bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Fluid Flow and Heat Transfer in 3D Dual-Beam Laser Keyhole Welding
Authors: Zhou Jun , Tsai Hai-Lung
Published: April 2011

Dual-beam laser welding has become an emerging joining technique. Studies have demonstrated that it can provide benefits over conventional single-beam laser welding, such as increasing keyhole stability, slowing down cooling rate and delaying the humping onset to a higher welding speed. It is also reported to be able to improve weld quality significantly. However, due to its complexity the development of this promising technique has been limited to the trial-and-error procedure. In this study, mathematical models are developed to investigate the heat transfer, melt flow, and solidification process in three-dimensional dual-beam laser keyhole welding. Effects of key parameters, such as laser-beam configuration on melt flow, weld shape, and keyhole dynamics are studied. Some experimentally observed phenomena, such as the changes of the weld pool shape from oval to circle and from circle to oval during the welding process are analyzed in current study.
Three-Dimensional Simulation of Cross-Flow Microfilter Fouling in Tortuous Pore Profiles With Semi-Synthetic Metalworking Fluids
Authors: Yu Bingyi , Kapoor Shiv G. , DeVor Richard E.
Published: April 2011

Fluid flow and fouling mechanisms are examined with a three-dimensional simulation of the tortuous, verisimilar geometry of an α-alumina microfilter. Reconstruction of the three-dimensional geometry was accomplished from two-dimensional cross-sectional cuts, obtained from a focused ion beam. A wall collision model and a particle trapping model are developed for the investigation of fouling mechanisms. The reconstructed geometry and the two models were used in computational fluid dynamics to simulate metalworking colloidal particles travelling through and trapping in the tortuous pore paths of a microfilter. Results reveal sharp flux decline initiating from partial pore blocking and subdued flux decline finalizing in cake layer development with steady-state flow. This flow behavior is in agreement with experimental data from earlier studies. The inclusion of the wall collision model and particle trapping model enabled the revelation of cake layer development as a fouling mechanism.
An Investigation Into Fixture Error Compensation in Micromilling Using Tool-Based Conductive Touch-Off
Authors: Kunz Jacob A. , Sodemann Angela , Mayor J. Rhett
Published: April 2011

In micro-milling, decreased tool size leads to a need for tighter tolerances for fixture error in order to avoid excessive tool load and maintain machining accuracy. In 4-axis machining on a curved surface, fixture errors propagate cumulatively leading to a significant error at the tool tip. As a result a compensation approach is essential to successful microfeature production on curved surfaces. Tool stresses are shown to be highly dependent on the amount of fixture error. The scaling down of tool sizes is shown to result in an exponential increase in tool stresses. This paper proposes the use of a conductive touch-off method that utilizes the milling tool in its spindle to perform an in-situ registration mapping of positional errors. The fixturing errors are characterized using the Denavit-Hartenberg robotic linkage convention. A forward kinematic solution uses homogeneous transformation matrices to investigate the effects of fixturing errors on milling tool path errors in 4-axis micro-milling on curved surfaces. The touch-off registration measures the positional error in the tool axis direction allowing for axial tool position compensation. This results in decreased tool stresses and increased channel depth accuracy which is necessary for successful milling. A preliminary implementation of the conductive touch-off registration approach has demonstrated the efficacy of the technique when applied to production of micro-features on concave surfaces.
Laser Coating of HAp/Ti Nanoparticles on Metal Implants: Interfacial Bonding Strength, Chemical Analysis and Biocompatibility
Authors: Zhang Martin Y. , Cheng Gary J.
Published: April 2011

In this paper, laser coating of hydroxyapatite (HAp) and Ti nanoparticles on Ti-6Al-4V implants was developed. An Nd:YAG laser was used to coat multilayers of HAp and Ti nanoparticles on implants. This coating process has the following advantages: (1) low temperature coating of nanoscale HAp is realized due to good sinterability of titanium nanoparticles; (2) high interfacial strength between layer and substrate because of the functional multilayer coating; (3) HAp nanoparticles provide better biocompability than micro-particles; (4) biphasic calcium phosphate (BCP) could be introduced, which has been reported to have excellent biocompatibility. In order to achieve these goals, careful selection of laser processing parameters is required. A multiphysics model is built and validated with experiments. This model is employed to determine the appropriate laser processing conditions. After laser processing, the features of the coated samples were characterized, including microstructures, chemical compositions, surface roughness, structure porosity and interfacial bonding strength. Qualitative cell culture studies with osteoblast-like UMR-105 cells were carried out to reveal the biocompatibility of so-coated implants. It is found that multilayer laser coated nanoHAp/Ti implants has beneficial biocompatibility, surface roughness, maintained chemical composition, porous microstructure and strong coating/substrate interfacial strength.
Nucleation of Highly Dense Nanoscale Precipitates Based on an Innovative Process: Warm Laser Shock Peening
Authors: Liao Yiliang , Ye Chang , Cheng Gary J.
Published: April 2011

Warm laser shock peening (WLSP) is an innovative thermo-mechanical processing technique, which combines the advantages of laser shock peening (LSP) and dynamic aging (DA). It has been found that a unique microstructure with highly dense nanoscale precipitates surrounded by dense dislocation structures is generated by WLSP. In order to understand the nucleation mechanism of the highly dense precipitates during WLSP, aluminum alloy 6061 (AA6061) has been used by investigating the WLSP process with experiments and analytical modeling. An analytical model has been proposed to estimate the nucleation rate in metallic materials after WLSP. The effects of the processing temperature and high strain rate deformation on the activation energy of nucleation have been considered in this model. This model is based on the assumption that dynamic aging during WLSP can be assisted by the dense dislocation structures and warm temperature. The effects of the working temperature and dislocation density on the activation energy of precipitation have been investigated. This model is validated by a series of experiments and characterizations after WLSP. The relationships between the processing conditions, the nucleation density of precipitates and the defect density have been investigated.
Wear of a Tool in Double-Disk Lapping of Silicon Wafers
Authors: Barylski Adam , Deja Mariusz
Published: April 2011

