bluuebunny/crossref_metadata_2025 huggingface dataset:
BLACK BOX MODELLING THE THERMAL BEHAVIOUR OF IHOUSE USING AUTO REGRESSIVE AND MOVING AVERAGE (ARMA) MODEL
Authors: Mohd Hussein Shamsul Faisal , Nguyen Hoaison , Abdullah Shahrum Shah , Lim Yuto , Tan Yasuo
Published: June 2016

Modelling and simulation of the dynamic thermal behaviour of a building is important to test any proposed thermal comfort control system and strategy in the building. A simulation model can be obtained by using either the white box, grey box or black box modelling method. This research focuses on the usage of auto regressive and moving average (ARMA) model, a type of black box model that represents the dynamic thermal behaviour of iHouse testbed and uses real recorded data from the testbed and limited knowledge regarding the physical characteristics of the testbed. The performance of the ARMA model developed in this research is compared with the performance of House Thermal Simulator, a previously developed model, based on grey box modelling. Results obtained shows that ARMA model works better than House Thermal Simulator in some aspects.
A MODIFIED ARTIFICIAL POTENTIAL FIELD METHOD FOR RIVERINE OBSTACLES AVOIDANCE
Authors: Hong Mei Jian , Arshad M. R.
Published: June 2016

This paper presents a modified artificial potential field (APF) based method for an Autonomous Surface Vessel (ASV) obstacles avoidance in a dynamic riverine environment. The APF method is combined with a balance control scheme to achieve river tracking and obstacles avoidance simultaneously. The APF method is further modified modification to comply with marine collision avoidance regulations (COLREGs). The overtaking and head-on scenarios are simulated in MATLAB platform. The simulation results are compared with other APF methods to prove that the proposed method is efficient for the ASV riverine navigation.
CALIBRATION OF A DRAG TILT CURRENT VELOCIMETER FOR AN OPEN CHANNEL APPLICATION
Authors: Ismail Zool Hilmi , Muharram Ibnu Akil Maitar
Published: June 2016

Water is one of the prime elements responsible for life on earth with two thirds of the earth's surface covered by it. Managing water resources effectively can promote conservation and make the best use of our limited water resources. Having knowledge about flow information on the river networks can be very beneficial for applications such as hydropower, transportation, irrigation, flood mitigation, water treatment, industrial and domestic needs. The development of simple and inexpensive instrument (<RM500) is to help researchers to produce and measure flows on spatial river at a very low cost. The analytic approximation was derived for giving relationship of the instrument’s tilting behavior on water velocity. Calibration process was held and the data are used to investigate the relationship between the measurement collected from the experiment and the known values. Analyzing the experiment results, it was concluded that the instrument tilting in response to the water velocities but not up to the expected known values. Random and systematic errors arise during calibration processes which contribute to the high uncertainties of the instrument. The documented experiments, procedure and facility used for the calibration are given in this paper.  It is shown that the accuracy relationship of this instrument against the analytic approximation identified is 66.45%.
CONTROLLER PARAMETER OPTIMIZATION FOR AN ELECTRO-HYDRAULIC ACTUATOR SYSTEM BASED ON PARTICLE SWARM OPTIMIZATION TECHNIQUE
Authors: Soon Chong Chee , Ghazali Rozaimi , Jaafar Hazriq Izzuan , Syed Hussien Sharifah Yuslinda , Md. Sam Yahaya , Rahmat Mohd Fua'ad
Published: June 2016

Motion control applications are widely applied in the industrial field with the assistance of electro-hydraulic actuator (EHA) system. EHA system is well known to be disclosed to the parameter variations, disturbances and uncertainties which are affected by the changes in the operating conditions such as friction, internal and external leakage. The complexity and nonlinear characteristic of the EHA system leads to a great challenge for controller development and system modelling. The performance of the utilized controller can be improved in order to achieve its best capability. In this paper, the basic knowledge in optimization of the proportional-integral-derivative (PID) controller through Gradient Descent (GD) and Particle Swarm Optimization (PSO) techniques are discussed. The PID parameters obtained through Ziegler-Nichols (ZN) tuning method has been optimized by using the GD method and is compared with PSO optimization technique via MATLAB/Simulink software. The findings show significant improvement in positioning tracking performance when the developed optimization technique is applied. Therefore, the issues degrading the EHA system performance have been reduced.
IMPROVED CROWD PSYCHOLOGICAL MODEL AND CONTROL
Authors: Siahkal Mahalleh Vahid Behtaji , Selamat Hazlina , Sandhu Fargham , Khamis Nurulaqilla
Published: June 2016

