage IIB). 6 months after surgery, recurrence of the para-aortic lymph node was shown in abdominal CT. 5 courses of tegafur/gimeracil/oteracil (S-1) plus cisplatin therapy was performed and the para-aortic lymph node disappeared, confirmed as complete response by imaging findings. The patient is alive without recurrence, 10 months after recurrence and chemotherapy.
Is body mass index associated with patellofemoral pain and patellofemoral osteoarthritis? A systematic review and meta-regression and analysis
Authors: Hart Harvi F , Barton Christian J , Khan Karim M , Riel Henrik , Crossley Kay M
Published: December 2016

Background

Patellofemoral pain (PFP) occurs frequently, and may be related to patellofemoral osteoarthritis (PFOA). Obesity is associated with increased risk of knee OA. This systematic review involves a meta-regression and analysis to determine the relationship between body mass index (BMI) and PFP and PFOA, and to determine the link between BMI and interventional outcomes.

Methods

We searched seven electronic databases and reference lists of relevant papers and systematic reviews, for cross-sectional, prospective, human-based observational and interventional studies reporting BMI in individuals with PFP or PFOA compared to healthy controls. Two independent reviewers appraised methodological quality (epidemiological appraisal instrument). Where possible, data from prospective studies were pooled to conduct meta-regression and case–control, and intervention studies to conduct meta-analysis using the following categories: adolescents with PFP, adults with PFP and PFOA.

Results

52 studies were included. We found greater BMI in adults with PFP (standardised mean difference: 0.24, 95% CI 0.12 to 0.36) and PFOA (0.73, 0.46 to 0.99) compared to healthy controls, but not in adolescents with PFP (−0.19, −0.56 to 0.18). We also observed statistical trends (p<0.10) towards higher BMI being a predictor for development of PFP in adults (0.34, −0.04 to 0.71). No significant link between BMI and intervention outcomes in adults with PFP was identified.

Conclusions

Higher BMI is present in PFP and PFOA, but not in adolescents with PFP.

PROSPERO registration number

CRD42015024812.
Hydration education: developing, piloting and evaluating a hydration education package for general practitioners
Authors: McCotter L , Douglas P , Laur C , Gandy J , Fitzpatrick L , Rajput-Ray M , Ray S
Published: December 2016

Objectives

To (1) assess the hydration knowledge, attitudes and practices (KAP) of doctors; (2) develop an evidence-based training package; and (3) evaluate the impact of the training package.

Design

Educational intervention with impact evaluation.

Setting

Cambridgeshire, UK.

Participants

General practitioners (GPs (primary care physicians)).

Interventions

Hydration and healthcare training.

Main outcome measures

Hydration KAP score before and immediately after the training session.

Results

Knowledge gaps of doctors identified before the teaching were the definition of dehydration, European Food Safety Authority water intake recommendations, water content of the human body and proportion of water from food and drink. A face-to-face teaching package was developed on findings from the KAP survey and literature search. 54 questionnaires were completed before and immediately after two training sessions with GPs. Following the training, total hydration KAP scores increased significantly (p<0.001; median (25th, 75th centiles); 32 (29, 34)). Attendees rated the session as excellent or good (90%) and reported the training was likely to influence their professional practice (100%).

Conclusions

The training package will continue to be developed and adapted, with increased focus on follow-up strategies as well as integration into medical curricula and standards of practice. However, further research is required in the area of hydration care to allow policymakers to incorporate hydration awareness and care with greater precision in local and national policies.
Development of a brief measure of intimate partner violence experiences: the Composite Abuse Scale (Revised)—Short Form (CASR-SF)
Authors: Ford-Gilboe Marilyn , Wathen C Nadine , Varcoe Colleen , MacMillan Harriet L , Scott-Storey Kelly , Mantler Tara , Hegarty Kelsey , Perrin Nancy
Published: December 2016

Objectives

Approaches to measuring intimate partner violence (IPV) in populations often privilege physical violence, with poor assessment of other experiences. This has led to underestimating the scope and impact of IPV. The aim of this study was to develop a brief, reliable and valid self-report measure of IPV that adequately captures its complexity.

Design

Mixed-methods instrument development and psychometric testing to evolve a brief version of the Composite Abuse Scale (CAS) using secondary data analysis and expert feedback.