Silicon wafers are the most widely used substrates for fabricating integrated circuits. A sequence of processes is needed to turn a silicon ingot into silicon wafers. One of the processes is flattening by lapping or by grinding to achieve a high degree of flatness and parallelism of the wafer [1, 2, 3]. Lapping can effectively remove or reduce the waviness induced by preceding operations [2, 4]. The main aim of this paper is to compare the simulation results with lapping experimental data obtained from the Polish producer of silicon wafers, the company Cemat Silicon from Warsaw (www.cematsil.com). Proposed model is going to be implemented by this company for the tool wear prediction. Proposed model can be applied for lapping or grinding with single or double-disc lapping kinematics [5, 6, 7]. Geometrical and kinematical relations with the simulations are presented in the work. Generated results for given workpiece diameter and for different kinematical parameters are studied using models programmed in the Matlab environment.
Integration of thin film transistors and vertical thin film field emitter arrays using ion-induced bending
Authors: Yoshida Tomoya , Nishi Takashi , Nagao Masayoshi , Shimizu Takashi , Kanemaru Seigo
Published: April 2011

A vertical thin film field emitter array (VTF-FEA) was integrated with a thin film transistor (TFT) through a simple fabrication process that is compatible with the existing TFT manufacturing process. Specifically, the authors integrated a poly-Si TFT and a previously reported VTF-FEA. The VTF-FEA was fabricated using the ion-induced bending (IIB) technique. The IIB is a technique that can bend a cantilever by ion-beam irradiation and can be used with a wide range of materials. The emission from the TFT-VTF-FEA was controlled from subnanoampere to microampere levels using the built-in TFT. This work demonstrated that VTF-FEAs can be integrated with poly-Si TFTs and other electronic devices, such as metal-oxide semiconductor field effect transistors.
Comparative Functional Genomics of the Fission Yeasts
Authors: Rhind Nicholas , Chen Zehua , Yassour Moran , Thompson Dawn A. , Haas Brian J. , Habib Naomi , Wapinski Ilan , Roy Sushmita , Lin Michael F. , Heiman David I. , Young Sarah K. , Furuya Kanji , Guo Yabin , Pidoux Alison , Chen Huei Mei , Robbertse Barbara , Goldberg Jonathan M. , Aoki Keita , Bayne Elizabeth H. , Berlin Aaron M. , Desjardins Christopher A. , Dobbs Edward , Dukaj Livio , Fan Lin , FitzGerald Michael G. , French Courtney , Gujja Sharvari , Hansen Klavs , Keifenheim Dan , Levin Joshua Z. , Mosher Rebecca A. , Müller Carolin A. , Pfiffner Jenna , Priest Margaret , Russ Carsten , Smialowska Agata , Swoboda Peter , Sykes Sean M. , Vaughn Matthew , Vengrova Sonya , Yoder Ryan , Zeng Qiandong , Allshire Robin , Baulcombe David , Birren Bruce W. , Brown William , Ekwall Karl , Kellis Manolis , Leatherwood Janet , Levin Henry , Margalit Hanah , Martienssen Rob , Nieduszynski Conrad A. , Spatafora Joseph W. , Friedman Nir , Dalgaard Jacob Z. , Baumann Peter , Niki Hironori , Regev Aviv , Nusbaum Chad
Published: April 2011

A combined analysis of genome sequence, structure, and expression gives insights into fission yeast biology.
RNA Splicing in a New Rhabdovirus from
Culex
Mosquitoes
Authors: Kuwata Ryusei , Isawa Haruhiko , Hoshino Keita , Tsuda Yoshio , Yanase Tohru , Sasaki Toshinori , Kobayashi Mutsuo , Sawabe Kyoko
Published: April 2011

Among members of the order
Mononegavirales
, RNA splicing events have been found only in the family
Bornaviridae
. Here, we report that a new rhabdovirus isolated from the mosquito
Culex tritaeniorhynchus
replicates in the nuclei of infected cells and requires RNA splicing for viral mRNA maturation. The virus, designated
Culex tritaeniorhynchus
rhabdovirus (CTRV), shares a similar genome organization with other rhabdoviruses, except for the presence of a putative intron in the coding region for the L protein. Molecular phylogenetic studies indicated that CTRV belongs to the family
Rhabdoviridae
, but it is yet to be assigned a genus. Electron microscopic analysis revealed that the CTRV virion is extremely elongated, unlike virions of rhabdoviruses, which are generally bullet shaped. Northern hybridization confirmed that a large transcript (approximately 6,500 nucleotides [nt]) from the CTRV L gene was present in the infected cells. Strand-specific reverse transcription-PCR (RT-PCR) analyses identified the intron-exon boundaries and the 76-nt intron sequence, which contains the typical motif for eukaryotic spliceosomal intron-splice donor/acceptor sites (GU-AG), a predicted branch point, and a polypyrimidine tract.
In situ
hybridization exhibited that viral RNAs are primarily localized in the nucleus of infected cells, indicating that CTRV replicates in the nucleus and is allowed to utilize the host's nuclear splicing machinery. This is the first report of RNA splicing among the members of the family
Rhabdoviridae
.
Blocking eIF4E-eIF4G Interaction as a Strategy To Impair Coronavirus Replication
Authors: Cencic Regina , Desforges Marc , Hall David R. , Kozakov Dima , Du Yuhong , Min Jaeki , Dingledine Raymond , Fu Haian , Vajda Sandor , Talbot Pierre J. , Pelletier Jerry
Published: April 2011

