bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose metabolism in pigs expressing human genes under an insulin promoter
Authors: Wijkstrom Martin , Bottino Rita , Iwase Hayoto , Hara Hidetaka , Ekser Burcin , van der Windt Dirk , Long Cassandra , Toledo Frederico G. S. , Phelps Carol J. , Trucco Massimo , Cooper David K. C. , Ayares David
Published: November 2014

Background

Xenotransplantation of porcine islets can reverse diabetes in non‐human primates. The remaining hurdles for clinical application include safe and effective T‐cell‐directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet‐targeted genetic manipulation of islet‐source pigs represents a powerful tool to protect against graft loss. However, whether these genetic alterations would impair islet function is unknown.

Methods

On a background of α1,3‐galactosyltransferase gene‐knockout (GTKO)/human (h)CD46, additional genes (hCD39, human tissue factor pathway inhibitor, porcine CTLA4‐Ig) were inserted in different combinations under an insulin promoter to promote expression in islets (confirmed by immunofluorescence). Seven pigs were tested for baseline and glucose/arginine‐challenged levels of glucose, insulin, C‐peptide, and glucagon.

Results

This preliminary study did not show definite evidence of β‐cell deficiencies, even when three transgenes were expressed under the insulin promoter. Of seven animals, all were normoglycemic at fasting, and five of seven had normal glucose disposal rates after challenge. All animals exhibited insulin, C‐peptide, and glucagon responses to both glucose and arginine challenge; however, significant interindividual variation was observed.

Conclusions

Multiple islet‐targeted transgenic expression was not associated with an overtly detrimental effect on islet function, suggesting that complex genetic constructs designed for islet protection warrants further testing in islet xenotransplantation models.
Dominant role of interstitial cells of Cajal in nitrergic relaxation of murine lower oesophageal sphincter
Authors: Groneberg Dieter , Zizer Eugen , Lies Barbara , Seidler Barbara , Saur Dieter , Wagner Martin , Friebe Andreas
Published: November 2014

Key points

Nitric oxide (NO) is an important inhibitory neurotransmitter in the gastrointestinal tract. Oesophageal achalasia may result from impairment of nitrergic relaxation.

Smooth muscle cells (SMCs) have been accepted to be the major targets for neuronal NO to mediate relaxation. However, besides SMCs, the receptor for NO, NO‐sensitive guanylyl cyclase (NO‐GC), has been shown in interstitial cells of Cajal (ICC).

Using cell‐specific knockout mice, this study shows that NO‐GC in SMC and ICC modulates lower oesophagus sphincter tone in vitro and in vivo.

More importantly, NO‐GC in ICC possesses a dominant role in mediating swallowing‐induced relaxation. Lack of functional nitrergic signalling, thus, results in deficits in relaxation of the lower oesophagus sphincter as seen in achalasic patients.

Oesophageal achalasia is a disease known to result from reduced relaxation of the lower oesophageal sphincter (LES). Nitric oxide (NO) is one of the main inhibitory transmitters. NO‐sensitive guanylyl cyclase (NO‐GC) acts as the key target of NO and, by the generation of cGMP, mediates nitrergic relaxation in the LES. To date, the exact mechanism of nitrergic LES relaxation is still insufficiently elucidated. To clarify the role of NO‐GC in LES relaxation, we used cell‐specific knockout (KO) mouse lines for NO‐GC. These include mice lacking NO‐GC in smooth muscle cells (SMC‐GCKO), in interstitial cells of Cajal (ICC‐GCKO) and in both SMC/ICC (SMC/ICC‐GCKO). We applied oesophageal manometry to study the functionality of LES in vivo. Isometric force studies were performed to monitor LES responsiveness to exogenous NO and electric field stimulation of intrinsic nerves in vitro. Cell‐specific expression/deletion of NO‐GC was monitored by immunohistochemistry. Swallowing‐induced LES relaxation is strongly reduced by deletion of NO‐GC in ICC. Basal LES tone is affected by NO‐GC deletion in either SMC or ICC. Lack of NO‐GC in both cells leads to a complete interruption of NO‐induced relaxation and, therefore, to an achalasia‐like phenotype similar to that seen in global GCKO mice. Our data indicate that regulation of basal LES tone is based on a dual mechanism mediated by NO‐GC in SMC and ICC whereas swallow‐induced LES relaxation is mainly regulated by nitrergic mechanisms in ICC.
Pannexin channels and ischaemia
Authors: Thompson Roger J.
Published: November 2014

