bluuebunny/crossref_metadata_2025 huggingface dataset:
Vestibular nucleus neurons respond to hindlimb movement in the decerebrate cat
Authors: Arshian Milad S. , Hobson Candace E. , Catanzaro Michael F. , Miller Daniel J. , Puterbaugh Sonya R. , Cotter Lucy A. , Yates Bill J. , McCall Andrew A.
Published: March 2014

The vestibular nuclei integrate information from vestibular and proprioceptive afferents, which presumably facilitates the maintenance of stable balance and posture. However, little is currently known about the processing of sensory signals from the limbs by vestibular nucleus neurons. This study tested the hypothesis that limb movement is encoded by vestibular nucleus neurons and described the changes in activity of these neurons elicited by limb extension and flexion. In decerebrate cats, we recorded the activity of 70 vestibular nucleus neurons whose activity was modulated by limb movements. Most of these neurons (57/70, 81.4%) encoded information about the direction of hindlimb movement, while the remaining neurons (13/70, 18.6%) encoded the presence of hindlimb movement without signaling the direction of movement. The activity of many vestibular nucleus neurons that responded to limb movement was also modulated by rotating the animal's body in vertical planes, suggesting that the neurons integrated hindlimb and labyrinthine inputs. Neurons whose firing rate increased during ipsilateral ear-down roll rotations tended to be excited by hindlimb flexion, whereas neurons whose firing rate increased during contralateral ear-down tilts were excited by hindlimb extension. These observations suggest that there is a purposeful mapping of hindlimb inputs onto vestibular nucleus neurons, such that integration of hindlimb and labyrinthine inputs to the neurons is functionally relevant.
Synaptic excitation is regulated by the postsynaptic dSK channel at theDrosophilalarval NMJ
Authors: Gertner Daniel M. , Desai Sunil , Lnenicka Gregory A.
Published: March 2014

In the mammalian central nervous system, the postsynaptic small-conductance Ca2+-dependent K+(SK) channel has been shown to reduce postsynaptic depolarization and limit Ca2+influx through N-methyl-d-aspartate receptors. To examine further the role of the postsynaptic SK channel in synaptic transmission, we studied its action at the Drosophila larval neuromuscular junction (NMJ). Repetitive synaptic stimulation produced an increase in postsynaptic membrane conductance leading to depression of excitatory postsynaptic potential amplitude and hyperpolarization of the resting membrane potential (RMP). This reduction in synaptic excitation was due to the postsynaptic Drosophila SK (dSK) channel; synaptic depression, increased membrane conductance and RMP hyperpolarization were reduced in dSK mutants or after expressing a Ca2+buffer in the muscle. Ca2+entering at the postsynaptic membrane was sufficient to activate dSK channels based upon studies in which the muscle membrane was voltage clamped to prevent opening voltage-dependent Ca2+channels. Increasing external Ca2+produced an increase in resting membrane conductance and RMP that was not seen in dSK mutants or after adding the glutamate-receptor blocker philanthotoxin. Thus it appeared that dSK channels were also activated by spontaneous transmitter release and played a role in setting membrane conductance and RMP. In mammals, dephosphorylation by protein phosphatase 2A (PP2A) increased the Ca2+sensitivity of the SK channel; PP2A appeared to increase the sensitivity of the dSK channel since PP2A inhibitors reduced activation of the dSK channel by evoked synaptic activity or increased external Ca2+. It is proposed that spontaneous and evoked transmitter release activate the postsynaptic dSK channel to limit synaptic excitation and stabilize synapses.
Phase maintenance in a rhythmic motor pattern during temperature changes in vivo
Authors: Soofi Wafa , Goeritz Marie L. , Kispersky Tilman J. , Prinz Astrid A. , Marder Eve , Stein Wolfgang
Published: March 2014

Central-pattern-generating neural circuits function reliably throughout an animal's life, despite constant molecular turnover and environmental perturbations. Fluctuations in temperature pose a problem to the nervous systems of poikilotherms because their body temperature follows the ambient temperature, thus affecting the temperature-dependent dynamics of various subcellular components that constitute neuronal circuits. In the crustacean stomatogastric nervous system, the pyloric circuit produces a triphasic rhythm comprising the output of the pyloric dilator, lateral pyloric, and pyloric constrictor neurons. In vitro, the phase relationships of these neurons are maintained over a fourfold change in pyloric frequency as temperature increases from 7°C to 23°C. To determine whether these temperature effects are also found in intact crabs, in the presence of sensory feedback and neuromodulator-rich environments, we measured the temperature dependence of the pyloric frequency and phases in vivo by implanting extracellular electrodes into Cancer borealis and Cancer pagurus and shifting tank water temperature from 11°C to 26°C. Pyloric frequency in the intact crab increased significantly with temperature (Q10= 2–2.5), while pyloric phases were generally conserved. For a subset of the C. borealis experiments, animals were subsequently dissected and the stomatogastric ganglion subjected to a similar temperature ramp in vitro. We found that the maximal frequency attained at high temperatures in vivo is lower than it is under in vitro conditions. Our results demonstrate that, over a wide temperature range, the phases of the pyloric rhythm in vivo are generally preserved, but that the frequency range is more restricted than it is in vitro.
Performance of Quantification of Modified Hodge Test: An Evaluation withKlebsiella pneumoniaeCarbapenemase-Producing Enterobacteriaceae Isolates
Authors: Ribeiro Vanessa Bley , Linhares Adriano Rostirolla , Zavascki Alexandre P. , Barth Afonso Luis
Published: March 2014