Coronaviruses are a family of enveloped single-stranded positive-sense RNA viruses causing respiratory, enteric, and neurologic diseases in mammals and fowl. Human coronaviruses are recognized to cause up to a third of common colds and are suspected to be involved in enteric and neurologic diseases. Coronavirus replication involves the generation of nested subgenomic mRNAs (sgmRNAs) with a common capped 5′ leader sequence. The translation of most of the sgmRNAs is thought to be cap dependent and displays a requirement for eukaryotic initiation factor 4F (eIF4F), a heterotrimeric complex needed for the recruitment of 40S ribosomes. We recently reported on an ultrahigh-throughput screen to discover compounds that inhibit eIF4F activity by blocking the interaction of two of its subunits (R. Cencic et al., Proc. Natl. Acad. Sci. U. S. A.108:1046–1051, 2011). Herein we describe a molecule from this screen that prevents the interaction between eIF4E (the cap-binding protein) and eIF4G (a large scaffolding protein), inhibiting cap-dependent translation. This inhibitor significantly decreased human coronavirus 229E (HCoV-229E) replication, reducing the percentage of infected cells and intra- and extracellular infectious virus titers. Our results support the strategy of targeting the eIF4F complex to block coronavirus infection.
Capturing the Herpes Simplex Virus Core Fusion Complex (gB-gH/gL) in an Acidic Environment
Authors: Cairns Tina M. , Whitbeck J. Charles , Lou Huan , Heldwein Ekaterina E. , Chowdary Tirumala K. , Eisenberg Roselyn J. , Cohen Gary H.
Published: April 2011

Herpes simplex virus (HSV) entry requires the core fusion machinery of gH/gL and gB as well as gD and a gD receptor. When gD binds receptor, it undergoes conformational changes that presumably activate gH/gL, which then activates gB to carry out fusion. gB is a class III viral fusion protein, while gH/gL does not resemble any known viral fusion protein. One hallmark of fusion proteins is their ability to bind lipid membranes. We previously used a liposome coflotation assay to show that truncated soluble gB, but not gH/gL or gD, can associate with liposomes at neutral pH. Here, we show that gH/gL cofloats with liposomes but only when it is incubated with gB at pH 5. When gB mutants with single amino acid changes in the fusion loops (known to inhibit the binding of soluble gB to liposomes) were mixed with gH/gL and liposomes at pH 5, gH/gL failed to cofloat with liposomes. These data suggest that gH/gL does not directly associate with liposomes but instead binds to gB, which then binds to liposomes via its fusion loops. Using monoclonal antibodies, we found that many gH and gL epitopes were altered by low pH, whereas the effect on gB epitopes was more limited. Our liposome data support the concept that low pH triggers conformational changes to both proteins that allow gH/gL to physically interact with gB.
Small Molecules Targeting Hepatitis C Virus-Encoded NS5A Cause Subcellular Redistribution of Their Target: Insights into Compound Modes of Action
Authors: Targett-Adams Paul , Graham Emily J. S. , Middleton Jenny , Palmer Amy , Shaw Stephen M. , Lavender Helen , Brain Philip , Tran Thien Duc , Jones Lyn H. , Wakenhut Florian , Stammen Blanda , Pryde David , Pickford Chris , Westby Mike
Published: April 2011

The current standard of care for hepatitis C virus (HCV)-infected patients consists of lengthy treatment with interferon and ribavirin. To increase the effectiveness of HCV therapy, future regimens will incorporate multiple direct-acting antiviral (DAA) drugs. Recently, the HCV-encoded NS5A protein has emerged as a promising DAA target. Compounds targeting NS5A exhibit remarkable potencyin vitroand demonstrate early clinical promise, suggesting that NS5A inhibitors could feature in future DAA combination therapies. Since the mechanisms through which these molecules operate are unknown, we have used NS5A inhibitors as tools to investigate their modes of action. Analysis of replicon-containing cells revealed dramatic phenotypic alterations in NS5A localization following treatment with NS5A inhibitors; NS5A was redistributed from the endoplasmic reticulum to lipid droplets. The NS5A relocalization did not occur in cells treated with other classes of HCV inhibitors, and NS5A-targeting molecules did not cause similar alterations in the localization of other HCV-encoded proteins. Time course analysis of the redistribution of NS5A revealed that the transfer of protein to lipid droplets was concomitant with the onset of inhibition, as judged by the kinetic profiles for these compounds. Furthermore, analysis of the kinetic profile of inhibition for a panel of test molecules permitted the separation of compounds into different kinetic classes based on their modes of action. Results from this approach suggested that NS5A inhibitors perturbed the function of new replication complexes, rather than acting on preformed complexes. Taken together, our data reveal novel biological consequences of NS5A inhibition, which may help enable the development of future assay platforms for the identification of new and/or different NS5A inhibitors.
Replication-Coupled and Host Factor-Mediated Encapsidation of the Influenza Virus Genome by Viral Nucleoprotein
Authors: Kawaguchi Atsushi , Momose Fumitaka , Nagata Kyosuke
Published: April 2011