An ischaemic stroke occurs during loss of blood flow in the brain from the occlusion of a blood vessel. The ischaemia itself comprises a complex array of insults, including oxygen and glucose deprivation (OGD), glutamate excitotoxicity, acidification/hypercapnia, and loss of sheer forces. A substantial amount of knowledge has accumulated that define the excitotoxic cascade downstream of N‐methyl‐d‐aspartate receptors (NMDARs). While the NMDAR can influence numerous downstream elements, one critical target during ischaemia is the ion channel, pannexin‐1 (Panx1). The C‐terminal region of Panx1 appears critical for its regulation under a host of physiological and pathological stimuli. We have shown using hippocampal brain slices that Panx1 is activated by NMDARs through Src family kinases. However, it is not yet certain if this involves direct phosphorylation of Panx1 or an allosteric interaction between the channel's C‐terminal tail and Src. Interestingly, Panx1 opening during ischaemia and NMDAR over‐activation is antagonized by an interfering peptide that comprises amino acids 305–318 of Panx1. Thus, targeting the activation of Panx1 by NMDARs and Src kinases is an attractive mechanism to reduce anoxic depolarizations and neuronal death.
RNASeq‐derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat
Authors: Puissant Madeleine M. , Echert Ashley E. , Yang Chun , Mouradian Gary C. , Novotny Tyler , Liu Pengyuan , Liang Mingyu , Hodges Matthew R.
Published: November 2014

Key points

Increases in carbon dioxide (CO2) provide a major chemical stimulus to breathe through activation of the ventilatory CO2 chemoreflex, which is heavily influenced by the brainstem serotonergic (5‐HT) system.

Brown Norway (BN) rats have an inherent and extremely low ventilatory sensitivity to hypercapnia, which can be augmented with selective serotonin reuptake inhibition.

Using mRNA sequencing, we show that BN rats have reduced medullary raphé expression of multiple 5‐HT neuron‐specific genes, predictive of lower monoamine levels by informatics pathway analyses and confirmed by high‐performance liquid chromatography measurements.

BN rats also showed reduced thyrotropin‐releasing hormone (TRH) expression, where injections of the TRH analogue Taltirelin caused greater increases in baseline ventilation, body temperature and the ventilatory CO2 chemoreflex in BN rats compared to control Sprague–Dawley rats.

These data establish a molecular basis of a neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex.

Raphé‐derived serotonin (5‐HT) and thyrotropin‐releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5‐HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé‐derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5‐HT neuron‐specific genes in BN compared to control Dahl salt‐sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high‐performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose‐dependently, with greater effects in BN versus control Sprague–Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague–Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex.
Microvascular perfusion heterogeneity contributes to peripheral vascular disease in metabolic syndrome
Authors: Frisbee Jefferson C. , Goodwill Adam G. , Frisbee Stephanie J. , Butcher Joshua T. , Wu Fan , Chantler Paul D.
Published: November 2014

A major challenge facing public health is the increased incidence and prevalence of the metabolic syndrome, a clinical condition characterized by excess adiposity, impaired glycaemic control, dyslipidaemia and moderate hypertension. The greatest concern for this syndrome is the profound increase in risk for development of peripheral vascular disease (PVD) in afflicted persons. However, ongoing studies suggest that reductions in bulk blood flow to skeletal muscle may not be the primary contributor to the premature muscle fatigue that is a hallmark of PVD. Compelling evidence has been provided suggesting that an increasingly spatially heterogeneous and temporally stable distribution of blood flow at successive arteriolar bifurcations in metabolic syndrome creates an environment where a large number of the pre‐capillary arterioles have low perfusion, low haematocrit, and are increasingly confined to this state, with limited ability to adapt perfusion in response to a challenged environment. Single pharmacological interventions are unable to significantly restore function owing to a divergence in their spatial effectiveness, although combined therapeutic approaches to correct adrenergic dysfunction, elevated oxidant stress and increased thromboxane A2improve perfusion‐based outcomes. Integrated, multi‐target therapeutic interventions designed to restore healthy network function and flexibility may provide for superior outcomes in subjects with metabolic syndrome‐associated PVD.
The Role of Contact Line (Pinning) Forces on Bubble Blockage in Microchannels
Authors: Mohammadi Mahshid , Sharp Kendra V.
Published: November 2014

This paper highlights the influence of contact line (pinning) forces on the mobility of dry bubbles in microchannels. Bubbles moving at velocities less than the dewetting velocity of liquid on the surface are essentially dry, meaning that there is no thin liquid film around the bubbles. For these “dry” bubbles, contact line forces and a possible capillary pressure gradient induced by pinning act on the bubbles and resist motion. Without sufficient driving force (e.g., external pressure), a dry bubble is brought to stagnation. For the first time, a bipartite theoretical model that estimates the required pressure difference across the length of stagnant bubbles with concave and convex back interfaces to overcome the contact line forces and stimulate motion is proposed. To validate our theory, the pressure required to move a single dry bubble in square microchannels exhibiting contact angle hysteresis has been measured. The working fluid was de-ionized water. The experiments have been conducted on coated glass channels with different surface hydrophilicities that resulted in concave and convex back interfaces for the bubbles. The experimental results were in agreement with the model's predictions for square channels. The predictions of the concave and convex back models were within 19% and 27% of the experimental measurements, respectively.
Experimental and Numerical Study of Heat Transfer and Flow Friction in Channels With Dimples of Different Shapes
Authors: Rao Yu , Feng Yan , Li Bo , Weigand Bernhard
Published: November 2014

