bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of gO Isoforms Reveals that Strains of Human Cytomegalovirus Differ in the Ratio of gH/gL/gO and gH/gL/UL128-131 in the Virion Envelope
Authors: Zhou Momei , Yu Qin , Wechsler Anya , Ryckman Brent J.
Published: June 2013

Herpesvirus glycoprotein complex gH/gL provides a core entry function through interactions with the fusion protein gB and can also influence tropism through receptor interactions. The Epstein-Barr virus gH/gL and gH/gL/gp42 serve both functions for entry into epithelial and B cells, respectively. Human cytomegalovirus (HCMV) gH/gL can be bound by the UL128-131 proteins or gO. The phenotypes of gO and UL128-131 mutants suggest that gO-gH/gL interactions are necessary for the core entry function on all cell types, whereas the binding of UL128-131 to gH/gL likely relates to a distinct receptor-binding function for entry into some specific cell types (e.g., epithelial) but not others (e.g., fibroblasts and neurons). There are at least eight isoforms of gO that differ by 10 to 30% of amino acids, and previous analysis of two HCMV strains suggested that some isoforms of gO function like chaperones, disassociating during assembly to leave unbound gH/gL in the virion envelope, while others remain bound to gH/gL. For the current report, we analyzed the gH/gL complexes present in the virion envelope of several HCMV strains, each of which encodes a distinct gO isoform. Results indicate that all strains of HCMV contain stable gH/gL/gO trimers and gH/gL/UL128-131 pentamers and little, if any, unbound gH/gL. TR, TB40/e, AD169, and PH virions contained vastly more gH/gL/gO than gH/gL/UL128-131, whereas Merlin virions contained mostly gH/gL/UL128-131, despite abundant unbound gO remaining in the infected cells. Suppression of UL128-131 expression during Merlin replication dramatically shifted the ratio toward gH/gL/gO. These data suggest that Merlin gO is less efficient than other gO isoforms at competing with UL128-131 for binding to gH/gL. Thus, gO diversity may influence the pathogenesis of HCMV through effects on the assembly of the core versus tropism gH/gL complexes.
Expression Strategy of Aedes albopictus Densovirus
Authors: Pham Hanh T. , Jousset Françoise-Xavière , Perreault Jonathan , Shike Hiroko , Szelei Jozsef , Bergoin Max , Tijssen Peter
Published: June 2013

The transcription map of the
Aedes albopictus
densovirus (AalDNV) brevidensovirus was identified by Northern blotting, rapid amplification of cDNA ends (RACE) analysis, and RNase protection assays. AalDNV produced mRNAs of 3,359 (NS1), 3,345 (NS2), and 1,246 (VP) nucleotides. The two overlapping P7/7.4 NS promoters employed closely located alternate transcription initiation sites, positioned at either side of the NS1 initiation codon. All NS mRNAs coterminated with VP mRNA. All promoters, explored using luciferase assays, were functional in insect and human cell lines.
Efficacy of Parainfluenza Virus 5 Mutants Expressing Hemagglutinin from H5N1 Influenza A Virus in Mice
Authors: Li Zhuo , Gabbard Jon D. , Mooney Alaina , Chen Zhenhai , Tompkins S. Mark , He Biao
Published: June 2013

Parainfluenza virus 5 (PIV5) is a promising viral vector for vaccine development. PIV5 is safe, stable, efficacious, cost-effective to produce and, most interestingly, it overcomes preexisting antivector immunity. We have recently reported that PIV5 expressing the hemagglutinin (HA) from highly pathogenic avian influenza (HPAI) virus H5N1 (PIV5-H5) provides sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. It is thought that induction of apoptosis can lead to enhanced antigen presentation. Previously, we have shown that deleting the SH gene and the conserved C terminus of the V gene in PIV5 results in mutant viruses (PIV5ΔSH and PIV5VΔC) that enhance induction of apoptosis. In this study, we inserted the HA gene of H5N1 into PIV5ΔSH (PIV5ΔSH-H5) or PIV5VΔC (PIV5VΔC-H5) and compared their efficacies as vaccine candidates to PIV5-H5. We have found that PIV5ΔSH-H5 induced the highest levels of anti-HA antibodies, the strongest T cell responses, and the best protection against an H5N1 lethal challenge in mice. These results suggest that PIV5ΔSH is a better vaccine vector than wild-type PIV5.
Immunological and Virological Analyses of Rhesus Macaques Immunized with Chimpanzee Adenoviruses Expressing the Simian Immunodeficiency Virus Gag/Tat Fusion Protein and Challenged Intrarectally with Repeated Low Doses of SIVmac
Authors: Cervasi Barbara , Carnathan Diane G. , Sheehan Katherine M. , Micci Luca , Paiardini Mirko , Kurupati Raj , Tuyishime Steven , Zhou Xiang Yang , Else James G. , Ratcliffe Sarah J. , Ertl Hildegund C. J. , Silvestri Guido
Published: June 2013

