bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Downsizing Prisons Dangerous?
Authors: Sundt Jody , Salisbury Emily J. , Harmon Mark G.
Published: March 2016

Research Summary

Recent declines in imprisonment raise a critical question: Can prison populations be reduced without endangering the public? This question is examined by testing the effect of California's dramatic efforts to comply with court‐mandated targets to reduce prison overcrowding using a pretest‐posttest design. The results showed that California's Realignment Act had no effect on violent or property crime rates in 2012, 2013, or 2014. When crime types were disaggregated, a moderately large, statistically significant association between Realignment and auto theft rates was observed in 2012. By 2014, however, this effect had decayed and auto theft rates returned to pre‐Realignment levels.

Policy Implications

Significant reductions in the size of prison populations are possible without endangering public safety. Within just 15 months of its passage, Realignment reduced the size of the total prison population by 27,527 inmates, prison crowding declined from 181% to 150% of design capacity, approximately $453 million was saved, and there was no adverse effect on the overall safety of Californians. With a mixture of jail use, community corrections, law enforcement and other preventive efforts, California counties have provided a comparable level of public safety to that previously achieved by state prisons. Nevertheless, sustaining these policy objectives will require greater attention to local implementation, targeted crime prevention, and sentencing reform.
High Amounts of Total and Extracellular Vesicle‐Derived Soluble HLA‐G are Associated with HLA‐G 14‐bp Deletion Variant in Women with Embryo Implantation Failure
Authors: Nardi Fabiola da Silva , Slowik Renata , Michelon Tatiana , Manvailer Luis Felipe dos Santos , Wagner Bettina , Neumann Jorge , Horn Peter , Bicalho Maria da Graça , Rebmann Vera
Published: March 2016

Problem

Human leukocyte antigen‐G (HLA‐G) expression is related to 14‐bp insertion/deletion polymorphism at the 3′UTR of the HLA‐G gene. Soluble forms of HLA‐G are released as free molecules or via extracellular vesicles (EVs). Due to the crucial role of HLA‐G during pregnancy, we analyzed the 14‐bp polymorphism and the two secreted forms in implantation failure women (IF) and in fertile women (FW).

Method of study

For the genetic analysis, 49 IF and 34 FW were genotyped. For sHLA‐G quantification, serum samples from 35 IF and 23 FW were available. ExoQuick™ kit was used for EVs precipitation. The total soluble HLA‐G (sHLA‐Gtot) and vesicular sHLA‐GEV were quantified by ELISA. The EVs size and concentration were determined by nanoparticle tracking analysis (NTA).

Results

An increased proportion of IF presented high levels of sHLA‐Gtot (P = 0.02) and vesicular sHLA‐GEV (P = 0.0003) compared to FW. The 14‐bp deletion allele is more frequent in IF (P = 0.0002) and associated with high levels of sHLA‐Gtot and vesicular sHLA‐GEV.

Conclusion

The high expression of sHLA‐Gtot and sHLA‐GEV, together with the presence of the 14‐bp deletion allele, might be involved in implantation failure.
Is there a difference between the STOP‐BANG and the Berlin Obstructive Sleep Apnoea Syndrome questionnaires for determining respiratory complications during the perioperative period?
Authors: Gokay Pervin , Tastan Sevinc , Orhan Mehmet Emin
Published: March 2016

Aims and Objectives

This study aimed to compare the efficiency of the STOP‐BANG and Berlin Obstructive Sleep Apnoea Syndrome questionnaires for evaluating potential respiratory complications during the perioperative period.

Background

Questionnaires that are used to determine obstructive sleep apnoea risk are not widely used for surgical patients. Among the questionnaires that are commonly used for obstructive sleep apnoea screening, it remains unclear whether the STOP‐BANG or Berlin Obstructive Sleep Apnoea Syndrome questionnaire is more effective in terms of ease of use, usage period and diagnosis of surgical patients with obstructive sleep apnoea risk.

Design

This study was designed as a descriptive and prospective study.

Methods

The study included 126 patients over 18 years of age who were American Society of Anesthesiologists classification class I–II and underwent laparoscopic cholecystectomy. To determine the potential obstructive sleep apnoea syndrome risk, the STOP‐BANG and Berlin questionnaires were administered. Respiratory complications were then observed during the perioperative period.

Results

During intubation and extubation, we observed statistically significant differences in difficult intubation, difficult facemask ventilation and desaturation frequency between the high‐ and low‐risk groups for obstructive sleep apnoea syndrome, as determined by the STOP‐BANG questionnaire. During extubation, statistically significant differences in coughing, breath‐holding and desaturation frequency were observed between the high‐risk and low‐risk groups, according to the Berlin questionnaire. In the post‐anaesthesia care unit, both questionnaires found statistically significant differences between the low‐ and high‐risk groups.

Conclusion

Obstructive sleep apnoea syndrome screening questionnaires administered during the preoperative period are useful for predicting perioperative respiratory complications. It may be most useful to administer the STOP‐BANG questionnaire as the initial evaluation.