An experimental and numerical study was conducted to investigate the effects of dimple shapes on the heat transfer and flow friction of a turbulent flow over dimpled surfaces with different dimple shapes: spherical, teardrop, elliptical, and inclined elliptical. These dimples all have the same depth. The heat transfer, friction factor, and flow structure characteristics in the cooling channels with dimples of different shapes have been obtained and compared with each other for a Reynolds number range of 8500–60,000. The study showed that the dimple shape can have distinctive effects on the heat transfer and flow structure in the dimpled channels. The teardrop dimples show the highest heat transfer, which is about 18% higher than the conventional spherical dimples; and the elliptical dimples have the lowest heat transfer, which is about 10% lower than the spherical dimples; and however the inclined elliptical dimples have comparable heat transfer and pressure loss performance with the spherical dimples. The experiments still showed the realistic heat transfer enhancement capabilities of the dimpled channels relative to a smooth rectangular channel flow under the same flow and thermal boundary conditions, even after considering the thermal entrance effects in the channel flow and the enlarged heat transfer (wetted) area due to the dimpled surface. The three-dimensional numerical computations showed different vortex flow structures and detailed heat transfer characteristics of the dimples with different shapes, which revealed the influential mechanisms of differently shaped dimples on the convective heat transfer enhancement.
The New Mathematical Models for Plain Fin-and-Tube Heat Exchangers With Dehumidification
Authors: Pirompugd Worachest , Wang Chi-Chuan , Wongwises Somchai
Published: November 2014

For evaluating performance of fin-and-tube heat exchangers under dehumidifying conditions, the recent lumped approach models are based on the enthalpy potential or equivalent dry bulb temperature. This study proposes a new lumped approach model based on the dry bulb temperature difference. The concept of dry bulb temperature was first presented by McQuiston for derivation of fin efficiency under dehumidifying conditions in 1975. This concept is simpler than the concepts of enthalpy potential and equivalent dry bulb temperature. Nevertheless, it cannot be found that this concept is applied to the fin-and-tube heat exchangers. Moreover, this study also presents the finite circular fin method (FCFM) based on the dry bulb temperature and equivalent dry bulb temperature. The FCFM was first presented in our published literature but it was based on the enthalpy potential. The FCFM is done by dividing the fin-and-tube heat exchanger into many small segments. Then, the segments are divided into three cases: fully dry condition, fully wet condition, and partially wet condition. From the results, the new lumped approach model based on dry bulb temperature gives a good result. It is the simplest method for evaluating heat transfer performance of fin-and-tube heat exchangers under fully wet conditions. For the FCFM, the heat and mass transfer characteristics obtained by dry bulb temperature and equivalent dry bulb temperature are nearly the same as those obtained by the enthalpy potential. However, the heat and mass transfer characteristics by the FCFM based on equivalent dry bulb temperature are higher than those obtained by the FCFM based on dry bulb temperature. This is because of the effect of the nonconstant term in the two methods. The correlations applicable for both fully wet and partially wet conditions for the FCFMs based on equivalent dry bulb temperature and dry bulb temperature are proposed to describe the heat and mass transfer characteristics for the present plain fin configuration.
The Use of Inverse Heat Conduction Models for Estimation of Transient Surface Heat Flux in Electroslag Remelting
Authors: Plotkowski Alex , Krane Matthew John M.
Published: November 2014

Three inverse heat conduction models were evaluated for their ability to predict the transient heat flux at the interior surface of the copper mold in the electroslag remelting (ESR) process for use in validating numerical ESR simulations and real-time control systems. The models were evaluated numerically using a simple one-dimensional (1D) test case and a 2D pseudo-ESR test case as a function of the thermocouple locations and sample frequency. The sensitivity of the models to measurement errors was then tested by applying random error to the numerically calculated temperature fields prior to the application of the inverse models. This error caused large fluctuations in the results of the inverse models, but these could be mitigated by implementing a simple Savitzky–Golay filter for data smoothing. Finally, the three inverse methods were applied to a fully transient ESR simulation to demonstrate their applicability to the industrial process. Based on these results, the authors recommend that the 2D control volume method described here be applied to industrial ESR trials.
The Effect of Honeycomb Core Geometry on the Sound Transmission
Performance of Sandwich Panels
Authors: Griese David , Summers Joshua D. , Thompson Lonny
Published: November 2014