Human adenovirus (AdHu)-based candidate AIDS vaccine can provide protection from simian immunodeficiency virus (SIV) transmission and disease progression. However, their potential use may be limited by widespread preexisting immunity to the vector. In contrast, preexisting immunity to chimpanzee adenoviruses (AdC) is relatively rare. In this study, we utilized two regimens of prime-boost immunizations with AdC serotype SAd-V23 (also called AdC6) and SAd-V24 (also called AdC7) expressing SIV Gag/Tat to test their immunogenicity and ability to protect rhesus macaques (RMs) from a repeated low-dose SIV
mac239
challenge. Both AdC6 followed by AdC7 (AdC6/7) and AdC7 followed by AdC6 (AdC7/6) induced robust SIV Gag/Tat-specific T cell responses as measured by tetramer staining and functional assays. However, no significant protection from SIV transmission was observed in either AdC7/6- or AdC7/6-vaccinated RMs. Interestingly, in the RMs showing breakthrough infections, AdC7/6-SIV immunization was associated with a transient but significant (
P
= 0.035 at day 90 and
P
= 0.033 at day 120 postinfection) reduction in the setpoint viral load compared to unvaccinated controls. None of the measured immunological markers (i.e., number or functionality of SIV-specific CD8
+
and CD4
+
T cell responses and level of activated and/or CCR5
+
CD4
+
target cells) at the time of challenge correlated with protection from SIV transmission in the AdC-SIV-vaccinated RMs. The robust immunogenicity observed in all AdC-immunized RMs and the transient signal of protection from SIV replication exhibited by AdC7/6-vaccinated RMs even in the absence of any envelope immunogen suggest that AdC-based vectors may represent a promising platform for candidate AIDS vaccines.
Aberrant Virion Assembly and Limited Glycoprotein C Production in Varicella-Zoster Virus-Infected Neurons
Authors: Grose Charles , Yu Xiaoli , Cohrs Randall J. , Carpenter John E. , Bowlin Jacqueline L. , Gilden Don
Published: June 2013

Highly pure (>95%) terminally differentiated neurons derived from pluripotent stem cells appear healthy at 2 weeks after infection with varicella-zoster virus (VZV), and the cell culture medium contains no infectious virus. Analysis of the healthy-appearing neurons revealed VZV DNA, transcripts, and proteins corresponding to the VZV immediate early, early, and late kinetic phases of replication. Herein, we further characterized virus in these neuronal cells, focusing on (i) transcription and expression of late VZV glycoprotein C (gC) open reading frame 14 (ORF14) and (ii) ultrastructural features of virus particles in neurons. The analysis showed that gC was not expressed in most infected neurons and gC expression was markedly reduced in a minority of VZV-infected neurons. In contrast, expression of the early-late VZV gE glycoprotein (ORF68) was abundant. Transcript analysis also showed decreased gC transcription compared with gE. Examination of viral structure by high-resolution transmission electron microscopy revealed fewer viral particles than typically observed in cells productively infected with VZV. Furthermore, viral particles were more aberrant, in that most capsids in the nuclei lacked a dense core and most enveloped particles in the cytoplasm were light particles (envelopes without capsids). Together, these results suggest a considerable deficiency in late-phase replication and viral assembly during VZV infection of neurons in culture.
MODELING OF INTERFACIAL BEHAVIOR OF WATER AND ORGANICS
Authors: GUN'KO VLADIMIR M.
Published: June 2013

Modeling of water structure at a surface of different adsorbents, as well as an influence of dissolved compounds or co-adsorbates on bound water, is of importance to understand the temperature dependence of the characteristics of bound water, especially at T < 273 K, in comparison with bulk water.1H NMR spectra giving useful information on the water structure can be obtained using different ways such as experimental measurements, direct ab initio and density functional theory (DFT) calculations or estimation using semiempirical calculations and appropriate calibration functions. Here, application of the last approach is analyzed with respect to a variety of relatively large hydrated systems. Despite the simplicity of this approach, it gives quantitative characterization of structural features of interfacial water and effects of different co-adsorbates and adsorbent surfaces on bound water.
SUDANESE WOMEN ENTREPRENEURS
Authors: WELSH DIANNE H. B. , MEMILI ESRA , KACIAK EUGENE , AHMED SADDIGA
Published: June 2013

The number of female entrepreneurs is growing around the globe. The rate of women's entrepreneurship in Africa is higher than in any other region of the world but no studies have focused on North Sudan. We investigate female entrepreneurs in North Sudan by addressing these questions: (1) What are the major challenges North Sudanese female entrepreneurs face in (a) venture startup, and (b) running their businesses, (2) What are the main support sources enabling North Sudanese female entrepreneurs' (a) venture startup, and (b) successful management of their new ventures?, and (3) Is there family involvement in the North Sudanese female entrepreneurs' businesses; and if so, how? Personal issues, management skills, and obtaining financing are challenges while sources of support include schooling and previous work experience, moral support, and institutional support. Implications are discussed.
HARNESSING AGGREGATION-INDUCED EMISSION (AIE) OF TETRAPHENYLETHYLENES IN METAL ION SENSING AND LUMINESCENT METAL-ORGANIC FRAMEWORKS
Authors: PIGGE F. CHRISTOPHER
Published: June 2013

Tetraphenylethylene derivatives have emerged as valuable building blocks for construction of luminescent molecular sensor materials based on their ability to display aggregation induced emission. This paper summarizes recent efforts aimed at combining the luminescent properties of tetraphenylethylenes with metal ligating capability as a means to achieve metal ion detection. Research describing the incorporation of tetraphenylethylene ligands in metal-organic frameworks is also discussed. Though these areas of investigation have not received a great deal of attention, metal coordination complexes of tetraphenylethylenes show tremendous promise as switchable fluorescent sensors/indicators with a variety of potential applications.
Regulation of L-type calcium channel sparklet activity by c-Src and PKC-α
Authors: Gulia Jyoti , Navedo Manuel F. , Gui Peichun , Chao Jun-Tzu , Mercado Jose L. , Santana Luis F. , Davis Michael J.
Published: June 2013