The behavior of human crowd is an interesting phenomenon in which individuals are set as a collection that comprises of a highly dynamic social group. The crowd behaviors have been investigated by researchers over the years. Recent works include the study in modeling and controlling of the dynamic psychological behavior of crowds such as students’ behavior in a classroom or people’s behavior in a one-dimensional queue. In this paper, an improved version of the psychological crowd model has been proposed, where the social interaction between two individuals in a crowd is represented by a weightage, called the weight of social interaction. It has been shown that the inclusion of the social interaction weight has allowed social interactions between individuals to be included and results in a more accurate representation of the crowd’s psychological factors propagations. Since the psychological dynamics of crowd is naturally unstable, this paper also discusses the application of two nonlinear control approaches to stabilise the crowd to make it calm. Results show that for a crowd of n number of agents, the single-agent controller gives similar performance with the n-agent controller but with much less resources. The simulation results also show that it takes less amount of time to stabilise a crowd when the crowd model includes social interaction weights
Maximal Thurston–Bennequin number and reducible Legendrian surgery
Authors: Yasui Kouichi
Published: June 2016

We give a method for constructing a Legendrian representative of a knot in $S^{3}$ which realizes its maximal Thurston–Bennequin number under a certain condition. The method utilizes Stein handle decompositions of $D^{4}$, and the resulting Legendrian representative is often very complicated (relative to the complexity of the topological knot type). As an application, we construct infinitely many knots in $S^{3}$ each of which yields a reducible 3-manifold by a Legendrian surgery in the standard tight contact structure. This disproves a conjecture of Lidman and Sivek.
Xanthine oxidoreductase mediates membrane docking of milk‐fat droplets but is not essential for apocrine lipid secretion
Authors: Monks Jenifer , Dzieciatkowska Monika , Bales Elise S. , Orlicky David J. , Wright Richard M. , McManaman James L.
Published: June 2016

Key points

Xanthine oxidoreductase (XOR) modulates milk lipid secretion and lactation initiation.

XOR is required for butyrophilin1a1 clustering in the membrane during milk lipid secretion.

XOR mediates apical membrane reorganization during milk lipid secretion.

Loss of XOR delays milk fat globule secretion.

XOR loss alters the proteome of milk fat globules.

Apocrine secretion is utilized by epithelial cells of exocrine glands. These cells bud off membrane‐bound particles into the lumen of the gland, losing a portion of the cytoplasm in the secretion product. The lactating mammary gland secretes milk lipid by this mechanism, and xanthine oxidoreductase (XOR) has long been thought to be functionally important. We generated mammary‐specific XOR knockout (MGKO) mice, expecting lactation to fail. Histology of the knockout glands showed very large lipid droplets enclosed in the mammary alveolar cells, but milk analysis showed that these large globules were secreted. Butyrophilin, a membrane protein known to bind to XOR, was clustered at the point of contact of the cytoplasmic lipid droplet with the apical plasma membrane, in the wild‐type gland but not in the knockout, suggesting that XOR mediates ‘docking’ to this membrane. Secreted milk fat globules were isolated from mouse milk of wild‐type and XOR MGKO dams, and subjected to LC‐MS/MS for analysis of protein component. Proteomic results showed that loss of XOR leads to an increase in cytoplasmic, cytoskeletal, Golgi apparatus and lipid metabolism proteins associated with the secreted milk fat globule. Association of XOR with the lipid droplet results in membrane docking and more efficient retention of cytoplasmic components by the secretory cell. Loss of XOR then results in a reversion to a more rudimentary, less efficient, apocrine secretion mechanism, but does not prevent milk fat globule secretion.
Newly Identified Enterovirus C Genotypes, Identified in the Netherlands through Routine Sequencing of All Enteroviruses Detected in Clinical Materials from 2008 to 2015
Authors: Van Leer-Buter Coretta C. , Poelman Randy , Borger Renze , Niesters Hubert G. M.
Published: June 2016

Enteroviruses (EVs) are a group of human and animal viruses that are capable of causing a variety of clinical syndromes. Different genotypes classified into species can be distinguished on the basis of sequence divergence in the VP1 capsid-coding region. Apparently new genotypes are discovered regularly, often as incidental findings in studies investigating respiratory syndromes or as part of poliovirus surveillance. Recently, some EVs have become recognized as significant respiratory pathogens, and a number of new genotypes belonging to species C have been identified. The circulation of these newly identified species C EVs, such as EV-C104, EV-C105, EV-C109, and EV-C117, nevertheless appears to be limited. In this report, we show the results of routine genotyping of all enteroviruses detected in our tertiary care hospital between January 2008 and April 2015. We detected 365 EVs belonging to 40 genotypes. Interestingly, several newly identified species C EVs were detected during the study period. Sequencing of the 5′ untranslated region (5′ UTR) of these viruses shows divergence in this region, which is a target region in many detection assays.
Stimulation of Bovine Whole-Blood Samples Cultured in Media Supplemented with Recombinant Interleukin-7 (IL-7) and IL-12 Extends the Life Span of the Gamma Interferon Assay To Detect Mycobacterium bovis-Infected Cattle
Authors: Gerace E. , Pasquali P. , Oesch B. , Falduto M. , Mandanici F. , Fiasconaro M. , Vitale M. , Di Marco Lo Presti V. , Amato B.
Published: June 2016

