bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon-Induced Protein Ifit2 Protects Mice from Infection of the Peripheral Nervous System by Vesicular Stomatitis Virus
Authors: Fensterl Volker , Wetzel Jaime L. , Sen Ganes C.
Published: July 2014

The interferon system provides the first line of host defense against virus infection. Mouse pathogenesis studies have revealed the importance of specific interferon-induced proteins in providing protection against specific viruses. We have previously reported that one such protein, Ifit2, protects neurons of the central nervous system from intranasal infection by the neurotropic rhabdovirus, vesicular stomatitis virus (VSV). Here, we demonstrate that Ifit2 protects the peripheral nervous system from VSV infection as well. In
Ifit2
−/−
mice, VSV, injected subcutaneously into the footpad, entered the proximal lymph node, where it replicated and infected the nodal nerve endings. The infection spread to the sciatic nerve, the spinal cord, and the brain, causing paralysis. In contrast, in the wild-type mice, although VSV replicated equally well in the lymph node, infection of the sciatic nerve and the rest of the nervous system was impaired, thus preventing paralysis. Ifit2 protected only the nervous system from VSV infection; other tissues were well protected even in
Ifit2
−/−
mice. These results indicate that Ifit2 is the interferon-induced protein that prevents VSV infection of neurons of both the peripheral and the central nervous systems, thus inhibiting the consequent neuropathy, but it is dispensable for protecting the cells of other tissues from VSV infection.

IMPORTANCE
Although viral infection is quite common, the immune system effectively protects us from viral diseases. A major part of this protection is mediated by interferon, the antiviral cytokine secreted by virus-infected cells. To empower the neighboring uninfected cells in combating the oncoming infection, interferon induces the synthesis of more than 200 new proteins, many of which have antiviral activities. The virus studied here, vesicular stomatitis virus (VSV), like its relative, rabies virus, can cause neuropathy in mice if it enters the peripheral nervous system through skin lesions; however, interferon can protect neurons from VSV infection. We have identified a specific interferon-induced protein, Ifit2, as the protein that protects neurons from VSV infection. Surprisingly, Ifit2 was not needed to protect other cell types from VSV. Our results indicate that the effector antiviral proteins of the interferon system have highly specialized functions.
Contribution of Glutamine Residues in the Helix 4-5 Loop to Capsid-Capsid Interactions in Simian Immunodeficiency Virus of Macaques
Authors: Tipper Christopher , Sodroski Joseph G.
Published: July 2014

Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transcription. Inspection of the CA sequences of lentiviruses reveals that several species of simian immunodeficiency viruses (SIVs) have lost the glycine-proline motif in the helix 4-5 loop important for CypA binding; instead, the helix 4-5 loop in these SIVs exhibits an increase in the number of glutamine residues. In this study, we investigated the role of these glutamine residues in SIVmac239 replication. Changes in these residues, particularly glutamine 89 and glutamine 92, resulted in a decreased efficiency of core condensation, decreased stability of the capsids in infected cells, and blocks to reverse transcription. In some cases, coexpression of two different CA mutants produced chimeric virions that exhibited higher infectivity than either parental mutant virus. For this complementation of infectivity, glutamine 89 was apparently required on one of the complementing pair of mutants and glutamine 92 on the other. Modeling suggests that glutamines 89 and 92 are located on the distal face of hexameric capsid spokes and thus are well positioned to contribute to interhexamer interactions. Requirements to evade host restriction factors like TRIMCyp may drive some SIV lineages to evolve means other than CypA binding to stabilize the capsid. One solution used by several SIV strains consists of glutamine-based bonding.

IMPORTANCE
The retroviral capsid is an assembly of individual capsid proteins that surrounds the viral RNA. After a retrovirus enters a cell, the capsid must disassemble, or uncoat, at a proper rate. The interactions among capsid proteins contribute to this rate of uncoating. We found that some simian immunodeficiency viruses use arrays of glutamine residues, which can form hydrogen bonds efficiently, to keep their capsids stable. This strategy may allow these viruses to forego the use of capsid-stabilizing factors from the host cell, some of which have antiviral activity.
Virus and Host Factors Affecting the Clinical Outcome of Bluetongue Virus Infection
Authors: Caporale Marco , Di Gialleonorado Luigina , Janowicz Anna , Wilkie Gavin , Shaw Andrew , Savini Giovanni , Van Rijn Piet A. , Mertens Peter , Di Ventura Mauro , Palmarini Massimo
Published: July 2014

Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted byCulicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype affect the clinical course of bluetongue. Results obtained indicate that in small ruminants, there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected toward the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging inCulicoidescells increased the overall number of low-frequency variants compared to virus never passaged in cell culture. Thus,Culicoidesmight be a source of new viral variants, and viral population diversity can be another factor influencing BTV virulence.

IMPORTANCEBluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected, while at the breed level differences were less evident. No differences were observed in the virulence of two different BTV serotypes (BTV-8 and BTV-2). In contrast, we show that the European BTV-8 strain isolated at the beginning of the bluetongue outbreak in 2006 was more virulent than a strain isolated toward the end of the outbreak. In addition, we show that there is a link between the variability of the BTV population as a whole and virulence, and our data also suggest thatCulicoidescells might function as an “incubator” of viral variants.
Legislative, educational, policy and other interventions targeting physicians’ interaction with pharmaceutical companies: a systematic review
Authors: Alkhaled Lina , Kahale Lara , Nass Hala , Brax Hneine , Fadlallah Racha , Badr Kamal , Akl Elie A
Published: July 2014

Background

Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians.

Objective

The objective of this study was to systematically review the effects of interventions targeting practising physicians’ interactions with pharmaceutical companies.

Eligibility criteria

We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies.

Data sources

The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias.

Appraisal and synthesis methods

We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology.

Results

Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a ‘collaborative approach’ between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour.

Limitations

We identified too few studies to allow strong conclusions.

Conclusions

Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians’ prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies.
Temporal relationship between hospital admissions for pneumonia and weather conditions in Shanghai, China: a time-series analysis
Authors: Liu Yuan , Kan Haidong , Xu Jianming , Rogers David , Peng Li , Ye Xiaofang , Chen Renjie , Zhang Yue , Wang Weibing
Published: July 2014

Objectives

To explore the association between weather conditions and hospital admissions for pneumonia in Shanghai.

Design

A time-series analysis was performed for a period of 4 years (January 2008–December 2011). A generalised additive model was used to calculate the relative risks.

Setting

Shanghai, China.

Participants

All daily hospital admissions for pneumonia were obtained from the Shanghai health insurance system between 1 January 2008 and 31 December 2011 (n=99 403).

Results

The relationship between the mean temperature and pneumonia hospital admissions followed a V-shaped curve, with an optimum temperature (OT) at 13°C. When the mean temperature was below the OT, a 1°C decrease corresponded to a 4.88% (95% CI 2.71% to 7.09%) and 5.34% (95% CI 2.04% to 8.74%) increase in pneumonia hospital admissions in lag 4 using a single-day lag structure and lag 0–7 using a multiday lag structure. When the mean temperature ≥OT, no adverse effects from the temperature on pneumonia hospital admissions were found. The magnitude of the effects of temperature varied across gender and age groups. Hospitalisations for pneumonia increased by 15.99% (95% CI 0.06% to 34.46%) in the cold period.

Conclusions

Cold temperature may be one of the important risk factors for pneumonia hospitalisations. Prevention programmes are needed to reduce the impact of cold temperature on pneumonia hospitalisations such as developing a weather warning system within a wide public health context.
The impact of chronic obstructive pulmonary disease on intensive care unit admission and 30-day mortality in patients undergoing colorectal cancer surgery: a Danish population-based cohort study
Authors: Platon Anna Maria , Erichsen Rune , Christiansen Christian Fynbo , Andersen Lea Kjær , Sværke Claus , Montomoli Jonathan , Sørensen Henrik Toft
Published: July 2014

Background and purpose

Chronic obstructive pulmonary disease (COPD) may increase the risk of postoperative complications and thus mortality after colorectal cancer (CRC) surgery, but the evidence is sparse.

Methods

We conducted this nationwide population-based cohort study in Denmark, including all patients undergoing CRC surgery in the period 2005–2011, identified through medical databases. We categorised the patients according to the history of COPD.

We assessed the rate of complications within 30 days. We computed 30-day mortality among patients with/without COPD using the Kaplan-Meier method. We used Cox regression to compute HRs for death, controlling for age, gender, type of admission, cancer stage, hospital volume, alcohol-related diseases, obesity and Charlson comorbidity score.