Modified Hodge Test (MHT) has been suggested as screening tests for carbapenemases, but concerns regarding its difficult interpretation and common false-positive results obtained in the presence of otherβ-lactamases have been noted. This study aimed to quantify the enhanced growth formed by the indicator strain and thus evaluate the performance of a quantitative interpretation of MHT for KPC screening. MHT was performed in 50 KPC-producing isolates and 334 non-carbapenemase-producing isolates, using ertapenem (ETP) and meropenem (MEM) as substrates. The size of enhanced growth of indicator strain was measured for each isolate tested and for the positive control used, and a ratio was calculated. Our results revealed 17 different ETP and MEM ratios, with distinct sensitivity (SN) and specificity (SP). Higher SN combined to higher SP was achieved when ETP and MEM ratios were 0.45, with a SN value of 96% for both substrates and SP values of 99.4% and 100% for ETP and MEM, respectively. The quantification with both substrates increased SP of the test for KPC detection. Considering that MHT is the unique phenotypic test that is referred to by CLSI, a more accurate approach for its interpretation could be applied to make it a more useful tool.
Prevalence and Seroincidence of Hepatitis B and Hepatitis C Infection in High Risk People Who Inject Drugs in China and Thailand
Authors: Jackson J. Brooks , Wei Liu , Liping Fu , Aramrattana Apinun , Celentano David D. , Walshe Louise , Xing Yi , Richardson Paul , Jun Ma , Beauchamp Geetha , Donnell Deborah , Ruan Yuhua , Ma Liying , Metzger David , Shao Yiming
Published: March 2014

We determined the prevalence and incidence of HBV and HCV infection in people who inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined the association of HBV and HCV incidence with urine opiate test results and with short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of 201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative participants, the HBsAg incidence rate was 2.7/100 person years in China and 0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence rate among HCV antibody negative PWIDs was 22/100 person years in China and 4.6/100 person years in Thailand. Incident HBsAg was not significantly different in the short-term versus long-term B-N arm in China or Thailand. Participants with positive opiate results in at least 75% of their urines during the time period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to 25.22; P=0.04)
in China, but not incident HCV conversion in China or Thailand.
Acute Ethanol-Induced Changes in Edema and Metabolite Concentrations in Rat Brain
Authors: Liu Huimin , Zheng Wenbin , Yan Gen , Liu Baoguo , Kong Lingmei , Ding Yan , Shen Zhiwei , Tan Hui , Zhang Guishan
Published: March 2014

The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCrand TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCrand TSCho, TSTau, and TSGluprovide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCrand TSADCwill help us to understand development of the ethanol-induced brain cytotoxic edema.
Optimization of Conditions for In Vitro Culture of the Microphallid DigeneanGynaecotyla adunca
Authors: West Jenna , Mitchell Alexandra , Pung Oscar J.
Published: March 2014

In vitro cultivation of digeneans would aid the development of effective treatments and studies of the biology of the parasites. The goal of this study was to optimize culture conditions for the trematode,Gynaecotyla adunca. Metacercariae of the parasite from fiddler crabs,Uca pugnax, excysted in trypsin, were incubated overnight to permit fertilization, and were cultured in different conditions to find those that resulted in maximum worm longevity and egg production. When cultured in media lacking serum, worms lived longer in Hanks balanced salt solution and Dulbecco’s Modified Eagle medium/F-12 (DME/F-12) than in RPMI-1640 but produced the most eggs in DME/F-12. Worm longevity and egg production increased when worms were grown in DME/F-12 supplemented with 20% chicken, horse, or newborn calf serum but the greatest number of eggs was deposited in cultures containing horse or chicken serum. Horse serum was chosen over chicken serum due to the formation of a precipitate in chicken serum. The optimal concentration of horse serum with respect to egg production ranged from 5 to 20%. Infectivity of eggs deposited by worms in culture was tested by feeding eggs to mud snails,Ilyanassa obsoleta. None of these snails producedG. aduncacercariae.
RNA Sequencing Reveals Upregulation of RUNX1-RUNX1T1 Gene Signatures in Clear Cell Renal Cell Carcinoma
Authors: Xiong Zuquan , Yu Hongjie , Ding Yan , Feng Chenchen , Wei Hanming , Tao Sha , Huang Dan , Zheng Siqun Lilly , Sun Jielin , Xu Jianfeng , Fang Zujun
Published: March 2014