Relevance to clinical practice

Questionnaires may be used to determine the risk of obstructive sleep apnoea syndrome, which could impact the anaesthetisation of surgical patients. Questionnaires for determining the risk of obstructive sleep apnoea syndrome should be used regularly for surgical patients, and these questionnaires should be used to improve clinical protocols for anaesthesia and postanaesthesia care.
Mindfulness‐based interventions for coping with cancer
Authors: Carlson Linda E.
Published: March 2016

Work in the development and evaluation of mindfulness‐based interventions (MBIs) for cancer care has been underway for the last 20 years, and a growing body of literature now supports their efficacy. MBIs are particularly helpful in dealing with common experiences related to cancer diagnosis, treatment, and survivorship, including loss of control, uncertainty about the future, and fears of recurrence, as well as a range of physical and psychological symptoms, including depression, anxiety, insomnia, and fatigue. Our adaptation, mindfulness‐based cancer recovery (MBCR), has resulted in improvements across a range of psychological and biological outcomes, including cortisol slopes, blood pressure, and telomere length, in various groups of cancer survivors. In this paper, I review the rationale for MBIs in cancer care and provide an overview of the state of the current literature, with a focus on results from three recent clinical trials conducted by our research group. These include a comparative efficacy trial comparing MBCR to supportive–expressive therapy in distressed breast cancer survivors, a non‐inferiority trial comparing MBCR to cognitive behavioral therapy for insomnia in cancer survivors with clinical insomnia, and an online adaptation of MBCR for rural and remote cancer survivors without access to in‐person groups. I conclude by outlining work in progress and future directions for MBI research and applications in cancer care.
Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients
Authors: Denies S. , Cicchelero L. , de Rooster H. , Daminet S. , Polis I. , Van de Maele I. , Sanders N. N.
Published: March 2016

Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin‐1 (TSP‐1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4 weeks after treatment with metronomic temozolomide (6.6 mg m−2), cyclophosphamide (12.5 mg m−2) or cyclophosphamide and temozolomide. The percentage of circulating CD25+Foxp3+CD4+ Tregs and the plasma levels of TSP‐1 and VEGF were measured. There was a significant difference in the percentage of Tregs between cancer patients and healthy dogs. A significant decrease in Tregs was noted in patients treated with metronomic cyclophosphamide and the combination. Treatment with temozolomide had no effect on the percentage of Tregs. TSP‐1 and VEGF levels were, respectively, significantly lower and higher in cancer patients than in healthy dogs, but they were not influenced by any of the studied metronomic treatment regimens.
The Effect of Rib Turbulators on Film Cooling Effectiveness of Round Compound Angle Holes Fed by an Internal Cross-Flow
Authors: Klavetter Sean R. , McClintic John W. , Bogard David G. , Dees Jason E. , Laskowski Gregory M. , Briggs Robert
Published: March 2016

Early stage gas turbine blades feature complicated internal geometries in order to enhance internal heat transfer and to supply coolant for film cooling. Most film cooling experiments decouple the effect of internal coolant feed from external film cooling effectiveness, even though engine parts are commonly fed by cross-flow and feature internal rib turbulators which can affect film cooling. Experiments measuring adiabatic effectiveness were conducted to investigate the effects of turbulated perpendicular cross-flow on a row of 45 deg compound angle cylindrical film cooling holes for a total of eight internal rib configurations. The ribs were angled to the direction of prevailing internal cross-flow at two different angles: 45 deg or 135 deg. The ribs were also positioned at two different spanwise locations relative to the cooling holes: in the middle of the cooling hole pitch and slightly intersecting the holes. Experiments were conducted at a density ratio of DR = 1.5 for a range of blowing ratios including M = 0.5, 0.75, 1.0, 1.5, and 2.0. This study demonstrates that peak effectiveness can be attained through the optimization of cross-flow direction relative to the compound angle direction and rib configuration, verifying the importance of hole inlet conditions in film cooling experiments. It was found that ribs tend to reduce adiabatic effectiveness relative to a baseline, smooth-walled configuration. Rib configurations that directed the internal coolant forward in the direction of the mainstream resulted in higher peak adiabatic effectiveness. However, no other parameters could consistently be identified correlating to increased film cooling performance. It is likely that a combination of factors is responsible for influencing performance, including internal local pressure caused by the ribs, the internal channel flow field, in-hole vortices, and jet exit velocity profiles. This study also attempted to replicate the possibility that film cooling holes may intersect ribs and found that a hole which partially intersects a rib still maintains moderate levels of effectiveness.
Remodeling of the Mandibular Bone Induced by Overdentures Supported by Different Numbers of Implants
Authors: Li Kai , Xin Haitao , Zhao Yanfang , Zhang Zhiyuan , Wu Yulu
Published: March 2016