The authors present numerical results for a systematic parametric study of the effect of honeycomb core geometry on the sound transmission and vibration properties of in-plane loaded honeycomb core sandwich panels using structural acoustic finite element analysis (FEA). Honeycomb cellular structures offer many distinct advantages over homogenous materials because their effective material properties depend on both their constituent material properties and their geometric cell configuration. From these structures, a wide range of targeted effective material properties can be achieved thus supporting forward design-by-tailoring honeycomb cellular structures for specific applications. One area that has not been fully explored is the set of acoustic properties of honeycomb and understanding of how designers can effectively tune designs in different frequency ranges. One such example is the insulation of target sound frequencies to prevent sound transmission through a panel. This work explored the effect of geometry of in-plane honeycomb cores in sandwich panels on the acoustic properties the panel. The two acoustic responses of interest are the general level of sound transmission loss (STL) of the panel and the location of the resonance frequencies that exhibit high levels of sound transmission, or low sound pressure transmission loss. Constant mass honeycomb core models were studied with internal cell angles ranging in increments from −45 deg to +45 deg. Effective honeycomb moduli based on static analysis of honeycomb unit cells are calculated and correlated to the shift in resonance frequencies for the different geometries, with all panels having the same total mass. This helps explain the direction of resonance frequency shift found in the panel natural frequency solutions. Results show an interesting trend of the first resonance frequencies in relation to effective structural properties. Honeycomb geometries with smaller core internal cell angles, under constant mass constraints, shifted natural frequencies lower, and had more resonances in the 1–1000 Hz range, but exhibited a higher sound pressure transmission loss between resonant frequencies.
Identification and Suppression of Unbalanced Magnetic Force and Cogging Torque in Permanent Magnet Motors With Magnetic Field Distortion
Authors: Wang Shiyu , Xie Bang , Wang Chenxin , Xiu Jie
Published: November 2014

Permanent magnet (PM) induced vibration is one of the major concerns for PM motors. This work aims at the identification and suppression of the vibration source from magnetic field distortions caused by magnet/slot combination, uneven-magnetization, and magnet shifting. Modulation method is employed to predict the relationships between parameters and unbalanced magnetic force (UMF) and cogging torque (CT). Motivated by the magnetic field periodicity and structure especially air-gap symmetry, a new concept of equivalent magnet (EM) wherein one or more real magnets are defined as an imaginary one is introduced to help predict the unexpected force harmonics normally lower than magnet number, and rotation-frequency is used to present unified interpretation on magnetic force regarding the three distortions. The results imply that the relationships are determined by magnet/EM/slot combination including their greatest common divisor (GCD). Compared with CT, the UMF is more sensitive to the uneven-magnetization and magnet shifting. Like ideal motors, if the GCD is greater than unity, the UMF is eliminated, but the CT is not simply via altering the combination. The results also show that magnetic forces for the same EM/slot combinations share similar behaviors regardless of specific magnetic field details. The results can be utilized to suppress undesirable force, or inspect magnetization and installation status by monitoring force frequency and its amplitude, or gain vibration suppression by magnet's selective assembly. The modulation method, EM concept, and main findings are successfully verified by the finite element method (FEM) and comparison with the existing results in the literature. Main contribution of this work is the unified explanation on the relationships between the three distortions and unique force behaviors, especially the prediction on those unexpected harmonic forces.
A Portrait of an ISO STEP Tolerancing Standard as an Enabler of Smart Manufacturing Systems
Authors: Feeney Allison Barnard , Frechette Simon P. , Srinivasan Vijay
Published: November 2014

The International Organization for Standardization (ISO) has just completed a major effort on a new standard ISO 10303-242 titled “Managed Model Based 3D Engineering.” It belongs to a family of standards called STEP (STandard for the Exchange of Product model data). ISO 10303-242 is also called the STEP Application Protocol 242 (STEP AP 242, for short). The intent of STEP AP 242 is to support a manufacturing enterprise with a range of standardized information models that flow through a long and wide “digital thread” that makes the manufacturing systems in the enterprise smart. One such standardized information model is that of tolerances specified on a product’s geometry so that the product can be manufactured according to the specifications. This paper describes the attributes of smart manufacturing systems, the capabilities of STEP AP 242 in handling tolerance information associated with product geometry, and how these capabilities enable the manufacturing systems to be smart.
A Computational and Experimental Investigation of Synthetic Jets for Cooling of Electronics
Authors: Arik Mehmet , Utturkar Yogen V.
Published: November 2014

Seamless advancements in electronics industry resulted in high performance computing. These innovations lead to smaller electronics systems with higher heat fluxes than ever. However, shrinking nature of real estate for thermal management has created a need for more effective and compact cooling solutions. Novel cooling techniques have been of interest to solve the demand. One such technology that functions with the principle of creating vortex rings is called synthetic jets. These jets are mesoscale devices operating as zero-net-mass-flux principle by ingesting and ejection of high velocity working fluid from a single opening. These devices produce periodic jet streams, which may have peak velocities over 20 times greater than conventional, comparable size fan velocities. These jets enhance heat transfer in both natural and forced convection significantly over bare and extended surfaces. Recognizing the heat transfer physics over surfaces require a fundamental understanding of the flow physics caused by microfluid motion. A comprehensive computational and experimental study has been performed to understand the flow physics of a synthetic jet. Computational study has been performed via FLUENT commercial software, while the experimental study has been performed by using laser Doppler anemometry (LDA). Since synthetic jets are typical sine-wave excited between 20 and 60 V range, they have an orifice peak velocity of over 60 m/s, resulting in a Reynolds number of over 2000. Computational fluid dynamics (CFD) predictions on the vortex dipole location fall within 10% of the experimental measurement uncertainty band.
Improved alignment algorithm for electron beam lithography
Authors: Thoms Stephen , Zhang Yuan , Weaver John M. R.
Published: November 2014

