bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a rapid bedside scoring system for microcirculation videos acquired from dogs
Authors: Gommeren Kris , Allerton Fergus J. , Morin Elise , Reynaud Arthur , Peeters Dominique , Silverstein Deborah C.
Published: August 2014

Objective

To appraise a novel scoring system (Bedside Evaluation of Microcirculation [BEM]) to provide qualitative and semiquantitative assessment of canine microcirculatory videos generated by sidestream dark field imaging.

Design

Prospective observational study.

Setting

University teaching hospital.

Animals

No animals were used in this study. Twenty microcirculatory videos (>20 s in length) acquired from the mucosa adjacent to the upper canine tooth of dogs were selected from a database of sidestream dark field microcirculatory videos with available current standard analysis (CSA).

Intervention

Three observers were trained to evaluate 5 video quality parameters (stability, content, illumination, focus, and pressure) and four perfusion parameters (total vessel density [TVD], capillary vessel density [CVD], perfused vessel density [PVD] and microvascular flow index [MFI]). Quality parameters were scored (excellent [0], sufficient [1], and insufficient [2]) similar to CSA recommendations. Each perfusion parameter was subjectively scored (1 lowest – 5 highest) using sample clips from the training video for comparison. Videos passed quality analysis if no parameter was scored insufficient. Repeatability and reproducibility were evaluated by assessing all films in a random order three times daily for 3 days. Strength of correlation of BEM with CSA for both qualitative and semiquantitative parameters was assessed.

Measurements and Main Results

The qualitative evaluation pass/fail assessment matched CSA 86% of the time with individual observer agreements of 84–88%. Agreement with CSA did not change significantly over the study period (84%, 88%, and 84% on days 1, 2, and 3, respectively). No significant correlations were demonstrated between any BEM perfusion parameter and the corresponding CSA values.

Conclusions

Rapid bedside assessment of microcirculatory video quality can be achieved. However, semiquantitative analysis by BEM demonstrated a lack of correlation with CSA for any of the perfusion parameters assessed.
Development of gasbag-assisted ultraviolet-based imprinting process for replication of microstructures onto cylindrical surface
Authors: Lin Cheng-Hui , Hong Rong-Hong , Li Tsui-Hua , Yang Sen-Yeu
Published: August 2014

In the conventional imprinting process, the substrate and the stamp are brought into contact and compressed directly by the plate and rigid mold. However, replicating microstructures onto a nonplanar surface is difficult due to the limited contact area and nonuniform pressure. In this study, a gasbag-assisted UV imprinting process and a flexible polydimethylsiloxane mold are employed to replicate microstructures onto a cylindrical surface, using gas to enhance the closeness of contact and uniformity of pressure during imprinting. A gas-assisted UV-based imprinting facility, which contains a gasbag, air pressure system, motor driving system, and exposure system, is designed and implemented. V-cut microstructures are imprinted on the inner surface of the cylindrical PMMA substrate. The optical performance and brightness enhancement are then verified.
Effects of minimum monitor unit threshold on spot scanning proton plan quality
Authors: Howard Michelle , Beltran Chris , Mayo Charles S. , Herman Michael G.
Published: August 2014

Purpose:

To investigate the influence of the minimum monitor unit (MU) on the quality of clinical treatment plans for scanned proton therapy.

Methods:

Delivery system characteristics limit the minimum number of protons that can be delivered per spot, resulting in a min‐MU limit. Plan quality can be impacted by the min‐MU limit. Two sites were used to investigate the impact of min‐MU on treatment plans: pediatric brain tumor at a depth of 5–10 cm; a head and neck tumor at a depth of 1–20 cm. Three‐field, intensity modulated spot scanning proton plans were created for each site with the following parameter variations: min‐MU limit range of 0.0000–0.0060; and spot spacing range of 2–8 mm. Comparisons were based on target homogeneity and normal tissue sparing. For the pediatric brain, two versions of the treatment planning system were also compared to judge the effects of the min‐MU limit based on when it is accounted for in the optimization process (Eclipse v.10 and v.13, Varian Medical Systems, Palo Alto, CA).

Results:

The increase of the min‐MU limit with a fixed spot spacing decreases plan quality both in homogeneous target coverage and in the avoidance of critical structures. Both head and neck and pediatric brain plans show a 20% increase in relative dose for the hot spot in the CTV and 10% increase in key critical structures when comparing min‐MU limits of 0.0000 and 0.0060 with a fixed spot spacing of 4 mm. The DVHs of CTVs show min‐MU limits of 0.0000 and 0.0010 produce similar plan quality and quality decreases as the min‐MU limit increases beyond 0.0020. As spot spacing approaches 8 mm, degradation in plan quality is observed when no min‐MU limit is imposed.

Conclusions:

Given a fixed spot spacing of ≤4 mm, plan quality decreases as min‐MU increased beyond 0.0020. The effect of min‐MU needs to be taken into consideration while planning proton therapy treatments.
Effect of dosimeter type for commissioning small photon beams on calculated dose distribution in stereotactic radiosurgery
Authors: García‐Garduño O. A. , Rodríguez‐Ponce M. , Gamboa‐deBuen I. , Rodríguez‐Villafuerte M. , Galván de la Cruz O. O. , Rivera‐Montalvo T.
Published: August 2014

Purpose:

To assess the impact of the detector used to commission small photon beams on the calculated dose distribution in stereotactic radiosurgery (SRS).