The objective of this study was to investigate the process of mandibular bone remodeling induced by implant-supported overdentures. computed tomography (CT) images were collected from edentulous patients to reconstruct the geometry of the mandibular bone and overdentures supported by implants. Based on the theory of strain energy density (SED), bone remodeling models were established using the user material subroutine (UMAT) in abaqus. The stress distribution in the mandible and bone density change was investigated to determine the effect of implant number on the remodeling of the mandibular bone. The results indicated that the areas where high Mises stress values were observed were mainly situated around the implants. The stress was concentrated in the distal neck region of the distal-most implants. With an increased number of implants, the biting force applied on the dentures was almost all taken up by implants. The stress and bone density in peri-implant bone increased. When the stress reached the threshold of remodeling, the bone density began to decrease. In the posterior mandible area, the stress was well distributed but increased with decreased implant numbers. Changes in bone density were not observed in this area. The computational results were consistent with the clinical data. The results demonstrate that the risk of bone resorption around the distal-most implants increases with increased numbers of implants and that the occlusal force applied to overdentures should be adjusted to be distributed more in the distal areas of the mandible.
Mars orbiter to sniff for methane
Authors: Hand Eric
Published: March 2016

Mission aims to settle whether gas exists—and whether it could hint at life.
Evidence grows for Zika virus as pregnancy danger
Authors: Vogel Gretchen
Published: March 2016

Lab experiments and new clinical data suggest that fast-spreading virus attacks developing brain.
In search of spacetime megawaves
Authors: Clery Daniel
Published: March 2016

Timing in celestial radio beacons could reveal gravitational tsunamis.
Why high ‘good cholesterol’ can be bad news
Authors: Couzin-Frankel Jennifer
Published: March 2016

A faulty transport system sometimes causes high HDL.
Evidence on trial
Authors: Enserink Martin
Published: March 2016

Forensic science is reforming in the wake of a landmark report.
Measurement of gene regulation in individual cells reveals rapid switching between promoter states
Authors: Sepúlveda Leonardo A. , Xu Heng , Zhang Jing , Wang Mengyu , Golding Ido
Published: March 2016

Stochastic properties of phage promoter

Full understanding of regulated gene expression requires characterization of stochastic variation in the activity of individual promoters. To avoid cell-to-cell variability and variation between the activity of specific gene copies, Sepúlveda
et al.
investigated the behavior of the lysogeny maintenance promoter of phage lambda in individual
Escherichia coli
cells. They measured the concentration of transcription factor and the actual number of mRNAs produced, and used mathematical modeling to discern the stochastic activity of the regulated promoter. The promoter underwent switching between configurations that occurred more rapidly than the lifetime of mRNA molecules produced, and individual copies of the same gene functioned independently in the same cell. Such studies can reveal new aspects of systems that have been well studied by more conventional techniques.

Science
, this issue p.
1218
Quasiparticle interference of the Fermi arcs and surface-bulk connectivity of a Weyl semimetal
Authors: Inoue Hiroyuki , Gyenis András , Wang Zhijun , Li Jian , Oh Seong Woo , Jiang Shan , Ni Ni , Bernevig B. Andrei , Yazdani Ali
Published: March 2016

Sinking into the bulk of a Weyl semimetal

A recently discovered class of topological materials, Weyl semimetals, have surface states in the form of so-called Fermi arcs. Inoue
et al.
used a high-resolution scanning tunneling microscope to explore the properties of these states in the material TaAs. They mapped the scattering of electrons off impurities on the surface of the material and compared the data to the predictions of density functional theory. The data could be reconciled with the theory only if electrons associated with Ta orbitals on the Fermi arcs sank into the bulk of the material.

Science
, this issue p.
1184
To see the world in a grain of spins
Authors: Wehner Stephanie
Published: March 2016

A universal simulator is developed that can model the workings of any classical spin system

[Also see Report by
De las Cuevas and Cubitt
]
The preschool paradox
The Importance of Being Little What Preschoolers Really Need from Grownups
Erika Christakis
Viking, 2016. 400 pp.
Authors: Hirsh-Pasek Kathy , Golinkof Roberta Michnick
Published: March 2016

It's time to rethink our approach to early education
Feeding on plastic
Authors: Bornscheuer Uwe T.
Published: March 2016

A bacterium completely degrades poly(ethylene terephthalate)

[Also see Report by

Yoshida
et al.