Results

We identified 18 302 CRC surgery patients. Of these, 7.9% had a prior diagnosis of COPD. Among patients with COPD, 16.1% were admitted postoperatively to the intensive care unit, 1.9% were treated with mechanical ventilation, and 3.6% were treated with non-invasive ventilation. In patients without COPD, the corresponding proportions were 9.7%, 1.1% and 1.1%. The reoperation rate was 10.6% among patients with COPD and 8% among patients with cancer without COPD. 30-day mortality was 13% (95% CI 11.4% to 14.9%) among patients with COPD and 5.3% (95% CI 5.0% to 5.7%) among patients without COPD, corresponding to an adjusted HR of 1.7 (95% CI 1.5 to 2.0).

Conclusions

COPD is a strong predictor for intensive care unit admission and mortality after CRC surgery.
The syndrome of inappropriate antidiuresis is associated with excess long-term mortality: a retrospective cohort analyses
Authors: Basu Ansu , Ryder Robert E J
Published: July 2014

Introduction

The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of euvolaemic hyponatraemia in patients admitted to hospital. The mortality after discharge from hospital has not been previously studied in patients with SIAD.

Aims

To compare mortality in patients with SIAD and those with kidney injury (KI). To identify underlying diagnoses associated with deaths due to SIAD.

Methods

Single-centre retrospective cohort analyses of 804 patients with severe hyponatraemia over a 3-year period. Five-year survival data in patients with SIAD and those with KI were compared. The underlying diagnoses that contributed to SIAD in this cohort were analysed using ICD-10 codes.

Results

202 patients had SIAD using biochemical cut-off parameters; 248 patients had KI. Patient with KI had a statistically significant (log-rank p<0.0001) shorter median survival time (2.24 months (95% CI 1.3 to 4.3)) compared with those with SIAD (31.0 months (95% CI 21.6 to 54.8)). 53.8% (n=78) of patients with hyponatraemia due to SIAD died within the first year after admission; the corresponding figure for those presenting with KI was 74.1% (n=166). Five years after admission, 80.8% (n=117) of those with SIAD had died; the corresponding figure for those with KI was 88.4% (n=200). In those patients with SIAD that died within the first year, malignancy appeared to be the most common cause (25.4%) followed by infection (23.8%).

Conclusions

Severe hyponatraemia in SIAD carries a high mortality after discharge, and although this seems often to be attributable to the underlying cause, the extent to which treatment with V2-recptor antagonists may help to correct the hyponatraemia associated with SIAD and influence the medium-to-long-term outcome in such patients is worthy of further study.
Web based pathology assessment in RTOG 98-04
Authors: Woodward Wendy A , Sneige Nour , Winter Kathryn , Kuerer Henry Mark , Hudis Clifford , Rakovitch Eileen , Smith Barbara L , Pierce Lori J , Germano Isabelle , Pu Anthony T , Walker Eleanor M , Grisell David Lawrence , White Julia R , McCormick Beryl
Published: July 2014

Aims

Radiation Therapy Oncology Group 98-04 sought to identify women with ‘good risk’ ductal carcinoma in situ (DCIS) who receive no significant benefit from radiation. Enrolment criteria excluded close or positive margins and grade 3 disease. To ensure reproducibility in identifying good risk pathology, an optional web based teaching tool was developed and a random sampling of 10% of submitted slides were reviewed by a central pathologist.

Methods

Submitting pathologists were asked to use the web based teaching tool and submit an assessment of the tool along with the pathology specimen form and DCIS H&E stained slide. Per protocol pathology was centrally reviewed for 10% of the cases.

Results

Of the 55 DCIS cases reviewed, three had close or positive margins and three were assessed to include grade 3 DCIS, therefore 95% of DCIS cases reviewed were correctly graded, and 89% reviewed were pathologically appropriate for enrolment. Regarding the teaching tool, 13% of DCIS cases included forms that indicated the website was used. One of these seven who used the website submitted DCIS of grade 3.

Conclusions

Central review demonstrates high pathological concordance with enrolment eligibility, particularly with regard to accurate grading. The teaching tool appeared to be underused.
IgE deficiency may indicate underlying hypogammaglobulinaemia?
Authors: McVicker Shireen , Karim M Yousuf
Published: July 2014

