bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of happiness on managers' contextual and task performance
Authors: Hosie Peter , Willemyns Michael , Sevastos Peter
Published: April 2012

The ‘happy–productive worker thesis’ has long intrigued organisational researchers and practitioners. Despite mixed empirical evidence from decades of research, there is support in the literature for this thesis. An account is provided on a variation on the enduring debate of the happiness–productivity theme, to support an emerging ‘happy–performing managers proposition’. An empirical study is presented to establish the dimensions of managers' job happiness (operationalised as affective well‐being and intrinsic job satisfaction) associated with contextual and task performance. The emphasis was on investigating an aspect of human behaviour with the potential to enhance managerial performance. These findings inform the broader debate on what determines the job performance of managers.
Prograde and retrograde black holes: whose jet is more powerful?
Authors: Tchekhovskoy Alexander , McKinney Jonathan C.
Published: April 2012

The outflow efficiency (η) from black hole (BH) accretion disc systems is known to depend upon both the BH spin (a) and the amount of large-scale magnetic flux threading the BH and disc. Semi-analytical flux-trapping models suggest retrograde BHs should trap much more large-scale magnetic flux near the BH leading to much higher η than for prograde BHs. We self-consistently determine the amount of large-scale magnetic flux trapped by rapidly spinning (a=−0.9 and 0.9) BHs using global 3D time-dependent non-radiative general relativistic magnetohydrodynamic simulations of thick (h/r≈ 0.3–0.6) discs. We find that BH-trapped flux builds up until it is strong enough to disrupt the inner accretion disc. Contrary to prior flux-trapping models, which do not include the back-reaction of magnetic flux on the disc, our simulations show prograde BHs trap more magnetic flux, leading to about three times higher η than retrograde BHs for |a|= 0.9. Both spin orientations can produce highly efficient jets, η∼ 100 per cent, with increasing η for increasing disc thickness. The similarity of η for prograde and retrograde BHs makes it challenging to infer the sign of a based on jet energetics alone.
Modelling the multiband spectrum of IGR J17177−3656
Authors: Ma Renyi
Published: April 2012

The correlation between radio and X-ray luminosity in the hard state of black hole X-ray binaries is important for unveiling the relation between the accretion flow and the jets. In this Letter, we have modelled the quasi-simultaneous multiband observations of a recently discovered transient X-ray source, IGR J17177−3656. It is found that the source is probably an outlier following the steep radio/X-ray correlation rather than an outlier in the transition region as suggested by Paizis et al. It is also found that the multiband spectrum can be successfully modelled by the luminous hot accretion flow (LHAF) but less likely by the advection dominated accretion flow. Our results support the point that LHAF can explain the steep radio/X-ray correlation.
p38β MAP Kinase as a Therapeutic Target for Pancreatic Cancer
Authors: Singh Abhay Kumar , Pandey Roshan , Gill Kamaldeep , Singh Ratnakar , Saraya Anoop , Chauhan Shyam S. , Yadav Savita , Pal Sujoy , Singh Nidhi , Dey Sharmistha
Published: April 2012

Pancreatic cancer is very difficult to diagnose in its early stage. Molecular marker and imaging have not proven to be accurate modalities for screening of pancreatic cancer. This study aims to develop p38β as a protein marker for pancreatic cancer and to design peptide inhibitor against the same. The serum p38β level of pancreatic cancer (n = 35; 5.06 μg/mL) was twofold higher compared to that of the chronic pancreatitis (n = 10; 2.92 μg/mL) and matched normal control (n = 10; 2.86 μg/ml) (p < 0.0005). Peptide inhibitors were designed to inhibit the activity of p38β and the kinetic assay had shown the dissociation constant, (KD) to be 3.16 × 10−8 M and IC50, 25 nM by Surface Plasmon Resonance (SPR) and Enzyme ‐Linked Immunosorbent Assay (ELISA), respectively. The peptide inhibitor also significantly reduced viability and induced cytotoxicity in Human Pancreatic carcinoma epithelial‐like cell line (PANC‐1) cells.
Perceptual Changes and Drivers of Liking in High Protein Extruded Snacks
Authors: Kreger Joseph W. , Lee Youngsoo , Lee Soo‐Yeun
Published: April 2012

Abstract:  Increasing the amount of protein in snack foods can add to their satiating ability, which aligns with many health‐based trends currently seen in the food industry. Understanding the effect of adding high levels of protein in a food matrix is essential for product development. The objective for this research was to determine the effects of varying protein type and level on the sensory‐related aspects of a model extruded snack food. Independent variables in the design of the snacks were the level of total protein and the protein type in the formulation. The level of protein ranged from 28% to 43% (w/w) in 5% increments. The protein type varied in the ratio of whey to soy protein ranging from 0: 100 to 100: 0, in 25% increments. Descriptive analysis was conducted on the samples to profile their sensory characteristics. Protein type was found to be the predominant variable in differentiating the sensory characteristics of the samples. Soy protein imparted nutty, grainy aromas‐by‐mouth, and increased expansion during processing, resulting in a lighter, crispier texture. Whey protein imparted dairy related aromas‐by‐mouth and inhibited expansion during processing, resulting in a more dense, crunchy texture. Separately, 100 consumers rated their acceptance of the samples using the 9‐point hedonic scale. It was found that protein type was also the predominant variable in affecting acceptance, with some clusters of consumers preferring samples comprised of soy protein, and others preferring samples with whey. Food product developers can use these findings to predict changes in a similar food product by varying protein level or protein type.