The authors describe a modification to the alignment algorithm typically used for electron beam lithography. Extra markers are used, which increases accuracy, but more importantly enables misplaced markers to be detected and discounted. This has the advantage of eliminating the effect of occasional poor markers and also gives a measure of the expected alignment accuracy after marker search and prior to writing. Two methods for identifying outliers are discussed, the first being a conventional least squares approach in which outliers are rejected one by one. The second approach uses the method of trimmed least squares, which is a more robust regression method, and was found to give better results. With 16 or more evenly distributed markers around the edge of the pattern both methods were found to give good results. Both modeled and experimental data were used to evaluate the use of additional markers. The experimental results showed that with 24 markers, 10 of which had position errors between 100 and 300 nm, a final alignment accuracy of 20 nm could be obtained. Finally this technique can be used to identify rogue markers, which is an important first step toward rectifying the process issues which led to the formation of poor markers in the first place. This is particularly important during process development, which is a major part of the typical throughput of an electron beam lithography tool.
Should the Equilibrium Point Hypothesis (EPH) Be Considered a Scientific Theory?
Authors: Sainburg Robert L.
Published: November 2014

The purpose of this commentary is to discuss factors that limit consideration of the equilibrium point hypothesis as a scientific theory. The EPH describes control of motor neuron threshold through the variable lambda, which corresponds to a unique referent configuration for a muscle, joint, or combination of joints. One of the most compelling features of the equilibrium point hypothesis is the integration of posture and movement control into a single mechanism. While the essential core of the hypothesis is based upon spinal circuitry interacting with peripheral mechanics, the proponents have extended the theory to include the higher-level processes that generate lambda, and in doing so, imposed an injunction against the supraspinal nervous system modeling, computing, or predicting dynamics. This limitation contradicts evidence that humans take account of body and environmental dynamics in motor selection, motor control, and motor adaptation processes. A number of unresolved limitations to the EPH have been debated in the literature for many years, including whether muscle resistance to displacement, measured during movement, is adequate to support this form of control, violations in equifinality predictions, spinal circuits that alter the proposed invariant characteristic for muscles, and limitations in the description of how the complexity of spinal circuitry might be integrated to yield a unique and stable equilibrium position for a given motor neuron threshold. In addition, an important empirical limitation of EPH is the measurement of the invariant characteristic, which needs to be done under a constant central state. While there is no question that the EPH is an elegant and generative hypothesis for motor control research, the claim that this hypothesis has reached the status of a scientific theory is premature.
Youth and Young Adult Physical Activity and Body Composition of Young Adult Women: Findings from the Dietary Intervention Study in Children
Authors: Hodge Melissa , Hovinga Mary , Gabriel Kelley , Snetselaar Linda , Shepherd John , Van Horn Linda , Stevens Victor , Egleston Brian , Robson Alan , Jung Seungyoun , Dorgan Joanne
Published: November 2014

This study prospectively investigates associations between youth moderate-to-vigorous-intensity physical activity (MVPA) and body composition in young adult women using data from the Dietary Intervention Study in Children (DISC) and the DISC06 Follow-Up Study. MVPA was assessed by questionnaire on 5 occasions between the ages 8 and 18 years and at age 25-29 years in 215 DISC female participants. Using whole body dual-energy x-ray absorptiometry (DXA), overall adiposity and body fat distribution were assessed at age 25-29 years by percent body fat (%fat) and android-to-gynoid (A:G) fat ratio, respectively. Linear mixed effects models and generalized linear latent and mixed models were used to assess associations of youth MVPA with both outcomes. Young adult MVPA, adjusted for other young adult characteristics, was significantly inversely associated with young adult %fat (%fat decreased from 37.4% in the lowest MVPA quartile to 32.8% in the highest (p-trend = 0.02)). Adjusted for youth and young adult characteristics including young adult MVPA, youth MVPA also was significantly inversely associated with young adult %fat (β=-0.40 per 10 MET-hrs/wk, p = .02) . No significant associations between MVPA and A:G fat ratio were observed. Results suggest that youth and young adult MVPA are important independent predictors of adiposity in young women.
Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65
Authors: Shinozaki Shohei , Chang Kyungho , Sakai Michihiro , Shimizu Nobuyuki , Yamada Marina , Tanaka Tomokazu , Nakazawa Harumasa , Ichinose Fumito , Yamada Yoshitsugu , Ishigami Akihito , Ito Hideki , Ouchi Yasuyoshi , Starr Marlene E. , Saito Hiroshi , Shimokado Kentaro , Stamler Jonathan S. , Kaneki Masao
Published: November 2014