The gamma interferon (IFN-γ) assay is widely used to measure cell-mediated immune (CMI) response for the early detection of tuberculosis infection. Processing whole-blood samples for CMI-based diagnostics is time sensitive and usually must occur within 8 h of collection to ensure optimal assay performance. In this study, we developed and tested a modified protocol, in which whole-blood samples from
Mycobacterium bovis
-infected cattle were diluted 1:1 in RPMI medium containing 0.3% fetal bovine serum (FBS) added or not to recombinant mouse interleukin-7 (rmIL-7) or rmIL-12, alone or in combination, and stored at 4°C. At 3 and 6 days postcollection, the diluted blood samples were adjusted to 10% FBS, dispensed into culture trays, stimulated with a bovine purified protein derivative from
M. bovis
, and incubated at 37°C in 5% CO
2
in air. Plasma was removed and assayed for an IFN-γ response using bovine IFN-γ enzyme-linked immunosorbent assay (ELISA) (Bovigam). The results were then compared with those obtained from the conventional procedure. The IFN-γ responses of the samples stored up to 6 days postcollection in the supplemented RPMI medium were similar to those observed in the samples processed within 8 h after sampling, indicating that lymphocyte vitality and response were preserved. The addition of rmIL-7 and rmIL-12, alone or in combination, to culture medium can enhance lymphocyte survival and thus extends the time limit within which the IFN-γ assay can be applied as a diagnostic tool in bovine tuberculosis surveillance and eradication.
Development of a Real-Time PCR Protocol Requiring Minimal Handling for Detection of Vancomycin-Resistant Enterococci with the Fully Automated BD Max System
Authors: Dalpke Alexander H. , Hofko Marjeta , Zimmermann Stefan
Published: June 2016

Vancomycin-resistant enterococci (VRE) are an important cause of health care-associated infections, resulting in significant mortality and a significant economic burden in hospitals. Active surveillance for at-risk populations contributes to the prevention of infections with VRE. The availability of a combination of automation and molecular detection procedures for rapid screening would be beneficial. Here, we report on the development of a laboratory-developed PCR for detection of VRE which runs on the fully automated Becton Dickinson (BD) Max platform, which combines DNA extraction, PCR setup, and real-time PCR amplification. We evaluated two protocols: one using a liquid master mix and the other employing commercially ordered dry-down reagents. The BD Max VRE PCR was evaluated in two rounds with 86 and 61 rectal elution swab (eSwab) samples, and the results were compared to the culture results. The sensitivities of the different PCR formats were 84 to 100% for
vanA
and 83.7 to 100% for
vanB
; specificities were 96.8 to 100% for
vanA
and 81.8 to 97% for
vanB
. The use of dry-down reagents and the ExK DNA-2 kit for extraction showed that the samples were less inhibited (3.3%) than they were by the use of the liquid master mix (14.8%). Adoption of a cutoff threshold cycle of 35 for discrimination of
vanB
-positive samples allowed an increase of specificity to 87.9%. The performance of the BD Max VRE assay equaled that of the BD GeneOhm VanR assay, which was run in parallel. The use of dry-down reagents simplifies the assay and omits any need to handle liquid PCR reagents.
Multicenter Evaluation of the Solana Group A Streptococcus Assay: Comparison with Culture
Authors: Uphoff Timothy S. , Buchan Blake W. , Ledeboer Nathan A. , Granato Paul A. , Daly Judy A. , Marti Tara N.
Published: June 2016

We compared group A
Streptococcus
(GAS) culture with a rapid helicase-dependent amplification (HDA) method using 1,082 throat swab specimens. The HDA method demonstrated 98.2% sensitivity and 97.2% specificity. GAS prevalence by culture was 20.7%, and it was 22.6% using the HDA method. In 35 min, the HDA method provided rapid, sensitive GAS detection, making culture confirmation unnecessary.
Evaluation of Elecsys Syphilis Assay for Routine and Blood Screening and Detection of Early Infection
Authors: Kremastinou J. , Polymerou V. , Lavranos D. , Aranda Arrufat A. , Harwood J. , Martínez Lorenzo M. J. , Ng K. P. , Queiros L. , Vereb I. , Cusini M.
Published: June 2016

Treponema pallidum
infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against
T. pallidum
. The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected
T. pallidum
antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results.
Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism
Authors: Pi Fengmei , Zhao Zhengyi , Chelikani Venkata , Yoder Kristine , Kvaratskhelia Mamuka , Guo Peixuan
Published: June 2016