The activity of persistent Ca2+ sparklets, which are characterized by longer and more frequent channel open events than low-activity sparklets, contributes substantially to steady-state Ca2+ entry under physiological conditions. Here, we addressed two questions related to the regulation of Ca2+ sparklets by PKC-α and c-Src, both of which increase whole cell Cav1.2 current: 1) Does c-Src activation enhance persistent Ca2+ sparklet activity? 2) Does PKC-α activate c-Src to produce persistent Ca2+ sparklets? With the use of total internal reflection fluorescence microscopy, Ca2+ sparklets were recorded from voltage-clamped tsA-201 cells coexpressing wild-type (WT) or mutant Cav1.2c (the neuronal isoform of Cav1.2) constructs ± active or inactive PKC-α/c-Src. Cells expressing Cav1.2c exhibited both low-activity and persistent Ca2+ sparklets. Persistent Ca2+ sparklet activity was significantly reduced by acute application of the c-Src inhibitor PP2 or coexpression of kinase-dead c-Src. Cav1.2c constructs mutated at one of two COOH-terminal residues (Y2122F and Y2139F) were used to test the effect of blocking putative phosphorylation sites for c-Src. Expression of Y2122F but not Y2139F Cav1.2c abrogated the potentiating effect of c-Src on Ca2+ sparklet activity. We could not detect a significant change in persistent Ca2+ sparklet activity or density in cells coexpressing Cav1.2c + PKC-α, regardless of whether WT or Y2122F Cav1.2c was used, or after PP2 application, suggesting that PKC-α does not act upstream of c-Src to produce persistent Ca2+ sparklets. However, our results indicate that persistent Ca2+ sparklet activity is promoted by the action of c-Src on residue Y2122 of the Cav1.2c COOH terminus.
Anti-ghrelin Spiegelmer inhibits exogenous ghrelin-induced increases in food intake, hoarding, and neural activation, but not food deprivation-induced increases
Authors: Teubner Brett J. W. , Bartness Timothy J.
Published: June 2013

Circulating concentrations of the stomach-derived “hunger-peptide” ghrelin increase in direct proportion to the time since the last meal. Exogenous ghrelin also increases food intake in rodents and humans, suggesting ghrelin may increase post-fast ingestive behaviors. Food intake after food deprivation is increased by laboratory rats and mice, but not by humans (despite dogma to the contrary) or by Siberian hamsters; instead, humans and Siberian hamsters increase food hoarding, suggesting the latter as a model of fasting-induced changes in human ingestive behavior. Exogenous ghrelin markedly increases food hoarding by ad libitum-fed Siberian hamsters similarly to that after food deprivation, indicating sufficiency. Here, we tested the necessity of ghrelin to increase food foraging, food hoarding, and food intake, and neural activation [c-Fos immunoreactivity (c-Fos-ir)] using anti-ghrelin Spiegelmer NOX-B11–2 (SPM), an l-oligonucleotide that specifically binds active ghrelin, inhibiting peptide-receptor interaction. SPM blocked exogenous ghrelin-induced increases in food hoarding the first 2 days after injection, and foraging and food intake at 1–2 h and 2–4 h, respectively, and inhibited hypothalamic c-Fos-ir. SPM given every 24 h across 48-h food deprivation inconsistently inhibited food hoarding after refeeding and c-Fos-ir, similarly to inabilities to do so in laboratory rats and mice. These results suggest that ghrelin may not be necessary for food deprivation-induced foraging and hoarding and neural activation. A possible compensatory response, however, may underlie these findings because SPM treatment led to marked increases in circulating ghrelin concentrations. Collectively, these results show that SPM can block exogenous ghrelin-induced ingestive behaviors, but the necessity of ghrelin for food deprivation-induced ingestive behaviors remains unclear.
Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis
Authors: Schauer Kevin L. , Freund Dana M. , Prenni Jessica E. , Curthoys Norman P.
Published: June 2013

Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis.
Role of fibrinogen in acute ischemic kidney injury
Authors: Sörensen-Zender I. , Rong S. , Susnik N. , Lange J. , Gueler F. , Degen J. L. , Melk A. , Haller H. , Schmitt R.
Published: June 2013

Renal ischemia-reperfusion (I/R) is associated with activation of the coagulation system and accumulation of blood clotting factors in the kidney. The aim of the present study was to examine the functional impact of fibrinogen on renal inflammation, damage, and repair in the context of I/R injury. In this study, we found that I/R was associated with a significant increase in the renal deposition of circulating fibrinogen. In parallel, I/R stress induced the de novo expression of fibrinogen in tubular epithelial cells, as reflected by RT-PCR, immunofluorescence, and in situ hybridization. In vitro, fibrinogen expression was induced by oncostatin M and hyper-IL-6 in primary tubular epithelial cells, and fibrinogen-containing medium had an inhibitory effect on tubular epithelial cell adhesion and migration. Fibrinogen+/−mice showed similar survival as wild-type mice but better preservation in early postischemic renal function. In fibrinogen−/−mice, renal function and survival were significantly worse than in fibrinogen+/−mice. Renal transplant experiments revealed reduced expression of tubular damage markers and attenuated proinflammatory cytokine expression but increased inflammatory cell infiltrates and transforming growth factor-β expression in fibrinogen−/−isografts. These data point to heterogeneous effects of fibrinogen in renal I/R injury. While a complete lack of fibrinogen may be detrimental, partial reduction of fibrinogen in heterozygous mice can improve renal function and overall outcome.
Long-latency muscle activity reflects continuous, delayed sensorimotor feedback of task-level and not joint-level error
Authors: Safavynia Seyed A. , Ting Lena H.
Published: June 2013