Methods:

In this study, six types of detectors were used to characterize small photon beams: three diodes [a silicon stereotactic field diode SFD, a silicon diode SRS, and a silicon diode E], an ionization chamber CC01, and two types of radiochromic film models EBT and EBT2. These detectors were used to characterize circular collimated beams that were generated by a Novalis linear accelerator. This study was conducted in two parts. First, the following dosimetric data, which are of particular interest in SRS, were compared for the different detectors: the total scatter factor (TSF), the tissue phantom ratios (TPRs), and the off‐axis ratios (OARs). Second, the commissioned data sets were incorporated into the treatment planning system (TPS) to compare the calculated dose distributions and the dose volume histograms (DVHs) that were obtained using the different detectors.

Results:

The TSFs data measured by all of the detectors were in good agreement with each other within the respective statistical uncertainties: two exceptions, where the data were systematically below those obtained for the other detectors, were the CC01 results for all of the circular collimators and the EBT2 film results for circular collimators with diameters below 10.0 mm. The OAR results obtained for all of the detectors were in excellent agreement for all of the circular collimators. This observation was supported by the gamma‐index test. The largest difference in the TPR data was found for the 4.0 mm circular collimator, followed by the 10.0 and 20.0 mm circular collimators. The results for the calculated dose distributions showed that all of the detectors passed the gamma‐index test at 100% for the 3 mm/3% criteria. The aforementioned observation was true regardless of the size of the calculation grid for all of the circular collimators. Finally, the dose volume histogram results were independent of the size of the calculation grid used.

Conclusions:

The results of this study showed that all of the studied detectors produced similar commissioned data sets for the TPS dose calculations. However, this result only validated the dose distribution calculation in the TPS and could not be used to assess the dose delivery to the target in which the TFS data were used to calculate the monitor units (the TFS data were not used in the TPS dose distribution calculation). Therefore, this study could not be used to determine the most accurate detector commissioning data set; however, all of the detectors exhibited superior performance for the relative dosimetry of small photon beams.
Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis
Authors: Hoegger Mark J. , Fischer Anthony J. , McMenimen James D. , Ostedgaard Lynda S. , Tucker Alex J. , Awadalla Maged A. , Moninger Thomas O. , Michalski Andrew S. , Hoffman Eric A. , Zabner Joseph , Stoltz David A. , Welsh Michael J.
Published: August 2014

A breathtaking tale of sticky mucus

Patients with cystic fibrosis have difficulty breathing because their airways are clogged with thick mucus. Does this mucus accumulate because there is a defect in the way it is produced? Or does it accumulate because of other disease features, such as dehydration or airway wall remodeling? Distinguishing between these possibilities is important for future drug development. In a study of piglets with cystic fibrosis, Hoegger
et al.
identify mucus production as the primary defect (see the Perspective by Wine). The airway glands of the piglets synthesized strands of mucus normally, but the strands were never released and stayed tethered to the gland ducts.

Science
, this issue p.
818
; see also p.
730
Debate erupts on ‘repurposed’ drugs for Ebola
Authors: Enserink Martin
Published: August 2014

With experimental treatments in short supply, some researchers think existing medicines might work.
Firing of Los Alamos researcher draws criticism
Authors: Mervis Jeffrey
Published: August 2014

Officials claim paper contained classified information.
The taste of things to come
Authors: Underwood Emily
Published: August 2014

Early postnatal, and even prenatal, experiences shape culinary tastes.
Effect of Human Immunodeficiency Virus Infection on Plasma Bactericidal Activity against Salmonella enterica Serovar Typhimurium
Authors: Trebicka Estela , Shanmugam Nanda Kumar N. , Mikhailova Anastassia , Alter Galit , Cherayil Bobby J.
Published: August 2014

Individuals with human immunodeficiency virus (HIV) infection have increased susceptibility to invasive disease caused bySalmonella entericaserovar Typhimurium. Studies from Africa have suggested that this susceptibility is related in part to the development of a high level of lipopolysaccharide (LPS)-specific IgG that is able to inhibit the killing ofS. Typhimurium by bactericidal antibodies in healthy individuals. To explore this issue further, we examined the bactericidal activity againstS. Typhimurium using serum and plasma samples from healthy controls and various clinical subgroups of HIV-infected adults in the United States. We found that the bactericidal activity in the samples from HIV-positive elite controllers was comparable to that from healthy individuals, whereas it was significantly reduced in HIV-positive viremic controllers and untreated chronic progressors. As demonstrated previously for healthy controls, the bactericidal activity of the plasma from the elite controllers was inhibited by preincubation withS. Typhimurium LPS, suggesting that it was mediated by anti-LPS antibodies.S. Typhimurium LPS-specific IgG was significantly reduced in all subgroups of HIV-infected individuals. Interestingly, and in contrast to the healthy controls, plasma from all HIV-positive subgroups inhibitedin vitrokilling ofS. Typhimurium by plasma from a healthy individual. Our results, together with the findings from Africa, suggest that multiple mechanisms may be involved in the HIV-induced dysregulation of humoral immunity toS. Typhimurium.
Apolipoprotein E Likely Contributes to a Maturation Step of Infectious Hepatitis C Virus Particles and Interacts with Viral Envelope Glycoproteins
Authors: Lee Ji-Young , Acosta Eliana G. , Stoeck Ina Karen , Long Gang , Hiet Marie-Sophie , Mueller Birthe , Fackler Oliver T. , Kallis Stephanie , Bartenschlager Ralf
Published: August 2014