S-nitrosylation of the deacetylase SIRT1 functions as a proinflammatory switch in aging and inflammatory disorders.
Neurons Halt Angiogenesis
Authors: Berndt Jason D.
Published: November 2014

Neurons sequester and degrade VEGF to prevent abnormal angiogenesis in the developing retina.
In Vitro
Antiviral Activity and Preclinical and Clinical Resistance Profile of Miravirsen, a Novel Anti-Hepatitis C Virus Therapeutic Targeting the Human Factor miR-122
Authors: Ottosen Søren , Parsley Todd B. , Yang Lu , Zeh Karin , van Doorn Leen-Jan , van der Veer Eva , Raney Anneke K. , Hodges Michael R. , Patick Amy K.
Published: November 2014

Miravirsen is a β-
d
-oxy-locked nucleic acid-modified phosphorothioate antisense oligonucleotide targeting the liver-specific microRNA-122 (miR-122). Miravirsen demonstrated antiviral activity against hepatitis C virus (HCV) genotype 1b replicons with a mean 50% effective concentration (EC
50
) of 0.67 μM. No cytotoxicity was observed up to the highest concentration tested (>320 μM) in different cell culture models, yielding a therapeutic index of ≥297. Combination studies of miravirsen with interferon α2b, ribavirin, and nonnucleoside (VX-222) and nucleoside (2′-methylcytidine) inhibitors of NS5B, NS5A (BMS-790052), or NS3 (telaprevir) indicated additive interactions. Miravirsen demonstrated broad antiviral activity when tested against HCV replicons resistant to NS3, NS5A, and NS5B inhibitors with less than 2-fold reductions in susceptibility. In serial passage studies, an A4C nucleotide change was observed in the HCV 5′ untranslated region (UTR) from cells passaged in the presence of up to 20 μM (40-fold the miravirsen EC
50
concentration) at day 72 of passage but not at earlier time points (up to 39 days of passage). Likewise, a C3U nucleotide change was observed in the HCV 5′UTR from subjects with viral rebound after the completion of therapy in a miravirsen phase 2 clinical trial. An HCV variant constructed to contain the A4C change was fully susceptible to miravirsen. A C3U HCV variant demonstrated overall reductions in susceptibility to miravirsen but was fully susceptible to all other anti-HCV agents tested. In summary, miravirsen has demonstrated broad antiviral activity and a relatively high genetic barrier to resistance. The identification of nucleotide changes associated with miravirsen resistance should help further elucidate the biology of miR-122 interactions with HCV. (The clinical trial study has been registered at ClinicalTrials.gov under registration no. NCT01200420).
The Two-Component System GrvRS (EtaRS) Regulates
ace
Expression in Enterococcus faecalis OG1RF
Authors: Roh Jung Hyeob , Singh Kavindra V. , La Rosa Sabina Leanti , Cohen Ana Luisa V. , Murray Barbara E.
Published: November 2014

Expression of
ace
(
a
dhesin to
c
ollagen of

E
nterococcus faecalis

), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism of
ace
/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of
ace
expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an
ace
promoter-
lacZ
fusion, we found transcription of
ace
to be virtually absent in a
grvR
deletion mutant under the conditions that increase
ace
expression in wild-type OG1RF and in the complemented strain. Moreover, a
grvR
mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of
ace
expression and
E. faecalis
virulence.
The EcoKI Type I Restriction-Modification System in Escherichia coli Affects but Is Not an Absolute Barrier for Conjugation
Authors: Roer Louise , Aarestrup Frank M. , Hasman Henrik
Published: November 2014

The rapid evolution of bacteria is crucial to their survival and is caused by exchange, transfer, and uptake of DNA, among other things. Conjugation is one of the main mechanisms by which bacteria share their DNA, and it is thought to be controlled by varied bacterial immune systems. Contradictory results about restriction-modification systems based on phenotypic studies have been presented as reasons for a barrier to conjugation with and other means of uptake of exogenous DNA. In this study, we show that inactivation of the R.EcoKI restriction enzyme in strainEscherichia coliK-12 strain MG1655 increases the conjugational transfer of plasmid pOLA52, which carriers two EcoKI recognition sites. Interestingly, the results were not absolute, and uptake of unmethylated pOLA52 was still observed in the wild-type strain (with an intacthsdRgene) but at a reduction of 85% compared to the uptake of the mutant recipient with a disruptedhsdRgene. This leads to the conclusion that EcoKI restriction-modification affects the uptake of DNA by conjugation but is not a major barrier to plasmid transfer.
Pyoderma gangrenosum as a first presentation of inflammatory bowel disease
Authors: Shahid Shahana , Myszor Margaret , De Silva Aminda
Published: November 2014