Setting

Data from 5 Canadian IPV studies; feedback from international IPV experts.

Participants

31 international IPV experts including academic researchers, service providers and policy actors rated CAS items via an online survey. Pooled data from 6278 adult Canadian women were used for scale development.

Primary/secondary outcome measures

Scale reliability and validity; robustness of subscales assessing different IPV experiences.

Results

A 15-item version of the CAS has been developed (Composite Abuse Scale (Revised)—Short Form, CASR-SF), including 12 items developed from the original CAS and 3 items suggested through expert consultation and the evolving literature. Items cover 3 abuse domains: physical, sexual and psychological, with questions asked to assess lifetime, recent and current exposure, and abuse frequency. Factor loadings for the final 3-factor solution ranged from 0.81 to 0.91 for the 6 psychological abuse items, 0.63 to 0.92 for the 4 physical abuse items, and 0.85 and 0.93 for the 2 sexual abuse items. Moderate correlations were observed between the CASR-SF and measures of depression, post-traumatic stress disorder and coercive control. Internal consistency of the CASR-SF was 0.942. These reliability and validity estimates were comparable to those obtained for the original 30-item CAS.

Conclusions

The CASR-SF is brief self-report measure of IPV experiences among women that has demonstrated initial reliability and validity and is suitable for use in population studies or other studies. Additional validation of the 15-item scale with diverse samples is required.
Focal depth distribution of the 1982 Miramichi earthquake sequence determined by modelling depth phases
Authors: Ma Shutian , Motazedian Dariush
Published: December 2016

On 9 January 1982, in the Miramichi region of New Brunswick, Canada, an earthquake with body-wave magnitude (mb) 5.7 occurred, and extensive aftershocks followed. The mainshock was felt throughout Eastern Canada and New England, USA. The mainshock and several principal aftershocks were digitally recorded worldwide, but smaller aftershocks were digitally recorded only at regional stations. Digital stations were not yet popular in 1982; therefore, available regional digital waveform records for modelling are very limited. Fortunately, two Eastern Canada Telemetered Network (ECTN) stations, EBN and KLN, produced excellent waveform records for most of the aftershocks until their closure at the end of 1990. The waveform records can be retrieved from the archive database at the Geological Survey of Canada (GSC). Since EBN had clear sPmP records of the larger aftershocks (with magnitude mN≥ 2.8), we were able to determine focal depths for these larger events. Most of the focal depth solutions for the 113 larger aftershocks were within a depth range of 3–6 km. The majority of the depths were at about 4.5 km. Some aftershocks had depths of about 1–2 km. The focal depth solutions for the shallow events were confirmed by the existence of prominent crustal Rayleigh waves. As the records for the foreshock and the mainshock at EBN were not available, we used the records at station LMN for the foreshock and a teleseismic depth phase for the mainshock. The teleseismic depth phase comparison shows that the mainshock and its three principal aftershocks migrated from a depth of about 7 km to near the Earth’s surface.
Scalable population estimates using spatial-stream-network (SSN) models, fish density surveys, and national geospatial database frameworks for streams
Authors: Isaak Daniel J. , Ver Hoef Jay M. , Peterson Erin E. , Horan Dona L. , Nagel David E.
Published: December 2016

Population size estimates for stream fishes are important for conservation and management, but sampling costs limit the extent of most estimates to small portions of river networks that encompass 100s–10 000s of linear kilometres. However, the advent of large fish density data sets, spatial-stream-network (SSN) models that benefit from nonindependence among samples, and national geospatial database frameworks for streams provide the components to create a broadly scalable approach to population estimation. We demonstrate such an approach with density surveys for trout species from 108 sites in a 735 km river network. Universal kriging was used to predict a continuous map of densities among survey locations, and block kriging (BK) was used to summarize discrete map areas and make population estimates at stream, river, and network scales. The SSN models also accommodate covariates, which facilitates hypothesis testing and provides insights about factors affecting patterns of abundance. The SSN–BK population estimator can be applied using free software and geospatial resources to develop valuable information at low cost from many existing fisheries data sets.
Deleterious effects of net clogging on the quantification of stream drift
Authors: Muehlbauer Jeffrey D. , Kennedy Theodore A. , Copp Adam J. , Sabol Thomas A.
Published: December 2016

