bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Heat Transfer Coefficient Increase on Tip Clearance Control in H.P. Compressors in Gas Turbine Engine
Authors: Ekong Godwin Ita , Long Christopher A. , Childs Peter R. N.
Published: April 2014

Compressor tip clearance for a gas turbine engine application is the radial gap between the stationary compressor casing and the rotating blades. The gap varies significantly during different operating conditions of the engine due to centrifugal forces on the rotor and differential thermal expansions in the discs and casing. The tip clearance in the axial flow compressor of modern commercial civil aero-engines is of significance in terms of both mechanical integrity and performance. In general, the clearance is of critical importance to civil airline operators and their customers alike because as the clearance between the compressor blade tips and the casing increases, the aerodynamic efficiency will decrease and therefore the specific fuel consumption and operating costs will increase. This paper reports on the development of a range of concepts and their evaluation for the reduction and control of tip clearance in H.P. compressors using an enhanced heat transfer coefficient approach. This would lead to improvement in cruise tip clearances. A test facility has been developed for the study at the University of Sussex, incorporating a rotor and an inner shaft scaled down from a Rolls-Royce Trent aero-engine to a ratio of 0.7:1 with a rotational speed of up to 10000 rpm. The idle and maximum take-off conditions in the square cycle correspond to in-cavity rotational Reynolds numbers of 3.1×106 ≤ Reφ ≤ 1.0×107. The project involved modelling of the experimental facilities, to demonstrate proof of concept. The analysis shows that increasing the thermal response of the high pressure compressor (HPC) drum of a gas turbine engine assembly will reduce the drum time constant, thereby reducing the re-slam characteristics of the drum causing a reduction in the cold build clearance (CBC), and hence the reduction in cruise clearance. A further reduction can be achieved by introducing radial inflow into the drum cavity to further increase the disc heat transfer coefficient in the cavity; hence a further reduction in disc drum time constant.
Tunable and Transferrable Bar Feeder Damping Design for Advanced Manufacturing
Authors: Pierson Harry A. , Singh Kumer V.
Published: April 2014

The economical production of high-value, low-volume, machined components is an important subtopic of advanced manufacturing. Bar feeders, a well-established technology for adding a high degree of automation to CNC turning centers by feeding 12′ lengths of stock through the machine spindle, have limitations in this realm. They rely on supporting the entire length of the stock in a continuous fluid bearing in order to suppress potential vibrations. Although this results in excellent vibration suppression, long tooling changeovers make them impractical for small batch sizes. Additionally, the expense of the tooling can render them cost-prohibitive. Thus a bar feeder technology is desired that provides comparable vibration suppression for a wide variety of stock sizes without the need for size-specific tooling changes. In this, a movable point support having tunable viscoelastic properties is studied for controlling the vibration of varying lengths of bar stock in a given speed range. The transverse vibration of mounted bar stock is modeled as a Bernoulli-Euler beam. The effects of the support position, viscoelastic model, and their associated parameters on the resonant frequencies, damping ratios, and vibration response of the bar stock are studied. Such a study will be instrumental in developing passive/active vibration control strategies for future bar feeders.
Computer-Aided Manufacturing (CAM) Software Development for Laser Machining
Authors: Bayesteh Abdolreza , Ahmad Farid , Jun Martin B. G.
Published: April 2014

A novel computer-aided manufacturing (CAM) software system is proposed for laser ablation machining process. The algorithms and prototype software system is designed to offer efficient optimization of tool path for controlled delivery of laser energy into work-piece. The software simplifies part program creation and maintains constant velocity of the sample stage for each segment of a complex tool trajectory. These features enable efficient deposition of laser energy into the work piece and therefore, reduction in heat-affected zone is expected in laser ablation based micromachining. The reported software provides fast modification of tool path, automatic and efficient sequencing of path elements in a complicated tool trajectory, location of reference point and automatic fixing of geometrical errors in imported drawing exchange files (DXF) or DWG format files.
Numerical Investigation of Heat Transfer Enhancement in Gas Turbine Blade by Air Film Cooling and Different Types of Ribs
Authors: Pourhasanzadeh Maryam
Published: April 2014

In this research, numerical studies have been carried out for a film cooling jet on a gas turbine blade in the presence of different kinds of ribs. Simulations are performed for a film cooling jet inclined at 30-degrees. The effect of coolant jet velocity on convection heat transfer coefficient (h) is investigated. In addition, various ribs geometries and their distance from the blade surface are examined. It is shown that a combination of the rib and the film cooling jet stimulate the momentum and thermal boundary layers and subsequently improve the convection heat transfer coefficient. It is indicated that the heat transfer coefficient is dependent on the height of the rib and there is an inverse relation with the rib distance from the plate. Moreover, an increase in coolant jet velocity causes the increase of the heat transfer coefficient. The results show a significant improvement of the heat transfer coefficient over three times more than h on a blade without any ribs or coolant jet.
Development of a Swirl Nozzle for Powder Technology
Authors: Sofuoglu Mehmet Alper , Erbas Murat , Uslan Ibrahim , Biyikoglu Atilla
Published: April 2014