In the past few years, therapies targeted at the von Hippel-Lindau (VHL) and hypoxia-inducible factor (HIF) pathways, such as sunitinib and sorafenib, have been developed to treat clear cell renal cell carcinoma (ccRCC). However, the majority of patients will eventually show resistance to antiangiogenesis therapies. The purpose of our study was to identify novel pathways that could be potentially used as targets for new therapies. Whole transcriptome sequencing (RNA-Seq) was conducted on eight matched tumor and adjacent normal tissue samples. A novel RUNX1-RUNX1T1 pathway was identified which was upregulated in ccRCC through gene set enrichment analysis (GSEA). We also confirmed the findings based on previously published gene expression microarray data. Our data shows that upregulated of the RUNX1-RUNX1T1 gene set maybe an important factor contributing to the etiology of ccRCC.
Optimal Management of the Critically Ill: Anaesthesia, Monitoring, Data Capture, and Point-of-Care Technological Practices in Ovine Models of Critical Care
Authors: Chemonges Saul , Shekar Kiran , Tung John-Paul , Dunster Kimble R. , Diab Sara , Platts David , Watts Ryan P. , Gregory Shaun D. , Foley Samuel , Simonova Gabriela , McDonald Charles , Hayes Rylan , Bellpart Judith , Timms Daniel , Chew Michelle , Fung Yoke L. , Toon Michael , Maybauer Marc O. , Fraser John F.
Published: March 2014

Animal models of critical illness are vital in biomedical research. They provide possibilities for the investigation of pathophysiological processes that may not otherwise be possible in humans. In order to be clinically applicable, the model should simulate the critical care situation realistically, including anaesthesia, monitoring, sampling, utilising appropriate personnel skill mix, and therapeutic interventions. There are limited data documenting the constitution of ideal technologically advanced large animal critical care practices and all the processes of the animal model. In this paper, we describe the procedure of animal preparation, anaesthesia induction and maintenance, physiologic monitoring, data capture, point-of-care technology, and animal aftercare that has been successfully used to study several novel ovine models of critical illness. The relevant investigations are on respiratory failure due to smoke inhalation, transfusion related acute lung injury, endotoxin-induced proteogenomic alterations, haemorrhagic shock, septic shock, brain death, cerebral microcirculation, and artificial heart studies. We have demonstrated the functionality of monitoring practices during anaesthesia required to provide a platform for undertaking systematic investigations in complex ovine models of critical illness.
Design and Analysis of Linear Fault-Tolerant Permanent-Magnet Vernier Machines
Authors: Xu Liang , Ji Jinghua , Liu Guohai , Du Yi , Liu Hu
Published: March 2014

This paper proposes a new linear fault-tolerant permanent-magnet (PM) vernier (LFTPMV) machine, which can offer high thrust by using the magnetic gear effect. Both PMs and windings of the proposed machine are on short mover, while the long stator is only manufactured from iron. Hence, the proposed machine is very suitable for long stroke system applications. The key of this machine is that the magnetizer splits the two movers with modular and complementary structures. Hence, the proposed machine offers improved symmetrical and sinusoidal back electromotive force waveform and reduced detent force. Furthermore, owing to the complementary structure, the proposed machine possesses favorable fault-tolerant capability, namely, independent phases. In particular, differing from the existing fault-tolerant machines, the proposed machine offers fault tolerance without sacrificing thrust density. This is because neither fault-tolerant teeth nor the flux-barriers are adopted. The electromagnetic characteristics of the proposed machine are analyzed using the time-stepping finite-element method, which verifies the effectiveness of the theoretical analysis.
Preemptive Circular Defence of Immature Insects: Definition and Occurrences of Cycloalexy Revisited
Authors: Dury Guillaume J. , Bede Jacqueline C. , Windsor Donald M.
Published: March 2014

Cycloalexy was coined by Vasconcellos-Neto and Jolivet in 1988 and further defined by Jolivet and collaborators in 1990 in reference to a specific type of circular defence. The term has been applied to numerous organisms, including adult insects, nymphs, and even vertebrates, but has lost precision with the accumulation of anecdotal reports not addressing key elements of the behaviour as first defined. We review the literature and propose three criteria that are sufficient and necessary to define the behaviour: (1) individuals form a circle; (2) defensive attributes of the individuals are positioned on the periphery of the circle, and as a result, the periphery of the circle uniformly contains either heads or abdomens; (3) animals preemptively adopt the circle as a resting formation, meaning it is not necessary to observe predation. When these considerations are taken into account, cycloalexy appears less common in nature than the literature suggests. We argue that unequivocal cases of cycloalexy have been found only in sawflies (Tenthredinoidea: Pergidae, Argidae), leaf beetles (Chrysolemidae: Galerucinae, Cassidinae, Chrysomelinae, Criocerinae), weevils (Curculionidae:Phelypera distigma), and midges (Diptera: Ceratopogonidae,Forcipomyia). Reports of cycloalexy in caterpillars (Saturniidae: Hemileucinae:Lonomia, Papilionidae) require further documentation. We report one new case of cycloalexy in thrips (Thysanoptera) and question reports of cycloalexic behaviour in other taxa.
Wormhole Solutions in the Presence of Nonlinear Maxwell Field
Authors: Hendi S. H.
Published: March 2014