Drift studies are central to stream and river ecological research. However, a fundamental aspect of quantifying drift — how net clogging affects the accuracy of results — has been widely ignored. Utilizing approaches from plankton and suspended sediment studies in oceanography and hydrology, we examined the rate and dynamics of net clogging across a range of conditions. We found that nets clog nonlinearly over time and that suspended solid concentrations and net mesh size exerted a strong effect on clogging rates. Critically, net clogging introduced unpredictable biases in resultant data due to the inaccuracies in water volume estimates introduced by progressive clogging. This renders the widespread approach to linearly “correct” for clogging inadequate. Using a meta-analysis of 77 drift studies spanning 25 years, we demonstrate that the detrimental effects of net clogging are routinely unappreciated, even though the results of most of these studies were likely affected by clogging. We close by describing an approach for avoiding net clogging, which will increase the accuracy and reproducibility of results in future freshwater, lotic drift studies.
Ciliary neurotrophic factor analogue aggravates CCl4-induced acute hepatic injury in rats
Authors: Cui Ming-Xia , Jiang Jun-Feng , Min Guang-Ning , Han Wei , Wu Yong-Jie
Published: December 2016

Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (CCl4). Unexpectedly, when combined with CCl4, CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation. While injected after CCl4 cessation, CNTF could improve liver function. These data suggest that CNTF could be a potential hepatoprotective agent against CCl4-induced hepatic injury after the cessation of CCl4 exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with CCl4.
SOI Technologies from Microelectronics to Microsystems — Meeting the More than Moore Roadmap Requirements
Authors: Raskin Jean-Pierre
Published: December 2016

This last decade Silicon-on-Insulator (SOI) MOSFET technology has demonstrated its potentialities for high frequency, reaching cut-off frequencies close to 500 GHz for nMOSFETs, and for harsh environments (high temperature, radiation) commercial applications. SOI also presents high resistivity substrate capabilities, leading to substantially reduced substrate losses and non-linearities. More recently, SOI technology has been emerging as a major contender for heterogeneous microsystems applications. In this work, we demonstrate the advantages of SOI technology for Radio Frequency CMOS integration as well as for building thin film sensors on thin dielectric membrane and three-dimensional micro-electro-mechanical (MEMS) sensors and actuators cointegrated with their associated SOI CMOS circuitry.
Towards High-Voltage MOSFETs in Ultrathin FDSOI
Authors: Litty Antoine , Ortolland Sylvie , Golanski Dominique , Dutto Christian , Dartigues Alexandres , Cristoloveanu Sorin
Published: December 2016

High-Voltage MOSFETs are essential devices for complementing and extending the domains of application of any core technology including low-power, low-voltage CMOS. In this paper, we propose and describe advanced Extended-Drain MOSFETs, designed, processed and characterized in ultrathin body and buried oxide Fully Depleted Silicon on Insulator technology (UTBB-FDSOI). These transistors have been implemented in two technology nodes (28 nm and 14 nm) with different silicon film and buried oxide thicknesses (TSi < 10nm and TBOX ≤ 25nm). Our innovative concept of Dual Ground Plane (DGP) provides RESURF-like effect (reduced surface field) and offers additional flexibility for HVMOS integration directly in the ultrathin film of the FDSOI wafer. In this configuration, the primary back-gate controls the threshold voltage (VTH) to ensure performance and low leakage current. The second back-gate, located underneath the drift region, acts as a field plate enabling the improvement of the ON resistance (RON) and breakdown voltage (BV). The trade-off RON.S versus BV is investigated as a function of doping level, length and thickness of the drift region. We report promising results and discuss further developments for successful integration of high-voltage MOSFETs in ultrathin CMOS FDSOI technology.
Advances in RRAM Technology: Identifying and Mitigating Roadblocks
Authors: Veksler D. , Bersuker G.
Published: December 2016

Superior scalability, endurance, low power operation, retention, and operating speed of filamentary crystalline HfOx-based resistive random access memory (RRAM) makes this technology promising for implementation in exascale neuromorphic computing systems. Challenges, roadblocks for the implementation, and possible resolutions are discussed. Technological solutions to overcome RRAM variability (both device-to-device and cycle-to-cycle) and read instability are discussed. Major material properties and operation conditions controlling performance of the crystalline HfOx-based RRAM devices are linked to physical processes determining RRAM characteristics.
Understanding the Formation of Conducting Filaments in RRAM Through the Design of Experiments
Authors: Bousoulas Panagiotis , Tsoukalas Dimitris
Published: December 2016