The influenza virus RNA-dependent RNA polymerase is capable of initiating replication but mainly catalyzes abortive RNA synthesis in the absence of viral and host regulatory factors. Previously, we reported that IREF-1/minichromosome maintenance (MCM) complex stimulates a
de novo
initiated replication reaction by stabilizing an initiated replication complex through scaffolding between the viral polymerase and nascent cRNA to which MCM binds. In addition, several lines of genetic and biochemical evidence suggest that viral nucleoprotein (NP) is involved in successful replication. Here, using cell-free systems, we have shown the precise stimulatory mechanism of virus genome replication by NP. Stepwise cell-free replication reactions revealed that exogenously added NP free of RNA activates the viral polymerase during promoter escape while it is incapable of encapsidating the nascent cRNA. However, we found that a previously identified cellular protein, RAF-2p48/NPI-5/UAP56, facilitates replication reaction-coupled encapsidation as an NP molecular chaperone. These findings demonstrate that replication of the virus genome is followed by its encapsidation by NP in collaboration with its chaperone.
Genetic Evidence for Rift Valley Fever Outbreaks in Madagascar Resulting from Virus Introductions from the East African Mainland rather than Enzootic Maintenance
Authors: Carroll Serena A. , Reynes Jean-Marc , Khristova Marina L. , Andriamandimby Soa Fy , Rollin Pierre E. , Nichol Stuart T.
Published: April 2011

Rift Valley fever virus (RVFV), a mosquito-borne phlebovirus, has been detected in Madagascar since 1979, with occasional outbreaks. In 2008 to 2009, a large RVFV outbreak was detected in Malagasy livestock and humans during two successive rainy seasons. To determine whether cases were due to enzootic maintenance of the virus within Madagascar or to importation from the East African mainland, nine RVFV whole genomic sequences were generated for viruses from the 1991 and 2008 Malagasy outbreaks. Bayesian coalescent analyses of available whole S, M, and L segment sequences were used to estimate the time to the most recent common ancestor for the RVFVs. The 1979 Madagascar isolate shared a common ancestor with strains on the mainland around 1972. The 1991 Madagascar isolates were in a clade distinct from that of the 1979 isolate and shared a common ancestor around 1987. Finally, the 2008 Madagascar viruses were embedded within a large clade of RVFVs from the 2006–2007 outbreak in East Africa and shared a common ancestor around 2003 to 2004. These results suggest that the most recent Madagascar outbreak was caused by a virus likely arriving in the country some time between 2003 and 2008 and that this outbreak may be an extension of the 2006–2007 East African outbreak. Clustering of the Malagasy sequences into subclades indicates that the viruses have continued to evolve during their short-term circulation within the country. These data are consistent with the notion that RVFV outbreaks in Madagascar result not from emergence from enzootic cycles within the country but from recurrent virus introductions from the East African mainland.
Pleiotropic Action of AP-1 in v-Src-Transformed Cells
Authors: Wang Lizhen , Rodrigues Natalie A. , Wu Ying , Maslikowski Bart M. , Singh Nishi , Lacroix Samantha , Bédard Pierre-André
Published: April 2011

The activation of AP-1 is a hallmark of cell transformation by tyrosine kinases. In this study, we characterize the role of AP-1 proteins in the transformation of chicken embryo fibroblasts (CEF) by v-Src. In normal CEF, the expression of a dominant negative mutant of c-Jun (TAM67) induced senescence. In contrast, three distinct phenotypes were observed when TAM67 was expressed in v-Src-transformed CEF. While senescent cells were also present, the inhibition of AP-1 caused apoptosis in a fraction of the v-Src-transformed cells. In addition, cells containing lipid-rich vesicles accumulated, suggesting that a subpopulation of the v-Src-transformed cells underwent differentiation in response to the inhibition of AP-1. JunD and Fra-2 were the main components of this factor, while c-Jun accounted for a minor fraction of AP-1 in v-Src-transformed CEF. The downregulation of c-Jun expression by short hairpin RNA (shRNA) induced senescence in normal and v-Src-transformed cells. In contrast, a high incidence of apoptosis was caused by the downregulation of JunD, suggesting that it is required for the survival of v-Src-transformed CEF. Levels of the p53 tumor suppressor were elevated under conditions of JunD inhibition. Repression of p53 by shRNA enhanced the survival and anchorage-independent proliferation of v-Src-transformed CEF with JunD/AP-1 inhibition. The inhibition of Fra-2 had no visible phenotype in normal CEF but caused the appearance of lipid-rich vesicles in v-Src-transformed CEF. Therefore, AP-1 facilitated transformation by acting as a survival factor, by inhibiting premature entry into senescence, and by blocking the differentiation of v-Src-transformed CEF.
Rhinovirus-Induced Barrier Dysfunction in Polarized Airway Epithelial Cells Is Mediated by NADPH Oxidase 1
Authors: Comstock Adam T. , Ganesan Shyamala , Chattoraj Asamanja , Faris Andrea N. , Margolis Benjamin L. , Hershenson Marc B. , Sajjan Umadevi S.
Published: April 2011