In both the upper and lower limbs, evidence suggests that short-latency electromyographic (EMG) responses to mechanical perturbations are modulated based on muscle stretch or joint motion, whereas long-latency responses are modulated based on attainment of task-level goals, e.g., desired direction of limb movement. We hypothesized that long-latency responses are modulated continuously by task-level error feedback. Previously, we identified an error-based sensorimotor feedback transformation that describes the time course of EMG responses to ramp-and-hold perturbations during standing balance ( Safavynia and Ting 2013 ; Welch and Ting 2008 , 2009 ). Here, our goals were 1) to test the robustness of the sensorimotor transformation over a richer set of perturbation conditions and postural states; and 2) to explicitly test whether the sensorimotor transformation is based on task-level vs. joint-level error. We developed novel perturbation trains of acceleration pulses such that perturbations were applied when the body deviated from the desired, upright state while recovering from preceding perturbations. The entire time course of EMG responses (∼4 s) in an antagonistic muscle pair was reconstructed using a weighted sum of center of mass (CoM) kinematics preceding EMGs at long-latency delays (∼100 ms). Furthermore, CoM and joint kinematic trajectories became decorrelated during perturbation trains, allowing us to explicitly compare task-level vs. joint feedback in the same experimental condition. Reconstruction of EMGs was poorer using joint kinematics compared with CoM kinematics and required unphysiologically short (∼10 ms) delays. Thus continuous, long-latency feedback of task-level variables may be a common mechanism regulating long-latency responses in the upper and lower limbs.
Thermoresponsive and Redox Behaviors of Poly(N-isopropylacrylamide)-Based Block Copolymers Having TEMPO Groups as Their Side Chains
Authors: Uemukai Toru , Hioki Tomoya , Ishifune Manabu
Published: June 2013

Thermoresponsive and redox-active block copolymers having 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) moieties have been synthesized by using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique.N-Isopropylacrylamide (NIPAAm) and 2,2,6,6-tetramethylpiperidyl methacrylate (TEMPMA) monomers were copolymerized stepwise under RAFT polymerization conditions to afford the thermoresponsive block copolymers, PNIPAAm-block-PTEMPMA and PNIPAAm-block-PTEMPMA-block-PNIPAAm. Oxidation of tetramethylpiperidine groups in the copolymers successfully afforded the corresponding TEMPO-containing block copolymers. The resulting triblock copolymer was found to be thermoresponsive showing lower critical solution temperature (LCST) at 34∘C in its aqueous solution. Redox behavior of the resulting copolymer was observed by cyclic voltammetry. The potential of anodic current peak changed below and above the LCST of the block copolymer. These results indicate that the phase transition of thermoresponsive polymer influences the redox potential of TEMPO moieties.
Intelligent Motion Compensation for Improving the Tracking Performance of Shipborne Phased Array Radar
Authors: Mar J. , Tsai K. C. , Wang Y. T. , Basnet M. B.
Published: June 2013

The shipborne phased array radar must be able to compensate the ship’s motion and track the maneuvering targets automatically. In this paper, the real-time beam pointing error compensation mechanism of a planar array antenna for ship’s motion is designed to combine with the Kalman filtering. The effect of beam pointing error on the tracking performance of shipborne phased array radar is examined. A compensation mechanism, which can automatically correct the beam pointing error of the planar antenna array, is proposed for shipborne phased array radar in order to achieve the required tracking accuracy over the long dwell time. The automatic beam pointing error compensation mechanism employs the parallel fuzzy basis function network (FBFN) architecture to estimate the beam pointing error caused by roll and pitch of the ship. In the simulation, the models of roll and pitch are used to evaluate the performance of beam pointing error estimation mechanism based on the proposed parallel FBFN architecture. In addition, the effect of automatic beam pointing error compensation mechanism on the tracking performance of adaptive extended Kalman filter (AEKF) implemented in ship borne phased array radar is also investigated. Simulations find out that the proposed algorithms are stable and accurate.
Factors Influencing Sputum Conversion among Smear-Positive Pulmonary Tuberculosis Patients in Morocco
Authors: Bouti Khalid , Aharmim Mohammed , Marc Karima , Soualhi Mouna , Zahraoui Rachida , Benamor Jouda , Bourkadi Jamal Eddine , Iraqi Ghali
Published: June 2013

Background. Sputum smear-positive pulmonary tuberculosis patients expel infectious viable bacilli for a period following the commencement of treatment.
Objective. To determine the time to sputum smear conversion and study the factors influencing it.
Design. A prospective study was undertaken at our hospital in Rabat over a six-month period on a cohort of 119 sputum smear positive patients. Patients were followed up fortnightly. At each followup, specimens were collected and processed for microscopy using standard protocol.
Results. 96.6% of our patients completed the study (4 deaths). Sputum conversion rate was 42% after two weeks, 73% after one month, and 95% after two months. Univariate and stepwise regression analysis showed that patients who had high smear grading, miliary, and bilateral radiologic lesions were more likely to undergo delayed sputum conversion (P<0.05). Other factors were thought to influence sputum conversion but were not statistically proven in our study.
Conclusion. Since viable bacilli continue to be expelled for up to two months, infection control measures should be maintained for such a time. Patients with high smear grading, miliary, and bilateral radiologic lesions need to be monitored more closely.
RhoA Regulation of Cardiomyocyte Differentiation
Authors: Kaarbø Mari , Crane Denis I. , Murrell Wayne G.
Published: June 2013