In generalizing the Maxwell field to nonlinear electrodynamics, we look for the magnetic solutions. We consider a suitable real metric with a lower bound on the radial coordinate and investigate the properties of the solutions. We find that in order to have a finite electromagnetic field near the lower bound, we should replace the Born-Infeld theory with another nonlinear electrodynamics theory. Also, we use the cut-and-paste method to construct wormhole structure. We generalize the static solutions to rotating spacetime and obtain conserved quantities.
Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination
Authors: Hewitson Laura , Thissen James B. , Gardner Shea N. , McLoughlin Kevin S. , Glausser Margaret K. , Jaing Crystal J.
Published: March 2014

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from theEnterobacteriaceae,Bacteroidaceae, andStreptococcaceaefamilies from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.
Stock Price Change Rate Prediction by Utilizing Social Network Activities
Authors: Deng Shangkun , Mitsubuchi Takashi , Sakurai Akito
Published: March 2014

Predicting stock price change rates for providing valuable information to investors is a challenging task. Individual participants may express their opinions in social network service (SNS) before or after their transactions in the market; we hypothesize that stock price change rate is better predicted by a function of social network service activities and technical indicators than by a function of just stock market activities. The hypothesis is tested by accuracy of predictions as well as performance of simulated trading because success or failure of prediction is better measured by profits or losses the investors gain or suffer. In this paper, we propose a hybrid model that combines multiple kernel learning (MKL) and genetic algorithm (GA). MKL is adopted to optimize the stock price change rate prediction models that are expressed in a multiple kernel linear function of different types of features extracted from different sources. GA is used to optimize the trading rules used in the simulated trading by fusing the return predictions and values of three well-known overbought and oversold technical indicators. Accumulated return and Sharpe ratio were used to test the goodness of performance of the simulated trading. Experimental results show that our proposed model performed better than other models including ones using state of the art techniques.
Enhanced Device and Circuit‐Level Performance Benchmarking of Graphene Nanoribbon Field‐Effect Transistor against a Nano‐MOSFET with Interconnects
Authors: Chin Huei Chaeng , Lim Cheng Siong , Wong Weng Soon , Danapalasingam Kumeresan A. , Arora Vijay K. , Tan Michael Loong Peng
Published: March 2014

Comparative benchmarking of a graphene nanoribbon field‐effect transistor (GNRFET) and a nanoscale metal‐oxide‐semiconductor field‐effect transistor (nano‐MOSFET) for applications in ultralarge‐scale integration (ULSI) is reported. GNRFET is found to be distinctly superior in the circuit‐level architecture. The remarkable transport properties of GNR propel it into an alternative technology to circumvent the limitations imposed by the silicon‐based electronics. Budding GNRFET, using the circuit‐level modeling software SPICE, exhibits enriched performance for digital logic gates in 16 nm process technology. The assessment of these performance metrics includes energy‐delay product (EDP) and power‐delay product (PDP) of inverter and NOR and NAND gates, forming the building blocks for ULSI. The evaluation of EDP and PDP is carried out for an interconnect length that ranges up to 100 μm. An analysis, based on the drain and gate current‐voltage (Id‐Vd and Id‐Vg), for subthreshold swing (SS), drain‐induced barrier lowering (DIBL), and current on/off ratio for circuit implementation is given. GNRFET can overcome the short‐channel effects that are prevalent in sub‐100 nm Si MOSFET. GNRFET provides reduced EDP and PDP one order of magnitude that is lower than that of a MOSFET. Even though the GNRFET is energy efficient, the circuit performance of the device is limited by the interconnect capacitances.
Synthesis and Gene Silencing Properties of siRNAs Containing Terminal Amide Linkages
Authors: Gaglione Maria , Mercurio M. Emilia , Potenza Nicoletta , Mosca Nicola , Russo Aniello , Novellino Ettore , Cosconati Sandro , Messere Anna
Published: March 2014