Practical Application:  This work shows how the perceivable appearance, aroma, and texture characteristics of puffed snack foods change when adding protein or changing the protein type. The type of protein incorporated was shown to have major effects on the characteristics of the snacks, partially because of their impact on how much the snacks puffed during processing. The findings from this research can help develop acceptable products that incorporate high levels of protein to be aligned with current health trends in the market.
Chitosan‐based Edible Coatings for Quality Preservation of Postharvest Whiteleg Shrimp (Litopenaeus vannamei)
Authors: Huang Jianying , Chen Qunchao , Qiu Miao , Li Siqi
Published: April 2012

Abstract:  Postharvest shrimp is highly susceptible to both microbiological spoilage and endogenous enzymatic browning, so it should be preserved properly using effective and appropriate methods. The effects of 1.0% and 1.5% O‐carboxymethyl chitosan (CMC) and 1.0% and 1.5% chitosan (CH) coatings on the quality changes of whiteleg shrimp (Litopenaeus vannamei) during refrigerated storage (0 ± 1 °C) of 10 d were investigated. The pretreatment with CMC and CH solution (1.0% or 1.5%) retarded growth of psychrophilic bacteria throughout storage in comparison with the control (P < 0.05). The lower increases in pH and total volatile base (TVB) content were obtained in the shrimp treated with CMC and CH solution at both levels, compared with the control samples (P < 0.05). Loss in freshness and melanosis decreased after the shrimp was treated with CMC and CH. In addition, CMC and CH (1.0% or 1.5%) showed inhibitory activity toward total viable bacteria counts of white shrimp in a dose‐dependent manner. Therefore, chitosan and O‐carboxymethyl chitosan can be used as promising melanosis inhibitors as well as antimicrobial agents during refrigerated storage.

Practical Application:  The main practical application behind the development of chitosan (CH) and O‐carboxymethyl chitosan (CMC) used to preserve postharvest whiteleg shrimp lies with the fact that these polysaccharides represent a renewable source of natural biodegradable polymers and meet with the emergence of more and more food safety problems. Both CMC and CH can be used as food preservatives to extend shrimp shelf life. However, CMC is more convenient due to its solubility. In the future, CMC will be used in the food processing industry because of its soluble, compatible, antimicrobial, and antioxidative characteristics.
Alkaloids from Areca (Betel) Nuts and Their Effects on Human Sperm Motility In Vitro
Authors: Yuan Jingsong , Yang Dajian , Liang Yonghong , Gao Wenping , Ren Zhipeng , Zeng Wei , Wang Baorong , Han Jian , Guo Dean
Published: April 2012

Abstract:  An improved high‐performance liquid chromatography (HPLC) method was established to rapidly and simultaneously determine 3 main alkaloids (arecoline, arecaidine, and guvacine) in areca (betel) nuts (AN), and 12 AN samples from the main betel palm growing areas on the Chinese Mainland were collected and determined. Semen samples from acceptable volunteers were treated in vitro with different concentrations of the 3 alkaloids to evaluate the effects on sperm motility (SM). Highly motile spermatozoa were selected from the samples and divided into 5 equal fractions. Various concentrations of each alkaloid were added to 4 of the 5 fractions, and 1 fraction was used as a control. All fractions were incubated for 4 h. A computer‐aided sperm analysis system was used to measure 5 SM parameters, motility, average path velocity, straight‐line velocity, curvilinear velocity, linearity, and amplitude of lateral head displacement. The results showed that the contents of the amount of alkaloids in AN differed markedly in different places in China and were higher in the kernel than in the husk, and higher in dried AN than in fresh AN. Arecoline had the strongest reduction effect on human SM and the effect was strongly dose dependent. Arecaidine had a much weaker reduction effect than arecoline, and guvacine had the least reduction effect. These findings also demonstrate that betel quid could have adverse effects on the gonadal functions of betel quid consumers.
Microbial Composition of the Korean Traditional Food “kochujang” Analyzed by a Massive Sequencing Technique
Authors: Nam Young‐Do , Park So‐lim , Lim Seong‐Il
Published: April 2012