Low serum immunoglobulin E (IgE) (<2 kU/L) found during allergy investigations may be a marker for other immunodeficiency states, in particular common variable immunodeficiency. The latter is characterised by recurrent infections, mainly respiratory, resulting in structural lung damage making early diagnosis important. We looked through 4013 samples retrospectively over a 12-month period to identify samples with IgE <2 kU/L. We identified 74/4013 (1.84%) with serum IgE levels <2 kU/L. Only 20 samples had serum immunoglobulin quantification and serum electrophoresis requested. Three of these samples were from the same patient, 10/18 (56%) had one or more classes of immunoglobulin above/below reference range for age and two of these had new diagnosis of immunodeficiency. Serum IgE <2 kU/L can be a marker for hypogammaglobulinaemia or common variable immunodeficiency. As early diagnosis is important to reduce morbidity and mortality, very low serum IgE should trigger further investigation—that is, serum protein electrophoresis and immunoglobulin quantification.
Suitability of Becton Dickinson Vacutainer rapid serum tube for collecting and storing blood samples for antibiotic and anticonvulsant drug monitoring
Authors: Yan Ronald , Colantonio David , Wong Pui-Yuen , Chen Yu
Published: July 2014

Aims

To investigate the suitability of newly developed Becton Dickinson Vacutainer rapid serum tube (RST) for therapeutic drug monitoring of antibiotics and anticonvulsants.

Methods

Two pools of citrated whole blood were created by spiking high and low concentrations of gentamicin, vancomycin, phenytoin, lamotrigine and carbamazepine. After recalcification with 15 mmol/L calcium chloride, spiked whole blood was added into four different Becton Dickinson blood collection tubes: RST, serum separator tube, red top tube and polyethylene plain tube. Serum aliquots were collected at baseline (0 h), 2 h, 24 h, day 3 and day 7. Drug concentrations were measured in batch by HPLC and the Architect c8000.

Results

Gentamicin and vancomycin concentrations were stable up to 7 days in all 4 blood collection tubes. Anticonvulsants results for the RST were stable and did not deviate substantially from those of the red top and plain tubes, and demonstrated better performance than the serum separator tubes that showed significant (≥10% bias, p<0.05) decrease in phenytoin and carbamazepine levels after 3 days of storage.

Conclusions

The RST provides acceptable drug stability over the course of 7 days for gentamicin, vancomycin, phenytoin and lamotrigine and over 3 days for carbamazepine.
Evaluation of sedation and clinical effects of midazolam with ketamine or dexmedetomidine in pet rabbits
Authors: Bellini L. , Banzato T. , Contiero B. , Zotti A.
Published: July 2014

The effects of two sedation protocols combining midazolam with ketamine (ketamine group) or dexmedetomidine (dexmedetomidine group) were studied in dwarf companion rabbits undergoing abdominal ultrasound scan. The onset of sedation was faster in the ketamine group; a few rabbits in the dexmedetomidine group required additional doses to lose the righting reflex, although sedation time was not different between groups. A semi‐quantitative scale was used to score sedation quality, which was higher in rabbits that received dexmedetomidine rather than ketamine. Pulse rate was lower in the dexmedetomidine group (206 vs 240 bpm), although Doppler blood pressure was higher than in the ketamine group (109 vs 89 mm Hg). Respiratory rate decreased in relation to the baseline values with both protocols but arterial haemoglobin saturation with oxygen was maintained similar to the pre‐sedation values throughout the entire procedure, regardless of protocol used and without oxygen supplementation. Both protocols allowed performance of ultrasound scanning, although dexmedetomidine may be preferred if a deep sedation level is required.
STRUCTURALLY ENHANCED INCREMENTAL NEURAL LEARNING FOR IMAGE CLASSIFICATION WITH SUBGRAPH EXTRACTION
Authors: YANG YU-BIN , LI YA-NAN , GAO YANG , YIN HUJUN , TANG YE
Published: July 2014

In this paper, a structurally enhanced incremental neural learning technique is proposed to learn a discriminative codebook representation of images for effective image classification applications. In order to accommodate the relationships such as structures and distributions among visual words into the codebook learning process, we develop an online codebook graph learning method based on a novel structurally enhanced incremental learning technique, called as "visualization-induced self-organized incremental neural network (ViSOINN)". The hidden structural information in the images is embedded into the graph representation evolving dynamically with the adaptive and competitive learning mechanism. Afterwards, image features can be coded using a sub-graph extraction process based on the learned codebook graph, and a classifier is subsequently used to complete the image classification task. Compared with other codebook learning algorithms originated from the classical Bag-of-Features (BoF) model, ViSOINN holds the following advantages: (1) it learns codebook efficiently and effectively from a small training set; (2) it models the relationships among visual words in metric scaling fashion, so preserving high discriminative power; (3) it automatically learns the codebook without a fixed pre-defined size; and (4) it enhances and preserves better the structure of the data. These characteristics help to improve image classification performance and make it more suitable for handling large-scale image classification tasks. Experimental results on the widely used Caltech-101 and Caltech-256 benchmark datasets demonstrate that ViSOINN achieves markedly improved performance and reduces the computational cost considerably.
Controllability of deterministic complex networks
Authors: Li Xin-Feng , Lu Zhe-Ming , Li Hui
Published: July 2014