The active components of the RNAi are 21 nucleotides long dsRNAs containing a 2 nucleotide overhang at the 3′ end, carrying 5′-phosphate and 3′-hydroxyl groups (siRNAs). Structural analysis revealed that the siRNA is functionally bound at both ends to RISC. Terminal modifications are considered with interest as the introduction of chemical moieties interferes with the 3′ overhang recognition by the PAZ domain and the 5′-phosphate recognition by the MID and PIWI domains of RISC. Herein, we report the synthesis of modified siRNAs containing terminal amide linkages by introducing hydroxyethylglycine PNA (hegPNA) moieties at 5′, and at 3′ positions and on both terminals. Results of gene silencing studies highlight that some of these modifications are compatible with the RNAi machinery and markedly increase the resistance to serum-derived nucleases even after 24 h of incubation. Molecular docking simulations were attained to give at atomistic level a clearer picture of the effect of the most performing modifications on the interactions with the human Argonaute 2 PAZ, MID, and PIWI domains. This study adds another piece to the puzzle of the heterogeneous chemical modifications that can be attained to enhance the silencing efficiency of siRNAs.
Role of Th17 Cells in the Pathogenesis of Human IBD
Authors: Gálvez Julio
Published: March 2014

The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn’s disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD.
Developmental Stage-Specific Regulation of the Circadian Clock by Temperature in Zebrafish
Authors: Lahiri Kajori , Froehlich Nadine , Heyd Andreas , Foulkes Nicholas S. , Vallone Daniela
Published: March 2014

The circadian clock enables animals to adapt their physiology and behaviour in anticipation of the day-night cycle. Light and temperature represent two key environmental timing cues (zeitgebers) able to reset this mechanism and so maintain its synchronization with the environmental cycle. One key challenge is to unravel how the regulation of the clock by zeitgebers matures during early development. The zebrafish is an ideal model for studying circadian clock ontogeny since the process of development occursex uteroin an optically transparent chorion and many tools are available for genetic analysis. However, the role played by temperature in regulating the clock during zebrafish development is poorly understood. Here, we have established a clock-regulated luciferase reporter transgenic zebrafish line (Tg (−3.1)per1b::luc) to study the effects of temperature on clock entrainment. We reveal that under complete darkness, from an early developmental stage onwards (48 to 72 hpf), exposure to temperature cycles is a prerequisite for the establishment of self-sustaining rhythms ofzfper1b,zfaanat2, andzfirbpexpression and also for circadian cell cycle rhythms. Furthermore, we show that following the 5–9 somite stage, the expression ofzfper1bis regulated by acute temperature shifts.
Nonlinear Dynamical Analysis for a Plain Bearing
Authors: Belhamra Ali , Meramria Ouafa , Kahine Khalil , Haj Chehade Fadi
Published: March 2014

This paper investigates the nonlinear dynamic behavior for a plain classic bearing (fluid bearing) lubricated by a non-Newtonian fluid of a turbo machine rotating with high speed; this type of fluid contains additives viscosity (couple-stress fluid film). The solution of the nonlinear dynamic problem of this type of bearing is determined with a spatial discretisation of the modified Reynolds' equation written in dynamic mode by using the optimized short bearing theory and a temporal discretisation for equations of rotor motion by the help of Euler's explicit diagram. This study analyzes the dynamic behavior of a rotor supported by two couple-stress fluid film journal lubricant enhances the dynamic stability of the rotor-bearing system considerably compared to that obtained when using a traditional Newtonian lubricant. The analysis shows that the dynamic behavior of a shaft which turns with high velocities is strongly nonlinear even for poor eccentricities of unbalance; the presence of parameters of couple stress allows strongly attenuating the will synchrony (unbalance) and asynchrony (whipping) amplitudes of vibrations of the shaft which supports more severe conditions (large unbalances).
Cancer Cell Dormancy in Novel Mouse Models for Reversible Pancreatic Cancer: A Lingering Challenge in the Development of Targeted Therapies
Authors: Lin Wan-Chi , Rajbhandari Nirakar , Wagner Kay-Uwe
Published: March 2014

Significant advances have been made in the identification of key molecular pathways that play pivotal roles in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). Among the common genetic and epigenetic changes, oncogenic mutations in Kras and upregulation of the c-Myc oncogene are frequent events in PDAC. Using genetically defined in vivo models, several studies have recently demonstrated that expression of mutant Kras and c-Myc is equally important for the initiation and maintenance of pancreatic cancer. The targeted downregulation of a single oncogene resulted in cancer cell death at primary and metastatic sites. These findings are very encouraging and provide a strong rationale for the development of targeted therapies against these oncogenic drivers. Despite what seemed to be a complete response to the ablation of the oncogene, a few dormant cancer cells remained present, and it was demonstrated that they are a cellular reservoir for a swift relapse of pancreatic cancer following oncogene reactivation. This review summarizes the basic principles of cancer dormancy and the applicability of the novel genetic models for reversible metastatic PDAC to elucidate the role of cancer stem cells as well as biologic and molecular mechanisms that mediate the survival of dormant tumor cells. Cancer Res; 74(8); 2138–43. ©2014 AACR.
In VivoFluorescence Lifetime Imaging for Monitoring the Efficacy of the Cancer Treatment
Authors: Ardeshirpour Yasaman , Chernomordik Victor , Hassan Moinuddin , Zielinski Rafal , Capala Jacek , Gandjbakhche Amir
Published: March 2014

Purpose: Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in vivo fluorescence lifetime imaging with HER2-targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors.