Abstract:  Kochujang is a traditional Korean fermented food that is made with red pepper, glutinous rice, salt, and soybean. Kochujang is fermented by naturally occurring microorganisms through which it obtains various health‐promoting properties. In this study, the bacterial diversities of 9 local and 2 commercial brands of kochujang were analyzed with a barcoded pyrosequencing technique targeting the hyper‐variable regions V1/V2 of the 16S rRNA gene. Through the analysis of 13524 bacterial pyrosequences, 223 bacterial species were identified, most of which converged on the phylum Firmicutes (average 93.1%). All of the kochujang samples were largely populated (>90.9% of abundance) by 12 bacterial families, and Bacillaceae showed the highest abundance in all but one sample. Bacillus subtilis and B. licheniformis were the most dominant bacterial species and were broadly distributed among the kochujang samples. Each sample contained a high abundance of region‐specific bacterial species, such as B. sonorensis, B. pumilus, Weissella salipiscis, and diverse unidentified Bacillus species. Phylotype‐ and phylogeny‐based community comparison analysis showed that the microbial communities of the two commercial brands were different from those of the local brands. Moreover, each local brand kochujang sample had region‐specific microbial community reflecting the manufacturing environment.
Neoadjuvant chemoradiotherapy and surgery as treatment for oral maxillary squamous cell carcinoma in a dog
Authors: Mestrinho LA , Bernardo E , Niza MMRE , Lloret A , Buracco P
Published: April 2012

A gingival maxillary squamous cell carcinoma was diagnosed in a 12‐year‐old male Yorkshire Terrier. After a complete diagnostic work‐up, including a computed tomography scan, the tumour was staged as T3bN1aM0 and considered non‐resectable at presentation. The combination of neoadjuvant megavoltage radiotherapy and neoadjuvant and adjuvant chemotherapy with carboplatin and doxorubicin decreased the size of the tumour, allowing for surgery. The dog was free from local disease for 421 days after which it was euthanased at the owners' request.
Glycerol as a substrate for aerobic succinate production in minimal medium with Corynebacterium glutamicum
Authors: Litsanov Boris , Brocker Melanie , Bott Michael
Published: April 2012

Corynebacterium glutamicum, an established microbial cell factory for the biotechnological production of amino acids, was recently genetically engineered for aerobic succinate production from glucose in minimal medium. In this work, the corresponding strains were transformed with plasmid pVWEx1‐glpFKD coding for glycerol utilization genes from Escherichia coli. This plasmid had previously been shown to allow growth of C. glutamicum with glycerol as sole carbon source. The resulting strains were tested in minimal medium for aerobic succinate production from glycerol, which is a by‐product in biodiesel synthesis. The best strain BL‐1/pVWEx1‐glpFKD formed 79 mM (9.3 g l−1) succinate from 375 mM glycerol, representing 42% of the maximal theoretical yield under aerobic conditions. A specific succinate production rate of 1.55 mmol g−1 (cdw) h−1 and a volumetric productivity of 3.59 mM h−1 were obtained, the latter value representing the highest one currently described in literature. The results demonstrate that metabolically engineered strains of C. glutamicum are well suited for aerobic succinate production from glycerol.
Do Transparent Firms Pay out More Cash to Shareholders? Evidence from International Cross‐Listings
Authors: Petrasek Lubomir
Published: April 2012

This paper examines the relation between agency costs and payout policy using a sample of 755 firms that cross‐list shares abroad. Firms increase cash payouts to shareholders by about 9% of earnings after cross‐listing on exchanges with high standards of transparency and shareholder protection. The shift in payout policy is more pronounced in firms controlled by management. No shift is observed if shareholder protection in the country of incorporation is already strong, or if the host exchange does not mandate additional disclosure. The findings support the theory that high corporate payouts are the outcome of transparency and shareholder protection.
Repeated suicide attempts among suicidal cases: Outcome of one‐year follow‐up
Authors: Lee Yu , Lin Pao‐Yen , Yeh Wei‐Chiang , Chiu Nien‐Mu , Hung Chi‐Fa , Huang Tsan‐Yu , Hsu Su‐Ting , Lee Chun‐Yi , Chen Chien‐Chih , Lin Huang‐Chi , Chong Mian‐Yoon
Published: April 2012

Introduction

To assess the mortality rates and risk factors involved in repeated suicide attempts.

Methods

Patients with a record of suicidal attempts were recruited from the emergency department of a medical center in Taiwan from August 2004 to July 2006. Their conditions were prospectively monitored for 12 months. The suicidal intention of the patients was ascertained using structured interview questions while their psychiatric diagnosis and depressive symptoms were assessed through the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression.

Results

A total of 46 males and 99 females were recruited and 70% (n = 102) of them were successfully monitored for one year. Among them, 38.2% had repeated suicide attempt(s) and 3.4% died as a result of suicide. Severe depression, aggression and positive suicide ideation were significantly associated with the repeated suicide attempts. Pessimistic repeaters had more previous suicide attempt(s) than the others.

Conclusion

 A higher rate of repeated suicide attempts and mortality rates were found among suicide attempters from the one‐year outcome. Repeated suicide attempts increased the risk of mortality while persevering suicide thoughts and previous suicide attempts were risks for repeated suicidal behavior.
Polymorphism of the serotonin transporter gene (5‐HTTLPR) in major depressive disorder patients in Malaysia
Authors: Mohamed Saini Suriati , Muhamad Radzi Azizah , Abdul Rahman Abdul Hamid
Published: April 2012

Introduction

The serotonin transporter promoter (5‐HTTLPR) is a potential susceptibility locus in the pathogenesis of major depressive disorder. However, data from Malaysia is lacking. The present study aimed to determine the association between the homozygous short variant of the serotonin transporter promoter gene (5‐HTTLPR) with major depressive disorder.