Recently, the controllability of complex networks has attracted wide attention of researchers. The main contribution comes from Liu et al. who proposed the structural controllability as an analytical framework for making predictions regarding the control of directed networks in Nature. Since then, the controllability of many model and real networks has been deeply investigated except deterministic complex networks. In this paper, we focus on studying the controllability of deterministic complex networks. We examine six typical deterministic networks, the simulation results show that the minimum number of driver nodes grows linearly with network size. When the network size is large enough, the controllability approximates to a constant not more than 0.4, indicating that the deterministic networks are relatively easy to control. Furthermore, we investigate the characteristics of driver nodes in deterministic complex networks, finding that the driver nodes tend to avoid high degree nodes but to have high clustering coefficients.
Structural and magnetic property studies on BaREBiO4 (where RE = Sm and Nd) system
Authors: Manigandan A. , Anbarasu V. , Sathyaseelan B. , Sivakumar K.
Published: July 2014

The new ceramic compounds type BaREBiO 4 (where RE = Sm and Nd ) have been reported for the first time. The sample was prepared by solid-state reaction technique. The orthorhombic crystallization with a = 6.429(4) Å, b = 6.536(5) Å, c = 8.648(4) Å for BaSmBiO 4 and a = 6.485(3) Å, b = 6.561(4) Å, c = 8.686(4) Å for BaNdBiO 4 was studied from powder X-ray diffraction studies. The semiconducting nature of the compounds was observed with the energy gap measurement from diffused reflectance spectroscopy (DRS) studies. The paramagnetic nature of the compounds at room temperature and low temperature conditions was identified by magnetization measurements as a function of magnetic fields and temperature. The effective magnetic moment of the samples was found to be 2.126 μB and 4.272 μB.
Analysis of structures and melting properties of the 19-atom Ni–Co clusters
Authors: Ren Shi-Wei , Sun Jing-Wei , Hao Yan-Zhong
Published: July 2014

In this paper, by using the classical molecular dynamics method and the GEAM potential, the geometric structure and the melting properties of the 19-atom Ni – Co clusters with different compositions are studied. It is found that all the clusters have the double icosahedron structures although some of the structures are slightly deformed. With the increase of the temperature, a pre-melting phenomenon is observed. The pre-melting temperatures of the pure cobalt and nickel clusters are very close. But on the whole, the pre-melting temperature decreases with the increase of the number of the nickel atom for the mixed clusters. The effects of the substitution atoms on the melting temperature of the clusters are similar to that on the pre-melting temperature although there are some oscillations in the decrease process. The mechanism of these findings are also investigated and analyzed.
SIMULATION-BASED OPTIMAL DESIGN OF HFCVD EQUIPMENT ADOPTED FOR MASS PRODUCTION OF DIAMOND FILMS ON INNER-HOLE SURFACES
Authors: WANG XINCHANG , LEI XUELIN , CHENG LEI , SUN FANGHONG , SHEN BIN
Published: July 2014

HFCVD diamond films have been extensively applied on inner-hole surfaces of some wear resistant components as protective coatings, the mass production of which puts forward a high request to the HFCVD equipment. In this paper, adopting a typical kind of drawing die as the substrate, several different substrate configurations are proposed to expand the capacity of the equipment. Temperature distributions on inner-hole surfaces of the substrates are respectively predicted and compared by the finite volume method (FVM) simulations. In summary, for parallel configurations, proper-designed auxiliary devices (e.g. the heat-insulated plate, the water-cooled plate and the heat-insulated cushion block) can provide sufficient effects on the uniformity of the substrate temperature distribution. Moreover, without any auxiliary devices, homogeneous substrate temperature distributions can also be obtained using circular pattern configurations (radial, hexagon and triangular). Accordingly, the HFCVD equipment referring to the design concept of the triangular configuration is trial-manufactured. In the verification experiments, similar substrate temperature values are detected in three different modules, and as-deposited microcrystalline diamond (MCD) and nanocrystalline diamond (NCD) films both present uniform grain size, thickness and quality, well validating the rationality and correctness of the simulation-based optimal design.
Investigation of Using Free-Standing Thick-Film Piezoelectric Energy Harvesters to Develop Wideband Devices
Authors: Bai Yang , Meggs Carl , Button Tim W.
Published: July 2014