Experimental Design: HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive tumor xenograft. The fluorescence lifetime was measured before treatment and monitored after the probe injections at 12 hours after the last treatment dose, when the response to the 17-DMAG therapy was the most pronounced as well as a week after the last treatment when the tumors grew back almost to their pretreatment size.

Results: Imaging results showed significant difference between the fluorescence lifetimes at the tumor and the contralateral site (∼0.13 ns) in the control group (before treatment) and 7 days after the last treatment when the tumors grew back to their pretreatment dimensions. However, at the time frame that the treatment had its maximum effect (12 hours after the last treatment), the difference between the fluorescence lifetime at the tumor and contralateral site decreased to 0.03 ns.

Conclusions: The results showed a good correlation between fluorescence lifetime and the efficacy of the treatment. These findings show that in vivo fluorescence lifetime imaging can be used as a promising molecular imaging tool for monitoring the treatment outcome in preclinical models and potentially in patients. Clin Cancer Res; 20(13); 3531–9. ©2014 AACR.
p38MAPK Plays a Crucial Role in Stromal-Mediated Tumorigenesis
Authors: Alspach Elise , Flanagan Kevin C. , Luo Xianmin , Ruhland Megan K. , Huang Hui , Pazolli Ermira , Donlin Maureen J. , Marsh Timothy , Piwnica-Worms David , Monahan Joseph , Novack Deborah V. , McAllister Sandra S. , Stewart Sheila A.
Published: March 2014

Neoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importance in tumorigenesis, the mechanisms that control TME-derived factor expression remain poorly understood. Here, we address a key unanswered question: how the SASP is sustained in senescent fibroblasts and CAFs. We find that the mitogen-activated protein kinase p38 (p38MAPK) controls AUF1 occupancy on SASP mRNAs and thus controls their stability. The importance of this regulatory mechanism is underscored by our findings that stromal-specific p38MAPK inhibition abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Our data suggest that targeting SASP mRNA stability through inhibition of p38MAPK will significantly aid the development of clinical strategies to target the TME.

Significance: The TME plays a key role in tumorigenesis. We demonstrate that p38MAPK governs a posttranscriptional mechanism that sustains the protumorigenic SASP. Inhibition of p38MAPK abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Thus, p38MAPK is a TME-specific Achilles' heel that may be exploited as a new therapeutic target. Cancer Discov; 4(6); 716–29. ©2014 AACR.

See related commentary by Isacke and Barcellos-Hoff, p. 637

This article is highlighted in the In This Issue feature, p. 621
Fibrin clot properties and their modulation in thrombotic disorders
Authors: Undas Anetta
Published: March 2014

Accumulating evidence indicates that accelerated formation of fibrin clots composed of compact, highly-branched networks with thin fibres which are relatively resistant to plasmin-mediated lysis can be commonly observed in patients with venous or arterial thrombosis. This review discusses characteristics of fibrin clot structure and function in patients with various thromboembolic manifestations, in particular myocardial infarction, ischaemic stroke and venous thromboembolism, based on the publications till December 2013. Moreover, factors will be presented that in vivo unfavourably determine altered fibrin clot properties in thrombotic disorders and modalities that can improve clot phenotype.
Platelet Immunoreceptor Tyrosine-Based Activation Motif (ITAM) Signaling and Vascular Integrity
Authors: Boulaftali Yacine , Hess Paul R. , Kahn Mark L. , Bergmeier Wolfgang
Published: March 2014

Platelets are well-known for their critical role in hemostasis, that is, the prevention of blood loss at sites of mechanical vessel injury. Inappropriate platelet activation and adhesion, however, can lead to thrombotic complications, such as myocardial infarction and stroke. To fulfill its role in hemostasis, the platelet is equipped with various G protein–coupled receptors that mediate the response to soluble agonists such as thrombin, ADP, and thromboxane A2. In addition to G protein–coupled receptors, platelets express 3 glycoproteins that belong to the family of immunoreceptor tyrosine-based activation motif receptors: Fc receptor γ chain, which is noncovalently associated with the glycoprotein VI collagen receptor, C-type lectin 2, the receptor for podoplanin, and Fc receptor γII A, a low-affinity receptor for immune complexes. Although both genetic and chemical approaches have documented a critical role for platelet G protein–coupled receptors in hemostasis, the contribution of immunoreceptor tyrosine-based activation motif receptors to this process is less defined. Studies performed during the past decade, however, have identified new roles for platelet immunoreceptor tyrosine-based activation motif signaling in vascular integrity in utero and at sites of inflammation. The purpose of this review is to summarize recent findings on how platelet immunoreceptor tyrosine-based activation motif signaling controls vascular integrity, both in the presence and absence of mechanical injury.
Calamus kebariensis (Arecaceae)—a new montane rattan from New Guinea
Authors: Maturbongs Rudi A. , Dransfield John , Baker William
Published: March 2014