The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to components of the very-low-density lipoprotein (VLDL) pathway. We and others have shown that apolipoprotein E (ApoE) plays a major role in production of infectious HCV particles. However, the mechanism by which ApoE contributes to virion assembly/release and how it gets associated with the HCV particle is poorly understood. We found that knockdown of ApoE reduces titers of infectious intra- and extracellular HCV but not of the related dengue virus. ApoE depletion also reduced amounts of extracellular HCV core protein without affecting intracellular core amounts. Moreover, we found that ApoE depletion affected neither formation of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step of assembly, such as particle maturation and infectivity. Importantly, we demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably E2. This interaction did not require any other viral proteins and depended on the transmembrane domain of E2 that also was required for recruitment of HCV envelope glycoproteins to detergent-resistant membrane fractions. These results suggest that ApoE plays an important role in HCV particle maturation, presumably by direct interaction with viral envelope glycoproteins.

IMPORTANCE
The HCV replication cycle is tightly linked to host cell lipid pathways and components. This is best illustrated by the dependency of HCV assembly on lipid droplets and the VLDL component ApoE. Although the role of ApoE for production of infectious HCV particles is well established, it is still poorly understood how ApoE contributes to virion formation and how it gets associated with HCV particles. Here, we provide experimental evidence that ApoE likely is required for an intracellular maturation step of HCV particles. Moreover, we demonstrate that ApoE associates with the viral envelope glycoproteins. This interaction appears to be dispensable for envelopment of virus particles but likely contributes to the quality control of secreted infectious virions. These results shed new light on the exploitation of host cell lipid pathways by HCV and the link of viral particle assembly to the VLDL component ApoE.
Stearoyl Coenzyme A Desaturase 1 Is Associated with Hepatitis C Virus Replication Complex and Regulates Viral Replication
Authors: Nguyen Lam N. , Lim Yun-Sook , Pham Long V. , Shin Hae-Young , Kim Yong-Sun , Hwang Soon B.
Published: August 2014

The hepatitis C virus (HCV) life cycle is tightly regulated by lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have recently screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet formation using cell culture-grown HCV (HCVcc)-infected cells. We selected and characterized the gene encoding stearoyl coenzyme A (CoA) desaturase 1 (SCD1). siRNA-mediated knockdown or pharmacological inhibition of SCD1 abrogated HCV replication in both subgenomic replicon and Jc1-infected cells, while exogenous supplementation of either oleate or palmitoleate, products of SCD1 activity, resurrected HCV replication in SCD1 knockdown cells. SCD1 was coimmunoprecipitated with HCV nonstructural proteins and colocalized with both double-stranded RNA (dsRNA) and HCV nonstructural proteins, indicating that SCD1 is associated with HCV replication complex. Moreover, SCD1 was fractionated and enriched with HCV nonstructural proteins at detergent-resistant membrane. Electron microscopy data showed that SCD1 is required for NS4B-mediated intracellular membrane rearrangement. These data further support the idea that SCD1 is associated with HCV replication complex and that its products may contribute to the proper formation and maintenance of membranous web structures in HCV replication complex. Collectively, these data suggest that manipulation of SCD1 activity may represent a novel host-targeted antiviral strategy for the treatment of HCV infection.

IMPORTANCE
Stearoyl coenzyme A (CoA) desaturase 1 (SCD1), a liver-specific enzyme, regulates hepatitis C virus (HCV) replication through its enzyme activity. HCV nonstructural proteins are associated with SCD1 at detergent-resistant membranes, and SCD1 is enriched on the lipid raft by HCV infection. Therein, SCD1 supports NS4B-mediated membrane rearrangement to provide a suitable microenvironment for HCV replication. We demonstrated that either genetic or chemical knockdown of SCD1 abrogated HCV replication in both replicon cells and HCV-infected cells. These findings provide novel mechanistic insights into the roles of SCD1 in HCV replication.
Probing the Functions of the Paramyxovirus Glycoproteins F and HN with a Panel of Synthetic Antibodies
Authors: Welch Brett D. , Paduch Marcin , Leser George P. , Bergman Zachary , Kors Christopher A. , Paterson Reay G. , Jardetzky Theodore S. , Kossiakoff Anthony A. , Lamb Robert A.
Published: August 2014