Previously, we showed that rhinovirus (RV), which is responsible for the majority of common colds, disrupts airway epithelial barrier function, as evidenced by reduced transepithelial resistance (R
T
), dissociation of zona occludins 1 (ZO-1) from the tight junction complex, and bacterial transmigration across polarized cells. We also showed that RV replication is required for barrier function disruption. However, the underlying biochemical mechanisms are not known. In the present study, we found that a double-stranded RNA (dsRNA) mimetic, poly(I:C), induced tight junction breakdown and facilitated bacterial transmigration across polarized airway epithelial cells, similar to the case with RV. We also found that RV and poly(I:C) each stimulated Rac1 activation, reactive oxygen species (ROS) generation, and Rac1-dependent NADPH oxidase 1 (NOX1) activity. Inhibitors of Rac1 (NSC23766), NOX (diphenylene iodonium), and NOX1 (small interfering RNA [siRNA]) each blocked the disruptive effects of RV and poly(I:C) on R
T
, as well as the dissociation of ZO-1 and occludin from the tight junction complex. Finally, we found that Toll-like receptor 3 (TLR3) is not required for either poly(I:C)- or RV-induced reductions in R
T
. Based on these results, we concluded that Rac1-dependent NOX1 activity is required for RV- or poly(I:C)-induced ROS generation, which in turn disrupts the barrier function of polarized airway epithelia. Furthermore, these data suggest that dsRNA generated during RV replication is sufficient to disrupt barrier function.
Opposing Effects of CD70 Costimulation during Acute and Chronic Lymphocytic Choriomeningitis Virus Infection of Mice
Authors: Penaloza-MacMaster Pablo , Rasheed Ata Ur , Iyer Smita S. , Yagita Hideo , Blazar Bruce R. , Ahmed Rafi
Published: April 2011

T cell costimulation is important for T cell activation. The CD27/CD70 pathway contributes to effector and memory T cell development and is involved in T cell and B cell activation. CD27/CD70 is known for having opposing roles during different models of antigenic challenges. During primary T cell responses to influenza virus infection or during tumor challenges, CD27/CD70 costimulation has a positive role on T cell responses. However, during some chronic infections, constitutive triggering of this signaling pathway has a negative role on T cell responses. It is currently unclear what specific characteristic of an antigen determines the outcome of CD27/CD70 costimulation. We investigated the effect of a transient CD70 blockade during an acute or a chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Blockade of this pathway during acute LCMV infection (Armstrong strain) resulted in delayed T cell responses and decreased CD127 (interleukin-7 receptor α [IL-7Rα] chain) conversion. Upregulation of CD127 is an important event in T cell differentiation that heralds the passage of an effector T cell to a long-lived memory T cell. In contrast to the reduced CD8 T cell responses after CD70 blockade during acute infection, CD70 blockade during chronic LCMV infection resulted in increased CD8 T cell responses. Our data show the dual roles of this costimulatory pathway in acute versus persistent antigen challenge. Our findings suggest that antigen persistence may determine the effect of CD27/CD70 signaling on CD8 T cell responses. Tailored triggering or blockade of this costimulatory pathway may be important in vaccination regimens against acute or chronic pathogens.
Inhibition of Dengue Virus through Suppression of Host Pyrimidine Biosynthesis
Authors: Wang Qing-Yin , Bushell Simon , Qing Min , Xu Hao Ying , Bonavia Aurelio , Nunes Sandra , Zhou Jing , Poh Mee Kian , Florez de Sessions Paola , Niyomrattanakit Pornwaratt , Dong Hongping , Hoffmaster Keith , Goh Anne , Nilar Shahul , Schul Wouter , Jones Susan , Kramer Laura , Compton Teresa , Shi Pei-Yong
Published: April 2011

Viral replication relies on the host to supply nucleosides. Host enzymes involved in nucleoside biosynthesis are potential targets for antiviral development. Ribavirin (a known antiviral drug) is such an inhibitor that suppresses guanine biosynthesis; depletion of the intracellular GTP pool was shown to be the major mechanism to inhibit flavivirus. Along similar lines, inhibitors of the pyrimidine biosynthesis pathway could be targeted for potential antiviral development. Here we report on a novel antiviral compound (NITD-982) that inhibits host dihydroorotate dehydrogenase (DHODH), an enzyme required for pyrimidine biosynthesis. The inhibitor was identified through screening 1.8 million compounds using a dengue virus (DENV) infection assay. The compound contains an isoxazole-pyrazole core structure, and it inhibited DENV with a 50% effective concentration (EC50) of 2.4 nM and a 50% cytotoxic concentration (CC50) of >5 μM. NITD-982 has a broad antiviral spectrum, inhibiting both flaviviruses and nonflaviviruses with nanomolar EC90s. We also show that (i) the compound inhibited the enzymatic activity of recombinant DHODH, (ii) an NITD-982 analogue directly bound to the DHODH protein, (iii) supplementing the culture medium with uridine reversed the compound-mediated antiviral activity, and (iv) DENV type 2 (DENV-2) variants resistant to brequinar (a known DHODH inhibitor) were cross resistant to NITD-982. Collectively, the results demonstrate that the compound inhibits DENV through depleting the intracellular pyrimidine pool. In contrast to thein vitropotency, the compound did not show any efficacy in the DENV-AG129 mouse model. The lack ofin vivoefficacy is likely due to the exogenous uptake of pyrimidine from the diet or to a high plasma protein-binding activity of the current compound.
Need for ethics support in healthcare institutions: views of Dutch board members and ethics support staff
Authors: Dauwerse Linda , Abma Tineke , Molewijk Bert , Widdershoven Guy
Published: April 2011

Objective

The purpose of this article is to investigate the need for ethics support in Dutch healthcare institutions in order to understand why ethics support is often not used in practice and which factors are relevant in this context.

Methods

This study had a mixed methods design integrating quantitative and qualitative research methods. Two survey questionnaires, two focus groups and 17 interviews were conducted among board members and ethics support staff in Dutch healthcare institutions.