This paper is concerned with the wideband behavior of single-frequency and multi-frequency free-standing thick-film piezoelectric energy harvesters. The energy harvesting devices have been fabricated and brief fabrication information is provided. The individual harvesters have been combined with either symmetric or asymmetric tip masses, with some being connected together to form a harvester array. Testing has been undertaken using harmonic vibrations with a wide range of frequencies and accelerations, and also using a random machinery vibration, and data have been recorded in terms of un-rectified and rectified open-circuit voltage, output power with matched resistive loads, peak-to-peak tip displacement, and even charging rates of capacitors. As a general result, the individual harvesters with asymmetric tip masses have vibrated nonlinearly below and in the vicinity of the resonant frequencies. An individual harvester vibrating at the resonant frequency with 0.5 g acceleration has been able to charge a 1000 μF capacitor to 1 V within 12 min and to 1.5 V within 30 min. Also, the harvester array has exhibited a wideband response, where an open-circuit voltage of above 0.8 V has been provided within a certain range of frequencies. Finally, the harvester array has successfully charged a capacitor on a vibrating test sieve shaker, proving the feasibility of the proposed device in real applications.
Phase space frames and frame operators
Authors: Easwaran Nambudiri T. C. , Parthasarathy K.
Published: July 2014

An explicit, simple characterization of those operators that arise as Weyl–Heisenberg frame operators on L2(ℝn) is obtained in terms of the concept of tile vertices of an operator. Generalizations of these frames to abstract Hilbert spaces are introduced and these and their frame operators are characterized in terms of Weyl–Heisenberg frames and frame operators in Euclidean spaces. Appropriate "window" versions of these concepts and results are also presented.
Two expansion formulas involving the Rogers–Szegő polynomials with applications
Authors: Liu Zhi-Guo , Zeng Jiang
Published: July 2014

Using two expansion formulas for the Rogers–Szegő polynomials and the Stieltjes–Wigert polynomials, we give new proofs of a variety of important classical formulas including Bailey's6ψ6summation, the Askey–Wilson integral and its extension. Furthermore, we give nontrivial extensions of the Andrews multiple version of the Rogers–Selberg identity, as well as the Sylvester identity.
Sextuples of integers whose sums in pairs are squares
Authors: Choudhry Ajai
Published: July 2014

This paper is concerned with the diophantine problem of finding six integers such that the sum of any two of them is a perfect square. Till now, only one numerical example of such a sextuple has been published. In this paper, we obtain infinitely many examples of sextuples of integers such that the sum of any two of them is a perfect square. These examples include sextuples which have three or four or five distinct integers as well as sextuples in which all the integers are distinct.
CU-PSHA: A MATLAB Software for Probabilistic Seismic Hazard Analysis
Authors: Pailoplee Santi , Palasri Chitti
Published: July 2014

In this study, an open source MATLAB software, called CU-PSHA, is developed in order to analyze probabilistic earthquake hazards. This software aims to provide a user friendly and flexible tool for evaluating reliable earthquake hazard estimates. With the CU-PSHA, the probability of distances between the earthquake sources and the study site can be estimated. Two choices for the estimation of earthquake frequency–magnitude distribution, the exponential magnitude distribution and the characteristic earthquake models, are provided. Some strong ground–motion attenuation models are available for both shallow crustal and subduction zone earthquakes. The probability of exceedance of any individual given ground shaking value can be obtained, allowing the display of a seismic hazard curve. In addition with the supplementary MATLAB scripts, this CU-PSHA software can be employed in general seismic hazard mapping, for both ground shaking level and probability of occurrence, in any specific given time span.
Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing
Authors: Scott Christopher , Bonner James , Min Danqing , Boughton Philip , Stokes Rebecca , Cha Kuan Minn , Walters Stacey N. , Maslowski Kendle , Sierro Frederic , Grey Shane T. , Twigg Stephen , McLennan Susan , Gunton Jenny E.
Published: July 2014

Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine (DFO) improves wound healing by increasing hypoxia-inducible factors, which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT and, more specifically, myeloid ARNT may be a therapeutic strategy to improve wound healing.
Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus
Authors: McGillick Erin V. , Morrison Janna L. , McMillen I. Caroline , Orgeig Sandra
Published: July 2014

Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein ( SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.
cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice
Authors: Blake Camille B. , Smith Bret N.
Published: July 2014