Methods

This is a candidate gene case‐control association study. The sample consists of 55 major depressive disorder probands and 66 controls. They were Malaysian descents and were unrelated. The Axis I diagnosis was determined using Mini International Neuropsychiatric Interview (M.I.N.I.). The control group comprised healthy volunteers without personal psychiatric history and family history of mood disorders. Participants' blood was sent to the Institute Medical Research for genotyping.

Results

The present study failed to detect an association between 5‐HTTLPR ss genotype with major depressive disorder (χ2 = 3.67, d.f. = 1, P = 0.055, odds ratio 0.25, 95% confidence interval = 0.07‐1.94). Sub‐analysis revealed that the frequency of l allele in healthy controls was higher (78.0%) than that of Caucasian and East Asian population. However, in view of the small sample size this study may be prone to type II error (and type I error).

Discussion

This preliminary study suggests that the homozygous short variant of the 5‐HTTLPR did not appear to be a risk factor for increasing susceptibility to major depressive disorder.
Interrogative suggestibility: Was it just compliance or a genuine false memory?
Authors: Mastroberardino Serena , Marucci Francesco S.
Published: April 2012

Purpose.Interrogative suggestibility, as measured by the Gudjonsson Suggestibility Scales (GSS), is an independent form of suggestibility arising in the forensic/legal context. So far, an unresolved issue that may have different implications when measuring suggestibility is to what extent the scales measure internalization of suggested materials or just compliance with the interrogator.

Methods. Internalization of suggested materials and compliance were here measured using a source identification task. In Experiment 1, participants were administered the GSS2 and immediately afterwards asked to perform the source identification task on the items presented in the scale. In Experiment 2, half of the participants were administered the source identification task immediately and half after a 24‐hr delay.

Results. In both experiments a higher proportion of compliant responses were found. Participants internalized more suggested information after questioning (Yield 1) and made more compliant responses after negative feedback (Shift). In Experiment 2, participants in the delayed condition internalized less material than those in the immediate condition.

Conclusions: Different processes appear to underlie Yield 1 and Shift scores in the GSS2. The former may include both internalization of suggested materials and compliance, while the second appears to be mostly due to compliance with the interrogator. When administering the GSS2 in a forensic/legal context as vulnerability predictor for making false confessions, or proneness to develop false memories through the internalization of suggested material, including a source identification task may provide additional information on the type of coping style and memory characteristics of the examinee.
Solar cell with built-in charge: Experimental studies of diode model parameters
Authors: Sablon Kimberly A. , Little John W. , Sergeev Andrei , Vagidov Nizami , Mitin Vladimir
Published: April 2012

Quantum dots acquire built-in charge due to selective n-doping of the interdot space. The quantum dots with built-in charge (Q-BIC) increase electron coupling to IR radiation and suppress photoelectron capture, which in turn decrease the recombination via quantum dots. To investigate effects of the built-in-dot charge on recombination processes and device performance, the light and dark I–V characteristics and their temperature dependences of Q-BIC solar cells are measured. Employing the diode model, the data are analyzed in terms of the ideality factor, shunt resistance, and reverse saturation current. The authors compare the n-doped Q-BIC solar cells with the GaAs p-i-n reference cell, undoped, and p-doped devices. The analysis provides a qualitative description of the effect of doping on carrier kinetics and transport. The authors show that n-doping substantially reduces the recombination via quantum dots.
Evaluation of the geometric accuracy of surrogate‐based gated VMAT using intrafraction kilovoltage x‐ray images
Authors: Li Ruijiang , Mok Edward , Han Bin , Koong Albert , Xing Lei
Published: April 2012

Purpose:

To evaluate the geometric accuracy of beam targeting in external surrogate‐based gated volumetric modulated arc therapy (VMAT) using kilovoltage (kV) x‐ray images acquired during dose delivery.

Methods:

Gated VMAT treatments were delivered using a Varian TrueBeam STx Linac for both physical phantoms and patients. Multiple gold fiducial markers were implanted near the target. The reference position was created for each implanted marker, representing its correct position at the gating threshold. The gating signal was generated from the RPM system. During the treatment, kV images were acquired immediately before MV beam‐on at every breathing cycle, using the on‐board imaging system. All implanted markers were detected and their 3D positions were estimated using in‐house developed software. The positioning error of a marker is defined as the distance of the marker from its reference position for each frame of the images. The overall error of the system is defined as the average over all markers. For the phantom study, both sinusoidal motion (1D and 3D) and real human respiratory motion was simulated for the target and surrogate. In the baseline case, the two motions were synchronized for the first treatment fraction. To assess the effects of surrogate–target correlation on the geometric accuracy, a phase shift of 5% and 10% between the two motions was introduced. For the patient study, intrafraction kV images of five stereotactic body radiotherapy (SBRT) patients were acquired for one or two fractions.