Up to 40% of patients with inflammatory bowel disease (IBD) develop an extraintestinal manifestation of the disease with the skin being the most commonly involved organ. Pyoderma gangrenosum (PG), an autoinflammatory non-infectious neutrophilic dermatosis, occurs in 1–2% of patients with IBD. PG can follow a course independent to that of the bowel disease, however, most reported cases describe PG occurring in patients with an established diagnosis of IBD. We present a case of a young patient who presented with axillary skin ulceration, which was subsequently diagnosed as PG. On further investigation for a possible underlying cause, she was found to have Crohn's disease. She had not developed any preceding change in her bowels and did not have abdominal pain; the IBD was diagnosed on endoscopic findings. This case is also unusual for the distribution of the PG lesions that typically occur in the lower limbs.
Beating heart myocardial revascularisation of a sudden cardiac death survivor with spontaneous coronary artery dissection: pitfalls from diagnosis to surgery
Authors: Cetin Erdem , Ozyuksel Arda
Published: November 2014

Spontaneous coronary artery dissection is a rare clinical condition with a wide range of clinical presentations ranging from asymptomatic cases to life-threatening ventricular arrhythmias and sudden cardiac death. The exact pathophysiological mechanism has not been fully established yet. We would like to present a survivor of sudden cardiac death presenting with ventricular fibrillation due to spontaneous coronary artery dissection. The prompt evaluation, medical management, surgical myocardial revascularisation and value of off-pump coronary artery bypass surgery are discussed.
Syringomyelia and Arnold-Chiari malformation associated with neck pain and left arm radiculopathy treated with spinal manipulation
Authors: Tieppo Francio Vinicius
Published: November 2014

An 18-year-old female patient presented with left dominant neck pain after a motor vehicle collision. Her cervical spine MRI revealed syringomyelia with associated Type I Arnold-Chiari malformation. Some researchers have reported that these might be considered contraindications to spinal manipulation. Nevertheless, her benign and functional clinical examination suggested otherwise and she underwent four manipulative treatments in 2 weeks. By the end of the treatment plan and after 1-month follow-up, she was asymptomatic, no adverse effects were noted and her outcome assessment score decreased from 56% to 0%. This case illustrates that spinal manipulation may be a useful adjunctive treatment procedure for spinal pain, even in the presence of syringomyelia and Chiari malformation, which may not necessarily be a contraindication to spinal manipulation, when performed by a skilled and well-trained physician.
Four minutes of in-class high-intensity interval activity improves selective attention in 9- to 11-year olds
Authors: Ma Jasmin K. , Le Mare Lucy , Gurd Brendon J.
Published: November 2014

The amount of time allocated to physical activity in schools is declining. Time-efficient physical activity solutions that demonstrate their impact on academic achievement-related outcomes are needed to prioritize physical activity within the school curricula. “FUNtervals” are 4-min, high-intensity interval activities that use whole-body actions to complement a storyline. The purpose of this study was to (i) explore whether FUNtervals can improve selective attention, an executive function posited to be essential for learning and academic success; and (ii) examine whether this relationship is predicted by students’ classroom off-task behaviour. Seven grade 3–5 classes (n = 88) were exposed to a single-group, repeated cross-over design where each student’s selective attention was compared between no-activity and FUNtervals days. In week 1, students were familiarized with the d2 test of attention and FUNterval activities, and baseline off-task behaviour was observed. In both weeks 2 and 3 students completed the d2 test of attention following either a FUNterval break or a no-activity break. The order of these breaks was randomized and counterbalanced between weeks. Neither motor nor passive off-task behaviour predicted changes in selective attention following FUNtervals; however, a weak relationship was observed for verbal off-task behaviour and improvements in d2 test performance. More importantly, students made fewer errors during the d2 test following FUNtervals. In supporting the priority of physical activity inclusion within schools, FUNtervals, a time efficient and easily implemented physical activity break, can improve selective attention in 9- to 11-year olds.
Insects can limit seed productivity at the treeline
Authors: Jameson Ryan G. , Trant Andrew J. , Hermanutz Luise
Published: November 2014