Pathologies in which insulin is dysregulated, including diabetes, can disrupt central vagal circuitry, leading to gastrointestinal and other autonomic dysfunction. Insulin affects whole body metabolism through central mechanisms and is transported into the brain stem dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarius (NTS), which mediate parasympathetic visceral regulation. The NTS receives viscerosensory vagal input and projects heavily to the DMV, which supplies parasympathetic vagal motor output. Normally, insulin inhibits synaptic excitation of DMV neurons, with no effect on synaptic inhibition. Modulation of synaptic inhibition in DMV, however, is often sensitive to cAMP-dependent mechanisms. We hypothesized that an effect of insulin on GABAergic synaptic transmission may be uncovered by elevating resting cAMP levels in GABAergic terminals. We used whole cell patch-clamp recordings in brain stem slices from control and diabetic mice to identify insulin effects on inhibitory neurotransmission in the DMV in the presence of forskolin to elevate cAMP levels. In the presence of forskolin, insulin decreased the frequency of inhibitory postsynaptic currents (IPSCs) and the paired-pulse ratio of evoked IPSCs in DMV neurons from control mice. This effect was blocked by brefeldin-A, a Golgi-disrupting agent, or indinavir, a GLUT4 blocker, indicating that protein trafficking and glucose transport were involved. In streptozotocin-treated, diabetic mice, insulin did not affect IPSCs in DMV neurons in the presence of forskolin. Results suggest an impairment of cAMP-induced insulin effects on GABA release in the DMV, which likely involves disrupted protein trafficking in diabetic mice. These findings provide insight into mechanisms underlying vagal dysregulation associated with diabetes.
Mechanisms of guanylin action on water and ion absorption at different regions of seawater eel intestine
Authors: Ando Masaaki , Wong Marty K. S. , Takei Yoshio
Published: July 2014

Guanylin (GN) inhibited water absorption and short-circuit current ( Isc) in seawater eel intestine. Similar inhibition was observed after bumetanide, and the effect of bumetanide was abolished by GN or vice versa, suggesting that both act on the same target, Na+-K+-2Cl−cotransporter (NKCC), which is a key player for the Na+-K+-Cl−transport system responsible for water absorption in marine teleost intestine. However, effect of GN was always greater than that of bumetanide: 10% greater in middle intestine (MI) and 40% in posterior intestine (PI) for Isc, and 25% greater in MI and 34% in PI for water absorption. After treatment with GN, Iscdecreased to zero, but 20–30% water absorption still remained. The remainder may be due to the Cl−/HCO3−exchanger and Na+-Cl−cotransporter (NCC), since inhibitors for these transporters almost nullified the remaining water absorption. Quantitative PCR analysis revealed the presence of major proteins involved in water absorption; the NKCC2β and AQP1 genes whose expression was markedly upregulated after seawater acclimation. The SLC26A6 (anion exchanger) and NCCβ genes were also expressed in small amounts. Consistent with the inhibitors' effect, expression of NKCC2β was MI > PI, and that of NCCβ was MI << PI. The present study showed that GN not only inhibits the bumetanide-sensitive Na+-K+-Cl−transport system governed by NKCC2β, but also regulates unknown ion transporters different from GN-insensitive SLC26A6 and NCC. A candidate is cystic fibrosis transmembrane conductance regulator Cl−channel, as demonstrated in mammals, but its expression is low in eel intestine, and its role may be minor, as indicated by the small effect of its inhibitors.
Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla
Authors: Zhou Xiaoming , Wang Hong , Koles Nancy L. , Zhang Aihong , Aronson Naomi E.
Published: July 2014