Earlier findings from our laboratory implicated RhoA in heart developmental processes. To investigate factors that potentially regulate RhoA expression, RhoA gene organisation and promoter activity were analysed. Comparative analysis indicated strict conservation of both gene organisation and coding sequence of the chick, mouse, and human RhoA genes. Bioinformatics analysis of the derived promoter region of mouse RhoA identified putative consensus sequence binding sites for several transcription factors involved in heart formation and organogenesis generally. Using luciferase reporter assays, RhoA promoter activity was shown to increase in mouse‐derived P19CL6 cells that were induced to differentiate into cardiomyocytes. Overexpression of a dominant negative mutant of mouse RhoA (mRhoAN19) blocked this cardiomyocyte differentiation of P19CL6 cells and led to the accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiac α‐actin. Taken together, these findings indicate a fundamental role for RhoA in the differentiation of cardiomyocytes.
Gene Expression Profile of the A549 Human Non-Small Cell Lung Carcinoma Cell Line following Treatment with the Seeds ofDescurainia sophia, a Potential Anticancer Drug
Authors: Kim Bu-Yeo , Lee Jun , Park Sung Joon , Bang Ok-Sun , Kim No Soo
Published: June 2013

Descurainia sophiahas been traditionally used in Korean medicine for treatment of diverse diseases and their symptoms, such as cough, asthma, and edema. Our previous results showed that ethanol extract of the seeds ofD. sophia(EEDS) has a potent cytotoxic effect on human cancer cells. In this study, we reveal the molecular events that are induced by EEDS treatment in A549 human lung cancer cells. The dose-dependent effect of EEDS on gene expression was measured via a microarray analysis. Gene ontology and pathway analyses were performed to identify functional involvement of genes regulated by EEDS. From gene expression analyses, two major dose-dependent patterns were observed after EEDS treatment. One pattern consisted of 1,680 downregulated genes primarily involved in metabolic processes (FDR < 0.01). The second pattern consisted of 1,673 upregulated genes primarily involved in signaling processes (FDR < 0.01). Pathway activity analyses revealed that the metabolism-related pathways and signaling-related pathways were regulated by the EEDS in dose-dependent and reciprocal manners. In conclusion, the identified biphasic regulatory mechanism involving activation of signaling pathways may provide molecular evidence to explain the inhibitory effect of EEDS on A549 cell growth.
Molecular Dynamics Studies on the Conformational Transitions of Adenylate Kinase: A Computational Evidence for the Conformational Selection Mechanism
Authors: Ping Jie , Hao Pei , Li Yi-Xue , Wang Jing-Fang
Published: June 2013

Escherichia coliadenylate kinase (ADK) is a monomeric phosphotransferase enzyme that catalyzes reversible transfer of phosphoryl group from ATP to AMP with a large-scale domain motion. The detailed mechanism for this conformational transition remains unknown. In the current study, we performed long time-scale molecular dynamics simulations on both open and closed states of ADK. Based on the structural analyses of the simulation trajectories, we detected over 20 times conformational transitions between the open and closed states of ADK and identified two novel conformations as intermediate states in the catalytic processes. With these findings, we proposed a possible mechanism for the large-scale domain motion ofEscherichia coliADK and its catalytic process: (1) the substrate free ADK adopted an open conformation; (2) ATP bound with LID domain closure; (3) AMP bound with NMP domain closure; (4) phosphoryl transfer occurred with ATP, and AMP converted into two ADPs, and no conformational transition was detected in the enzyme; (5) LID domain opened with one ADP released; (6) another ADP released with NMP domain open. As both open and closed states sampled a wide range of conformation transitions, our simulation strongly supported the conformational selection mechanism forEscherichia coliADK.
Redistribution and Effect of Various Elements on the Morphology of Primary Graphite in Cast Iron
Authors: Lacaze J. , Valle N. , Theuwissen K. , Sertucha J. , El Adib B. , Laffont L.
Published: June 2013

It has been shown repeatedly that many elements present as traces or at low level can affect graphite shape in cast irons. As part of a long term project aimed at clarifying the growth and the alteration of spheroidal graphite, a study on the effect of a few elements (Cu, Sn, Sb, and Ti) on primary graphite growth was undertaken and analysed with reference to an alloy without any such additions. This work was performed by remelting alloys in graphite crucibles thus saturating the melt in carbon and enabling primary graphite to grow by controlled cooling of the melt above the eutectic temperature. Primary graphite growth in the reference alloy was observed to be lamellar, while the added elements were found to affect bulk graphite and to modify its outer shape, with Sb leading eventually to rounded agglomerates together with wavy lamellae. Secondary ion mass spectrometry was used to analyze the distribution of elements, and no build-up of trace elements at the graphite surface could be observed. Instead, it is established that the perturbation of bulk graphite is associated with inhomogeneous distribution of metallic elements inside graphite precipitates.
Ginsenoside RK3 Prevents Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes via AKT and MAPK Pathway
Authors: Sun Jing , Sun Guibo , Meng Xiangbao , Wang Hongwei , Wang Min , Qin Meng , Ma Bo , Luo Yun , Yu Yingli , Chen Rongchang , Ai Qidi , Sun Xiaobo
Published: June 2013