]
PREview of new products
Authors: McNutt Marcia
Published: March 2016

This week, the
Science
family of journals launches some new and important initiatives. The first is that when authors visit the manuscript submittal portal for
Science, Science Translational Medicine
, and
Science Signaling
, they will notice an additional choice:
Science Immunology
. The newest member of the
Science
family is open for submissions!
Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus
Authors: Lagerqvist Nina , Hagström Åsa , Lundahl Malin , Nilsson Elin , Juremalm Mikael , Larsson Inger , Alm Erik , Bucht Göran , Ahlm Clas , Klingström Jonas
Published: March 2016

Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription-quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS.
Mycobacterium arupense, Mycobacterium heraklionense, and a Newly Proposed Species, “Mycobacterium virginiense” sp. nov., but Not Mycobacterium nonchromogenicum, as Species of the Mycobacterium terrae Complex Causing Tenosynovitis and Osteomyelitis
Authors: Vasireddy Ravikiran , Vasireddy Sruthi , Brown-Elliott Barbara A. , Wengenack Nancy L. , Eke Uzoamaka A. , Benwill Jeana L. , Turenne Christine , Wallace Richard J.
Published: March 2016

Mycobacterium terrae
complex has been recognized as a cause of tenosynovitis, with
M. terrae
and
Mycobacterium nonchromogenicum
reported as the primary etiologic pathogens. The molecular taxonomy of the
M. terrae
complex causing tenosynovitis has not been established despite approximately 50 previously reported cases. We evaluated 26 isolates of the
M. terrae
complex associated with tenosynovitis or osteomyelitis recovered between 1984 and 2014 from 13 states, including 5 isolates reported in 1991 as
M. nonchromogenicum
by nonmolecular methods. The isolates belonged to three validated species, one new proposed species, and two novel related strains. The majority of isolates (20/26, or 77%) belonged to two recently described species:
Mycobacterium arupense
(10 isolates, or 38%) and
Mycobacterium heraklionense
(10 isolates, or 38%). Three isolates (12%) had 100% sequence identity to each other by 16S rRNA and 99.3 to 100% identity by
rpoB
gene region V sequencing and represent a previously undescribed species within the
M. terrae
complex. There were no isolates of
M. terrae
or
M. nonchromogenicum
, including among the five isolates reported in 1991. The 26 isolates were susceptible to clarithromycin (100%), rifabutin (100%), ethambutol (92%), and sulfamethoxazole or trimethoprim-sulfamethoxazole (70%). The current study suggests that
M. arupense
,
M. heraklionense
, and a newly proposed species (“
M. virginiense
” sp. nov.; proposed type strain MO-233 [DSM 100883, CIP 110918]) within the
M. terrae
complex are the major causes of tenosynovitis and osteomyelitis in the United States, with little change over 20 years. Species identification within this complex requires sequencing methods.
Comparison of the Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV QuantiFERON Cell-Mediated Immune Assays in CMV-Seropositive and -Seronegative Pregnant and Nonpregnant Women
Authors: Saldan Alda , Forner Gabriella , Mengoli Carlo , Tinto Daniel , Fallico Loredana , Peracchi Marta , Gussetti Nadia , Palù Giorgio , Abate Davide
Published: March 2016

Human cytomegalovirus (CMV) infection is a major cause of congenital infection leading to birth defects and sensorineural anomalies, including deafness. Recently, cell-mediated immunity (CMI) in pregnant women has been shown to correlate with congenital CMV transmission. In this study, two interferon gamma release assays (IGRA), the CMV enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, detecting CMV-specific CMI were compared. These assays were performed for 80 CMV-infected (57 primarily and 23 nonprimarily) pregnant women and 115 controls, including 89 healthy CMV-seropositive pregnant women without active CMV infection, 15 CMV-seronegative pregnant women, and 11 seropositive or seronegative nonpregnant women. Statistical tests, including frequency distribution analysis, nonparametric Kruskal-Wallis equality-of-populations rank test, Wilcoxon rank sum test for equality on unmatched data, and lowess smoothing local regression, were employed to determine statistical differences between groups and correlation between the assays. The CMV ELISPOT and CMV QuantiFERON assay data were not normally distributed and did not display equal variance. The CMV ELISPOT but not CMV QuantiFERON assay displayed significant higher values for primarily CMV-infected women than for the healthy seropositive pregnant and nonpregnant groups (
P
= 0.0057 and 0.0379, respectively) and those with nonprimary infections (
P
= 0.0104). The lowess local regression model comparing the assays on an individual basis showed a value bandwidth of 0.8. Both assays were highly accurate in discriminating CMV-seronegative pregnant women. The CMV ELISPOT assay was more effective than CMV-QuantiFERON in differentiating primary from the nonprimary infections. A substantial degree of variability exists between CMV ELISPOT and CMV QuantiFERON assay results for CMV-seropositive pregnant women.
New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides
Authors: Crotty Matthew P. , Krekel Tamara , Burnham Carey-Ann D. , Ritchie David J.
Published: March 2016

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibit
in vitro
activity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstrate
in vitro
activity against VRE. These new Gram-positive agents are reviewed here.
Plum Pox Virus
6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection
Authors: Cui Hongguang , Wang Aiming
Published: March 2016

The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian
Plum pox virus
(PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The
trans
expression of 6K1 or the
cis
expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage.