Findings

Most respondents see a need for ethics support. This need is related to the complexity of contemporary healthcare, the contribution of ethics support to the core business of the organisation and to the surplus value of paying structural attention to ethical issues. The need for ethics support is, however, not unconditional. Reasons for a lacking need include: aversion of innovations, negative associations with the notion of ethics support service, and organisational factors like resources and setting.

Conclusion

There is a conditioned need for ethics support in Dutch healthcare institutions. The promotion of ethics support in healthcare can be fostered by focusing on formats which fit the needs of (practitioners in) healthcare institutions. The emphasis should be on creating a (culture of) dialogue about the complex situations which emerge daily in contemporary healthcare practice.
Lactic Acidosis in Channel Catfish
Authors: Caillouet Jr. Charles W.
Published: April 2011

Channel catfish (Ictalurus punctatus) were subjected to 5 or 10 min of anoxia (removed from water) to rapidly increase blood lactic acid concentration metabolically. Blood pH decreased as blood lactic acid concentration increased. Respiratory rate increased in fish with lowered blood pH and with increased blood lactic acid concentration during the 10 min after fish were returned to water after anoxia. Fish not treated had a mean blood pH of 7.8. Blood pH decreased in catfish subjected to anoxia 5, 10, and 15 min and decreased further when the fish were returned to water. Lowered blood pH was associated with loss of equilibrium and death in catfish subjected to transportation and handling.
Fluorimetric Method for the Determination of Cortisol in Small Quantities of Salmonid Plasma
Authors: Donaldson Edward M. , Fagerlund Ulf H. , Schmidt Peter J.
Published: April 2011

A method is described for the fluorimetric determination of cortisol in 1-ml aliquots of salmonid plasma. Validation experiments are presented which indicate that the reliability of the method is satisfactory. The method provides the means for the determination of low cortisol concentrations, such as those encountered in hypophysectomized or resting salmonids (0.01–0.05 μg/ml).
Hybridization and Isolating Mechanisms Between Catostomus commersonii and C. macrocheilus (Pisces: Catostomidae)
Authors: Nelson J. S.
Published: April 2011

Catostomus commersonii and C. macrocheilus are sympatric in three major drainages of British Columbia. Morphological analysis employing a character index and discriminant function analysis of allopatric and sympatric populations revealed that hybrids were in 9 of the 11 lakes examined in which both species occurred. Presumed F1 hybrids made up an average of 7% of the individuals of the combined populations where hybrids occurred. There was no evidence of backcrossing or swamping.Segregation in spawning time and habitat was not apparent in four confined inlets which have migrations of both species. Some lakes supporting both species were found to have inlets in which only one species spawned. Temporal isolation was absent but habitat isolation was present in some areas of Cluculz River, an outlet with diversified habitat. Where segregation was apparent, C. commersonii spawned in shallow gravelly areas and C. macrocheilus in deep sandy areas. Artificial crosses of the species, two backcrosses involving hybrid females, and microscopic examination of hybrid testes failed to show any effective postmating isolating mechanism. An interaction of temporal, habitat, and postmating isolating mechanisms was not considered sufficient to prevent swamping. Ethological isolation is inferred to be of major importance in reducing initial hybridization. No explanation was found for the apparent failure of hybrids to successfully reproduce.Hybridization could not be attributed to environmental factors commonly associated with this phenomenon. Males of one species entering the spawning act with males and a female of the other species is considered the main cause of hybridization. Mis-mated individuals, however, have much opportunity for conspecific matings at other times. There was no evidence of reinforcement of isolating mechanisms despite the probable occurrence of hybridization in some areas for at least several hundred years. Characters of each species were as distinctive in the areas of sympatry as in the areas of allopatry. Natural selection against individuals producing hybrids is apparently slow.
Two New Specimens of the Notacanthid Fish Macdonaldia challengeri in the Eastern North Pacific Ocean
Authors: Peden Alex E.
Published: April 2011

not available
The Occurrence and Retention of Dimethyl-β-Propiothetin in Some Filter-Feeding Organisms
Authors: Ackman R. G. , Hingley H. J.
Published: April 2011

Determinations of dimethyl-β-propiothetin (DMPT) levels are reported for 10 filter-feeding organisms, 1 browsing mollusc, 1 carnivorous mollusc, and 1 crustacean. Mature oysters, scallops, and the pteropod Limacina helicina showed high (ca. 0.1 mg/g) DMPT levels, mussels showed generally lower levels, and quahogs and a tunicate showed negligible amounts of DMPT. The periwinkle accumulated DMPT only when feeding on an alga rich in DMPT. Retention of DMPT over prolonged periods was studied in the oyster and in mussels.Seasonal variations, year-to-year variations, and variations with locations were studied for oysters and to a limited extent for mussels. The findings are discussed in terms of food availability and feeding habits and indicate that together with tocopherol it may be possible to correlate DMPT levels with the availability of phytoplankters in the food intake or some species. It is suggested that phagocytes may be responsible for prolonged retention of DMPT in oysters.
Some Chondracanthidae (Copepoda) from Fishes of British Columbia
Authors: Kabata Z.
Published: April 2011

This paper redescribes three species of Chondracanthidae (Copepoda) parasitic on the fishes of British Columbia and previously recorded by earlier writers (Chondracanthus irregularis, Ch. pinguis, and Ch. gracilis). Two new species are described (Ch. pusillus and Acanthochoniria holocephalarum). Finer structural details of the chondracanthid appendages are illustrated and the taxonomic status of the previously known species is discussed.
Occurrence of Parasudis truculentus (Goode and Bean) 1895 (Iniomi: Chlorophthalmidae) off LaHave Bank, Nova Scotia
Authors: Halliday R. G.
Published: April 2011

not available
Infection of Brook Trout (Salvelinus fontinalis) by Nocardiae
Authors: Campbell Gordon , MacKelvie R. M.
Published: April 2011

not available
Description of Laboratory-Reared Larvae of Paralithodes platypus (Decapoda, Anomura, Lithodidae)
Authors: Hoffman Ethelwyn G.
Published: April 2011