Visceral leishmaniasis patients have been reported to have a urine concentration defect. Concentration of urine by the renal inner medulla is essentially dependent on a transcription factor, NFAT5/TonEBP, because it activates expression of osmoprotective genes betaine/glycine transporter 1 (BGT1) and sodium/myo-inositol transporter (SMIT), and water channel aquaporin-2, all of which are imperative for concentrating urine. Leishmania parasites evade macrophage immune defenses by activating protein tyrosine phosphatases, among which SHP-1 is critical. We previously demonstrated that SHP-1 inhibits tonicity-dependent activation of NFAT5/TonEBP in HEK293 cells through screening a genome-wide small interfering (si) RNA library against phosphatases (Zhou X, Gallazzini M, Burg MB, Ferraris JD. Proc Natl Acad Sci USA 107: 7072–7077, 2010). We sought to examine whether Leishmania can activate SHP-1 and inhibit NFAT5/TonEBP activity in the renal inner medulla in a murine model of visceral leishmaniasis by injection of female BALB/c mice with a single intravenous dose of 5 × 105 L. chagasi metacyclic promastigotes. We found that SHP-1 is expressed in the kidney inner medulla. L. chagasi activates SHP-1 with an increase in stimulatory phosphorylation of SHP-1-Y536 in the region. L. chagasi reduces expression of NFAT5/TonEBP mRNA and protein as well as expression of its targeted genes: BGT1, SMIT, and aquaporin-2. The culture supernatant from L. chagasi metacyclic promastigotes increases SHP-1 protein abundance and potently inhibits NFAT5 transcriptional activity in mIMCD3 cells. However, L. chagasi in our animal model has no significant effect on urinary concentration. We conclude that L. chagasi, most likely through its secreted virulence factors, activates SHP-1 and reduces NFAT5/TonEBP gene expression, which leads to reduced NFAT5/TonEBP transcriptional activity in the kidney inner medulla.
Myeloperoxidase deficiency ameliorates progression of chronic kidney disease in mice
Authors: Lehners Alexander , Lange Sascha , Niemann Gianina , Rosendahl Alva , Meyer-Schwesinger Catherine , Oh Jun , Stahl Rolf , Ehmke Heimo , Benndorf Ralf , Klinke Anna , Baldus Stephan , Wenzel Ulrich Otto
Published: July 2014

Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice.
Mechanism of impaired afferent arteriole myogenic response in Dahl salt-sensitive rats: role of 20-HETE
Authors: Ren YiLin , D'Ambrosio Martin A. , Garvin Jeffrey L. , Peterson Edward L. , Carretero Oscar A.
Published: July 2014

The afferent arteriole (Af-Art) controls glomerular capillary pressure, an important determinant of glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt-resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (−3.1 ± 0.8 vs. 0.5 ± 0.8 μm, P < 0.01). The 20-HETE antagonist 20-HEDE (10−6 M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10−6 M). Maximum ATP-induced constriction was attenuated in Dahl SS compared with Dahl SR (1.5 ± 0.5 vs. 7.4 ± 0.8 μm, P < 0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.
Rectification is required to extract oscillatory envelope modulation from surface electromyographic signals
Authors: Dakin Christopher J. , Dalton Brian H. , Luu Billy L. , Blouin Jean-Sébastien
Published: July 2014

Rectification of surface electromyographic (EMG) recordings prior to their correlation with other signals is a widely used form of preprocessing. Recently this practice has come into question, elevating the subject of EMG rectification to a topic of much debate. Proponents for rectifying suggest it accentuates the EMG spike timing information, whereas opponents indicate it is unnecessary and its nonlinear distortion of data is potentially destructive. Here we examine the necessity of rectification on the extraction of muscle responses, but for the first time using a known oscillatory input to the muscle in the form of electrical vestibular stimulation. Participants were exposed to sinusoidal vestibular stimuli while surface and intramuscular EMG were recorded from the left medial gastrocnemius. We compared the unrectified and rectified surface EMG to single motor units to determine which method best identified stimulus-EMG coherence and phase at the single-motor unit level. Surface EMG modulation at the stimulus frequency was obvious in the unrectified surface EMG. However, this modulation was not identified by the fast Fourier transform, and therefore stimulus coherence with the unrectified EMG signal failed to capture this covariance. Both the rectified surface EMG and single motor units displayed significant coherence over the entire stimulus bandwidth (1–20 Hz). Furthermore, the stimulus-phase relationship for the rectified EMG and motor units shared a moderate correlation ( r = 0.56). These data indicate that rectification of surface EMG is a necessary step to extract EMG envelope modulation due to motor unit entrainment to a known stimulus.
Cell adhesion proteins and the pathogenesis of autism spectrum disorders
Authors: Stewart Luke T.
Published: July 2014

Current theories on the pathogenesis of autism spectrum disorders (ASD) maintain that the associated cognitive and behavioral symptoms are caused by aberrant synaptic transmission affecting specific brain circuits. Transgenic mouse models have implicated the involvement of cell adhesion proteins in synaptic dysfunction and ASD pathogenesis. Recently, Aoto et al. ( Cell 154: 75–88, 2013) has shown that alternatively spliced neurexin proteins affect the efficacy of AMPA receptor-mediated excitatory currents in both cultured neuronal networks and acute hippocampal slices constituting a potential ASD-related electrophysiological phenotype.