IMPORTANCE
Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically processed into 11 mature proteins, with the majority of them having been at least partially functionally characterized. However, the functional role of a small protein named 6K1 remains obscure. In this study, we showed that deletion of 6K1 or a short motif/region of 6K1 in the full-length cDNA clones of plum pox virus abolishes viral replication and that mutation of the N- or C-terminal cleavage sites of 6K1 to prevent its release from the polyprotein greatly attenuates or completely inhibits viral replication, suggesting its important role in potyviral infection. We report that 6K1 forms punctate structures and targets the replication vesicles in PPV-infected plant leaf cells at the early infection stage. Our data reveal that 6K1 is an important viral protein of the potyviral replication complex.
Characterization of the Adeno-Associated Virus 1 and 6 Sialic Acid Binding Site
Authors: Huang Lin-Ya , Patel Ami , Ng Robert , Miller Edward Blake , Halder Sujata , McKenna Robert , Asokan Aravind , Agbandje-McKenna Mavis
Published: March 2016

The adeno-associated viruses (AAVs), which are being developed as gene delivery vectors, display differential cell surface glycan binding and subsequent tissue tropisms. For AAV serotype 1 (AAV1), the first viral vector approved as a gene therapy treatment, and its closely related AAV6, sialic acid (SIA) serves as their primary cellular surface receptor. Toward characterizing the SIA binding site(s), the structure of the AAV1-SIA complex was determined by X-ray crystallography to 3.0 Å. Density consistent with SIA was observed in a pocket located at the base of capsid protrusions surrounding icosahedral 3-fold axes. Site-directed mutagenesis substitution of the amino acids forming this pocket with structurally equivalent residues from AAV2, a heparan sulfate binding serotype, followed by cell binding and transduction assays, further mapped the critical residues conferring SIA binding to AAV1 and AAV6. For both viruses five of the six binding pocket residues mutated (N447S, V473D, N500E, T502S, and W503A) abolished SIA binding, whereas S472R increased binding. All six mutations abolished or decreased transduction by at least 50% in AAV1. Surprisingly, the T502S substitution did not affect transduction efficiency of wild-type AAV6. Furthermore, three of the AAV1 SIA binding site mutants—S472R, V473D, and N500E—escaped recognition by the anti-AAV1 capsid antibody ADK1a. These observations demonstrate that common key capsid surface residues dictate both virus binding and entry processes, as well as antigenic reactivity. This study identifies an important functional capsid surface “hot spot” dictating receptor attachment, transduction efficiency, and antigenicity which could prove useful for vector engineering.

IMPORTANCE
The adeno-associated virus (AAV) vector gene delivery system has shown promise in several clinical trials and an AAV1-based vector has been approved as the first gene therapy treatment. However, limitations still exist with respect to transduction efficiency and the detrimental effects of preexisting host antibodies. This study aimed to identify key capsid regions which can be engineered to overcome these limitations. A sialic glycan receptor recognition pocket was identified in AAV1 and its closely related AAV6, using X-ray crystallography. The site was confirmed by mutagenesis followed by cell binding and transduction assays. Significantly, residues controlling gene expression efficiency, as well as antibody escape variants, were also identified. This study thus provides, at the amino acid level, information for rational structural engineering of AAV vectors with improved therapeutic efficacy.
Effects of Filovirus Interferon Antagonists on Responses of Human Monocyte-Derived Dendritic Cells to RNA Virus Infection
Authors: Yen Benjamin C. , Basler Christopher F.
Published: March 2016

Dendritic cells (DCs) are major targets of filovirus infection
in vivo
. Previous studies have shown that the filoviruses Ebola virus (EBOV) and Marburg virus (MARV) suppress DC maturation
in vitro
. Both viruses also encode innate immune evasion functions. The EBOV VP35 (eVP35) and the MARV VP35 (mVP35) proteins each can block RIG-I-like receptor signaling and alpha/beta interferon (IFN-α/β) production. The EBOV VP24 (eVP24) and MARV VP40 (mVP40) proteins each inhibit the production of IFN-stimulated genes (ISGs) by blocking Jak-STAT signaling; however, this occurs by different mechanisms, with eVP24 blocking nuclear import of tyrosine-phosphorylated STAT1 and mVP40 blocking Jak1 function. MARV VP24 (mVP24) has been demonstrated to modulate host cell antioxidant responses. Previous studies demonstrated that eVP35 is sufficient to strongly impair primary human monocyte-derived DC (MDDC) responses upon stimulation induced through the RIG-I-like receptor pathways. We demonstrate that mVP35, like eVP35, suppresses not only IFN-α/β production but also proinflammatory responses after stimulation of MDDCs with RIG-I activators. In contrast, eVP24 and mVP40, despite suppressing ISG production upon RIG-I activation, failed to block upregulation of maturation markers or T cell activation. mVP24, although able to stimulate expression of antioxidant response genes, had no measurable impact of DC function. These data are consistent with a model where filoviral VP35 proteins are the major suppressors of DC maturation during filovirus infection, whereas the filoviral VP24 proteins and mVP40 are insufficient to prevent DC maturation.