Paramyxoviruses are enveloped negative-strand RNA viruses that are significant human and animal pathogens. Most paramyxoviruses infect host cells via the concerted action of a tetrameric attachment protein (variously called HN, H, or G) that binds either sialic acid or protein receptors on target cells and a trimeric fusion protein (F) that merges the viral envelope with the plasma membrane at neutral pH. F initially folds to a metastable prefusion conformation that becomes activated via a cleavage event during cellular trafficking. Upon receptor binding, the attachment protein, which consists of a globular head anchored to the membrane via a helical tetrameric stalk, triggers a major conformation change in F which results in fusion of virus and host cell membranes. We recently proposed a model for F activation in which the attachment protein head domains move following receptor binding to expose HN stalk residues critical for triggering F. To test the model in the context of wild-type viral glycoproteins, we used a restricted-diversity combinatorial Fab library and phage display to rapidly generate synthetic antibodies (sAbs) against multiple domains of the paramyxovirus parainfluenza 5 (PIV5) pre- and postfusion F and HN. As predicted by the model, sAbs that bind to the critical F-triggering region of the HN stalk do not disrupt receptor binding or neuraminidase (NA) activity but are potent inhibitors of fusion. An inhibitory prefusion F-specific sAb recognized a quaternary antigenic site and may inhibit fusion by preventing F refolding or by blocking the F-HN interaction.

IMPORTANCEThe paramyxovirus family of negative-strand RNA viruses cause significant disease in humans and animals. The viruses bind to cells via their receptor binding protein and then enter cells by fusion of their envelope with the host cell plasma membrane, a process mediated by a metastable viral fusion (F) protein. To understand the steps in viral membrane fusion, a library of synthetic antibodies to F protein and the receptor binding protein was generated in bacteriophage. These antibodies bound to different regions of the F protein and the receptor binding protein, and the location of antibody binding affected different processes in viral entry into cells.
Isolated cranial nerve palsies may point to primary histiocytic sarcoma
Authors: Moulignier Antoine , Mikol Jacqueline , Heran Françoise , Galicier Lionel
Published: August 2014

Primary histiocytic sarcoma (HS) of the central nervous system (CNS) is a rare haematopoietic neoplasm. The inconsistent terminology and diagnostic criteria currently used for CNS HS have complicated the appreciation of the clinical aspects of the disease. The main differential diagnoses are non-Hodgkin's lymphoma, reactive histiocytic proliferation, dendritic cell neoplasm, undifferentiated carcinoma, inflammatory pseudotumour, Rosai-Dorfman disease and abscess. The true diagnosis of CNS HS requires an extensive immunophenotypic workup using specific histiocytic markers, such as CD163, with the exclusion of markers of other cell lineages. This clinicopathological case report describes an improved approach towards the differential diagnosis of CNS HS.
Anal heterosex among young people and implications for health promotion: a qualitative study in the UK
Authors: Marston C , Lewis R
Published: August 2014

Objective

To explore expectations, experiences and circumstances of anal sex among young people.

Design

Qualitative, longitudinal study using individual and group interviews.

Participants

130 men and women aged 16–18 from diverse social backgrounds.

Setting

3 contrasting sites in England (London, a northern industrial city, rural southwest).

Results

Anal heterosex often appeared to be painful, risky and coercive, particularly for women. Interviewees frequently cited pornography as the ‘explanation’ for anal sex, yet their accounts revealed a complex context with availability of pornography being only one element. Other key elements included competition between men; the claim that ‘people must like it if they do it’ (made alongside the seemingly contradictory expectation that it will be painful for women); and, crucially, normalisation of coercion and ‘accidental’ penetration. It seemed that men were expected to persuade or coerce reluctant partners.

Conclusions

Young people's narratives normalised coercive, painful and unsafe anal heterosex. This study suggests an urgent need for harm reduction efforts targeting anal sex to help encourage discussion about mutuality and consent, reduce risky and painful techniques and challenge views that normalise coercion.
Risk factors of falls in inpatients and their practical use in identifying high-risk persons at admission: Fukushima Medical University Hospital cohort study
Authors: Hayakawa Takehito , Hashimoto Shigeatsu , Kanda Hideyuki , Hirano Noriko , Kurihara Yumi , Kawashima Takako , Fukushima Tetsuhito
Published: August 2014

Objectives

To clarify the risk factors for falls in hospital settings and to propose the use of such factors to identify high-risk persons at admission.

Design

Prospective cohort study.

Setting

Fukushima Medical University Hospital, Japan, from August 2008 and September 2009.

Participants

9957 adult consecutive inpatients admitted to our hospital.

Methods

Information was collected at admission from clinical records obtained from a structured questionnaire conducted in face-to-face interviews with subjects by nurses and doctors and fall events were collected from clinical records.

Results

The proportion of patients who fell during follow-up was 2.5% and the incidence of falls was 3.28 per 100 person-days. There were significant differences in age, history of falling, cognitive dysfunction, planned surgery, wheelchair use, need for help to move, use of a remote caring system, rehabilitation, use of laxative, hypnotic or psychotropic medications and need for help with activities of daily living (ADL) between patients who did and did not fall. Multivariable adjusted ORs for falls showed that age, history of falls and need for help with ADL were common risk factors in both men and women. Using psychotropic medication also increased the risk of falling in men while cognitive dysfunction and use of hypnotic medication increased the risk of falling in women. Planned surgery was associated with a low risk of falls in women.