In this study, a gas atomization nozzle for metal powder production has been designed and modeled numerically. The design has been performed in two stages. At the first stage of the design, the size and geometry of the nozzle have been developed to obtain circulated flow through the nozzle as a pre-design. At the second stage, a parametrical analysis has been done using a CFD code. The geometry of the nozzle has been changed and the effect of geometric parameters was determined to find out the more efficient nozzle design parameters. Gas behavior at the nozzle exit and effect of the gas on the melt delivery tube tip has been investigated. Appropriate values for the investigated parameters have been determined to get maximum pressure in vacuum condition at the tip of the melt. The pressure observed at the melt delivery tube was compared with the experimental melt tip pressure data. These results suggest that the CFD solutions can be used in the design of the nozzle. Thus, the lower cost and shorter time would be possible to develop highly efficient nozzle geometry.
Fe2O3-CuO Nanocomposites Prepared by a Two-step Vapor Phase Strategy and Analyzed by XPS
Authors: Carraro Giorgio , Gasparotto Alberto , Maccato Chiara , Peeters Daniel , Barreca Davide
Published: April 2014

β-Fe2O3-CuO nanosystems were developed by using a two-step vapor-phase strategy. β-Fe2O3 matrices (hosts) were initially deposited by Plasma Enhanced-Chemical Vapor Deposition (PE-CVD) on Indium Tin Oxide (ITO) substrates. Subsequently, CuO nanoparticles (NPs, guests) were over-deposited by means of Radio Frequency (RF)-sputtering under mild preparation conditions. A thorough characterization highlighted the dispersion of CuO NPs inside the host iron oxide. To this regard, X-ray Photoelectron and X-ray Excited Auger Electron Spectroscopies (XPS and XE-AES) analyses provided valuable information on the system chemical composition. In particular, attention has been devoted to the analysis of the O 1s, Fe 2p, Cu 2p core levels and Cu LMM Auger peak, employing a non-monochromated MgKα source. The investigation confirmed the presence of Fe(III) and Cu(II) oxides, highlighting the formation of nanocomposites in which the host and guest species maintained their chemical identity.
A Perceptually-regulated Exercise Test Predicts Peak Oxygen Uptake in Older Active Adults
Authors: Smith Ashleigh E. , Eston Roger G. , Norton Belinda , Parfitt Gaynor
Published: April 2014

Peak oxygen uptake (V̇O2peak) is reliably predicted in young and middle-aged adults using a submaximal perceptually-regulated exercise test (PRET). It is unknown whether older adults can use a PRET to accurately predict V̇O2peak. In this study, the validity of a treadmill-based PRET to predict V̇O2peak was assessed in 24 participants (65.2 ± 3.9 years, 11 males). The PRET required a change in speed or incline corresponding to ratings of perceived exertion (RPE) 9, 11, 13, and 15. Extrapolation of submaximal V̇O2 from the PRET to RPE endpoints 19 and 20 and age-predicted HRmax were compared with measured V̇O2peak. The V̇O2 extrapolated to both RPE19 and 20 over-predicted V̇O2peak (p < .001). However, extrapolating V̇O2 to age-predicted HRmax accurately predicted V̇O2peak (r = .84). Results indicate older adults can use a PRET to predict V̇O2peak by extrapolating V̇O2 from submaximal intensities to an age-predicted HRmax.
Measuring Physical Activity and Sports Participation After Autologous Cartilage Implantation: A Systematic Review
Authors: Santos-Magalhaes Andre Filipe , Hambly Karen
Published: April 2014

Context:

The assessment of physical activity and return to sport and exercise activities is an important component in the overall evaluation of outcome after autologous cartilage implantation (ACI).

Objective:

To identify the patient-report instruments that are commonly used in the evaluation of physical activity and return to sport after ACI and provide a critical analysis of these instruments from a rehabilitative perspective.

Evidence Acquisition:

A computerized search was performed in January 2013 and repeated in March 2013. Criteria for inclusion required that studies (1) be written in English and published between 1994 and 2013; (2) be clinical studies where knee ACI cartilage repair was the primary treatment, or comparison studies between ACI and other techniques or between different ACI generations; (3) report postoperative physical activity and sport participation outcomes results, and (4) have evidence level of I–III.

Evidence Synthesis:

Twenty-six studies fulfilled the inclusion criteria. Three physical activity scales were identified: the Tegner Activity Scale, Modified Baecke Questionnaire, and Activity Rating Scale. Five knee-specific instruments were identified: the Lysholm Knee Function Scale, International Knee Documentation Committee Score Subjective Form, Knee Injury and Osteoarthritis Outcome Score, Modified Cincinnati Knee Score, and Stanmore-Bentley Functional Score.

Conclusions:

Considerable heterogeneity exists in the reporting of physical activity and sports participation after ACI. Current instruments do not fulfill the rehabilitative needs in the evaluation of physical activity and sports participation. The validated instruments fail in the assessment of frequency, intensity, and duration of sports participation.
Concurrent Validity of Resting Pulse-Rate Measurements: A Comparison of 2 Smartphone Applications, the Polar H7 Belt Monitor, and a Pulse Oximeter With Bluetooth
Authors: Cheatham Scott W. , Kolber Morey J. , Ernst Michael P.
Published: April 2014

Context:

Pulse rate is commonly measured manually or with commercial wrist or belt monitors. More recently, pulse-rate monitoring has become convenient with the use of mobile technology that allows monitoring through a smartphone camera. This optical technology offers many benefits, although the clinimetric properties have not been extensively studied.

Design:

Observational study of reliability.

Setting:

University kinesiology laboratory.

Participants:

30 healthy, recreationally active adults.

Intervention:

Concurrent measurement of pulse rate using 2 smartphone applications (fingertip, face-scan,) with the Polar H7 belt and pulse oximeter.