IMPORTANCE
The ability to suppress the function of dendritic cells (DCs) likely contributes to the pathogenesis of disease caused by the filoviruses Ebola virus and Marburg virus. To clarify the basis for this DC suppression, we assessed the effect of filovirus proteins known to antagonize innate immune signaling pathways, including Ebola virus VP35 and VP24 and Marburg virus VP35, VP40, and VP24, on DC maturation and function. The data demonstrate that the VP35s from Ebola virus and Marburg virus are the major suppressors of DC maturation and that the effects on DCs of the remaining innate immune inhibitors are minor.
CD8
+
T Cells Play a Bystander Role in Mice Latently Infected with Herpes Simplex Virus 1
Authors: Mott Kevin R. , Gate David , Matundan Harry H. , Ghiasi Yasamin N. , Town Terrence , Ghiasi Homayon
Published: March 2016

Based on an explant reactivation model, it has been proposed that CD8
+
T cells maintain latency in trigeminal ganglia (TG) of mice latently infected with herpes simplex virus 1 (HSV-1) [T. Liu, K. M. Khanna, X. Chen, D. J. Fink, and R. L. Hendricks, J Exp Med 191:1459–1466, 2000, doi:10.1084/jem.191.9.1459; K. M. Khanna, R. H. Bonneau, P. R. Kinchington, and R. L. Hendricks, Immunity 18:593-603, 2003, doi:10.1016/S1074-7613(03)00112-2]. In those studies, BALB/c mice were ocularly infected with an avirulent HSV-1 strain (RE) after corneal scarification. However, in our studies, we typically infect mice with a virulent HSV-1 strain (McKrae) that does not require corneal scarification. Using a combination of knockout mice, adoptive transfers, and depletion studies, we recently found that CD8α
+
dendritic cells (DCs) contribute to HSV-1 latency and reactivation in TG of ocularly infected mice (K. R. Mott, S. J. Allen, M. Zandian, B. Konda, B. G. Sharifi, C. Jones, S. L. Wechsler, T. Town, and H. Ghiasi, PLoS One 9:e93444, 2014, doi:10.1371/journal.pone.0093444). This suggested that CD8
+
T cells might not be the major regulators of HSV-1 latency in the mouse TG. To investigate this iconoclastic possibility, we used a blocking CD8 antibody and CD8
+
T cells in reactivated TG explants from mice latently infected with (i) the avirulent HSV-1 strain RE following corneal scarification or (ii) the virulent HSV-1 strain McKrae without corneal scarification. Independently of the strain or approach, our results show that CD8α
+
DCs, not CD8
+
T cells, drive latency and reactivation. In addition, adoptive transfer of CD8
+
T cells from wild-type (wt) mice to CD8α
−/−
mice did not restore latency to the level for wt mice or wt virus. In the presence of latency-associated transcript (LAT
(+)
; wt virus), CD8
+
T cells seem to play a bystander role in the TG. These bystander T cells highly express PD-1, most likely due to the presence of CD8α
+
DCs. Collectively, these results support the notion that CD8
+
T cells do not play a major role in maintaining HSV-1 latency and reactivation.

IMPORTANCE
This study addresses a fundamentally important and widely debated issue in the field of HSV latency—reactivation. In this article, we directly compare the effects of anti-CD8 antibody, CD8
+
T cells, LAT, and CD8α
+
DCs in blocking explant reactivation in TG of mice latently infected with avirulent or virulent HSV-1. Our data suggest that CD8
+
T cells are not responsible for an increase or maintenance of latency in ocularly infected mice. However, they seem to play a bystander role that correlates with the presence of LAT, higher subclinical reactivation levels, and higher PD-1 expression levels.
Intrauterine device infection causing concomitant streptococcal toxic shock syndrome and pelvic abscess withActinomyces odontolyticusbacteraemia
Authors: Wu Carolyn M Yu , Noska Amanda
Published: March 2016

Intrauterine devices (IUDs) are rarely associated with serious infections. We report an unusual concomitant infection of group AStreptococcus(GAS) causing toxic shock syndrome and pelvic abscess withActinomyces odontolyticusassociated with an IUD in a healthy 50-year-old patient. The IUD was subsequently removed and the patient recovered on the appropriate antibiotics. This case highlights the importance of clinicians’ high index of suspicion of an IUD infection and prompt removal of the infected foreign body to obtain source control.
Assessing comorbidity and correlates of wasting and stunting among children in Somalia using cross-sectional household surveys: 2007 to 2010
Authors: Kinyoki Damaris K , Kandala Ngianga-Bakwin , Manda Samuel O , Krainski Elias T , Fuglstad Geir-Arne , Moloney Grainne M , Berkley James A , Noor Abdisalan M
Published: March 2016

Objective

Wasting and stunting may occur together at the individual child level; however, their shared geographic distribution and correlates remain unexplored. Understanding shared and separate correlates may inform interventions. We aimed to assess the spatial codistribution of wasting, stunting and underweight and investigate their shared correlates among children aged 6–59 months in Somalia.