Results:

For the phantom study, a high geometric accuracy was achieved in the baseline case (average error: 0.8 mm in the superior–inferior or SI direction). However, the treatment delivery is prone to geometric errors if changes in the target–surrogate relation occur during the treatment: the average error was increased to 2.3 and 4.7 mm for the phase shift of 5% and 10%, respectively. Results obtained with real human respiratory curves show a similar trend. For a target with 3D motion, the technique is able to detect geometric errors in the left–right (LR) and anterior–posterior (AP) directions. For the patient study, the average intrafraction positioning errors are 0.8, 0.9, and 1.4 mm and 95th percentile errors are 1.7, 2.1, and 2.7 mm in the LR, AP, and SI directions, respectively.

Conclusions:

The correlation between external surrogate and internal target motion is crucial to ensure the geometric accuracy of surrogate‐based gating. Real‐time guidance based on kV x‐ray images overcomes the potential issues in surrogate‐based gating and can achieve accurate beam targeting in gated VMAT.
FDA's Approach to Regulation of Products of Nanotechnology
Authors: Hamburg Margaret A.
Published: April 2012

A broadly inclusive initial approach may become more nuanced in light of experience, scientific information, and public input.
Nanoparticle Treatment Reverses Cerebral Palsy in Rabbits
Authors: Miller Greg
Published: April 2012

This week in
Science Translational Medicine
, researchers describe a treatment that restores nearly normal movement to rabbits with an induced form of cerebral palsy when given a few hours after birth.
Biofuels and City Air: A Marginal Effect
Authors: Service Robert F.
Published: April 2012

The first citywide air quality study of its kind, reported at the meeting, suggests that unless more than 26% of cars switch to biofuels, it will have negligible effect on air pollution.
New Genetic Letters Augment DNA, and Soon Perhaps Life
Authors: Service Robert F.
Published: April 2012

At the ACS meeting, a pair of research groups reported that they now have synthetic nucleotides that can be incorporated into DNA and can be copied with near perfection by enzymes that copy natural DNA.
Development of a Fourfold Multiplexed Opsonophagocytosis Assay for Pneumococcal Antibodies against Additional Serotypes and Discovery of Serological Subtypes in Streptococcus pneumoniae Serotype 20
Authors: Burton Robert L. , Nahm Moon H.
Published: April 2012

Opsonophagocytic killing assays (OPAs) are important
in vitro
surrogate markers of protection in vaccine studies of
Streptococcus pneumoniae
. We have previously reported the development of a 4-fold multiplexed OPA (MOPA) for the 13 serotypes in Prevnar 13. Because new conjugate vaccines with increased valence are being developed, we developed 4-fold MOPAs for an additional 13 serotypes: serotypes 6C and 6D, plus the 11 serotypes contained in Pneumovax but not in Prevnar 13. A high level of nonspecific killing (NSK) was observed for three serotypes (10A, 15B, and 33F) in multiple batches of baby rabbit complement. The NSK could be reduced by preadsorbing the complement with encapsulated, as well as unencapsulated, pneumococcal strains. The MOPA results compared well with the results of single-serotype OPA for all serotypes except for serotype 3. For serotype 3, the results obtained from the MOPA format were ∼40% higher than those of the single-serotype format. Interassay precision of MOPA was determined with 5 serum samples, and the coefficient of variation was generally <30% for all serotypes. MOPA was also specific for all serotypes except for serotype 20; i.e., free homologous polysaccharide (PS), but not unrelated PS, could completely and efficiently inhibit opsonization. However, serotype 20 PS from ATCC could efficiently inhibit opsonization of one serotype 20 target strain but not three other type 20 target strains even at a high (>80 mg/liter) PS concentration. This suggests the presence of serologic heterogeneity among serotype 20 strains.
Mutations in the GM1 Binding Site of Simian Virus 40 VP1 Alter Receptor Usage and Cell Tropism
Authors: Magaldi Thomas G. , Buch Michael H. C. , Murata Haruhiko , Erickson Kimberly D. , Neu Ursula , Garcea Robert L. , Peden Keith , Stehle Thilo , DiMaio Daniel
Published: April 2012

Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM1 more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution.
Elite Controllers with Low to Absent Effector CD8
+
T Cell Responses Maintain Highly Functional, Broadly Directed Central Memory Responses
Authors: Ndhlovu Zaza M. , Proudfoot Jacqueline , Cesa Kevin , Alvino Donna Marie , McMullen Ashley , Vine Seanna , Stampouloglou Eleni , Piechocka-Trocha Alicja , Walker Bruce D. , Pereyra Florencia
Published: April 2012