Reperfusion therapy is widely utilized for acute myocardial infarction (AMI), but further injury induced by rapidly initiating reperfusion of the heart is often encountered in clinical practice. Ginsenoside RK3 (RK3) is reportedly present in the processed Radix notoginseng that is often used as a major ingredient of the compound preparation for ischemic heart diseases. This study aimed to investigate the possible protective effect of RK3 against hypoxia-reoxygenation (H/R) induced H9c2 cardiomyocytes damage and its underlying mechanisms. Our results showed that RK3 pretreatment caused increased cell viability and decreased levels of LDH leakage compared with the H/R group. Moreover, RK3 pretreatment inhibited cell apoptosis, as evidenced by decreased caspase-3 activity, TUNEL-positive cells, and Bax expression, as well as increased Bcl-2 level. Further mechanism investigation revealed that RK3 prevented H9c2 cardiomyocytes injury and apoptosis induced by H/R via AKT/Nrf-2/HO-1 and MAPK pathways. These observations indicate that RK3 has the potential to exert cardioprotective effects against H/R injury, which might be of great importance to clinical efficacy for AMI treatment.
Enhancing the Long-Term Yield Competitiveness of a Semiconductor Manufacturing Factory Using a Multiobjective Fuzzy Nonlinear Programming Approach
Authors: Chen Toly , Wang Yi-Chi
Published: June 2013

This study proposes a multiobjective fuzzy nonlinear programming (MOFNP) approach to enhance the long-term yield competitiveness of a semiconductor manufacturing factory. By modeling the long-term competitiveness of every product in a semiconductor manufacturing plant with the fuzzy correlation coefficient (FCC) between time and instantaneous competitiveness, the proposed model considers the various viewpoints when interpreting the overall competitiveness of the semiconductor manufacturing plant in the long-term. All noninferior solutions of the MOFNP solutions are then derived using a systematic procedure. A real example is employed to illustrate the applicability of the proposed methodology.
Legendre Invariance and Geometrothermodynamics Description of the 3D Charged-Dilaton Black Hole
Authors: Han Yiwen , Zeng XiaoXiong
Published: June 2013

We first review Weinhold information geometry and Ruppeiner information geometry of 3D charged-dilaton black hole. Then, we use the Legendre invariant to introduce a 2-dimensional thermodynamic metric in the space of equilibrium states, which becomes singular at those points. According to the analysis of the heat capacities, these points are the places where phase transitions occur. This result is valid for the black hole, therefore, provides a geometrothermodynamics description of black hole phase transitions in terms of curvature singularities.
A Two-Period Newsvendor Model with Product Extension and Shortage-Making Strategy
Authors: Wang Kuo-Hsien , Tung Che-Tsung , Huang Yuan-Chih
Published: June 2013

This study deals with a two-period newsvendor setting in which the item in the second period is a product extension of the item in the first period. A shortage strategy toward the first item is intentionally made so as to stimulate more sales amounts of the second item. The stochastic demand of these two items is assumed to be a linear-additive pattern comprising a deterministic demand and an error demand, where the deterministic demand consists of a primary demand and a consumer price elasticity, and the error demand is hypothesized to be exponentially distributed. The objective of this study is to optimize system's overall expected profit by jointly determining the optimal order quantities and selling prices of these two items. We first compare our proposed model with the classical newsvendor model in light of profit performances, and it reveals that a higher shifting demand rate makes our model a more profitable setting. Impact on profit performances caused by an increasing primary demand of the second item is then demonstrated by numerical examples that an unthought-of ripple effect of an increasing error demand of the second item also occurs.
Which Aspects of Postural Control Differentiate between Patients with Parkinson’s Disease with and without Freezing of Gait?
Authors: Vervoort Griet , Nackaerts Evelien , Mohammadi Farshid , Heremans Elke , Verschueren Sabine , Nieuwboer Alice , Vercruysse Sarah
Published: June 2013

This exploratory study aimed to identify which aspects of postural control are able to distinguish between subgroups of patients with Parkinson’s disease (PD) and controls. Balance was tested using static and dynamic posturography. Freezers (n=9), nonfreezers (n=10), and controls (n=10) stood on a movable force platform and performed 3 randomly assigned tests: (1) sensory organization test (SOT) to evaluate the effective use of sensory information, (2) motor control test (MCT) to assess automatic postural reactions in response to platform perturbations, and (3) rhythmic weight shift test (RWS) to evaluate the ability to voluntarily move the center of gravity (COG) mediolaterally and anterior-posteriorly (AP). The respective outcome measures were equilibrium and postural strategy scores, response strength and amplitude of weight shift. Patients were in the “on” phase of the medication cycle. In general, freezers performed similarly on SOT and MCT compared to nonfreezers. Freezers showed an intact postural strategy during sensory manipulations and an appropriate response to external perturbations. However, during voluntary weight shifting, freezers showed poorer directional control compared to nonfreezers and controls. This suggests that freezers have adequate automatic postural control and sensory integration abilities in quiet stance, but show specific directional control deficits when weight shifting is voluntary.
DACT2 Is a Candidate Tumor Suppressor and Prognostic Marker in Esophageal Squamous Cell Carcinoma
Authors: Hou Jian , Liao Lian-Di , Xie Yang-Min , Zeng Fa-Min , Ji Xia , Chen Bo , Li Li-Yan , Zhu Meng-Xiao , Yang Cui-Xia , Qing-Zhao  , Chen Tao , Xu Xiu-E , Shen Jian , Guo Ming-Zhou , Li En-Min , Xu Li-Yan
Published: June 2013