Setting

Cross-sectional nutritional assessments surveys were conducted using structured interviews among communities in Somalia biannually from 2007 to 2010. A two-stage cluster sampling methodology was used to select children aged 6–59 months from households across three livelihood zones (pastoral, agropastoral and riverine). Using these data and environmental covariates, we implemented a multivariate spatial technique to estimate the codistribution and divergence of the risks and correlates of wasting and stunting at the 1×1 km spatial resolution.

Participants

73 778 children aged 6–59 months from 1066 survey clusters in Somalia.

Results

Observed pairwise child level empirical correlations were 0.30, 0.70 and 0.73 between weight-for-height and height-for-age; height-for-age and weight-for-age, and weight-for-height and weight-for-age, respectively. Access to foods with high protein content and vegetation cover, a proxy of rainfall or drought, were associated with lower risk of wasting and stunting. Age, gender, illness, access to carbohydrates and temperature were correlates of all three indicators. The spatial codistribution was highest between stunting and underweight with relative risk values ranging between 0.15 and 6.20, followed by wasting and underweight (range: 0.18–5.18) and lowest between wasting and stunting (range: 0.26–4.32).

Conclusions

The determinants of wasting and stunting are largely shared, but their correlation is relatively variable in space. Significant hotspots of different forms of malnutrition occurred in the South Central regions of the country. Although nutrition response in Somalia has traditionally focused on wasting rather than stunting, integrated programming and interventions can effectively target both conditions to alleviate common risk factors.
Who stops selling? A systematic analysis of ex-tobacco retailers
Authors: Feletto Eleonora , Burton Suzan , Williams Kelly , Fry Rae , Sutton Clare , Bagus Lachlan , Egger Sam
Published: March 2016

Objective

There is evidence that wide distribution of cigarettes contributes to smoking, and multiple commentators have called for a review of tobacco retailing. This study analyses retailers who stop selling cigarettes, why they do so, and discusses the implications for tobacco control.

Method

An audit of tobacco retailers in the Australian state of NSW was used to identify retailers who had stopped selling tobacco, and they were then compared with current retailers to determine how many, and what types of outlets stop selling tobacco. Attempts were made to contact and interview all former tobacco retailers identified in three audited regions. In-depth interviews were conducted with 13 ex-tobacco retailers, or 31% of the subset of ex-tobacco retailers.

Results

Low-volume outlet types were over-represented as a proportion of retailers exiting the market, and some had resumed selling within 18 months of the audit. Low profits were often cited as a contributor to stopping; however, in all but one case, the decision to stop selling was also influenced by a significant change in business circumstances—either legislative or other business changes.

Conclusions

Few retailers stop selling tobacco while continuing in the same business, and those who stop disproportionately represent retailer types with low sales volume. The results suggest that legislative changes provide a window where retailers could be prompted to exit the market.
Canine parvovirus in vaccinated dogs: a field study
Authors: Miranda C. , Thompson G.
Published: March 2016

The authors report a field study that investigated the canine parvovirus (CPV) strains present in dogs that developed the disease after being vaccinated. Faecal samples of 78 dogs that have been vaccinated against CPV and later presented with clinical signs suspected of parvovirus infection were used. Fifty (64.1 per cent) samples tested positive by PCR for CPV. No CPV vaccine type was detected. The disease by CPV‐2b occurred in older and female dogs when compared with that by CPV‐2c. The clinical signs presented by infected dogs were similar when any of both variants were involved. In most cases of disease, the resulting infection by field variants occurred shortly after CPV vaccination. Two dogs that had been subjected to a complete vaccination schedule and presented with clinical signs after 10 days of vaccination, had the CPV‐2c variant associated. The phylogenetic studies showed a close relationship of the isolates in vaccinated dogs to European field strains. Despite the limited sample size in this study, the findings point to the significance of the continuous molecular typing of the virus as a tool to monitor the prevalent circulating CPV strains and access the efficacy of current vaccines. Adjustments on the vaccine types to be used may have to be evaluated again according to each epidemiological situation in order to achieve the dog's optimal immune protection against CPV.
Trends of elemental adsorption on graphene
Authors: Widjaja Hantarto , Altarawneh Mohammednoor , Jiang Zhong-Tao
Published: March 2016

Adding impurities or doping through adsorption is an effective way to tailor the properties of graphene-based materials. The capability of making predictions with regard to the trends of elemental adsorption on graphene is crucial to a better understanding of the more complex adsorption cases. It also provides useful guidelines for fabricating 2D graphene materials with novel properties. In this review, we show trends of elemental adsorption on graphene with elements of the periodic table, based on previous studies and supplemented with our recent calculations. We also discuss the effects of atomic ratios on some properties of this element-adsorbed graphene system. Trends of properties studied include binding energy, most stable site, adatom height, migration energy, Fermi energy shift, graphene distortion, magnetization, charge transfer, and electronic energy band gap at Fermi energy. Certainly, there is ample scope to investigate the electronic structures of elemental adsorption on graphene based on period and group of the periodic table, and atomic ratio.
Shock-Sensitivity in Shell-Like Structures: With Simulations of Spherical Shell Buckling
Authors: Thompson J. Michael T. , Sieber Jan
Published: March 2016