Conclusions

To prevent falls in inpatients it is important to identify high-risk persons. Age, history of falling and the need for help with ADL are the most important pieces of information to be obtained at admission. Care plans for patients including fall prevention should be clear and considered.
Relative risk values of age, acrolein, IL-6 and CRP as markers of periventricular hyperintensities: a cross-sectional study
Authors: Abe Arata , Nishiyama Yasuhiro , Harada-Abe Mina , Okubo Seiji , Ueda Masayuki , Mishina Masahiro , Katayama Yasuo
Published: August 2014

Objective

Brain white matter hyperintensities can be divided into periventricular hyperintensity (PVH) and deep-and-subcortical white matter hyperintensity (DSWMH); the former contributes more to cognitive dysfunction and infarction risk. We conducted the present investigation to define the relationship between PVH and DSWMH.

Design

Cross-sectional study.

Setting

University hospital.

Participants

We prospectively enrolled 228 healthy Japanese volunteers with relative risk values (RRVs) >0.5.

Primary outcome measures

We investigated whether it is possible to use the RRV to predict PVH and DSWMH.

Results

Among 228 volunteers, 103 (45.1%) and 157 (68.8%) exhibited PVH and DSWMH, respectively. Age, body mass index and PVH were significant independent determinants of RRV. A significant OR for PVH was noted in the highest RRV tertile compared with the lowest, after adjusting for potential confounding factors. A significant OR for high predicted PVH risk was found for RRV levels as well.

Conclusions

Elevated RRV levels were significantly associated with increased predicted PVH, suggesting that measuring the plasma protein-conjugated acrolein, interleukin 6 and C reactive protein levels may be useful for identifying Japanese at high risk for PVH.
Responding to concerns about complaints
Authors: Bishop Luke
Published: August 2014

When the RCVS asked members of the profession and public about its complaints and disciplinary system, it received a great deal of feedback – some positive, but much of it critical. Here, Luke Bishop, RCVS communications officer, describes how the process has now been overhauled with the aim of making it quicker, more efficient and a more satisfactory experience for all involved
ASSOCIATIONS BETWEEN ULNAR NERVE STRAIN AND ACCOMPANYING CONDITIONS IN PATIENTS WITH CUBITAL TUNNEL SYNDROME
Authors: Ochi Kensuke , Horiuchi Yukio , Nakamura Toshiyasu , Sato Kazuki , Morita Kozo , Horiuchi Koichi
Published: August 2014

Pathophysiology of cubital tunnel syndrome (CubTS) is still controversial. Ulnar nerve strain at the elbow was measured intraoperatively in 13 patients with CubTS before simple decompression. The patients were divided into three groups according to their accompanying conditions: compression/adhesion, idiopathic, and relaxation groups. The mean ulnar nerve strain was 43.5 ± 30.0%, 25.5 ± 14.8%, and 9.0 ± 5.0% in the compression/adhesion, idiopathic, and relaxation groups respectively. The mean ulnar nerve strains in patients with McGowan's classification grades I, II, and III were 18.0 ± 4.2%, 27.1 ± 22.7%, and 33.7 ± 24.7%, respectively. The Jonckheere-Terpstra test showed that there were significant reductions in the ulnar nerve strain among the first three groups, but not in the three groups according to McGowan's classification. Our results suggest that the pathophysiology, not disease severity, of CubTS may be explained at least in part by the presence of ulnar nerve strain.
Stabilization of the Gear–Grimshaw system on a periodic domain
Authors: Capistrano Filho R. A. , Komornik V. , Pazoto A. F.
Published: August 2014

This paper is devoted to the study of a nonlinear coupled system of two Korteweg–de Vries equations in a periodic domain under the effect of an internal damping term. The system was introduced by Gear and Grimshaw to model the interactions of two-dimensional, long, internal gravity waves propagation in a stratified fluid. Designing a time-varying feedback law and using a Lyapunov approach, we establish the exponential stability of the solutions in Sobolev spaces of any positive integral order.
MHD Boundary Layer Slip Flow and Heat Transfer of Nanofluid Past a Vertical Stretching Sheet with Non-Uniform Heat Generation/Absorption
Authors: Das S. , Jana R. N. , Makinde O. D.
Published: August 2014

An investigation of the magnetohydrodynamics (MHD) boundary layer slip flow over a vertical stretching sheet in nanofluid with non-uniform heat generation/absorbtion in the presence of a uniform transverse magnetic field has been carried out. The governing non-linear partial differential equations are transformed into a system of coupled non-linear ordinary differential equations using similarity transformations and then solved numerically using the Runge–Kutta fourth order method with shooting technique. Numerical results are obtained for the fluid velocity, temperature as well as the shear stress and the rate of heat transfer at the surface of the sheet. The results show that there are significant effects of various pertinent parameters on velocity and temperature profiles.
Two-dimensional decaying turbulence in confined geometries
Authors: Toth Gabor , Hazi Gabor
Published: August 2014

Several interesting phenomena have been observed simulating two-dimensional decaying turbulence in bounded domains. In this paper, an overview is given about our observations obtained by simulating freely decaying turbulence in different regular polygon shaped containers with no-slip walls. For these simulations the lattice Boltzmann method has been used as a numerical approach. The initial Reynolds number based on the container dimension was in the order of 10,000. The initial condition was the same in each simulation, therefore, we were able to compare the effect of geometrical constraints on the evolution of relevant physical quantities such as the kinetic energy and the enstrophy.
Biomechanical strain vehicles for fibroblast-directed skeletal myoblast differentiation and myotube functionality in a novel coculture
Authors: Hicks Michael R. , Cao Thanh V. , Standley Paul R.
Published: August 2014