Main Outcome Measure:

Average resting pulse rate for 5 min in 3 positions (supine, sitting, and prone).

Results:

Concurrent validity in supine and standing was good between the 2 applications and the Polar H7 (intraclass correlation coefficient [ICC] .80–.98) and pulse oximeter (ICC .82–98). For sitting, the validity was good between the fingertip application, Polar H7 (ICC .97), and pulse oximeter (ICC .97). The face-scan application had moderate validity with the Polar H7 (ICC .74) and pulse oximeter (ICC .69). The minimal detectable change (MDC90) between the fingertip application and Polar H7 ranged from 1.38 to 4.36 beats/min (BPM) and from 0.69 to 2.97 BPM for the pulse oximeter with both positions. The MDC90 between the face-scan application and Polar H7 ranged from 11.88 to 12.83 BPM and from 0.59 to 17.72 BPM for the pulse oximeter. The 95% limits of agreement suggest that the fingertip application may vary between 2.40 and 3.59 BPM with the Polar H7 and between 3.40 and 3.42 BPM with the pulse oximeter. The face-scan application may vary between 3.46 and 3.52 BPM with the Polar H7 and between 2.54 and 3.46 BPM with the pulse oximeter.

Conclusion:

Pulse-rate measurements may be effective using a fingertip application, belt monitor, and pulse oximeter. The fingertip scanner showed superior results compared with the face scanner, which only demonstrated modest validity compared with the Polar H7 and pulse oximeter.
Optogenetic Regeneration
Authors: Iyer Shrivats M. , Delp Scott L.
Published: April 2014

Applying tools from optogenetics with ideas from regenerative medicine may herald a new era of translational optogenetics.

[Also see Report by

Bryson
et al.

]
Thinking outside the lab: Finding a fulfilling non-research career
Authors: Conlan Lori , Goel Anish , McNutt Marcia
Published: April 2014

Thinking outside the lab: Finding a fulfilling non-research career, April 8, 2014 - 12:00pm - 1:00pm, ET

Wondering where can a Ph.D. take you today? Is there life beyond the bench? Absolutely! There are now more non-research fields for STEM professionals than ever before—in private industry, public policy, government, nonprofit, journalism, grants management, analytics, and a host of emerging career paths. Learn what mix of skills, experience and preparation you need to leap from the lab into a satisfying non-research career:

On April 8 at 12 noon ET, join Science Editor-in-Chief Marcia McNutt; Lori Conlin, director for the NIH Office of Postdoctoral Studies; and Anish Goel, former AAAS S&T Policy Fellow and Director of Market Analysis and Geopolitical Affairs at Boeing, for a webinar on "Thinking outside the lab: Finding a fulfilling non-research career."

Take this opportunity to learn firsthand from accomplished Ph.D.s who have successfully navigated a career outside of the research realm. They'll talk about their own experiences, examine a range of career options open to STEM professionals across different sectors, and discuss the analytic, communication and teamworking skills needed for these kinds of roles.
Even for Slide-Prone Region, Landslide Was Off the Chart
Authors: Stone Richard , Service Robert F.
Published: April 2014

While some experts have suggested that the deadly Oso landslide in Washington on 22 March could have been foreseen, others argue that it was an extreme event that could not have been anticipated.
Cassini Plumbs the Depths of the Enceladus Sea
Authors: Kerr Richard A.
Published: April 2014

Suspicions that Saturn's icy moon Enceladus harbors an internal ocean—one that could host life—have hardened into near certainty with exquisitely precise observations from the Cassini spacecraft.
Kurdistan Offers an Open Window on the Ancient Fertile Crescent
Authors: Curry Andrew
Published: April 2014

This week, archaeologists from around the world will gather in the ancient city of Erbil to discuss its long history and the suddenly promising future for archaeological research in surrounding Iraqi Kurdistan.
Court Slams Japan's Scientific Whaling
Authors: Morell Virginia
Published: April 2014

The United Nations' highest court dealt a blow to Japan's scientific whaling program in the Antarctic, saying it isn't science.
The Vulnerable: Talene Yacoubian
Authors: Kaiser Jocelyn
Published: April 2014

A young Parkinson's researcher struggles to establish herself, a task made much harder by the challenge of landing her first big grant.
The Administrator: Jay Walsh
Authors: Kaiser Jocelyn
Published: April 2014

A vice president for research enjoys a healthy budget and strategizes to pull more dollars in.
Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs
Authors: Baum Elisabeth , Grosenbaugh Deborah A. , Barbour Alan G.
Published: April 2014

Lyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agentBorrelia burgdorferi. While immunoassays based on individual subunits have mostly supplanted the use of whole-cell preparations for canine serology, only a limited number of informative antigens have been identified. To more broadly characterize the antibody responses toB. burgdorferiinfection and to assess the diversity of those responses in individual dogs, we examined sera from 32 adult colony-bred beagle dogs that had been experimentally infected withB. burgdorferithrough tick bites and compared those sera in a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encodedB. burgdorferiproteins, including 24 serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural-reservoir rodents; these proteins included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, the fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals studied here demonstrated diversity in antibody responses in measures of antibody levels and specificities for conserved proteins, such as DbpB, and polymorphic proteins, such as OspC.
Complete Genome Sequence of an F8-Like Lytic Myovirus (φSPM-1) That Infects Metallo-β-Lactamase-Producing Pseudomonas aeruginosa
Authors: Neves Patrícia R. , Cerdeira Louise T. , Mitne-Neto Miguel , Oliveira Théo G. M. , McCulloch John A. , Sampaio Jorge L. M. , Mamizuka Elsa M. , Levy Carlos E. , Sato Maria I. Z. , Lincopan Nilton
Published: April 2014