Under increasing compression, an unbuckled shell is in a metastable state which becomes increasingly precarious as the buckling load is approached. So to induce premature buckling, a lateral disturbance will have to overcome a decreasing energy barrier which reaches zero at buckling. Two archetypal problems that exhibit a severe form of this behavior are the axially-compressed cylindrical shell and the externally pressurized spherical shell. Focusing on the cylinder, a nondestructive technique was recently proposed to estimate the “shock-sensitivity” of a laboratory specimen using a lateral probe to measure the nonlinear load-deflection characteristic. If a symmetry-breaking bifurcation is encountered on the path, computer simulations showed how this can be suppressed by a controlled secondary probe. Here, we extend our understanding by assessing in general terms how a single control can capture remote saddle solutions: in particular, how a symmetric probe could locate an asymmetric solution. Then, more specifically, we analyze the spherical shell with point and ring probes, to test the procedure under challenging conditions to assess its range of applicability. Rather than a bifurcation, the spherical shell offers the challenge of a destabilizing fold (limit point) under the rigid control of the probe.
Analytic Integrability of Two Lopsided Systems
Authors: Li Feng , Yu Pei , Liu Yirong
Published: March 2016

In this paper, we present two classes of lopsided systems and discuss their analytic integrability. The analytic integrable conditions are obtained by using the method of inverse integrating factor and theory of rotated vector field. For the first class of systems, we show that there are [Formula: see text] small-amplitude limit cycles enclosing the origin of the systems for [Formula: see text], and ten limit cycles for [Formula: see text]. For the second class of systems, we prove that there exist [Formula: see text] small-amplitude limit cycles around the origin of the systems for [Formula: see text], and nine limit cycles for [Formula: see text].
Limit Cycle Analysis in a Class of Hybrid Systems
Authors: Favela-Contreras Antonio , Beltrán-Carbajal Francisco , Piñón Alejandro , Raimondi Angelo
Published: March 2016

Hybrid systems are those that inherently combine discrete and continuous dynamics. This paper considers the hybrid system model to be an extension of the discrete automata associating a continuous evolution with each discrete state. This model is called the hybrid automaton. In this work, we achieve a mathematical formulation of the steady state and we show a way to obtain the initial conditions region to reach a specific limit cycle for a class of uncoupled and coupled continuous-linear hybrid systems. The continuous-linear term is used in the sense of the system theory and, in this sense, continuous-linear hybrid automata will be defined. Thus, some properties and theorems that govern the hybrid automata dynamic behavior to evaluate a limit cycle existence have been established; this content is explained under a theoretical framework.
Two-Stage Stratified Randomized Response Model with Fuzzy Numbers
Authors: Khan Mohammad Faisal , Gupta Neha , Ali Irfan
Published: March 2016

We consider an allocation problem in two-stage stratified Warner’s randomized response model and minimize the variance subject to cost constraint. The costs (measurement costs and total budget of the survey) in the cost constraint are assumed as fuzzy numbers, in particular triangular and trapezoidal fuzzy numbers due to the ease of use. The problem formulated is solved by using Lagrange multipliers technique and the optimum allocation obtained in the form of fuzzy numbers is converted into crisp form usingα-cut method at a prescribed value ofα. An illustrative numerical example is presented to demonstrate the proposed problem.
Assessment of Potential Live Kidney Donors and Computed Tomographic Renal Angiograms at Christchurch Hospital
Authors: Alsulaiman Thamer , Mark Stephen , Armstrong Sarah , McGregor David
Published: March 2016

Aims. To examine the outcome of potential live kidney donors (PLKD) assessment program at Christchurch Hospital and, also, to review findings of Computed Tomographic (CT) renal angiograms that led to exclusion in the surgical assessment.Methods. Clinical data was obtained from the database of kidney transplants, Proton. Radiological investigations were reviewed using the hospital database, Éclair. The transplant coordinator was interviewed to clarify information about PLKD who did not proceed to surgery, and a consultant radiologist was interviewed to explain unfavorable findings on CT renal angiograms.Results. 162 PLKD were identified during the period January 04–June 08. Of those, 65 (40%) proceeded to have nephrectomy, 15 were accepted and planned to proceed to surgery, 13 were awaiting further assessment, and 69 (42.5%) did not proceed to nephrectomy. Of the 162 PLKD, 142 (88%) were directed donors. The proportion of altruistic PLKD who opted out was significantly higher than that of directed PLKD (45% versus 7%,P=0.00004).Conclusions. This audit demonstrated a positive experience of live kidney donation at Christchurch Hospital. CT renal angiogram can potentially detect incidental or controversial pathologies in the kidney and the surrounding structures. Altruistic donation remains controversial with higher rates of opting out.