Skeletal muscle functionality is governed by multiple stimuli, including cytokines and biomechanical strain. Fibroblasts embedded within muscle connective tissue respond to biomechanical strain by secreting cytokines that induce myoblast differentiation and, we hypothesize, regulate myotube function. A coculture was established to allow cross talk between fibroblasts in Bioflex wells and myoblasts on nondeformable coverslips situated above Bioflex wells. Cyclic short-duration strain (CSDS) modeling repetitive stress/injury, acyclic long-duration strain (ALDS) modeling manipulative therapy, and combined strain paradigms (CSDS + ALDS) were applied to fibroblasts. Nonstrained myoblasts in uniculture and coculture served as controls. After fibroblasts had induced myoblast differentiation, myotube contraction was assessed by perfusion of ACh (10−11–10−3 M). CSDS-treated fibroblasts increased myotube contractile sensitivity vs. uniculture ( P < 0.05). As contraction is dependent on ACh binding, expression and clustering of nicotinic ACh receptors (nAChRs) were measured. CSDS-treated fibroblasts increased nAChR expression ( P < 0.05), which correlated with myotube contraction. ALDS-treated fibroblasts did not significantly affect contraction or nAChR expression. Agrin-treated myotubes were then used to design a computer algorithm to identify α-bungarotoxin-stained nAChR clusters. ALDS-treated fibroblasts increased nAChR clustering ( P < 0.05), while CSDS-treated fibroblasts disrupted cluster formation. CSDS-treated fibroblasts produced nAChRs preferentially located in nonclustered regions ( P < 0.05). Strain-activated fibroblasts mediate myotube differentiation with multiple functional phenotypes. Similar to muscle injury, CSDS-treated fibroblasts disrupted nAChR clusters and hypersensitized myotube contraction, while ALDS-treated fibroblasts aggregated nAChRs in large clusters, which may have important clinical implications. Cellular strategies aimed at improving muscle functionality, such as through biomechanical strain vehicles that activate fibroblasts to stabilize postsynaptic nAChRs on nearby skeletal muscle, may serve as novel targets in neuromuscular disorders.
Cold water immersion enhances recovery of submaximal muscle function after resistance exercise
Authors: Roberts Llion A. , Nosaka Kazunori , Coombes Jeff S. , Peake Jonathan M.
Published: August 2014

We investigated the effect of cold water immersion (CWI) on the recovery of muscle function and physiological responses after high-intensity resistance exercise. Using a randomized, cross-over design, 10 physically active men performed high-intensity resistance exercise followed by one of two recovery interventions: 1) 10 min of CWI at 10°C or 2) 10 min of active recovery (low-intensity cycling). After the recovery interventions, maximal muscle function was assessed after 2 and 4 h by measuring jump height and isometric squat strength. Submaximal muscle function was assessed after 6 h by measuring the average load lifted during 6 sets of 10 squats at 80% of 1 repetition maximum. Intramuscular temperature (1 cm) was also recorded, and venous blood samples were analyzed for markers of metabolism, vasoconstriction, and muscle damage. CWI did not enhance recovery of maximal muscle function. However, during the final three sets of the submaximal muscle function test, participants lifted a greater load ( P < 0.05, Cohen's effect size: 1.3, 38%) after CWI compared with active recovery. During CWI, muscle temperature decreased ∼7°C below postexercise values and remained below preexercise values for another 35 min. Venous blood O2saturation decreased below preexercise values for 1.5 h after CWI. Serum endothelin-1 concentration did not change after CWI, whereas it decreased after active recovery. Plasma myoglobin concentration was lower, whereas plasma IL-6 concentration was higher after CWI compared with active recovery. These results suggest that CWI after resistance exercise allows athletes to complete more work during subsequent training sessions, which could enhance long-term training adaptations.
Analysis of the long-term actions of gabapentin and pregabalin in dorsal root ganglia and substantia gelatinosa
Authors: Biggs James E. , Boakye Paul A. , Ganesan Naren , Stemkowski Patrick L. , Lantero Aquilino , Ballanyi Klaus , Smith Peter A.
Published: August 2014

The α2δ-ligands pregabalin (PGB) and gabapentin (GBP) are used to treat neuropathic pain. We used whole cell recording to study their long-term effects on substantia gelatinosa and dorsal root ganglion (DRG) neurons. Spinal cord slices were prepared from embryonic day 13 rat embryos and maintained in organotypic culture for >5 wk (neuronal age equivalent to young adult rats). Exposure of similarly aged DRG neurons (dissociated and cultured from postnatal day 19 rats) to GBP or PGB for 5–6 days attenuated high-voltage-activated calcium channel currents (HVA ICa). Strong effects were seen in medium-sized and in small isolectin B4-negative (IB4−) DRG neurons, whereas large neurons and small neurons that bound isolectin B4 (IB4+) were hardly affected. GBP (100 μM) or PGB (10 μM) were less effective than 20 μM Mn2+ in suppression of HVA ICa in small DRG neurons. By contrast, 5–6 days of exposure to these α2δ-ligands was more effective than 20 μM Mn2+ in reducing spontaneous excitatory postsynaptic currents at synapses in substantia gelatinosa. Spinal actions of gabapentinoids cannot therefore be ascribed to decreased expression of HVA Ca2+ channels in primary afferent nerve terminals. In substantia gelatinosa, 5–6 days of exposure to PGB was more effective in inhibiting excitatory synaptic drive to putative excitatory neurons than to putative inhibitory neurons. Although spontaneous inhibitory postsynaptic currents were also attenuated, the overall long-term effect of α2δ-ligands was to decrease network excitability as monitored by confocal Ca2+ imaging. We suggest that selective actions of α2δ-ligands on populations of DRG neurons may predict their selective attenuation of excitatory transmission onto excitatory vs. inhibitory neurons in substantia gelatinosa.
Learning-related neuronal activity in the ventral lateral geniculate nucleus during associative cerebellar learning
Authors: Kashef Alireza , Campolattaro Matthew M. , Freeman John H.
Published: August 2014