Pseudomonas aeruginosa
is an important cause of infection, especially in immunocompromised patients. In this regard, strains producing carbapenemases, mainly metallo-β-lactamases (MBLs), have become a significant public health concern. Here, we present the complete annotated genome sequence (65.7 kb) of an F8-related lytic myovirus (
Pbunalikevirus
genus) that infects MBL-producing
P. aeruginosa
strains.
Loop-Mediated Isothermal Amplification for Rapid and Semiquantitative Detection of Loa loa Infection
Authors: Drame Papa M. , Fink Doran L. , Kamgno Joseph , Herrick Jesica A. , Nutman Thomas B.
Published: April 2014

Rapid and accurate tests are currently needed to identify individuals with high levels of
Loa loa
microfilaria (mf), so that these individuals may be excluded from mass ivermectin administration campaigns against onchocerciasis and lymphatic filariasis being conducted in areas where
Onchocerca volvulus
,
Wuchereria bancrofti
, and
L. loa
are coendemic. To address this need, colorimetric loop-mediated isothermal amplification (LAMP) assays targeting the
L. loa
-specific gene sequences LLMF72 and LLMF342 were developed for the detection and quantification of
L. loa
microfilaremia. Both LAMP assays were highly specific (100%) for
L. loa
infection compared to the absence of infection or infection with related filarial pathogens. The LLMF72-based LAMP assay showed greater analytic sensitivity (limit of detection, 0.1 pg/ml of genomic DNA [gDNA] and/or 5 mf/ml) than the LLMF342-based LAMP assay (10 pg/ml of gDNA and/or 50 mf/ml), and its analytic sensitivity was similar to that of LLMF72-based quantitative PCR (qPCR). A high level of correlation was observed between microfilaria counts as determined by LLMF72-based qPCR and time to positivity by the LAMP assay, and performance measures of sensitivity, specificity, and positive and negative predictive values were similar for both assays when applied to field-collected clinical samples. By simply varying the run time, the LAMP assay was able to accurately distinguish individuals at risk for serious adverse events (SAEs) after exposure to ivermectin, using thresholds of >5,000 mf/ml and >30,000 mf/ml as indicators of increasing levels of risk. In summary, LLMF72 LAMP represents a new molecular diagnostic tool that is readily applicable as a point-of-care method for
L. loa
microfilarial detection and quantification in resource-limited countries where
L. loa
infection is endemic.
Rab18 Facilitates Dengue Virus Infection by Targeting Fatty Acid Synthase to Sites of Viral Replication
Authors: Tang Wei-Chun , Lin Ren-Jye , Liao Ching-Len , Lin Yi-Ling
Published: April 2014

Positive-sense RNA viruses, such as dengue virus (DENV), hijack the intracellular membrane machinery for their own replication. The Rab18 protein, a member of the Rab GTPase family, key regulators of membrane trafficking, is located on the organelles involved in DENV infection, such as the endoplasmic reticulum (ER) and lipid droplets (LDs). In this study, we addressed the potential involvement of Rab18 in DENV infection by using cells overexpressing the wild-type, GTP-bound active form, or GDP-bound inactive form of Rab18 and cells with Rab18 knockdown. DENV replication, measured by viral protein, viral RNA, and viral progeny production, as well as LD induction, was reduced in cells with inactive Rab18 and in cells deprived of Rab18 expression, suggesting a positive role of Rab18 in the DENV life cycle. Interestingly, the interaction of fatty acid synthase (FASN), a key lipogenic enzyme in lipid biosynthesis, with DENV NS3 protein relied on the conversion of the GDP-bound to the GTP-bound form of Rab18. Furthermore, the targeting of FASN to sites participating in DENV infection, such as the ER and LDs, depends on functional Rab18. Thus, Rab18-mediated membrane trafficking of FASN and NS3 facilitates DENV replication, probably by ensuring a sufficient and coordinated lipid supply for membrane proliferation and arrangement.

IMPORTANCE
Infection by dengue virus (DENV), an important mosquito-borne virus threatening ∼40% of the world's population, can cause mild dengue fever or severe dengue hemorrhagic fever and dengue shock syndrome. The pathogenesis mechanisms of DENV-related diseases are not clear, but high viral replication is believed to be a risk factor for the severe form of DENV infection. Thus, understanding the detailed mechanism of DENV replication might help address this devastating virus. Here, we found that Rab18, a small GTPase involved in vesicle trafficking and located in the endoplasmic reticulum network and on the surfaces of lipid droplets, positively regulates DENV replication. The functional machinery of Rab18 is required to recruit the enzyme fatty acid synthase to sites of DENV replication and to interact with DENV NS3 protein to promote fatty acid biosynthesis. Thus, DENV usurps Rab18 to facilitate its own replication.
Inhibition of KAP1 Enhances Hypoxia-Induced Kaposi's Sarcoma-Associated Herpesvirus Reactivation through RBP-Jκ
Authors: Zhang Liming , Zhu Caixia , Guo Yi , Wei Fang , Lu Jie , Qin Jing , Banerjee Shuvomoy , Wang Junwen , Shang Hong , Verma Subhash C. , Yuan Zhenghong , Robertson Erle S. , Cai Qiliang
Published: April 2014