The intracellular parasitic nature of viruses and the emergence of antiviral drug resistance necessitate the development of new potent antiviral drugs. Recently, a method for developing potent inhibitory drugs by targeting biological machines with high stoichiometry and a sequential-action mechanism was described. Inspired by this finding, we reviewed the development of antiviral drugs targeting viral DNA-packaging motors. Inhibiting multisubunit targets with sequential actions resembles breaking one bulb in a series of Christmas lights, which turns off the entire string. Indeed, studies on viral DNA packaging might lead to the development of new antiviral drugs. Recent elucidation of the mechanism of the viral double-stranded DNA (dsDNA)-packaging motor with sequential one-way revolving motion will promote the development of potent antiviral drugs with high specificity and efficiency. Traditionally, biomotors have been classified into two categories: linear and rotation motors. Recently discovered was a third type of biomotor, including the viral DNA-packaging motor, beside the bacterial DNA translocases, that uses a revolving mechanism without rotation. By analogy, rotation resembles the Earth's rotation on its own axis, while revolving resembles the Earth's revolving around the Sun (see animations at
http://rnanano.osu.edu/movie.html
). Herein, we review the structures of viral dsDNA-packaging motors, the stoichiometries of motor components, and the motion mechanisms of the motors. All viral dsDNA-packaging motors, including those of dsDNA/dsRNA bacteriophages, adenoviruses, poxviruses, herpesviruses, mimiviruses, megaviruses, pandoraviruses, and pithoviruses, contain a high-stoichiometry machine composed of multiple components that work cooperatively and sequentially. Thus, it is an ideal target for potent drug development based on the power function of the stoichiometries of target complexes that work sequentially.
Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+T CellsIn Vitro
Authors: Zerbato Jennifer M. , Serrao Erik , Lenzi Gina , Kim Baek , Ambrose Zandrea , Watkins Simon C. , Engelman Alan N. , Sluis-Cremer Nicolas
Published: June 2016

The latent HIV-1 reservoir primarily resides in resting CD4+T cells which are a heterogeneous population composed of both naive (TN) and memory cells. In HIV-1-infected individuals, viral DNA has been detected in both naive and memory CD4+T cell subsets although the frequency of HIV-1 DNA is typically higher in memory cells, particularly in the central memory (TCM) cell subset. TNand TCMcells are distinct cell populations distinguished by many phenotypic and physiological differences. In this study, we used a primary cell model of HIV-1 latency that utilizes direct infection of highly purified TNand TCMcells to address differences in the establishment and reversal of HIV-1 latency. Consistent with what is seenin vivo, we found that HIV-1 infected TNcells less efficiently than TCMcells. However, when the infected TNcells were treated with latency-reversing agents, including anti-CD3/CD28 antibodies, phorbol myristate acetate/phytohemagglutinin, and prostratin, as much (if not more) extracellular virion-associated HIV-1 RNA was produced per infected TNcell as per infected TCMcell. There were no major differences in the genomic distribution of HIV-1 integration sites between TNand TCMcells that accounted for these observed differences. We observed decay of the latent HIV-1 cells in both T cell subsets after exposure to each of the latency-reversing agents. Collectively, these data highlight significant differences in the establishment and reversal of HIV-1 latency in TNand TCMCD4+T cells and suggest that each subset should be independently studied in preclinical and clinical studies.

IMPORTANCEThe latent HIV-1 reservoir is frequently described as residing within resting memory CD4+T cells. This is largely due to the consistent finding that memory CD4+T cells, specifically the central (TCM) and transitional memory compartments, harbor the highest levels of HIV-1 DNA in individuals on suppressive therapy. This has yielded little research into the contribution of CD4+naive T (TN) cells to the latent reservoir. In this study, we show that although TNcells harbor significantly lower levels of HIV-1 DNA, following latency reversal, they produced as many virions as did the TCMcells (if not more virions). This suggests that latently infected TNcells may be a major source of virus following treatment interruption or failure. These findings highlight the need for a better understanding of the establishment and reversal of HIV-1 latency in TNcells in evaluating therapeutic approaches to eliminate the latent reservoir.
Distinct Particle Morphologies Revealed through Comparative Parallel Analyses of Retrovirus-Like Particles
Authors: Martin Jessica L. , Cao Sheng , Maldonado Jose O. , Zhang Wei , Mansky Louis M.
Published: June 2016

The Gag protein is the main retroviral structural protein, and its expression alone is usually sufficient for production of virus-like particles (VLPs). In this study, we sought to investigate—in parallel comparative analyses—Gag cellular distribution, VLP size, and basic morphological features using Gag expression constructs (Gag or Gag-YFP, where YFP is yellow fluorescent protein) created from all representative retroviral genera:Alpharetrovirus,Betaretrovirus,Deltaretrovirus,Epsilonretrovirus,Gammaretrovirus,Lentivirus, andSpumavirus. We analyzed Gag cellular distribution by confocal microscopy, VLP budding by thin-section transmission electron microscopy (TEM), and general morphological features of the VLPs by cryogenic transmission electron microscopy (cryo-TEM). Punctate Gag was observed near the plasma membrane for all Gag constructs tested except for the representativeBeta- andEpsilonretrovirusGag proteins. This is the first report ofEpsilonretrovirusGag localizing to the nucleus of HeLa cells. While VLPs were not produced by the representativeBeta- andEpsilonretrovirusGag proteins, the other Gag proteins produced VLPs as confirmed by TEM, and morphological differences were observed by cryo-TEM. In particular, we observedDeltaretrovirus-like particles with flat regions of electron density that did not follow viral membrane curvature,Lentivirus-like particles with a narrow range and consistent electron density, suggesting a tightly packed Gag lattice, andSpumavirus-like particles with large envelope protein spikes and no visible electron density associated with a Gag lattice. Taken together, these parallel comparative analyses demonstrate for the first time the distinct morphological features that exist among retrovirus-like particles. Investigation of these differences will provide greater insights into the retroviral assembly pathway.