During delay eyeblink conditioning, rats learn to produce an eyelid-closure conditioned response (CR) to a conditioned stimulus (CS), such as a light, which precedes and coterminates with an unconditioned stimulus (US). Previous studies have suggested that the ventral lateral geniculate nucleus (LGNv) might play an important role in visual eyeblink conditioning by supplying visual sensory input to the pontine nuclei (PN) and also receiving feedback from the cerebellum. No prior study has investigated LGNv neuronal activity during eyeblink conditioning. The present study used multiple tetrodes to monitor single-unit activity in the rat LGNv during pre-exposure (CS only), unpaired CS/US, and paired CS-US training conditions. This behavioral-training sequence was used to investigate nonassociative- and associative-driven neuronal activity in the LGNv during training. LGNv neuronal activity habituated during unpaired training and then recovered from habituation during subsequent paired training, which may indicate that the LGNv plays a role in attention to the CS. The amplitude of LGNv neuronal activity correlated with CR production during paired but not unpaired CS/US training. Cerebellar feedback to the LGNv may play a role in modulating LGNv activity and attention to the CS during paired training. Based on the present findings, we hypothesize that the role of LGNv in visual eyeblink conditioning goes beyond simply routing visual CS information to the PN and involves modulation of attention.
Effects of millimeter wave irradiation and equivalent thermal heating on the activity of individual neurons in the leech ganglion
Authors: Romanenko Sergii , Siegel Peter H. , Wagenaar Daniel A. , Pikov Victor
Published: August 2014

Many of today's radiofrequency-emitting devices in telecommunication, telemedicine, transportation safety, and security/military applications use the millimeter wave (MMW) band (30–300 GHz). To evaluate the biological safety and possible applications of this radiofrequency band for neuroscience and neurology, we have investigated the physiological effects of low-intensity 60-GHz electromagnetic irradiation on individual neurons in the leech midbody ganglia. We applied incident power densities of 1, 2, and 4 mW/cm2 to the whole ganglion for a period of 1 min while recording the action potential with a standard sharp electrode electrophysiology setup. For comparison, the recognized U.S. safe exposure limit is 1 mW/cm2 for 6 min. During the exposure to MMWs and gradual bath heating at a rate of 0.04°C/s (2.4°C/min), the ganglionic neurons exhibited similar dose-dependent hyperpolarization of the plasma membrane and decrease in the action potential amplitude. However, narrowing of the action potential half-width during MMW irradiation at 4 mW/cm2 was 5 times more pronounced compared with that during equivalent bath heating of 0.6°C. Even more dramatic difference in the effects of MMW irradiation and bath heating was noted in the firing rate, which was suppressed at all applied MMW power densities and increased in a dose-dependent manner during gradual bath heating. The mechanism of enhanced narrowing of action potentials and suppressed firing by MMW irradiation, compared with that by gradual bath heating, is hypothesized to involve specific coupling of MMW energy with the neuronal plasma membrane.
Decoding stimulus duration from neural responses in the auditory midbrain
Authors: Aubie Brandon , Sayegh Riziq , Fremouw Thane , Covey Ellen , Faure Paul A.
Published: August 2014

Neurons with responses selective for the duration of an auditory stimulus are called duration-tuned neurons (DTNs). Temporal specificity in their spiking suggests that one function of DTNs is to encode stimulus duration; however, the efficacy of duration encoding by DTNs has yet to be investigated. Herein, we characterize the information content of individual cells and a population of DTNs from the mammalian inferior colliculus (IC) by measuring the stimulus-specific information (SSI) and estimated Fisher information (FI) of spike count responses. We found that SSI was typically greatest for those stimulus durations that evoked maximum spike counts, defined as best duration (BD) stimuli, and that FI was maximal for stimulus durations off BD where sensitivity to a change in duration was greatest. Using population data, we demonstrate that a maximum likelihood estimator (MLE) can accurately decode stimulus duration from evoked spike counts. We also simulated a two-alternative forced choice task by having MLE models decide whether two durations were the same or different. With this task we measured the just-noticeable difference threshold for stimulus duration and calculated the corresponding Weber fractions across the stimulus domain. Altogether, these results demonstrate that the spiking responses of DTNs from the mammalian IC contain sufficient information for the CNS to encode, decode, and discriminate behaviorally relevant auditory signal durations.
Dopamine transporter gene susceptibility to methylation is associated with impulsivity in nonhuman primates
Authors: Rajala Abigail Z. , Zaitoun Ismail , Henriques Jeffrey B. , Converse Alexander K. , Murali Dhanabalan , Epstein Miles L. , Populin Luis C.
Published: August 2014