Hypoxia-inducible factor 1α (HIF-1α) has been frequently implicated in many cancers as well as viral pathogenesis. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several human malignancies. It can stabilize HIF-1α during latent infection and undergoes lytic replication in response to hypoxic stress. However, the mechanism by which KSHV controls its latent and lytic life cycle through the deregulation of HIF-1α is not fully understood. Our previous studies showed that the hypoxia-sensitive chromatin remodeler KAP1 was targeted by the KSHV-encoded latency-associated nuclear antigen (LANA) to repress expression of the major lytic replication and transcriptional activator (RTA). Here we further report that an RNA interference-based knockdown of KAP1 in KSHV-infected primary effusion lymphoma (PEL) cells disrupted viral episome stability and abrogated sub-G
1
/G
1
arrest of the cell cycle while increasing the efficiency of KSHV lytic reactivation by hypoxia or using the chemical 12-
O
-tetradecanoylphorbol-13-acetate (TPA) or sodium butyrate (NaB). Moreover, KSHV genome-wide screening revealed that four hypoxia-responsive clusters have a high concurrence of both RBP-Jκ and HIF-1α binding sites (RBS+HRE) within the same gene promoter and are tightly associated with KAP1. Inhibition of KAP1 greatly enhanced the association of RBP-Jκ with the HIF-1α complex for driving RTA expression not only in normoxia but also in hypoxia. These results suggest that both KAP1 and the concurrence of RBS+HRE within the RTA promoter are essential for KSHV latency and hypoxia-induced lytic reactivation.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV), a DNA tumor virus, is an etiological agent linked to several human malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). HIF-1α, a key hypoxia-inducible factor, is frequently elevated in KSHV latently infected tumor cells and contributes to KSHV lytic replication in hypoxia. The molecular mechanisms of how KSHV controls the latent and lytic life cycle through deregulating HIF-1α remain unclear. In this study, we found that inhibition of hypoxia-sensitive chromatin remodeler KAP1 in KSHV-infected PEL cells leads to a loss of viral genome and increases its sensitivity to hypoxic stress, leading to KSHV lytic reactivation. Importantly, we also found that four hypoxia-responsive clusters within the KSHV genome contain a high concurrence of RBP-Jκ (a key cellular regulator involved in Notch signaling) and HIF-1α binding sites. These sites are also tightly associated with KAP1. This discovery implies that KAP1, RBP-Jκ, and HIF-1α play an essential role in KSHV pathogenesis through subtle cross talk which is dependent on the oxygen levels in the infected cells.
Differential Contributions of Tacaribe Arenavirus Nucleoprotein N-Terminal and C-Terminal Residues to Nucleocapsid Functional Activity
Authors: D'Antuono Alejandra , Loureiro Maria Eugenia , Foscaldi Sabrina , Marino-Buslje Cristina , Lopez Nora
Published: April 2014

The arenavirus nucleoprotein (NP) is the main protein component of viral nucleocapsids and is strictly required for viral genome replication mediated by the L polymerase. Homo-oligomerization of NP is presumed to play an important role in nucleocapsid assembly, albeit the underlying mechanism and the relevance of NP-NP interaction in nucleocapsid activity are still poorly understood. Here, we evaluate the contribution of the New World Tacaribe virus (TCRV) NP self-interaction to nucleocapsid functional activity. We show that alanine substitution of N-terminal residues predicted to be available for NP-NP interaction strongly affected NP self-association, as determined by coimmunoprecipitation assays, produced a drastic inhibition of transcription and replication of a TCRV minigenome RNA, and impaired NP binding to RNA. Mutagenesis and functional analysis also revealed that, while dispensable for NP self-interaction, key amino acids at the C-terminal domain were essential for RNA synthesis. Furthermore, mutations at these C-terminal residues rendered NP unable to bind RNA both
in vivo
and
in vitro
but had no effect on the interaction with the L polymerase. In addition, while all oligomerization-defective variants tested exhibited unaltered capacities to sustain NP-L interaction, NP deletion mutants were fully incompetent to bind L, suggesting that, whereas NP self-association is dispensable, the integrity of both the N-terminal and C-terminal domains is required for binding the L polymerase. Overall, our results suggest that NP self-interaction mediated by the N-terminal domain may play a critical role in TCRV nucleocapsid assembly and activity and that the C-terminal domain of NP is implicated in RNA binding.

IMPORTANCE
The mechanism of arenavirus functional nucleocapsid assembly is still poorly understood. No detailed information is available on the nucleocapsid structure, and the regions of full-length NP involved in binding to viral RNA remain to be determined. In this report, novel findings are provided on critical interactions between the viral ribonucleoprotein components. We identify several amino acid residues in both the N-terminal and C-terminal domains of TCRV NP that differentially contribute to NP-NP and NP-RNA interactions and analyze their relevance for binding of NP to the L polymerase and for nucleocapsid activity. Our results provide insight into the contribution of NP self-interaction to RNP assembly and activity and reveal the involvement of the NP C-terminal domain in RNA binding.
Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses
Authors: Elbahesh Husni , Cline Troy , Baranovich Tatiana , Govorkova Elena A. , Schultz-Cherry Stacey , Russell Charles J.
Published: April 2014