Calamus kebariensis (Arecaceae or Palmae), a new species of rattan from the Bird’s Head Peninsula in West Papua, Indonesia, is described and illustrated. This species, which, among the New Guinea Calamus species, most closely resembles C. cuthbertsonii and C. spanostachys, is distinguished by its short and extremely slender stems, finely pinnate leaves and short, erect inflorescences that are branched to one order only in pistillate specimens.
Effects of Diabatic Heating and Cooling in the Rapid Filamentation Zone on Structure and Intensity of a Simulated Tropical Cyclone
Authors: Li Qingqing , Wang Yuqing , Duan Yihong
Published: March 2014

The effects of diabatic heating and cooling in the rapid filamentation zone (RFZ), within which inner rainbands are often active, on tropical cyclone (TC) structure and intensity are investigated based on idealized numerical experiments using a cloud-resolving TC model (TCM4). The results show that removal of heating (cooling) in the RFZ would reduce (increase) the TC intensity. Diabatic heating in the RFZ plays an important role in increasing the inner-core size whereas diabatic cooling tends to limit the inner-core size increase or even reduce the inner-core size of a TC. Removal of both diabatic heating and cooling in the RFZ greatly suppresses the activity of inner rainbands but leads to the quasi-periodic development of a convective ring immediately outside of the inner core. A similar convective ring also develops in an experiment with the removal of diabatic heating only in the RFZ. With diabatic cooling removed only in the RFZ, an annular-hurricane-like structure arises with the outer rainbands largely suppressed.
The Convective Boundary Layer in the Terra Incognita
Authors: Zhou Bowen , Simon Jason S. , Chow Fotini K.
Published: March 2014

Numerical simulations of a convective boundary layer (CBL) are performed to investigate model behavior in the terra incognita, also known as the gray zone. The terra incognita of the CBL refers to a range of model grid spacing that is comparable to the size of the most energetic convective eddies, which are on the order of the boundary layer depth. Using the Rayleigh–Bénard thermal instability as reference, a set of idealized simulations is used to show that gray zone modeling is not only a numerical challenge, but also poses dynamical difficulties. When the grid spacing falls within the CBL gray zone, grid-dependent convection can occur. The size of the initial instability structures is set by the grid spacing rather than the natural state of the flow. This changes higher-order flow statistics and poses fundamental difficulties for gray zone modeling applications.
Quality of the Target Area for Metrics with Different Nonlinearities in a Mesoscale Convective System
Authors: Huang Ling , Meng Zhiyong
Published: March 2014

A direct piece-by-piece data assimilation targeting strategy through observing system simulation experiments was used to examine the quality of the target area for forecast metrics with different nonlinearities in a mesoscale convective vortex–associated rainfall event from both a deterministic and probabilistic perspective.

The target area was determined based on the impact of assimilating synthetic wind-profiler observations, piece by piece, on the forecast error of strongly nonlinear rainfall and weakly nonlinear total energy around the initial vortex center. The quality of the target area in terms of its effectiveness and variability was examined for members of a reasonable ensemble. Apparently different target areas were found for different members, even for those with very small differences for both forecast metrics, with a larger variability observed for rainfall than for total energy. This result indicated that target areas estimated in deterministic scenarios are likely unreliable.

Probabilistic target areas were created by averaging data-impact index values over the ensemble. Significant differences were also observed in the ensemble-based target areas for rainfall and total energy. For total energy, assimilating data in an inaccurate target area could decrease the forecast error at a similar magnitude as that in the target area. For rainfall, however, much less error reduction was obtained, the magnitude of which was almost comparable to the no-data-assimilation experiment. Overall, the results of this study suggest that designing a particular observation plan based on an estimated target area could be unnecessary for total energy and useless for rainfall, given the difficulty involved in accurately determining a target area in an operational setting.
Neutrophil–Lymphocyte Ratio and Carotid–Intima Media Thickness in Patients With Behçet Disease Without Cardiovascular Involvement
Authors: Ozturk Cengiz , Balta Sevket , Balta Ilknur , Demirkol Sait , Celik Turgay , Turker Turker , Iyisoy Atila , Eksioglu Meral
Published: March 2014

Behçet disease (BD) is associated with endothelial dysfunction and chronic inflammation. The neutrophil–lymphocyte (N/L) ratio and carotid intima–media thickness (cIMT) are markers of inflammation and vascular risk, respectively. We assessed the relationship between cIMT values and N/L ratio in BD (65 patients and 62 control participants). There were statistically significant differences in N/L ratios and cIMT values between the patients with BD and control group ( P < .001). There were moderate positive correlations between cIMT value, C-reactive protein, and N/L ratio in patients with BD. Receiver–operating characteristic curve analysis suggested that the optimum N/L ratio cutoff point for patients with BD was 1.29, with a sensitivity, specificity, negative predictive value, and positive predictive value of 97, 77, 96, and 75%, respectively (area under curve: 0.691, 95% confidence interval = 0.600-0.782, P < .001). The N/L ratio may be a useful index of BD activity.
Comparison of Hearing Results of Malleovestibulopexy and Total Ossicular Replacement Prosthesis for Chronic Otitis Media Patients With a Mobile Stapes Footplate
Authors: Chen Zhengnong , Sun Xiaoqiang , Zhou Huiqun , Shi Haibo , Wu Yaqin , Yin Shankai
Published: March 2014