Analyses of the breadth and specificity of virus-specific CD8
+
T cell responses associated with control of HIV have largely relied on measurement of cytokine secretion by effector T cells. These have resulted in the identification of HIV elite controllers with low or absent responses in which non-T-cell mechanisms of control have been suggested. However, successful control of HIV infection may be associated with central memory T cells, which have not been consistently examined in these individuals. Gag-specific T cells were characterized using a peptide-based cultured enzyme-linked immunosorbent spot assay (ELISpot). Peripheral blood mononuclear cells from HIV elite controllers (
n
= 10), progressors (
n
= 12), and antiretroviral-treated individuals (
n
= 9) were cultured with overlapping peptides for 12 days. Specificity was assessed by tetramer staining, functional features of expanded cells were assessed by cytokine secretion, and virus inhibition and phenotypic characteristics were assessed by cell sorting and coculture assays. After peptide stimulation, elite controllers showed a greater number of previously undetectable (new) responses compared to progressors (
P
= 0.0008). These responses were highly polyfunctional, with 64.5% of responses having 3 to 5 functions. Expandable epitope-specific CD8
+
T cells from elite controllers had strong virus inhibitory capacity and predominantly displayed a central memory phenotype. These data indicate that elite controllers with minimal T cell responses harbor a highly functional, broadly directed central memory T cell population that is capable of suppressing HIV
in vitro
. Comprehensive examination of this cell population could provide insight into the immune responses associated with successful containment of viremia.
Evasion of the Innate Immune Response: the Old World Alphavirus nsP2 Protein Induces Rapid Degradation of Rpb1, a Catalytic Subunit of RNA Polymerase II
Authors: Akhrymuk Ivan , Kulemzin Sergey V. , Frolova Elena I.
Published: April 2012

The Old World alphaviruses are emerging human pathogens with an ability to cause widespread epidemics. The latest epidemic of Chikungunya virus, from 2005 to 2007, affected over 40 countries in Africa, Asia, and Europe. The Old World alphaviruses are highly cytopathic and known to evade the cellular antiviral response by inducing global inhibition of transcription in vertebrate cells. This function was shown to be mediated by their nonstructural nsP2 protein; however, the detailed mechanism of this phenomenon has remained unknown. Here, we report that nsP2 proteins of Sindbis, Semliki Forest, and Chikungunya viruses inhibit cellular transcription by inducing rapid degradation of Rpb1, a catalytic subunit of the RNAPII complex. This degradation of Rpb1 is independent of the nsP2-associated protease activity, but, instead, it proceeds through nsP2-mediated Rpb1 ubiquitination. This function of nsP2 depends on the integrity of the helicase and
S
-adenosylmethionine (SAM)-dependent methyltransferase-like domains, and point mutations in either of these domains abolish Rpb1 degradation. We go on to show that complete degradation of Rpb1 in alphavirus-infected cells occurs within 6 h postinfection, before other previously described virus-induced changes in cell physiology, such as apoptosis, autophagy, and inhibition of STAT1 phosphorylation, are detected. Since Rpb1 is a subunit that catalyzes the polymerase reaction during RNA transcription, degradation of Rpb1 plays an indispensable role in blocking the activation of cellular genes and downregulating cellular antiviral response. This indicates that the nsP2-induced degradation of Rpb1 is a critical mechanism utilized by the Old World alphaviruses to subvert the cellular antiviral response.
Glycoprotein B of Herpes Simplex Virus 2 Has More than One Intracellular Conformation and Is Altered by Low pH
Authors: Muggeridge Martin I.
Published: April 2012

The crystal structure of herpes simplex virus (HSV) gB identifies it as a class III fusion protein, and comparison with other such proteins suggests this is the postfusion rather than prefusion conformation, although this is not proven. Other class III proteins undergo a pH-dependent switch between pre- and postfusion conformations, and a low pH requirement for HSV entry into some cell types suggests that this may also be true for gB. Both gB and gH undergo structural changes at low pH, but there is debate about the extent and significance of the changes in gB, possibly due to the use of different soluble forms of the protein and different assays for antigenic changes. In this study, a complementary approach was taken, examining the conformations of full-length intracellular gB by quantitative confocal microscopy with a panel of 26 antibodies. Three conformations were distinguished, and low pH was found to be a major influence. Comparison with previous studies indicates that the intracellular conformation in low-pH environments may be the same as that of the soluble form known as s-gB at low pH. Interestingly, the antibodies whose binding was most affected by low pH both have neutralizing activity and consequently must block either the function of a neutral pH conformation or its switch from an inactive form to an activated form. If one of the intracellular conformations is the fusion-active form, another factor required for fusion is presumably absent from wherever that conformation is present in infected cells so that inappropriate fusion is avoided.
Feline Tetherin Is Characterized by a Short N-Terminal Region and Is Counteracted by the Feline Immunodeficiency Virus Envelope Glycoprotein
Authors: Celestino Michele , Calistri Arianna , Del Vecchio Claudia , Salata Cristiano , Chiuppesi Flavia , Pistello Mauro , Borsetti Alessandra , Palù Giorgio , Parolin Cristina
Published: April 2012

Tetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2
504
and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2
504
is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2
504
failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2
504
was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2
504
also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.
Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial
Authors: Garg Amit X , Devereaux P J , Yusuf Salim , Cuerden Meaghan S , Parikh Chirag R , Coca Steven G , Walsh Michael , Cook Richard J , Whitlock Richard P , Noiseux Nicolas , Novick Richard J , Ou Yongning , Lamy Andre
Published: April 2012

Introduction

CORONARY is a large international randomised controlled trial comparing coronary artery bypass graft (CABG) surgery done with and without a bypass pump. Compared with on-pump, off-pump surgery may prevent acute kidney injury (AKI) in the short term and may better preserve kidney function 1 year following surgery. Secondary analyses may also clarify whether effects are similar in patients with and without pre-operative chronic kidney disease and whether AKI avoidance mediates preserved 1-year kidney function.