The resistive switching effect in TiO2-x memory devices is thoroughly investigated in order to obtain optimum memory performance, in terms of switching ratio, uniformity of the switching characteristics and multilevel capability. As a result, various fabrication procedures were followed with the aim to enhance the above properties. The main body of our devices was TiO2-x thin film, with constant thickness of 45 nm, while different approaches were implemented during the fabrication process, such as increasing the oxygen content during film growth, depositing top electrodes with different thicknesses, inserting a layer of nanocrystals (NCs) within the middle of the dielectric and using two various oxygen contents during film deposition in order to create a homobilayer structure. The common feature of these techniques is to control the regions where oxygen vacancy creation will take place in order to control the formation/rupture of the conducting filaments (CFs). Conductive-Atomic Force Microscopy (C-AFM) results support the localized nature of the switching effect. The gradual transition during the SET process, which allows precise CF control through proper external stimulus, as well as the self-rectification effect, which alleviates the sneakpath issue in crossbar architecture, are also important assets of our experimental approach.
Fundamental and Technological Limitations of Optical Communications
Authors: Mynbaev Djafar K.
Published: December 2016

Optical communications is at the turning point of its development: To deliver exponentially increasing volume of telecommunications traffic, the industry must adequately increase the transmission capacity of optical networks, which is approaching the nonlinear Shannon limit. In other words, current optical communications technology based on silica optical fiber faces its spectral and other limits. The traditional way to increase the transmission capacity—increasing the frequency of a carrier—can’t be employ any longer and possible solutions to this problem must be found within the optical spectrum. Therefore, the industry should seek the non-traditional optical and electronic approaches to developing new devices and systems capable of meeting the future demands. This paper will consider the main problems optical communications technology is encountering at this stage and deliberate the possible directions of its future development.
Q-balls of clusterized baryonic matter
Authors: Mişicu Ş. , Mishustin I. N. , Greiner W.
Published: December 2016

Properties of baryonic matter made of nucleons and [Formula: see text]-particles are studied within a relativistic mean-field (RMF) model. The Lagrangian describing the relativistic field [Formula: see text] of [Formula: see text]-particles is allowed to contain also self-interaction terms. Various types of RMF parametrizations are employed to calculate the energy of [Formula: see text]-particles embedded in the baryonic matter. We first consider baryonic systems with small admixtures of [Formula: see text]-particles and calculate the energy spectrum as a function of baryon density. Then we turn to the case of pure [Formula: see text]-matter and derive once again the energy spectrum, this time as a function of [Formula: see text]-particle density, with and without quartic self-interaction. In the second part of the paper, we focus on the ground-state properties (energy per particle, radii of the spherical lumps made of [Formula: see text]-particles) of charge neutralized Q-balls formed of baryonic [Formula: see text]-particles for the case of linear [Formula: see text] and [Formula: see text] fields and nonlinear (quartic[Formula: see text]+[Formula: see text]sextic) self-interactions of the [Formula: see text] field.
Parallel Splitting Positive Definite Mixed Element Method for Parabolic Problem
Authors: Zhang Jiansong , Yang Danping
Published: December 2016

On the basis of overlapping domain decomposition, a new parallel mixed finite element algorithm is constructed to solve the parabolic problem. The algorithm is combined with splitting positive definite mixed element procedure using the method of subspace correction and is fully parallel. The a priori error estimate and some numerical experiments are presented.
Image-based modeling: A novel tool for realistic simulations of artificial bone cultures
Authors: Alam Taseen A. , Pham Quang L. , Sikavitsas Vassilios I. , Papavassiliou Dimitrios V. , Shambaugh Robert L. , Voronov Roman S.
Published: December 2016

Computational modeling has been promulgated as a means of optimizing artificial bone tissue culturing ex vivo. In the present report, we show, as a proof-of-concept, that it is possible to model the exact microenvironment within the scaffolds while accounting for their architectural complexities and the presence of cells/tissues in their pores. Our results clearly indicate that image-based modeling has the potential to be a powerful tool for computer-assisted tissue engineering.
Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract
Authors: Subramanian Veedamali S. , Srinivasan Padmanabhan , Wildman Alexis J. , Marchant Jonathan S. , Said Hamid M.
Published: December 2016

Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), Na+-dependent vitamin C transporter SVCT-1 and SVCT-2. In the intestine, these transporters are involved in AA absorption and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression. We used mouse and human intestinal cDNAs to address these issues. The results showed a significantly lower rate of carrier-mediated AA uptake by mouse colon than jejunum. This was associated with a significantly lower level of expression of SVCT-1 and SVCT-2 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels in the colon than the jejunum, implying the involvement of transcriptional mechanism(s). Similarly, expression levels of SVCT-1 and SVCT-2 mRNA and hnRNA were significantly lower in human colon. We also examined the levels of expression of hepatocyte nuclear factor 1α and specificity protein 1, which drive transcription of the Slc23a1 and Slc23a2 promoters, respectively, and found them to be markedly lower in the colon. Furthermore, significantly lower levels of the activating markers for histone (H3) modifications [H3 trimethylation of lysine 4 (H3K4me3) and H3 triacetylation of lysine 9 (H3K9ac)] were observed in the Slc23a1 and Slc23a2 promoters in the colon. These findings show, for the first time, that SVCT-1 and SVCT-2 are differentially expressed along the intestinal tract and that this pattern of expression is, at least in part, mediated via transcriptional/epigenetic mechanisms.

NEW & NOTEWORTHY Our findings show, for the first time, that transporters of the water-soluble vitamin ascorbic acid (i.e., the vitamin C transporters SVCT-1 and SVCT-2) are differentially expressed along the length of the intestinal tract and that the pattern of expression is mediated, at least in part, by transcriptional and epigenetic mechanism(s) affecting both Slc23a1 and Slc23a2 genes.
Cerebral blood flow autoregulation in ischemic heart failure
Authors: Caldas J. R. , Panerai R. B. , Haunton V. J. , Almeida J. P. , Ferreira G. S. R. , Camara L. , Nogueira R. C. , Bor-Seng-Shu E. , Oliveira M. L. , Groehs R. R. V. , Ferreira-Santos L. , Teixeira M. J. , Galas F. R. B. G. , Robinson T. G. , Jatene F. B. , Hajjar L. A.
Published: December 2016

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20–45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.
Cellular transport ofl-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity
Authors: Persson Patrik , Fasching Angelica , Teerlink Tom , Hansell Peter , Palm Fredrik
Published: December 2016

Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or Nω-nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes.
Coupling of EIT with computational lung modeling for predicting patient-specific ventilatory responses
Authors: Roth Christian J. , Becher Tobias , Frerichs Inéz , Weiler Norbert , Wall Wolfgang A.
Published: December 2016

Providing optimal personalized mechanical ventilation for patients with acute or chronic respiratory failure is still a challenge within a clinical setting for each case anew. In this article, we integrate electrical impedance tomography (EIT) monitoring into a powerful patient-specific computational lung model to create an approach for personalizing protective ventilatory treatment. The underlying computational lung model is based on a single computed tomography scan and able to predict global airflow quantities, as well as local tissue aeration and strains for any ventilation maneuver. For validation, a novel “virtual EIT” module is added to our computational lung model, allowing to simulate EIT images based on the patient's thorax geometry and the results of our numerically predicted tissue aeration. Clinically measured EIT images are not used to calibrate the computational model. Thus they provide an independent method to validate the computational predictions at high temporal resolution. The performance of this coupling approach has been tested in an example patient with acute respiratory distress syndrome. The method shows good agreement between computationally predicted and clinically measured airflow data and EIT images. These results imply that the proposed framework can be used for numerical prediction of patient-specific responses to certain therapeutic measures before applying them to an actual patient. In the long run, definition of patient-specific optimal ventilation protocols might be assisted by computational modeling.

NEW & NOTEWORTHY In this work, we present a patient-specific computational lung model that is able to predict global and local ventilatory quantities for a given patient and any selected ventilation protocol. For the first time, such a predictive lung model is equipped with a virtual electrical impedance tomography module allowing real-time validation of the computed results with the patient measurements. First promising results obtained in an acute respiratory distress syndrome patient show the potential of this approach for personalized computationally guided optimization of mechanical ventilation in future.