Impulsivity, the predisposition to act without regard for negative consequences, is a characteristic of several psychiatric disorders and is thought to result in part from genetic variation in the untranslated region of the dopamine transporter (DAT) gene. As the exact link between genetic mutations and impulsivity has not been established, we used oculomotor behavior to characterize rhesus monkeys as impulsive or calm and genetic/epigenetic analysis and positron emission tomography (PET) to correlate phenotype to DAT genotype, DAT gene methylation, and DAT availability. We found three single nucleotide polymorphisms (SNPs) in the 3′-UTR of the DAT gene, one of which provided a potential site for methylation in the impulsive group. Bisulfite analysis showed that the DNA of the impulsive but not the calm subjects was methylated at one SNP. Because genetic/epigenetic modifications could lead to differences in protein expression, we measured DAT availability using [18F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane ([18F]FECNT) PET and found higher DAT availability in the internal globus pallidus, an output nucleus of the basal ganglia, of the impulsive group. Higher DAT availability lowers dopamine levels, potentially altering neuronal circuits involved in the initiation of action, thus contributing to the impulsive phenotype. The association between increased methylation in the DAT gene and greater DAT availability suggests that mutations to the regulatory portion of the DAT gene lead to a susceptibility to epigenetic modification resulting in a discrete behavioral phenotype.
Opposed optimal strategies of weighting somatosensory inputs for planning reaching movements toward visual and proprioceptive targets
Authors: Blouin Jean , Saradjian Anahid H. , Lebar Nicolas , Guillaume Alain , Mouchnino Laurence
Published: August 2014

Behavioral studies have suggested that the brain uses a visual estimate of the hand to plan reaching movements toward visual targets and somatosensory inputs in the case of somatosensory targets. However, neural correlates for distinct coding of the hand according to the sensory modality of the target have not yet been identified. Here we tested the twofold hypothesis that the somatosensory input from the reaching hand is facilitated and inhibited, respectively, when planning movements toward somatosensory (unseen fingers) or visual targets. The weight of the somatosensory inputs was assessed by measuring the amplitude of the somatosensory evoked potential (SEP) resulting from vibration of the reaching finger during movement planning. The target sensory modality had no significant effect on SEP amplitude. However, Spearman's analyses showed significant correlations between the SEPs and reaching errors. When planning movements toward proprioceptive targets without visual feedback of the reaching hand, participants showing the greater SEPs were those who produced the smaller directional errors. Inversely, participants showing the smaller SEPs when planning movements toward visual targets with visual feedback of the reaching hand were those who produced the smaller directional errors. No significant correlation was found between the SEPs and radial or amplitude errors. Our results indicate that the sensory strategy for planning movements is highly flexible among individuals and also for a given sensory context. Most importantly, they provide neural bases for the suggestion that optimization of movement planning requires the target and the reaching hand to both be represented in the same sensory modality.
Antibacterial Activity ofPseudonocardiasp. JB05, a Rare Salty Soil Actinomycete againstStaphylococcus aureus
Authors: Jafari Nesa , Behroozi Reza , Farajzadeh Davoud , Farsi Mohammad , Akbari-Noghabi Kambiz
Published: August 2014

Staphylococcus aureusis a Gram-positive bacterium that causes many harmful and life-threatening diseases. Some strains of this bacterium are resistant to available antibiotics. This study was designed to evaluate the ability of indigenous actinomycetes to produce antibacterial compounds againstS. aureusand characterize the structure of the resultant antibacterial compounds. Therefore, a slightly modified agar well diffusion method was used to determine the antibacterial activity of actinomycete isolates against the test microorganisms. The bacterial extracts with antibacterial activity were fractionated by silica gel and G-25 sephadex column chromatography. Also, the active fractions were analyzed by thin layer chromatography. Finally, the partial structure of the resultant antibacterial compound was characterized by Fourier transform infrared spectroscopy. One of the isolates, which had a broad spectrum and high antibacterial activity, was designated asPseudonocardiasp. JB05, based on the results of biochemical and 16S rDNA gene sequence analysis. Minimum inhibitory concentration for this bacterium was 40 AU mL−1againstS. aureus. The antibacterial activity of this bacterium was stable after autoclaving, 10% SDS, boiling, and proteinase K. Thin layer chromatography, using anthrone reagent, showed the presence of carbohydrates in the purified antibacterial compound. Finally, FT-IR spectrum of the active compound illustrated hydroxyl groups, hydrocarbon skeleton, and double bond of polygenic compounds in its structure. To the best of our knowledge, this is the first report describing the efficient antibacterial activity by a local strain ofPseudonocardia.The results presented in this work, although at the initial stage in bioactive product characterization, will possibly contribute toward thePseudonocardiascale-up for the production and identification of the antibacterial compounds.
Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa
Authors: Vergotine Z. , Kengne A. P. , Erasmus R. T. , Yako Y. Y. , Matsha T. E.
Published: August 2014

Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population.Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR),β-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated.Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (P=0.215). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95)).Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes.