bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer preventive effect of pegylated interferon α‐2b plus ribavirin in a real‐life clinical setting in Japan: PERFECT interim analysis
Authors: Watanabe Sumio , Enomoto Nobuyuki , Koike Kazuhiko , Izumi Namiki , Takikawa Hajime , Hashimoto Etsuko , Moriyasu Fuminori , Kumada Hiromitsu , Imawari Michio ,   PERFECT Study Group
Published: June 2011

Aim:  This study was conducted to clarify the incidence of hepatocellular carcinoma (HCC) and the factors contributing to its occurrence by following chronic hepatitis C patients who received pegylated interferon (PEG‐IFN) α‐2b plus ribavirin (RBV) combination therapy.

Methods:  Patients who received PEG‐IFN α‐2b and RBV combination therapy with no history of HCC or HCC within 3 months after the start of treatment were observed for the onset of HCC at 67 centers.

Results:  Sustained virological response (SVR) was observed in 999 (53.5%) of 1865 patients eligible for analysis. During the observation period (median duration: 4 years and 3 months), HCC developed in 59 patients (3.1%). A significant difference was observed in the 5‐year cumulative incidence of HCC between SVR and non‐SVR patients (1.1% vs. 7.1%). Factors contributing to HCC selected in multivariate analysis were therapeutic efficacy, sex, age, alanine aminotransferase (ALT) level at 24 weeks after the end of treatment, and platelet count. Non‐SVR patients with ALT improvement after the end of treatment had a significantly lower 5‐year cumulative incidence of HCC than those without (3.4% vs. 11.0%). HCC developed in 10 patients who achieved SVR, and multivariate analysis indicated that ALT level at 24 weeks after the end of treatment was the only significant factor contributing to HCC.

Conclusion:  Several known risk factors for HCC contributed to HCC in patients who received PEG‐IFN α‐2b and RBV combination therapy, and ALT abnormality after the end of treatment contributes to the onset of HCC in both non‐SVR and SVR patients.
Exploration of tektite formation processes through water and metal content measurements
Authors: WATT Nigel , BOUCHET Romain A. , LEE Cin‐Ty A.
Published: June 2011

Abstract– Impact events are a significant surface‐modifying process on solar system objects lacking frequent resurfacing by atmospheric or igneous processes. To better explore the effects of impacts on surface materials, we measured the water and trace element compositions of tektites from Da Lat, Vietnam. Fourier transform infrared spectroscopy was used for water measurements and laser ablation inductively coupled plasma mass spectrometry was used for trace element measurements. Consistent with previous investigations of tektites, we found that the samples are depleted in volatile metals (e.g., Zn, Pb) as well as in water compared with the average continental crust, although water contents are still extremely high for rocks melted at atmospheric pressure. While Zn and Pb concentrations are linearly correlated with each other, there is no correlation between H2O and Zn or Pb contents. Combined with water contents of other tektites in the Australasian strewn field, our results demonstrate that the source impact occurred at a wet site in or off the coast of the Indochina peninsula.
Screening for caries in targeted schools in the Blue Mountains and Hawkesbury districts, New South Wales, Australia: an evaluation of the School Assessment Program
Authors: Chong Gabriel Tse Feng , Evans Robin Wendell , Dennison Peter John
Published: June 2011

Aim:  To determine if the school dental screening program in New South Wales, the School Assessment Program, achieved its aim of being the key entry point for high‐risk children to receive care.

Methods:  A secondary analysis was conducted on epidemiological data gathered in 16 primary schools in New South Wales (10 for the School Assessment Program and six for the non‐School Assessment Program) in 2003. The validity of the School Assessment Program targeting criteria in identifying high‐risk schools was determined. Post‐screening treatment outcomes were evaluated from the assessment of treatment ratios.

Results:  There were negligible differences in the caries experience and proportions of high‐risk children, irrespective of their School Assessment Program status. Sensitivity and specificity values were approximately 60% and 40%, respectively, using various case definitions of high risk applied to both children and schools. Deciduous dentition treatment ratios for School Assessment Program and non‐School Assessment Program children with decayed, missing, and filled teeth (dmft) ≥1 ranged from 0.48 to 0.79 and from 0.47 to 0.73, respectively. Respective permanent dentition treatment ratios for School Assessment Program and non‐School Assessment Program children with Decayed, Missing, and Filled Teeth (DMFT) ≥1 were 0.49–0.82 and 0.64–1.08.