Numerous factors contribute to the variability in treeline change; however, the potential role of insect predation in limiting seed productivity is not well documented. Conditions for seed germination, establishment, and survival are not limiting at the Mealy Mountains treeline (Labrador, Canada), but seedlings are rarely encountered, suggesting a seed-related bottleneck to recruitment. Mature cones were collected in 2008 from four tree species (black spruce (Picea mariana (Mill.) Britton, Sterns & Poggenb.), balsam fir (Abies balsamea (L.) Mill.), eastern larch (Larix laricina (Du Roi) K. Koch), and white spruce (Picea glauca (Moench) Voss)) across three treeline zones (forest, transition, and krummholz) to assess potential seed limitation. During that year, an unexpectedly high diversity of insect larvae caused extensive reproductive loss and damaged the cones of ∼85% of trees sampled, confirming that treeline change models should include seed predation. Seed germination was low and variable in all treeline zones, although significantly higher in black spruce and eastern larch. Most reproductive quality measures decreased significantly with elevation, although no differences among zones or tree species in the percentages of seeds damaged by insects were found (mean ± standard deviation: 31% ± 23%). Based on tree density and seed production, black spruce is predicted to lead the treeline expansion in the Mealy Mountains. Although climate warming may create conditions conducive for increased seed production, predispersal seed predation may limit future treeline expansion.
Numerical investigation of laminar jet arrays impinging onto dimpled target surface
Authors: Qu Huancheng , Liu Tianyuan , Chen Huiyong , Xie Yonghui
Published: November 2014

The flow and heat transfer of three-by-eight laminar jet arrays impinging onto a dimpled surface with Reynolds number 100 in steady state have been investigated numerically in the present study. Grid independence was confirmed and good agreement was reached through comparison between the results obtained from the literature and the present work. The effect of jet-to-plate spacing (H/d = 1–10) dimple diameter (Dd/d = 2–4) and the dimple relative depth (δ/Dd = 0.10–0.30) on the flow and heat transfer characteristics of laminar impinging jet arrays was explored numerically. The average Nusselt number decreases with increasing jet-to-plate spacing, dimple relative depth, and dimple diameter. The jet flow in the downstream jets is deflected by crossflow, which makes low-velocity fluid appear in the corresponding dimples and the area is enlarged. Thus, the presence of dimples causes overall heat transfer deterioration in the laminar impinging jet arrays.
Conflicting effects of microhabitats on Long-toed Salamander (Ambystomamacrodactylum) movement: implications for landscape connectivity
Authors: Lee-Yaw J.A. , Sechley T.H. , Irwin D.E.
Published: November 2014

Understanding dispersal requires multiple lines of investigation, from the study of broad patterns of population connectivity to the identification of factors impacting movement at local scales. To determine the potential effects of different microhabitats on dispersal in the Long-toed Salamander (Ambystoma macrodactylum Baird, 1850), we experimentally evaluated mobility, moisture loss, and habitat choice in response to five common substrates (deciduous and coniferous leaf litter, grass, moss, and sand). Specifically, we examined differences in the efficiency with which salamanders moved across substrates when motivated to move. We then quantified moisture loss in each substrate and evaluated habitat preference. Our results point to a trade-off between substrates that are easily traversed and those that offer high protection against desiccation. Habitat choice appeared to balance these two aspects of performance, with salamanders favouring a substrate that offered both low resistance to movement and high protection against desiccation. This result was context-dependent, as preferences shifted towards wetter but less easily traversed substrates when supplemental cover objects were made available. Overall, our study highlights the potential for individuals to respond to a given substrate in ways that can both facilitate and limit dispersal and thus underscores the need to consider different aspects of individual performance and behaviour when studying population connectivity.
Spatial patterns and spread of exotic earthworms at local scales
Authors: Cameron Erin K. , Bayne Erin M.
Published: November 2014

Given the substantial impacts of non-native species on invaded systems, an understanding of the rates and spatial patterns of invasive spread is critical. Spread may vary across spatial scales, with dispersal of invasive species occurring both via diffusive spread at local sites and long-distance jump dispersal at larger scales. Research on earthworm invasions in North American forests has focused on patterns of spread across landscapes, with less examination of spread at local sites. We sampled the exotic earthworm Dendrobaena octaedra (Savigny, 1826) on 500 m × 500 m grids at three sites in the boreal forest of northeastern Alberta in 2006 and again in 2012–2013 to examine distributional changes over time. Earthworms spread farther from roads (the presumed site of initial introduction) over time, and spatial patterns at our sites suggest transport by vehicles and waterways are key vectors of dispersal at the local level. Spread was estimated to be occurring at a rate of at least 17.9 m/year. Our study indicates that both diffusive spread and jump dispersal of earthworms can be important at local scales and that local diffusive spread may be substantially higher than previously estimated.
A New Work Mechanism on Neuronal Activity
Authors: Wang Rubin , Tsuda Ichiro , Zhang Zhikang
Published: November 2014

By re-examining the neuronal activity energy model, we show the inadequacies in the current understanding of the energy consumption associated with neuron activity. Specifically, we show computationally that a neuron first absorbs and then consumes energy during firing action potential, and this result cannot be produced from any current neuron models or biological neural networks. Based on this finding, we provide an explanation for the observation that when neurons are excited in the brain, blood flow increases significantly while the incremental oxygen consumption is very small. We can also explain why external stimulation and perception emergence are synchronized. We also show that negative energy presence in neurons at the sub-threshold state is an essential reason that leads to blood flow incremental response time in the brain rather than neural excitation to delay.