Viruses modulate cellular signaling pathways at almost every step of the infection cycle. Cellular signaling pathways activated at later times of influenza infection have previously been investigated; however, early influenza virus-host cell interactions remain understudied. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates phosphatidylinositol 3-kinase (PI3K) activation and actin reorganization, two critical processes during influenza A virus (IAV) infection in most cell types. Using 6 influenza A virus strains (A/Puerto Rico/8/1934, A/Aichi/2/1968 × A/Puerto Rico/8/1934 reassortant [X-31], A/California/04/2009, mouse-adapted A/California/04/2009, A/WSN/1933, and A/New Caledonia/20/1999), we examined the role of FAK during IAV entry. We found that influenza virus attachment induced PI3K-dependent FAK-Y397 phosphorylation. Pharmacological FAK inhibition or expression of a kinase-dead mutant of FAK led to disruption of the actin meshwork that resulted in sequestration of IAV at the cell periphery and reduced virion localization to early endosomes. Additionally, FAK inhibition impeded viral RNA replication at later times of infection and ultimately resulted in significantly reduced viral titers in both A549 and differentiated normal human bronchial epithelial (NHBE) cells. Although not all tested strains activated FAK, all of them exhibited a reduction in viral replication in response to inhibition of FAK signaling. These findings highlight novel biphasic roles of FAK activation during IAV infection and indicate that FAK serves as a central link between receptor-mediated PI3K activation and actin reorganization during IAV infection.

IMPORTANCE
We found that FAK links early activation of PI3K and actin reorganization, thereby regulating influenza virus entry. Surprisingly, we also found that FAK can regulate viral RNA replication independently of its role in entry. Our study addresses a knowledge gap in the understanding of signaling events triggered by influenza virus that mediate its internalization and initiation of the infection cycle. Understanding of these fundamental molecular events will be necessary to identify novel host targets, such as FAK, and development of future anti-influenza virus therapeutics.
A non-ischaemic cause of elevated troponin
Authors: Lefort Guy , D'Antonio Claude , Caffery Terrell
Published: April 2014

A 27-year-old woman with chest pain was admitted for elevated troponin levels. Troponin remained mildly elevated upon repeat testing, and a review of the medical record revealed that she had had an elevated troponin level in the past. She had a cardiac catheterisation that revealed angiographically normal coronary arteries. Repeat troponin testing with and without ethylene glycol revealed a negative troponin level after addition of ethylene glycol, suggesting antibodies were interfering with the assay.
Overexpression of integrin αv correlates with poor prognosis in colorectal cancer
Authors: Ha Sang Yun , Shin Juyoun , Kim Jeong Hoon , Kang Myung Soo , Yoo Hae-Yong , Kim Hyeon-Ho , Um Sung-Hee , Kim Seok-Hyung
Published: April 2014

Aims

Integrin αv subunits are involved in tumour angiogenesis and tumour progression in various types of cancers. Clinical trials evaluating agents targeting integrin αv are ongoing. Integrin αv expression has been reported in several cancers in association with tumour progression or poor survival. However, no study has addressed the prognostic influence of integrin αv expression on survival of patients with colorectal cancer (CRC).

Methods

Immunohistochemical staining of integrin αv was performed in 198 CRC samples to evaluate its prognostic significance.

Results

High expression of integrin αv was observed in 58.1% (115/189) of colorectal adenocarcinoma samples, while only in 11.5% (3/26) of tubular adenoma samples and in none of normal mucosa or hyperplastic polyp samples. It was more frequently found in female patients and less frequently observed in well differentiated tumours. The proportion of cases with high expression of integrin αv showed an increasing trend with increased T stage (p=0.032), N stage (p=0.006) and TNM stage (p=0.001). Patients displaying exuberant expression of integrin αv showed shorter overall survival (p=0.001) and disease-free survival (p=0.004). Elevated integrin αv expression was an independent prognostic factor for overall survival (HR: 2.04, 95% CI 1.16 to 3.56; p=0.013) and disease-free survival (HR: 2.19, 95% CI 1.16 to 4.13; p=0.015).

Conclusions

Overexpression of integrin αv is associated with advanced T and N stage and as an independent prognostic factor in CRC.
Return to contingency: developing a coherent strategy for future R2E/R3 land medical capabilities
Authors: Ingram Mike , Mahan J
Published: April 2014

Key to deploying forces in the future will be the provision of a rapidly deployable Deployed Hospital Capability. Developing this capability has been the focus of 34 Field Hospital and 2nd Medical Brigade over the last 18 months and this paper describes a personal account of this development work to date. Future contingent Deployed Hospital Capability must meet the requirements of Defence; that is to be rapidly deployable delivering a hospital standard of care. The excellence seen in clinical delivery on recent operations is intensive; in personnel, equipment, infrastructure and sustainment. The challenge in developing a coherent capability has been in balancing the clinical capability and capacity against strategic load in light of recent advances in battlefield medicine. This paper explores the issues encountered and solutions found to date in reconstituting a Very High Readiness Deployed Hospital Capability.
Skeleton graph expansion of critical exponents in "cultural revolution" years
Authors: Hao Bailin
Published: April 2014

Kenneth Wilson's Nobel Prize winning breakthrough in the renormalization group theory of phase transition and critical phenomena almost overlapped with the violent "cultural revolution" years (1966–1976) in China. An unexpected chance in 1972 brought the author of these lines close to the Wilson–Fisher ϵ-expansion of critical exponents and eventually led to a joint paper with Lu Yu published entirely in Chinese without any English title and abstract. Even the original acknowledgment was deleted because of mentioning foreign names like Kenneth Wilson and Kerson Huang. In this article I will tell the 40-year old story as a much belated tribute to Kenneth Wilson and to reproduce the essence of our work in English. At the end, I give an elementary derivation of the Callan–Symanzik equation without referring to field theory.
Temperature dependence of diffusion coefficient of nitrogen gas in water: A molecular dynamics study
Authors: Sharma Keshav , Adhikari Narayan P.
Published: April 2014