Conclusion:  The School Assessment Program failed to identify schools with high caries‐risk children or confer post‐screening caries treatment benefits.
Age biases in face processing: The effects of experience across development
Authors: Macchi Cassia Viola
Published: July 2011

In this paper, I review studies investigating discrimination and recognition abilities for faces of different ages in children and adults. Contrary to the earlier assertion that own‐age faces are better recognized than other‐age faces (own‐age bias; OAB), I discuss recent evidence for a processing advantage for adult versus non‐adult faces. This evidence is interpreted as suggesting that the precocious and continuous exposure to adult faces may shape the individual's face representation across development. Moreover, by testing how experience with faces of various ages acquired at different times in development modulates face‐processing skills, this evidence shows that plasticity of face recognition abilities decreases with age, but early‐acquired experience has enduring effects that impact our ability to learn from encounters with new types of faces in adulthood.
Compact slanted comb two-axis micro-mirror scanner fabricated by silicon-on-insulator micromachining
Authors: Chu Hoang Manh , Mizuno Jun , Hane Kazuhiro , Takagi Toshiyuki
Published: June 2011

We present a two-axis micro-mirror scanner with compact slanted comb-drive actuator. The slanted comb-drive actuator is analyzed by comparing with a rectangular comb-drive actuator. The angle magnification factor of slanted comb-drive actuator is 1.6 times larger than that of rectangular comb-drive actuator. The slanted comb-drive actuator is designed for operations in both static and dynamic modes. The proposed scanner is realized from silicon-on-insulator (SOI) wafer. Electronic isolation between movable comb electrodes in device layer and fixed comb electrodes in handle layer are performed using isolation trenches, buried oxide layer, and silicon V-shaped conductive hinges. Movable and fixed parts are physically connected via buried oxide layer and silicon frame fabricated from the handle layer of SOI wafer using time-controlled etching process. The resonant frequencies of horizontal and vertical axes are 25.88 kHz and 592 Hz, respectively. The rotation angles are 0.7° and 5.8° at 80V dc voltage in the static mode for inner mirror and gimbal frame, respectively, and 21° and 24° using the differential ac driving method with 80Vbias+70Vac and 25Vbias+12.5Vac voltages.
Monte Carlo dose enhancement studies in microbeam radiation therapy
Authors: Martínez‐Rovira I. , Prezado Y.
Published: June 2011

Purpose:

A radical radiation therapy treatment for gliomas requires extremely high absorbed doses resulting in subsequent deleterious side effects in healthy tissue. Microbeam radiation therapy (MRT) is an innovative technique based on the fact that normal tissue can withstand high radiation doses in small volumes without any significant damage. The synchrotron‐generated x‐ray beam is collimated and delivered to an array of narrow micrometer‐sized planar rectangular fields. Several preclinical experiments performed at the Brookhaven National Laboratory (BNL) and at the European Synchrotron Radiation Facility (ESRF) confirmed that MRT yields a higher therapeutic index than nonsegmented beams of the same characteristics. This index can be greatly improved by loading the tumor with high atomic number (Z) contrast agents. The aim of this work is to find the high‐Z element that provides optimum dose enhancement.

Methods:

Monte Carlo simulations (PENELOPE/penEasy) were performed to assess the peak and valley doses as well as their ratio (PVDR) in healthy tissue and in the tumor, loaded with different contrast agents. The optimization criteria used were maximization of the ratio between the PVDR values in healthy tissue respect to the PVDR in the tumor and minimization of bone and brain valley doses.

Results:

Dose enhancement factors, PVDR, and valley doses were calculated for different high‐Z elements. A significant decrease of PVDR values in the tumor, accompanied by a gain in the valley doses, was found in the presence of high‐Z elements. This enables the deposited dose in the healthy tissue to be reduced. The optimum high‐Z element depends on the irradiation configuration. As a general trend, the best outcome is provided by the highest Z contrast agents considered, i.e., gold and thallium. However, lanthanides (especially Lu) and hafnium also offer a satisfactory performance.

Conclusions:

The remarkable therapeutic index in microbeam radiation therapy can be further improved by loading the tumor with a high‐Z element. This study reports quantitative data on several dosimetric magnitudes in order to find the optimum contrast agent. Although the final choice of the element will also depend on possible cytotoxicity, three elements were found to be worthy of mention: gold, thallium, and lutetium.
Reconfigurable Knots and Links in Chiral Nematic Colloids
Authors: Tkalec Uroš , Ravnik Miha , Čopar Simon , Žumer Slobodan , Muševič Igor
Published: June 2011

Colloidal particles inside a liquid crystalline solvent can be manipulated to create knots of arbitrary shape and complexity.
Revealing Virus-Host Interplay
Authors: Krupovic Mart , Bamford Dennis H.
Published: June 2011

A new microfluidic technique offers a culture-independent method of studying virus-host interactions.
Antismoking Drive Tries Cigarette Ads, in Reverse
Authors: Reardon Sara
Published: June 2011

Some psychologists argue that the graphic new health warning labels that will appear on all cigarette packages sold in the United States by September 2012 will likely become a joke to the would-be quitters that FDA hopes to reach and white noise in a society accustomed to blood and gore on TV.
Effect of Chemotherapy on Whole-Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in a Small Cohort of Patients with Pulmonary Tuberculosis
Authors: Bertholet Sylvie , Horne David J. , Laughlin Elsa M. , Savlov Margery , Tucakovic Ines , Coler Rhea N. , Narita Masahiro , Reed Steven G.
Published: June 2011

The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to
Mycobacterium tuberculosis
, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of
M. tuberculosis
, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71
M. tuberculosis
antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected
M. tuberculosis
proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients.
N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity
Authors: Tachibana Mayumi , Wu Yimin , Iriko Hideyuki , Muratova Olga , MacDonald Nicholas J. , Sattabongkot Jetsumon , Takeo Satoru , Otsuki Hitoshi , Torii Motomi , Tsuboi Takafumi
Published: June 2011