In animals ranging from fish to mice, the function of DACT2 as a negative regulator of the TGF-β/Nodal signal pathway is conserved in evolution, indicating that it might play an important role in human cancer. In this study, we showed that tumors with higher DACT2 protein level were correlated with better differentiation and better survival rate in patients with esophageal squamous cell carcinoma. Restored expression of DACT2 significantly inhibited growth, migration, and invasion of ESCC cells in vitro, and reduced tumorigenicity in vivo. Furthermore, when DACT2 expression was restored, the activity of TGF-β/SMAD2/3 was suppressed via both proteasome and lysosomal degradation pathways, leading to F-actin rearrangement that might depend on the involvement of cofilin and ezrin–redixin–moesin (ERM) proteins. Taken together, we propose here that DACT2 serves as a prognostic marker that reduces tumor cell malignancy by suppressing TGF-β signaling and promotes actin rearrangement in ESCC. Cancer Prev Res; 6(8); 791–800. ©2013 AACR.
Garcinol, a Polyisoprenylated Benzophenone Modulates Multiple Proinflammatory Signaling Cascades Leading to the Suppression of Growth and Survival of Head and Neck Carcinoma
Authors: Li Feng , Shanmugam Muthu K. , Chen Luxi , Chatterjee Snehajyoti , Basha Jeelan , Kumar Alan Prem , Kundu Tapas K. , Sethi Gautam
Published: June 2013

Constitutive activation of proinflammatory transcription factors such as STAT3 and NF-κB plays a pivotal role in the proliferation and survival of squamous cell carcinoma of the head and neck (HNSCC). Thus, the agents that can modulate deregulated STAT3 and NF-κB activation have a great potential both for the prevention and treatment of HNSCC. In the present report, we investigated the potential effects of garcinol, an active component of Garcinia indica on various inflammatory mediators involved in HNSCC progression using cell lines and xenograft mouse model. We found that garcinol inhibited constitutively activated STAT3 in HNSCC cells in a time- and dose-dependent manner, which correlated with the suppression of the upstream kinases (c-Src, JAK1, and JAK2) in HNSCC cells. Also, we noticed that the generation of reactive oxygen species is involved in STAT3 inhibitory effect of garcinol. Furthermore, garcinol exhibited an inhibitory effect on the constitutive NF-κB activation, mediated through the suppression of TGF-β–activated kinase 1 (TAK1) and inhibitor of IκB kinase (IKK) activation in HNSCC cells. Garcinol also downregulated the expression of various gene products involved in proliferation, survival, and angiogenesis that led to the reduction of cell viability and induction of apoptosis in HNSCC cells. When administered intraperitoneally, garcinol inhibited the growth of human HNSCC xenograft tumors in male athymic nu/nu mice. Overall, our results suggest for the first time that garcinol mediates its antitumor effects in HNSCC cells and mouse model through the suppression of multiple proinflammatory cascades. Cancer Prev Res; 6(8); 843–54. ©2013 AACR.
The vulnerable coronary plaque: update on imaging technologies
Authors: Rosa Gian Marco , Bauckneht Matteo , Masoero Giovanni , Mach François , Quercioli Alessandra , Seitun Sara , Balbi Manrico , Brunelli Claudio , Parodi Antonello , Nencioni Alessio , Vuilleumier Nicolas , Montecucco Fabrizio
Published: June 2013

Several studies have been carried out on vulnerable plaque as the main culprit for ischaemic cardiac events. Historically, the most important diagnostic technique for studying coronary atherosclerotic disease was to determine the residual luminal diameter by angiographic measurement of the stenosis. However, it has become clear that vulnerable plaque rupture as well as thrombosis, rather than stenosis, triggers most acute ischaemic events and that the quantification of risk based merely on severity of the arterial stenosis is not sufficient. In the last decades, substantial progresses have been made on optimisation of techniques detecting the arterial wall morphology, plaque composition and inflammation. To date, the use of a single technique is not recommended to precisely identify the progression of the atherosclerotic process in human beings. In contrast, the integration of data that can be derived from multiple methods might improve our knowledge about plaque destabilisation. The aim of this narrative review is to update evidence on the accuracy of the currently available non-invasive and invasive imaging techniques in identifying components and morphologic characteristics associated with coronary plaque vulnerability.
Three new species of the genus Pergalumna (Acari: Oribatida: Galumnidae) from India
Authors: ERMILOV SERGEY G. , SHTANCHAEVA UMUKUSUM YA. , KALÚZ STANISLAV , SUBÍAS LUIS S.
Published: June 2013