Larvae of the blue king crab, Paralithodes platypus (Brandt), were hatched and reared in the laboratory. All larval stages obtained developed in a manner similar to the development reported for other lithodid anomurans. In culture, P. platypus had four zoeal stages and a single glaucothoeal stage. The feature which distinguishes all zoeal stages of this species from zoeae of the other two North Pacific species of Paralithodes — P. camtschatica and P. brevipes — is the presence of 9 + 9 telson processes (including a hair-like second process) rather than 8 + 8 telson processes. Glaucothoes of P. platypus have one more pair of spines in the branchial region of the carapace than do those of P. camtschatica. Glaucothoes of P. platypus have 15 pairs of spines on the dorsal surface of the carapace, not including the spines of the frontal area (rostral complex) or the suborbital spines, whereas glaucothoes of P. camtschatica have 14 pairs of spines, and those of P. brevipes have 13 pairs.
The Aquiferous System of Polinices lewisi (Gastropoda, Prosobranchiata)
Authors: Bernard F. R.
Published: April 2011

Polinices lewisi (Gould) possesses an aquiferous system for the expansion of the podial complex. The haemal system is highly modified and entirely separate from the aquiferous system. Postpodial ostia and haemal sheaths are demonstrated. The morphology of the aquiferous and blood systems is traced.
Design of a Controlled-Environment Incubator for Small Marine Fish Eggs
Authors: Alderdice D. F. , Velsen F. P. J.
Published: April 2011

not available
Ichthyophonus Infection in Yellowtail Flounder (Limanda ferruginea) off Nova Scotia
Authors: Powles P. M. , Garnett D. G. , Ruggieri S.J. G. D. , Nigrelli R. F.
Published: April 2011

not available
Some Enzymatic Properties of Brain Acetylcholinesterase from Bluegill and Channel Catfish
Authors: Hogan James W. , Knowles Charles O.
Published: April 2011

Using a manometric technique an acetylcholinesterase (EC 3.1.1.7, acetylcholine acetyl-hydrolase) was demonstrated in brain tissue from the bluegill, Lepomis macrochirus Rafinesque, and the channel catfish, Ictalurus punctatus (Walbaum). The activities were 19 and 37 μmoles acetylcholine hydrolyzed/milligram protein per hour for the bluegill and channel catfish enzymes, respectively. The optimum substrate concentration for the hydrolysis of acetylcholine was 10 mM for the enzymes from both species. Generally, the catfish acetylcholinesterase was somewhat more susceptible than the bluegill to the inhibitors tested; however, the bluegill enzyme was more susceptible to inhibition by malathion and malaoxon.
Heavy Metal Ions and the Development of Rancidity in Blended Fish Muscle
Authors: Castell C. H. , Spears D. M.
Published: April 2011

From 1 to 50 ppm of 10 different heavy metal ions were added to blended muscle taken from freshly killed cod, haddock, flounders, redfish, herring, mackerel, scallops, and lobster, and stored for 24 hr at 0 C. The resulting rancidities were determined by thiobarbituric acid (TBA) values and odours. With some exceptions, Fe++, V++, and Cu++ were the most active catalysts. Fe++ was always more effective than Fe+++. Cd++, Co++, and Zn+ produced randicity with the fatty species but not with any of the other species that were tested. Ni++, Cr++, Ce++, and Mn++ did not accelerate rancidity in any of the muscles. There was considerable difference in the relative susceptibility of muscle from different species to rancidity induced by specific metals. During frozen storage, changes in fish muscle took place that rendered it less susceptible to subsequent metal-induced rancidities.
Age and Growth of Round Whitefish (Prosopium cylindraceum) from Ungava
Authors: Mackay Isobel , Power G.
Published: April 2011

Growth in length and weight of round whitefish was similar in two localities in Ungava, northern Quebec. The pattern of growth, however, differed from those reported previously for round whitefish from the Great Lakes. Round whitefish from Ungava are slow growing and approach their maximum size at a constant growth rate, whereas those from the Great Lakes approach their upper size limit rapidly within the first 3 years and thereafter growth is slow. The maturing age was greater for both Ungava males and females (4+ and 3+ years respectively for the earliest specimens) than for round whitefish from the Great Lakes. Though round whitefish are abundant in the Ungava region, they are of no commercial interest because of their slow growth and small average size.
Influence of Changing Seasons on Schooling Behavior of Yellow Perch
Authors: Hergenrader Gary L. , Hasler Arthur D.
Published: April 2011