IMPORTANCEComparative analysis among retroviruses has been critically important in enhancing our understanding of retroviral replication and pathogenesis, including that of important human pathogens such as human T-cell leukemia virus type 1 (HTLV-1) and HIV-1. In this study, parallel comparative analyses have been used to study Gag expression and virus-like particle morphology among representative retroviruses in the known retroviral genera. Distinct differences were observed, which enhances current knowledge of the retroviral assembly pathway.
Structure-Function Analysis of the ϕX174 DNA-Piloting Protein Using Length-Altering Mutations
Authors: Roznowski Aaron P. , Fane Bentley A.
Published: June 2016

Although the ϕX174 H protein is monomeric during procapsid morphogenesis, 10 proteins oligomerize to form a DNA translocating conduit (H-tube) for penetration. However, the timing and location of H-tube formation are unknown. The H-tube's highly repetitive primary and quaternary structures made it amenable to a genetic analysis using in-frame insertions and deletions. Length-altered proteins were characterized for the ability to perform the protein's three known functions: participation in particle assembly, genome translocation, and stimulation of viral protein synthesis. Insertion mutants were viable. Theoretically, these proteins would produce an assembled tube exceeding the capsid's internal diameter, suggesting that virions do not contain a fully assembled tube. Lengthened proteins were also used to test the biological significance of the crystal structure. Particles containing H proteins of two different lengths were significantly less infectious than both parents, indicating an inability to pilot DNA. Shortened H proteins were not fully functional. Although they could still stimulate viral protein synthesis, they either were not incorporated into virions or, if incorporated, failed to pilot the genome. Mutant proteins that failed to incorporate contained deletions within an 85-amino-acid segment, suggesting the existence of an incorporation domain. The revertants of shortened H protein mutants fell into two classes. The first class duplicated sequences neighboring the deletion, restoring wild-type length but not wild-type sequence. The second class suppressed an incorporation defect, allowing the use of the shortened protein.

IMPORTANCE
The H-tube crystal structure represents the first high-resolution structure of a virally encoded DNA-translocating conduit. It has similarities with other viral proteins through which DNA must travel, such as the α-helical barrel domains of P22 portal proteins and T7 proteins that form tail tube extensions during infection. Thus, the H protein serves as a paradigm for the assembly and function of long α-helical supramolecular structures and nanotubes. Highly repetitive in primary and quaternary structure, they are amenable to structure-function analyses using in-frame insertions and deletions as presented herein.
The Evolutionary Histories of Antiretroviral Proteins SERINC3 and SERINC5 Do Not Support an Evolutionary Arms Race in Primates
Authors: Murrell Ben , Vollbrecht Thomas , Guatelli John , Wertheim Joel O.
Published: June 2016

Molecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses and their antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-α, SAMHD1, and BST-2. Host restriction factors have experienced some of the most intense and pervasive adaptive evolution documented in primates. Recently, two novel host factors, SERINC3 and SERINC5, were identified as the targets of HIV-1 Nef, a protein crucial for the optimal infectivity of virus particles. Here, we compared the evolutionary fingerprints of SERINC3 and SERINC5 to those of other primate restriction factors and to a set of other genes with diverse functions. SERINC genes evolved in a manner distinct from the canonical arms race dynamics seen in the other restriction factors. Despite their antiviral activity against HIV-1 and other retroviruses, SERINC3 and SERINC5 have a relatively uneventful evolutionary history in primates.

IMPORTANCE
Restriction factors are host proteins that block viral infection and replication. Many viruses, like HIV-1 and related retroviruses, evolved accessory proteins to counteract these restriction factors. The importance of these interactions is evidenced by the intense adaptive selection pressures that dominate the evolutionary histories of both the host and viral genes involved in this so-called arms race. The dynamics of these arms races can point to mechanisms by which these viral infections can be prevented. Two human genes, SERINC3 and SERINC5, were recently identified as targets of an HIV-1 accessory protein important for viral infectivity. Unexpectedly, we found that these SERINC genes, unlike other host restriction factor genes, show no evidence of a recent evolutionary arms race with viral pathogens.
Flow Cytometric and Cytokine ELISpot Approaches To Characterize the Cell-Mediated Immune Response in Ferrets following Influenza Virus Infection
Authors: DiPiazza Anthony , Richards Katherine , Batarse Frances , Lockard Laura , Zeng Hui , García-Sastre Adolfo , Albrecht Randy A. , Sant Andrea J.
Published: June 2016