Objective:

This study aimed to assess differences in hearing outcomes using the malleostapedotomy or malleovestibulopexy (MVP) and total ossicular replacement prosthesis (TORP) techniques in chronic otitis media patients with a mobile stapes footplate.

Study Design:

Case series with planned data collection.

Setting:

A university medical center.

Subjects and Methods:

In total, 27 patients with chronic otitis media at the Sixth Hospital affiliated with Shanghai Jiao Tong University, between January and October 2010, were included. All patients had destruction of incus and stapes superstructures and a mobile stapes footplate. In all patients, surgery was performed under general anesthesia by a retroauricular approach. After the lesions were removed completely, ossicular reconstruction was performed using 1 of the techniques. In all patients, pure-tone audiograms were assessed before and 12 months after surgery.

Results:

Thirteen patients underwent MVP surgery, whereas the other 14 cases received traditional TORP surgery. All patients showed improvements in functional hearing after surgery. Although the numbers of ears that had closure of the air–bone gap within 20 dB in the MVP group were not statistically significantly higher than those in the TORP group (Fisher’s exact test, P > .05), the average postoperative gain of the MVP group was significantly higher than that of the TORP group ( t test, P < .05).

Conclusion:

Functional hearing in chronic otitis media patients with a mobile stapes footplate was better in those who underwent MVP surgery than in those who underwent TORP surgery.
Evaluation of a Social Pediatrics Elective
Authors: van den Heuvel Meta , Au Hosanna , Levin Leo , Bernstein Stacey , Ford-Jones Elizabeth , Martimianakis Maria Athina (Tina)
Published: March 2014

Objective. The aim of this study was to examine aspects of a social pediatrics elective that led to student self-reflection and transformation. Methods. To assess student learning from our social pediatric elective, we retrospectively evaluated self-reflection papers. We focused on the effectiveness of the educational approach to inspire students to incorporate the social determinants of health into their practice. Furthermore, in each reflection paper, we looked for evidence of different phases of transformation. Results. The social determinants of health were the most commonly described theme. Poverty was mentioned directly or described implicitly in almost all papers. For many students, seeing the social context of patients in real life, whether in a special clinic or at a home visit, was a disturbing and disorienting experience that triggered transformation. Conclusion. The use of reflection papers in the evaluation of a social pediatric elective documented transformative learning.
A Survey of the Preferences of Primary Care Physicians Regarding the Comanagement With Specialists of Children With Rare or Complex Conditions
Authors: McClain Monica R. , Cooley W. Carl , Keirns Tracy , Smith Andrew
Published: March 2014

Objectives. To assess primary care pediatric providers’ comfort with co-managing patients with rare conditions. Methods. A survey was sent via an electronic link to pediatricians and family practitioners. Chi-square test of significance and Fisher’s exact test were used for categorical variable comparisons and the Student’s t test was used for continuous variable comparisons. Results. Most of the providers believed that care decisions are most frequently made by the specialist with consultation with the primary care clinician. The most common source of information is direct communication from the specialist. The most effective tool to increase clarity and comfort about provider roles was an active care plan identifying current care needs, who will act on the plan, and when the action should be completed. Conclusions. Coordinated co-management in which caregiving roles are explicitly defined and tools are available for the timely exchange of information among all key participants warrants further study.
How Well Are We Preparing Pediatricians to Manage Seizures and Epilepsy? A Single-Center Questionnaire-Based Pilot Study
Authors: Agarwal Rajkumar L. , Agarwal Roshani R. , Sivaswamy Lalitha
Published: March 2014

Objective: To assess the knowledge of pediatric residents regarding principles of management of seizures and epilepsy. Methods: A 10-item multiple-choice questionnaire with single correct response each (scored as 1) was administered to pediatric residents at an academic hospital. Results: Out of 92 questionnaires, 73 were returned (79.3%). The mean score was 5 ± 1.9 (range = 1 to 9). Most correct responses (53/70, 75.5%) were received for the question on diagnosis of epilepsy. Questions on febrile seizures and on pharmacology of valproic acid received <50% correct responses among senior as well as junior residents, with no significant improvement in the correct response rate of senior residents. Conclusions: Deficiencies exist in pediatric residents’ knowledge of seizures and epilepsy, especially with respect to febrile seizures and pharmacology of antiepileptic medications. Improved mechanisms to promote understanding in these areas are needed during pediatric training.