Methods and analysis

With respect to the study schedule, the last of 4752 patients from 79 sites in 19 countries were randomised in November 2011 to cardiac surgery performed with an on-pump or off-pump procedure. The authors will use regression models to compare the groups in the outcome of peri-operative AKI (per cent change in serum creatinine, ≥50% increase in serum creatinine) and 1-year kidney function (per cent change in estimated glomerular filtration rate (eGFR), ≥20% eGFR loss 1 year after surgery). The authors will use interaction terms in regression models to determine if there is a differential impact of the intervention in those with and without pre-existing chronic kidney disease. The authors will use regression-based tests to determine the proportion of the total effect of surgery type (off-pump vs on-pump CABG) on 1-year eGFR that is mediated by peri-operative AKI.

Ethics and dissemination

In the year 2009, the authors were competitively awarded a grant from the Canadian Institutes of Health Research to answer these kidney questions in CORONARY. Ethics approval was obtained for additional renal data collection in centres that agreed to study participation (>90% of participating centres). This collection began for patients enrolled after 1 January 2010. Remaining 1-year renal outcome data will be collected throughout 2012. Results will be reported in 2013.

Clinical trial registration number

NCT 00463294.
BANDWIDTH ENHANCEMENT IN CHAOTIC SEMICONDUCTOR LASERS WITH STRONG CHAOTIC OPTICAL INJECTION
Authors: YANG HUI-MIN
Published: April 2012

The bandwidth properties of chaotic signals generated by semiconductor lasers subject to strong chaotic optical injection (COI) are investigated numerically. The chaotic output of an injection master laser (ML) is injected into the slave laser (SL). The effects of feedback strength, injection strength and bias current on the bandwidth properties are discussed in detail. Some novel results are found, the bandwidth for SL increases with the injection strength firstly until reaches a maximum, and then decrease to approach the bandwidth of ML due to the injection-locking chaos synchronization. Large feedback strength and bias current contributes to higher maximum chaotic bandwidth in the range of injection strength. That is to say, for given parameters, optimal injection strength exists contributing to highest chaotic bandwidth, and moves to a large value for a large feedback strength and bias current, which is extremely useful for increasing the transmission rate of the optical chaotic communication system.
MAGNETOELASTIC PROPERTIES DEPENDENCE ON COMPRESSIVE STRESS IN 〈110〉 ORIENTED Tb0.45Dy0.55Fe1.95 POLYCRYSTALLINE ALLOYS WITH HIGH DRIVE LEVELS
Authors: ZHAO PEI , ZHOU YOU-HE
Published: April 2012

This paper presents the magnetoelastic properties for the relative high Tb / Dy composition ratio 〈110〉 oriented Tb 0.45 Dy 0.55 Fe 1.95 polycrystalline alloys. The simultaneous measurements of the magnetization and magnetostriction are carried out as a function of applied magnetic field range of 0 to 800 kA/m and compressive stress from 0 to 60 MPa. The maximum piezomagnetic coefficient $(d^{\rm max}_{33})$ and magnetostriction hysteresis (Wh) are obtained by differential calculation from the experimental curves. According to the increase of compressive stress, an obvious magnetostriction "jump" effect is observed, and the magnetostriction with the magnetic field of 800 kA/m (λ800) and magnetostriction hysteresis monotonously increase, while the maximum piezomagnetic coefficient increases first from 0 to 10 MPa and then decreases from 10 to 60 MPa. Here, results of measuring and calculating on this material are important complement to further understand the rules of the magnetoelastic properties in high Tb/Dy composition ratio Tb 0.45 Dy 0.55 Fe 1.95 polycrystalline alloys for theoretical approaches and modern technology applications.
PERFORMANCE EVALUATION OF SOURCE HETEROJUNCTION STRAINED CHANNEL GATE ALL AROUND NANOWIRE TRANSISTOR
Authors: HOSSEINI REZA , FATHIPOUR MORTEZA , FAEZ RAHIM
Published: April 2012