Influenza virus infections represent a significant socioeconomic and public health burden worldwide. Although ferrets are considered by many to be ideal for modeling human responses to influenza infection and vaccination, efforts to understand the cellular immune response have been severely hampered by a paucity of standardized procedures and reagents. In this study, we developed flow cytometric and T cell enzyme-linked immunosorbent spot (ELISpot) approaches to characterize the leukocyte composition and antigen-specific T cell response within key lymphoid tissues following influenza virus infection in ferrets. Through a newly designed and implemented set of serological reagents, we used multiparameter flow cytometry to directly quantify the frequency of CD4+and CD8+T cells, Ig+B cells, CD11b+myeloid-derived cells, and major histocompatibility complex (MHC) class II-positive antigen-presenting cells (APCs) both prior to and after intranasal infection with A/California/04/09 (H1N1). We found that the leukocyte composition was altered at 10 days postinfection, with notable gains in the frequency of T cells and myeloid cells within the draining lymph node. Furthermore, these studies revealed that the antigen specificity of influenza virus-reactive CD4 and CD8 T cells was very broad, with recognition of the viral HA, NA, M1, NS1, and NP proteins, and that total reactivity to influenza virus postinfection represented approximately 0.1% of the circulating peripheral blood mononuclear cells (PBMC). Finally, we observed distinct patterns of reactivity between individual animals, suggesting heterogeneity at the MHC locus in ferrets within commercial populations, a finding of considerable interest in efforts to move the ferret model forward for influenza vaccine and challenge studies.

IMPORTANCEFerrets are an ideal animal model to study transmission, diseases, and vaccine efficacies of respiratory viruses because of their close anatomical and physiological resemblances to humans. However, a lack of reagents has limited our understanding of the cell-mediated immune response following infection and vaccination. In this study, we used cross-reactive and ferret-specific antibodies to study the leukocyte composition and antigen-specific CD4 and CD8 T cell responses following influenza A/California/04/09 (H1N1) virus infection. These studies revealed strikingly distinct patterns of reactivity between CD4 and CD8 T cells, which were overlaid with differences in protein-specific responses between individual animals. Our results provide a first, in-depth look at the T cell repertoire in response to influenza infection and suggest that there is considerable heterogeneity at the MHC locus, which is akin to that in humans and an area of intense research interest.
Major Histocompatibility Complex Class II HLA-DRα Is Downregulated by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Lytic Transactivator RTA and MARCH8
Authors: Sun Zhiguo , Jha Hem Chandra , Pei Yong-gang , Robertson Erle S.
Published: June 2016

Kaposi's sarcoma-associated herpesvirus (KSHV) maintains two modes of life cycle, the latent and lytic phases. To evade the attack of the cell host's immune system, KSHV switches from the lytic to the latent phase, a phase in which only a few of viral proteins are expressed. The mechanism by which KSHV evades the attack of the immune system and establishes latency has not been fully understood. Major histocompatibility complex class II (MHC-II) molecules are key components of the immune system defense mechanism against viral infections. Here we report that HLA-DRα, a member of the MHC-II molecules, was downregulated by the replication and transcription activator (RTA) protein encoded by KSHV ORF50, an important regulator of the viral life cycle. RTA not only downregulated HLA-DRα at the protein level through direct binding and degradation through the proteasome pathway but also indirectly downregulated the protein level of HLA-DRα by enhancing the expression of MARCH8, a member of the membrane-associated RING-CH (MARCH) proteins. Our findings indicate that KSHV RTA facilitates evasion of the virus from the immune system through manipulation of HLA-DRα.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV) has a causal role in a number of human cancers, and its persistence in infected cells is controlled by the host's immune system. The mechanism by which KSHV evades an attack by the immune system has not been well understood. This work represents studies which identify a novel mechanism by which the virus can facilitate evasion of an immune system. We now show that RTA, the replication and transcription activator encoded by KSHV (ORF50), can function as an E3 ligase to degrade HLA-DRα. It can directly bind and induce degradation of HLA-DRα through the ubiquitin-proteasome degradation pathway. In addition to the direct regulation of HLA-DRα, RTA can also indirectly downregulate the level of HLA-DRα protein by upregulating transcription of MARCH8. Increased MARCH8 results in the downregulation of HLA-DRα. Furthermore, we also demonstrate that expression of HLA-DRα was impaired in KSHV
de novo
infection.
Asymmetric exhumation of the Mount Everest region: Implications for the tectono-topographic evolution of the Himalaya
Authors: Carrapa B. , Robert X. , DeCelles P.G. , Orme D.A. , Thomson S.N. , Schoenbohm L.M.
Published: June 2016