Analysis of echo-sounder and sonar records made on Lake Mendota during summer and winter indicated that the schooling behavior of yellow perch, Perca flavescens (Mitchill), changed markedly between the two seasons. The distance separating individuals in schools during summer was less than 1.5–2.0 ft, consequently producing dense traces on the recorder charts which showed no definition of individuals. During winter, however, the fish-to-fish distances often were greater than 1.5–2.0 ft, producing many traces showing the individual fishes in a school. The mean distance between the top and bottom fish in a school during winter was 22.1 ft (6.7 m); in summer only 8.5 ft (2.5 m). High correlations existed between light transmission of the water and school size (r =.77) and between temperature and school size (r = −.89). The possible adaptive significance of this seasonal change in behavior is discussed.
Very Rapid Accumulation of Hypoxanthine in the Muscle of Redfish Stored in Ice
Authors: Fraser Doris I. , Simpson Sylvia G. , Dyer W. J.
Published: April 2011

not available
Method for Counting Coho Fry in Small Streams
Authors: Caulfield W.
Published: April 2011

not available
Thaw Drip in Frozen American Plaice Fillets, Its Seasonal Variation and Development During Storage
Authors: Dyer W. J. , Fraser Doris I. , Greenwell M.
Published: April 2011

not available
Occurrence of the Larvae of Meganyctiphanes norvegica (Crustacea, Euphausiacea) off West Greenland
Authors: Jones Leslie T.
Published: April 2011

not available
An Occurrence of the Pelagic Stingray Dasyatis violacea in the Northwest Atlantic
Authors: Scott W. B. , Tibbo S. N.
Published: April 2011

not available
Extension of Recorded Range of Butter Sole, Isopsetta isolepis, Into the Bering Sea
Authors: Yesaki Mitsuo , Wolotira Jr. Robert J.
Published: April 2011

not available
Subdivisions of the Benthic Environment of the Upper Great Lakes, with Emphasis on Lake Michigan
Authors: Powers Charles F. , Robertson Andrew
Published: April 2011

An effort has been made to introduce a greater degree of standardization and reliability into descriptions of the benthic environment made by biologically oriented observers. Comparisons of field descriptions and mechanical analyses showed an encouraging ability to distinguish among four major sediment types in Lake Michigan. The bottom of the lake has been described in terms of these types, which usually occur in the following order with respect to depth: sand, silty sand–sandy silt, silt–clayey silt in a thin layer overlying stiff plastic clay, and silt–clayey silt only. Each sediment type tends to exhibit its own range of organic carbon values, with the amount of carbon increasing with depth. Hard or rocky bottom occurs in more restricted areas and is considered a fifth recognizable bottom category. Certain features of the distribution of the sediments may be related to gross water movements and to the locations of the mouths of large tributary rivers. Limited comparative studies in Lakes Huron and Superior showed similar distributions of sediment types and organic carbon content. It is suggested that the observed uniformity of maximum organic carbon values in the sediments of all three lakes may be related to processes of oxidation.
An Estimate of Ocean Mortality of Bristol Bay Sockeye Salmon Three Years at Sea
Authors: Mathews Stephen B.
Published: April 2011

The method of population estimation based on change in composition of a dichotomous population was applied to Bristol Bay sockeye salmon to estimate the mortality rate of 3-ocean (3 years at sea) fish during their final year in the ocean. A difference in freshwater age composition between 1-ocean immatures in 1964 and 2-ocean immatures in 1965 was evident in samples taken in the high seas. This difference was apparently due to a greater tendency of 2-freshwater fish than 1-freshwater fish to mature after 2 years at sea. The known quantities of these two freshwater categories in the mature 2-ocean run of 1965 enabled an estimate of the population of 2-ocean immatures at sea in 1965. From this estimate and the quantity of 3-ocean matures in the 1966 run, the annual mortality rate was estimated to be.42.
Distribution of Transaminases (Aminotransferases) in the Tissues of Pacific Salmon (Oncorhynchus), with Emphasis on the Properties and Diagnostic Use of Glutamic-Oxalacetic Transaminase
Authors: Bell Gordon R.
Published: April 2011

A partially purified glutamic-oxalacetic transaminase (GOT) from salmon liver was shown likely to function best at a pH > 7.5, to be specific for the L isomer of aspartic acid, and to require pyridoxal phosphate for activity. The coenzyme appeared to be tightly bound to the apoenzyme.A survey of the scope of apparent transaminations in dialyzed homogenates of brain, heart, kidney, liver, and muscle indicated that GOT and glutamic-pyruvic transaminase were active in all tissues and that α-ketoglutarate (α-KG) was a more widely used amino acceptor than pyruvate. No transamination to the amino acceptors α-KG or pyruvate could be detected using as donors β-alanine, D-alanine, γ-aminobutyrate, glycine, histidine, proline, serine, or threonine. The following amino acids showed various degrees of transamination with α-KG in at least some tissue homogenates: L-leucine, L-norvaline, L-ornithine, L-phenylalanine, L-tyrosine, and L-valine. Interpretation of these results is discussed, particularly in relation to comparative biochemistry.Spectrophotometric estimations of plasma or serum GOT levels were used to distinguish at a significant level (p < 0.01), apparently healthy fish from those treated with the hepatic poisons bromobenzene and CCl4or those affected by bacterial kidney disease. The practical value of using GOT estimations as a diagnostic tool is discussed.It is tentatively suggested from limited data that the activity (units of enzyme/milligram tissue N) of GOT in various tissues decreases in the following order: heart, liver, kidney, and muscle.
Influence of Light on Activity of Brown Trout (Salmo trutta)
Authors: Chaston I.
Published: April 2011

not available
Comparative Electrophoretic Patterns of Lactate Dehydrogenase in Three Species of Trout
Authors: Bouck G. R. , Ball R. C.
Published: April 2011

The isozyme patterns of lactate dehydrogenase (LDH) were examined in three species of trout using electrophoresis in polyacrylamide gel slabs. Each pattern was species specific and contained 15 isozymes of LDH, but a hybrid trout had at least 27 LDH isozymes. Tissue specificity of these isozymes was low except for skeletal muscle. These results suggest that LDH isozyme patterns could be used for taxonomic and diagnostic purposes.