Three new oribatid mite species of the genus Pergalumna (Galumnidae), P. paratsurusakii sp. nov., P. asetosa sp. nov. and P. mahunkai sp. nov., are described from India. Pergalumna paratsurusakii sp. nov. is most similar morphologically to P. tsurusakii Starý from Japan, however it differs from latter by the body surface, body size and morphology of some notogastral porose areas. Pergalumna asetosa sp. nov. is most similar morphologically to P. rotunda Starý from Japan and Pergalumna yurtaevi Ermilov & Anichkin from Vietnam, however it differs from both by the absence of interlamellar se-tae and the presence of notogastral furrows. Pergalumna mahunkai sp. nov. is most similar morphologically to P. marga-ritata Mahunka from Vietnam and P. pseudomargaritata Mahunka from Thailand, however it differs from both by the structure of anterior notogastral margin, body size and morphology of prodorsal setae.
Well, what about intraspecific variation? Taxonomic and phylogenetic characters in the genus Synoeca de Saussure (Hymenoptera, Vespidae)
Authors: CARPENTER JAMES M. , ANDENA SERGIO R. , NOLL FERNANDO B. , WENZEL JOHN W.
Published: June 2013

Cely and Sarmiento (2011) took issue with the cladistic analysis of relationships among species of the genus Synoeca by Andena et al. (2009a), and presented a reanalysis. They claimed that intraspecific variation in the genus is meaningful, and proper consideration yields a conclusion different from that of Andena et al. Both their critique and reanalysis are vitiated by numerous errors, as is shown in the present paper.
Hydrolutos gransabanensis sp.n. (Orthoptera: Anostostomatidae), a new semi-aquatic Lutosini species from Gran Sabana (Venezuela)
Authors: DERKA TOMÁŠ , FEDOR PETER , SVITOK MAREK , TRIZNA MILAN
Published: June 2013

Hydrolutos gransabanensis, a new species of Lutosini (Orthoptera: Anostostomatidae) from the cave Cueva El Tigre (Santa Elena de Uairén, SE Venezuela) is described and figured for both sexes. This is the first record of Hydrolutos spe-cies out of tepui systems. The genus is recently known by 6 apterous species from Venezuelan Guayana region.
Revision of the Mesoamerican Genus Cataractocoris Usinger (Hemiptera: Heteroptera: Nepomorpha: Naucoridae)
Authors: SITES ROBERT W. , REYNOSO-VELASCO DANIEL , NOVELO-GUTIÉRREZ RODOLFO
Published: June 2013

The genus Cataractocoris includes large waterfall-inhabiting insects that occur from Mexico to El Salvador and has re-ceived very little attention in the literature. Based on extensive field work during the past three years, we have collected saucer bugs (Heteroptera: Naucoridae) from many localities in central and southern Mexico. We here present detailed dis-tributions and diagnostic information of the two described species of Cataractocoris and the description of a third species that occurs from Nayarit state in Mexico south to Guatemala. An illustrated taxonomic key to identify the species also is presented.
Scale-Selective Ridge Regression for Multimodel Forecasting
Authors: DelSole Timothy , Jia Liwei , Tippett Michael K.
Published: June 2013

This paper proposes a new approach to linearly combining multimodel forecasts, called scale-selective ridge regression, which ensures that the weighting coefficients satisfy certain smoothness constraints. The smoothness constraint reflects the “prior assumption” that seasonally predictable patterns tend to be large scale. In the absence of a smoothness constraint, regression methods typically produce noisy weights and hence noisy predictions. Constraining the weights to be smooth ensures that the multimodel combination is no less smooth than the individual model forecasts. The proposed method is equivalent to minimizing a cost function comprising the familiar mean square error plus a “penalty function” that penalizes weights with large spatial gradients. The method reduces to pointwise ridge regression for a suitable choice of constraint. The method is tested using the Ensemble-Based Predictions of Climate Changes and Their Impacts (ENSEMBLES) hindcast dataset during 1960–2005. The cross-validated skill of the proposed forecast method is shown to be larger than the skill of either ordinary least squares or pointwise ridge regression, although the significance of this difference is difficult to test owing to the small sample size. The model weights derived from the method are much smoother than those obtained from ordinary least squares or pointwise ridge regression. Interestingly, regressions in which the weights are completely independent of space give comparable overall skill. The scale-selective ridge is numerically more intensive than pointwise methods since the solution requires solving equations that couple all grid points together.
Correction of Radar QPE Errors for Nonuniform VPRs in Mesoscale Convective Systems Using TRMM Observations
Authors: Qi Youcun , Zhang Jian , Cao Qing , Hong Yang , Hu Xiao-Ming
Published: June 2013

Mesoscale convective systems (MCSs) contain both regions of convective and stratiform precipitation, and a bright band (BB) is often found in the stratiform region. Inflated reflectivity intensities in the BB often cause positive biases in radar quantitative precipitation estimation (QPE). A vertical profile of reflectivity (VPR) correction is necessary to reduce such biases. However, existing VPR correction methods for ground-based radars often perform poorly for MCSs owing to their coarse resolution and poor coverage in the vertical direction, especially at far ranges. Spaceborne radars such as the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR), on the other hand, can provide high resolution VPRs. The current study explores a new approach of incorporating the TRMM VPRs into the VPR correction for the Weather Surveillance Radar-1988 Doppler (WSR-88D) radar QPE. High-resolution VPRs derived from the Ku-band TRMM PR data are converted into equivalent S-band VPRs using an empirical technique. The equivalent S-band TRMM VPRs are resampled according to the WSR-88D beam resolution, and the resampled (apparent) VPRs are then used to correct for BB effects in the WSR-88D QPE when the ground radar VPR cannot accurately capture the BB bottom. The new scheme was tested on six MCSs from different regions in the United States and it was shown to provide effective mitigation of the radar QPE errors due to BB contamination.