We have carried out the molecular dynamics (MD) simulation to study the structural properties and to estimate the diffusivity of molecular nitrogen ( N 2) gas (solute) in extended simple point charge model (SPC/E) water (solvent) with N 2 mole fraction of 0.018 at different temperatures. For the structural properties of the system, we have determined radial distribution function (RDF). The solute–solute, solute–solvent and solvent–solvent RDF have been evaluated. Self-diffusion coefficient of N 2 was estimated by evaluating mean-squared displacement (MSD) and velocity autocorrelation function (VACF) separately. The diffusion coefficients obtained from the two methods agree within 3%. The results are in agreement with the experimentally determined values within 10%. The self-diffusion coefficient of water ( H 2 O ) was also estimated by evaluating MSD. Mutual diffusion coefficient of the system have also been estimated invoking Darken's relation. The temperature dependance of the diffusion coefficients were found to follow Arrhenius relation.
Microstructure and nonohmic properties of SnO2–Ta2O5–TiO2 varistor system doped with CuO
Authors: Peng Zhijian , Gao Ruichao , Jiang Feng , He Jianfeng , Fu Xiuli
Published: April 2014

The microstructure and nonohmic properties of SnO 2– Ta 2 O 5– TiO 2- CuO varistor system were investigated. The proposed samples were doped with different contents of CuO (0–6 mol%) and sintered at 1400°C for 2 h with conventional ceramic processing method. In all the samples, the commonly identified phase was SnO 2 (rutile); however, with increasing doping amount of CuO , the peaks of CuO phase emerged in the X-ray diffraction (XRD) patterns. Scanning electron microscopy (SEM) examination on the fractured surfaces of the samples revealed that a minor amount of CuO dopant can facilitate the sintering of the varistor ceramics, but excessive CuO would mainly segregate at grain-boundaries. The doped CuO may also act as a modifier in the SnO 2 based varistors. The measured electric-field versus current-density characteristics of the samples indicated that both nonlinear exponent and varistor voltage increased with increasing doping amount of CuO up to 3 mol% and then decreased with excessive CuO .
DEVELOPMENT OF BIO-IMPLANTED MICRO-SYSTEM WITH SELF-RECOVERY ASK DEMODULATOR FOR TRANSCUTANEOUS APPLICATIONS
Authors: MUTASHAR SAAD , HANNAN M. A. , SAMAD S. A. , HUSSAIN A.
Published: April 2014

This paper deals with the development of bio-implanted micro-system with low-power and high data rate based on amplitude shift keying (ASK) modulation technique to stimulate nerves and muscles. The modified system is operated by a low-frequency band 13.56 MHz according to the industrial-scientific-medical (ISM) bands to avoid the biological tissue damage. The data rate on the demodulator side is from 1 Mb/s and up to 1.5 Mb/s depending of generating binary signal (T BIT = 1 μs or 0.5 μs) with modulation index of 13% and modulation rate 7.3%, 9% and 11%, respectively. The proposed inductive coupling link achieves 73% of link efficiency. The modified rectifier with self-threshold voltage cancellation techniques and voltage regulator without thermal protection circuit and without passive elements occupies small area that is modified to generate adequate and stable DC voltages of 1.8 V. A new ASK demodulator structure based on two comparators is developed to extract a synchronized demodulated signal with minimum error. Thereby no need for clock recovery circuit and delay-locked loops (DLL) circuits for data synchronization at 1 Mb/s and 1.250 Mb/s of speed. The system designed using OrCAD Pspice 16.2 is based on 0.35 μm technologies.
Dynamic analysis of a stage-structured predator–prey system with disturbed time delay and birth pulse
Authors: Wang Weihua , Xiong Zuoliang , Wang Fang
Published: April 2014

In this paper, a stage-structured predator–prey system with birth pulse and disturbed time delay is investigated. The conditions of the prey-extinction periodic solution of the system which are globally attractive have been obtained. Furthermore, the sufficient conditions for the permanence of the system are established. Finally, numerical analysis is given to confirm the theoretical results.
Biophysical Challenges to Axonal Transport: Motor-Cargo Deficiencies and Neurodegeneration
Authors: Encalada Sandra E. , Goldstein Lawrence S.B.
Published: April 2014

Axonal transport is indispensable for the distribution of vesicles, organelles, messenger RNAs (mRNAs), and signaling molecules along the axon. This process is mediated by kinesins and dyneins, molecular motors that bind to cargoes and translocate on microtubule tracks. Tight modulation of motor protein activity is necessary, but little is known about the molecules and mechanisms that regulate transport. Moreover, evidence suggests that transport impairments contribute to the initiation or progression of neurodegenerative diseases, or both, but the mechanisms by which motor activity is affected in disease are unclear. In this review, we discuss some of the physical and biophysical properties that influence motor regulation in healthy neurons. We further discuss the evidence for the role of transport in neurodegeneration, highlighting two pathways that may contribute to transport impairment–dependent disease: genetic mutations or variation, and protein aggregation. Understanding how and when transport parameters change in disease will help delineate molecular mechanisms of neurodegeneration.
mTOR ensures increased release and reduced uptake of the organic osmolyte taurine under hypoosmotic conditions in mouse fibroblasts
Authors: Lambert Ian Henry , Jensen Jane Vendelbo , Pedersen Per Amstrup
Published: April 2014