The tectonic and topographic history of the Himalaya-Tibet orogenic system remains controversial, with several competing models that predict different exhumation histories. Here, we present new low-temperature thermochronological data from the Mount Everest region, which, combined with thermal-kinematic landscape evolution modeling, indicate asymmetric exhumation of Mount Everest consistent with a scenario in which the southern edge of the Tibetan Plateau was located >100 km farther south during the mid-Miocene. Northward plateau retreat was caused by erosional incision during the Pliocene. Our results suggest that the South Tibetan Detachment was a localized structure and that no coupling between precipitation and erosion is required for Miocene exhumation of Greater Himalayan Sequence rocks on Mount Everest.
Sedimentary record of plate coupling and decoupling during growth of the Andes
Authors: Horton Brian K. , Fuentes Facundo
Published: June 2016

Geochronologic, provenance, and sediment accumulation records from the long-lived (>100 m.y.) retroarc basin at the transition from the central to southern Andes provide improved resolution to examine the duration and controls on mixed-mode deformation and an enigmatic foreland depositional hiatus. Detrital zircon U-Pb ages for the Malargüe and Neuquén basin systems of western Argentina reveal shifts in exhumation and accumulation compatible with magmatic-arc and thrust-belt sources during unsteady Cretaceous–Neogene deformation. Fully developed foreland basin conditions were only achieved during separate periods of Late Cretaceous and Neogene shortening contemporaneous with possible episodes of enhanced coupling between a westward-advancing South American plate and the subducting Nazca slab. Separating these two contractional episodes is a 20–40 m.y. phase of reduced sedimentation and unconformity development, potentially signifying a neutral to extensional mode across the retroarc hinterland to forearc region during diminished plate coupling. We propose that the Andean orogen and its foreland and forearc basins have always been sensitive to variations in subduction dynamics, such that regional shifts in slab buoyancy and subduction geometry (particularly slab dip) superimposed on plate-scale shifts in convergence have governed mechanical coupling along the plate boundary and resulting fluctuations among contractional, extensional, and neutral tectonic regimes.
Evidence for Cretaceous-Paleogene boundary bolide “impact winter” conditions from New Jersey, USA
Authors: Vellekoop Johan , Esmeray-Senlet Selen , Miller Kenneth G. , Browning James V. , Sluijs Appy , van de Schootbrugge Bas , Sinninghe Damsté Jaap S. , Brinkhuis Henk
Published: June 2016

Abrupt and short-lived “impact winter” conditions have commonly been implicated as the main mechanism leading to the mass extinction at the Cretaceous-Paleogene (K-Pg) boundary (ca. 66 Ma), marking the end of the reign of the non-avian dinosaurs. However, so far only limited evidence has been available for such a climatic perturbation. Here we perform high-resolution TEX86 organic paleothermometry on three shallow cores from the New Jersey paleoshelf, (northeastern USA) to assess the impact-provoked climatic perturbations immediately following the K-Pg impact and to place these short-term events in the context of long-term climate evolution. We provide evidence of impact-provoked, severe climatic cooling immediately following the K-Pg impact. This so-called “impact winter” occurred superimposed on a long-term cooling trend that followed a warm phase in the latest Cretaceous.
2016 Consensus statement on return to sport from the First World Congress in Sports Physical Therapy, Bern
Authors: Ardern Clare L , Glasgow Philip , Schneiders Anthony , Witvrouw Erik , Clarsen Benjamin , Cools Ann , Gojanovic Boris , Griffin Steffan , Khan Karim M , Moksnes Håvard , Mutch Stephen A , Phillips Nicola , Reurink Gustaaf , Sadler Robin , Grävare Silbernagel Karin , Thorborg Kristian , Wangensteen Arnlaug , Wilk Kevin E , Bizzini Mario
Published: June 2016

Deciding when to return to sport after injury is complex and multifactorial—an exercise in risk management. Return to sport decisions are made every day by clinicians, athletes and coaches, ideally in a collaborative way. The purpose of this consensus statement was to present and synthesise current evidence to make recommendations for return to sport decision-making, clinical practice and future research directions related to returning athletes to sport. A half day meeting was held in Bern, Switzerland, after the First World Congress in Sports Physical Therapy. 17 expert clinicians participated. 4 main sections were initially agreed upon, then participants elected to join 1 of the 4 groups—each group focused on 1 section of the consensus statement. Participants in each group discussed and summarised the key issues for their section before the 17-member group met again for discussion to reach consensus on the content of the 4 sections. Return to sport is not a decision taken in isolation at the end of the recovery and rehabilitation process. Instead, return to sport should be viewed as a continuum, paralleled with recovery and rehabilitation. Biopsychosocial models may help the clinician make sense of individual factors that may influence the athlete's return to sport, and the Strategic Assessment of Risk and Risk Tolerance framework may help decision-makers synthesise information to make an optimal return to sport decision. Research evidence to support return to sport decisions in clinical practice is scarce. Future research should focus on a standardised approach to defining, measuring and reporting return to sport outcomes, and identifying valuable prognostic factors for returning to sport.
Evidence from prospective cohort studies did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review
Authors: Harcombe Zoë , Baker Julien S , Davies Bruce
Published: June 2016

Objectives

National dietary guidelines were introduced in 1977 and 1983, by the USA and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2015 systematic review examined randomised controlled trial (RCT) evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. What epidemiological evidence was available to the dietary guideline committees in 1983?