A Gate All Around Nanowire Transistor (GAA NWT) which employs source heterojunction and strained channel is proposed which improves device characteristics. A quantum mechanical transport approach based on nonequilibrium Green's function (NEGF) method in the frame work of effective mass theory is employed in this analysis. We evaluate the variation of the threshold voltage, the subthreshold slope, ON and OFF state currents when channel length decreases. It is shown that the source heterojunction strained channel GAA NWT gives high performance transistors values of the scaled transconductance and ON current that are greater than conventional silicon GAA NWT. Furthermore, comparison of switching delay τdand unity current gain frequency fTof the devices shows that the performance of source heterojunction strained channel GAA NWT is better than the conventional silicon GAA NWT.
RNA-binding protein IGF2BP2/IMP2 is required for laminin-β2 mRNA translation and is modulated by glucose concentration
Authors: Schaeffer Valerie , Hansen Kim M. , Morris David R. , LeBoeuf Renée C. , Abrass Christine K.
Published: April 2012

Laminin-β2 (LAMB2) is a critical component of the glomerular basement membrane as content of LAMB2 in part determines glomerular barrier permeability. Previously, we reported that high concentrations of glucose reduce expression of this laminin subunit at the translational level. The present studies were undertaken to further define systems that control Lamb2 translation and the effect of high glucose on those systems. Complementary studies were performed using in vitro differentiation of cultured podocytes and mesangial cells exposed to normal and elevated concentrations of glucose, and tissues from control and diabetic rats. Together, these studies provide evidence for regulation of Lamb2 translation by IMP2, an RNA binding protein that targets Lamb2 mRNA to the actin cytoskeleton. Expression of Imp2 itself is regulated by the transcription factor HMGA2, which in turn is regulated by the microRNA let-7b. Elevated concentrations of glucose increase let-7b, which reduces HMGA2 expression, in turn reducing IMP2 and LAMB2. Correlative changes in kidney tissues from control and streptozotocin-induced diabetic rats suggest these control mechanisms are operative in vivo and may contribute to proteinuria in diabetic nephropathy. To our knowledge, this is the first time that translation of Lamb2 mRNA has been linked to the actin cytoskeleton, as well as to specific RNA-binding proteins. These translational control points may provide new targets for therapy in proteinuric disorders such as diabetic nephropathy where LAMB2 levels are reduced.
Elevated urinary excretion of immunoglobulins in nonproteinuric patients with type 1 diabetes
Authors: Gohda Tomohito , Walker William H. , Wolkow Pawel , Lee Jung Eun , Warram James H. , Krolewski Andrzej S. , Niewczas Monika A.
Published: April 2012

Increased albuminuria is a hallmark of early diabetic nephropathy, whereas the role of immunoglobulins (Igs), such as IgG (its 1–4 subtypes), IgA, and IgM, different in charge and size, has not been examined in early nephropathy in the past due to lack of a sensitive and reliable method. Our study group consisted of subjects with type 1 diabetes (T1D) and normoalbuminuria ( n = 78), microalbuminuria ( n = 78), and of 75 healthy subjects (HS). A Luminex-based immunoassay (1,000 time more sensitive than nephelometry-based method) was validated for the urine matrix and used for the measurements of IgG1–4, IgA, and IgM in our study groups. The Luminex-based assay detected Igs in 87% of HS subjects and in 100% of T1D subjects. Recovery of known amounts of Igs added to urine was 92–118%. In the normoalbuminuria group, urinary concentrations of albumin, IgG2, IgA, and IgM were significantly higher than in HS, whereas in the microalbuminuria, further elevation of IgG2, IgG4, and IgA was the most pronounced. In all three groups, fractional excretion of Igs was at least 100 times lower than that of albumin. Fractional excretion of IgG2 was the highest among all Igs. We validated a sensitive method for measuring Igs in urine using Luminex. We found that elevated concentrations of Igs, particularly in IgG2 and IgA, is present in subjects with T1D and no proteinuria. Elevation of those particular Ig subtypes suggests a contribution of novel mechanisms in early diabetic nephropathy, different from charge and size barrier impairment.
How is a motor skill learned? Change and invariance at the levels of task success and trajectory control
Authors: Shmuelof Lior , Krakauer John W. , Mazzoni Pietro
Published: April 2012

The public pays large sums of money to watch skilled motor performance. Notably, however, in recent decades motor skill learning (performance improvement beyond baseline levels) has received less experimental attention than motor adaptation (return to baseline performance in the setting of an external perturbation). Motor skill can be assessed at the levels of task success and movement quality, but the link between these levels remains poorly understood. We devised a motor skill task that required visually guided curved movements of the wrist without a perturbation, and we defined skill learning at the task level as a change in the speed–accuracy trade-off function (SAF). Practice in restricted speed ranges led to a global shift of the SAF. We asked how the SAF shift maps onto changes in trajectory kinematics, to establish a link between task-level performance and fine motor control. Although there were small changes in mean trajectory, improved performance largely consisted of reduction in trial-to-trial variability and increase in movement smoothness. We found evidence for improved feedback control, which could explain the reduction in variability but does not preclude other explanations such as an increased signal-to-noise ratio in cortical representations. Interestingly, submovement structure remained learning invariant. The global generalization of the SAF across a wide range of difficulty suggests that skill for this task is represented in a temporally scalable network. We propose that motor skill acquisition can be characterized as a slow reduction in movement variability, which is distinct from faster model-based learning that reduces systematic error in adaptation paradigms.