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that modulates translation in response to growth factors and alterations in nutrient availability following hypoxia and DNA damage. Here we demonstrate that mTOR activity in Ehrlich Lettré ascites (ELA) cells is transiently increased within minutes following osmotic cell swelling and that inhibition of phosphatidylinositol-3-phosphatase (PTEN) counteracts the upstream phosphatidylinositol kinase and potentiates mTOR activity. PTEN inhibition concomitantly potentiates swelling-induced taurine release via the volume-sensitive transporter for organic osmolytes and anion channels (VSOAC) and enhances swelling-induced inhibition of taurine uptake via the taurine-specific transporter (TauT). Chronic osmotic stress, i.e., exposure to hypotonic or hypertonic media for 24 h, reduces and increases mTOR activity in ELA cells, respectively. Using rapamycin, we demonstrate that mTOR inhibition is accompanied by reduction in TauT activity and increase in VSOAC activity in cells expressing high (NIH3T3 fibroblasts) or low (ELA) amounts of mTOR protein. The effect of mTOR inhibition on TauT activity reflects reduced TauT mRNA, TauT protein abundance, and an overall reduction in protein synthesis, whereas the effect on VSOAC is mimicked by catalase inhibition and correlates with reduced catalase mRNA abundance. Hence, mTOR activity favors loss of taurine following hypoosmotic cell swelling, i.e., release via VSOAC and uptake via TauT during acute hypotonic exposure is potentiated and reduced, respectively, by phosphorylation involving mTOR and/or the kinases upstream to mTOR. Decrease in TauT activity during chronic hypotonic exposure, on the other hand, involves reduction in expression/activity of TauT and enzymes in antioxidative defense.
Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury
Authors: Lagishetty Venu , Parthasarathy Prasanna Tamarapu , Phillips Oluwakemi , Fukumoto Jutaro , Cho Young , Fukumoto Itsuko , Bao Huynh , Cox Ruan , Galam Lakshmi , Lockey Richard F. , Kolliputi Narasaiah
Published: April 2014

Hyperoxic acute lung injury (HALI) is characterized by inflammation and epithelial cell death. CLOCK genes are master regulators of circadian rhythm also implicated in inflammation and lung diseases. However, the relationship of CLOCK genes in hyperoxia-induced lung injury has not been studied. This study will determine if HALI alters CLOCK gene expression. To test this, wild-type and NALP3−/− mice were exposed to room air or hyperoxia for 24, 48, or 72 h. In addition, mice were exposed to different concentrations of hyperoxia (50, 75, or 100% O2) or room air for 72 h. The mRNA and protein levels of lung CLOCK genes, based on quantitative PCR and Western blot analysis, respectively, and their target genes are significantly elevated in mice exposed to hyperoxia compared with controls. Alterations in CLOCK genes are associated with increased inflammatory markers in bronchoalveolar lavage fluid of hyperoxic mice compared with controls. Histological examination of mice lungs exposed to hyperoxia show increased inflammation and alveolar congestion compared with controls. Our results indicate sequential increase in CLOCK gene expression in lungs of mice exposed to hyperoxia compared with controls. Additionally, data suggest a dose-dependent increase in CLOCK gene expression with increased oxygen concentrations. To validate if the expression changes related to CLOCK genes are indeed associated with inflammation, NALP3−/− was introduced to analyze loss of function in inflammation. Western blot analysis showed significant CLOCK gene downregulation in NALP3−/− mice compared with wild-type controls. Together, our results demonstrate that hyperoxia-mediated lung inflammation is associated with alterations in CLOCK gene expression.
Transient complex I inhibition at the onset of reperfusion by extracellular acidification decreases cardiac injury
Authors: Xu Aijun , Szczepanek Karol , Maceyka Michael W. , Ross Thomas , Bowler Elizabeth , Hu Ying , Kenny Barrett , Mehfoud Chris , Desai Pooja N. , Baumgarten Clive M. , Chen Qun , Lesnefsky Edward J.
Published: April 2014

A reversible inhibition of mitochondrial respiration by complex I inhibition at the onset of reperfusion decreases injury in buffer-perfused hearts. Administration of acidic reperfusate for a brief period at reperfusion decreases cardiac injury. We asked if acidification treatment decreased cardiac injury during reperfusion by inhibiting complex I. Exposure of isolated mouse heart mitochondria to acidic buffer decreased the complex I substrate-stimulated respiration, whereas respiration with complex II substrates was unaltered. Evidence of the rapid and reversible inhibition of complex I by an acidic environment was obtained at the level of isolated complex, intact mitochondria and in situ mitochondria in digitonin-permeabilized cardiac myocytes. Moreover, ischemia-damaged complex I was also reversibly inhibited by an acidic environment. In the buffer-perfused mouse heart, reperfusion with pH 6.6 buffer for the initial 5 min decreased infarction. Compared with untreated hearts, acidification treatment markedly decreased the mitochondrial generation of reactive oxygen species and improved mitochondrial calcium retention capacity and inner mitochondrial membrane integrity. The decrease in infarct size achieved by acidic reperfusion approximates the reduction obtained by a reversible, partial blockade of complex I at reperfusion. Extracellular acidification decreases cardiac injury during reperfusion in part via the transient and reversible inhibition of complex I, leading to a reduction of oxyradical generation accompanied by a decreased susceptibility to mitochondrial permeability transition during early reperfusion.