Methods

A systematic review of prospective cohort studies, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD.

Results

Across 6 studies, involving 31 445 participants, there were 1521 deaths from all-causes and 360 deaths from CHD during the mean follow-up of 7.5±6.2 years. The death rates were 4.8% and 1.1% from all-causes and CHD respectively. One study included men with previous heart disease. The death rate from CHD for those with, and without previous myocardial infarction was 20.9% and 1.0% respectively. None of the six studies found a significant relationship between CHD deaths and total dietary fat intake. One of the six studies found a correlation between CHD deaths and saturated dietary fat intake across countries; none found a relationship between CHD deaths and saturated dietary fat in the same population.

Conclusions

1983 dietary recommendations for 220 million US and 56 million UK citizens lacked supporting evidence from RCT or prospective cohort studies. The extant research had been undertaken exclusively on males, so lacked generalisability for population-wide guidelines.
Retrospective analysis of changing characteristics of treatment-seeking smokers: implications for further reducing smoking prevalence
Authors: Leyro Teresa M , Crew Erin E , Bryson Susan W , Lembke Anna , Bailey Steffani R , Prochaska Judith J , Henriksen Lisa , Fortmann Stephen P , Killen Joel D , Killen Diana T , Hall Sharon M , David Sean P
Published: June 2016

Objective

The goal of the current study was to empirically compare successive cohorts of treatment-seeking smokers who enrolled in randomised clinical trials in a region of the USA characterised by strong tobacco control policies and low smoking prevalence, over the past three decades.

Design

Retrospective treatment cohort comparison.

Setting

Data were collected from 9 randomised clinical trials conducted at Stanford University and the University of California, San Francisco, between 1990 and 2013.

Participants

Data from a total of 2083 participants were included (Stanford, n=1356; University of California San Francisco, n=727).

Primary and secondary outcomes

One-way analysis of variance and covariance, χ2and logistic regression analyses were used to examine relations between nicotine dependence, cigarettes per day, depressive symptoms and demographic characteristics among study cohorts.

Results

Similar trends were observed at both settings. When compared to earlier trials, participants in more recent trials smoked fewer cigarettes, were less nicotine-dependent, reported more depressive symptoms, were more likely to be male and more likely to be from a minority ethnic/racial group, than those enrolled in initial trials (all p's<0.05). Analysis of covariances revealed that cigarettes per day, nicotine dependence and current depressive symptom scores were each significantly related to trial (all p's<0.001).

Conclusions

Our findings suggest that more recent smoking cessation treatment-seeking cohorts in a low prevalence region were characterised by less smoking severity, more severe symptoms of depression and were more likely to be male and from a minority racial/ethnic group.
Risk factors associated with RSV hospitalisation in the first 2 years of life, among different subgroups of children in NSW: a whole-of-population-based cohort study
Authors: Homaira Nusrat , Mallitt Kylie-Ann , Oei Ju-Lee , Hilder Lisa , Bajuk Barbara , Lui Kei , Rawlinson William , Snelling Tom , Jaffe Adam
Published: June 2016

Background

Data on risk factors for respiratory syncytial virus (RSV)-associated hospitalisation in Australian children may be informative for preventive measures.

Methods

A whole-of-population-based study was conducted to identify comparable risk factors for RSV hospitalisation in different subgroups of children aged <2 years in New South Wales. The cohort was divided into Indigenous children and high-risk and standard risk non-Indigenous children. Data on risk factors were obtained from the Perinatal Data Collection. RSV hospitalisations were ascertained from the Admitted Patient Data Collection. Adjusted HRs were calculated for each subgroup. Population-attributable risk associated with risk factors was estimated.

Results

Four factors were associated with increased risk of RSV hospitalisation: maternal smoking during pregnancy, male sex, multiparity and birth during the first half of the RSV season. Increase in relative socioeconomic advantage was associated with decreased risk of hospitalisation. Among high and standard risk non-Indigenous children, the hazard was approximately double for children born to multiparous women compared to those born to primiparous women and among Indigenous children the hazard was approximately double among those born during the first half of the RSV season. Maternal smoking during pregnancy was associated with a 26–45% increased risk across subgroups and accounted for 17% (95% CI 9.3% to 24%) of RSV hospitalisations in Indigenous children, 5% (95% CI 2.5% to 8%) in high-risk and 6% (95% 5% to 7%) in standard risk non-Indigenous children.

Discussion

Promoting avoidance of smoking during pregnancy may help in lowering the disease burden, with Indigenous children likely to benefit most.