The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluatedEscherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of thePlasmodium falciparumNF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites toAnopheles stefensimosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity againstP. falciparum.
Immunogenicity and Safety of the Influenza A/H1N1 2009 Inactivated Split-Virus Vaccine in Young and Older Adults: MF59-Adjuvanted Vaccine versus Nonadjuvanted Vaccine
Authors: Cheong Hee Jin , Song Joon Young , Heo Jung Yeon , Noh Ji Yun , Choi Won Suk , Park Dae Won , Wie Seong-Heon , Kim Woo Joo
Published: June 2011

Since initial reports in April 2009, the pandemic influenza A (H1N1) virus has spread globally. Influenza vaccines are the primary method for the control of influenza and its complications. We conducted a multicenter clinical trial to evaluate the immunogenicity and safety of H1N1 vaccine (Green Cross Co.) in young adults (18 to 64 years) and the elderly (≥65 years) using a two-dose regimen, with the doses administered 21 days apart. Three different regimens of hemagglutinin antigen were comparatively analyzed: 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) versus 15 μg (nonadjuvanted) in young adults and 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) in the elderly. In young adults, all three vaccine regimens met the European Agency for the Evaluation of Medicinal Products (EMA) criteria after the first dose. In the elderly, on day 21 after the first dose, the rates of seroprotection and seroconversion were significantly higher for the 7.5-μg dose of MF59 adjuvanted vaccine than for the 3.75-μg dose (58.0% versus 44.3% [
P
= 0.03] and 53.7% versus 37.2% [
P
< 0.01], respectively). After the second dose, the geometric mean titer (GMT) increment was blunted with a 15-μg dose of nonadjuvanted vaccine, whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In conclusion, a single 7.5-μg dose of MF59 adjuvanted vaccine would have a practical advantage over a two-dose, 3.75-μg, MF59 adjuvanted vaccine priming schedule. Following a two-dose priming schedule, the increase in hemagglutinin inhibition titers was higher with MF59 adjuvanted vaccine than with nonadjuvanted vaccine.
Does Immunotherapy Protect Equines from Reinfection by the Oomycete Pythium insidiosum?
Authors: Santos Carlos E. P. , Marques Luiz C. , Zanette Régis A. , Jesus Francielli P. K. , Santurio Janio M.
Published: June 2011

A cutaneousPythium insidiosumreinfection was diagnosed in an equine in Brazil. Lesions with focal presentation appeared 2 years apart. The first infection and even immunotherapy were not likely to develop enough immune response to prevent reinfection. The use of adjuvants should be considered in the immunotherapy of pythiosis.
Immunochromatographic Test with Recombinant Em18 Antigen for the Follow-Up Study of Alveolar Echinococcosis
Authors: Sako Yasuhito , Tappe Dennis , Fukuda Kenta , Kobayashi Yukuharu , Itoh Sonoyo , Frosch Matthias , Grüner Beate , Kern Peter , Ito Akira
Published: June 2011

The performance of a rapid and simple immunochromatographic test (ICT) with recombinant Em18 (rEm18) antigen for serological follow-up ofEchinococcus multilocularisinfection was evaluated by comparison with that of an enzyme-linked immunosorbent assay (ELISA) with rEm18, using serum samples from patients who underwent surgery and/or received antiparasitic chemotherapy. The degree of Em18-band intensity on the ICT correlated highly with the absorbance value obtained by the ELISA. The kinetics of antibody levels obtained by the ICT paralleled those of the ELISA. These data suggest that the ICT has high potential as an easy-to-handle, fast, and reliable follow-up tool to monitor the status of alveolar echinococcosis in different stages.
Diagnosis of Mediterranean Visceral Leishmaniasis by Detection of Leishmania Antibodies and Leishmania DNA in Oral Fluid Samples Collected Using an Oracol Device
Authors: Galaï Yousr , Chabchoub Najla , Ben-Abid Meriem , Ben-Abda Imène , Ben-Alaya-Bouafif Nissaf , Amri Fethi , Aoun Karim , Bouratbine Aïda
Published: June 2011

Current methods for diagnosis of visceral leishmaniasis (VL) require invasive sampling procedures such as visceral aspiration and/or blood drawing. The use of diagnostic tests using oral fluid, which is easier to collect, would be more simple and practical for VL diagnosis, especially under field conditions. Oral fluids from 37 VL patients and 40 healthy controls were collected using Oracol devices. Blood samples and oral fluid specimens from both groups were analyzed by recombinant protein K39 (rK39) enzyme-linked immunosorbent assay and quantitative real-time PCR. Detection of antibodies in the oral fluid had a sensitivity of 100% and a specificity of 97.5%. Antibody levels measured in serum and oral fluid showed a significant positive correlation (ρ = 0.655 and
P
= 0.01). Detection of
Leishmania
DNA in oral fluid had a sensitivity of 94.6% and a specificity of 90%. The median parasite load estimated in blood was 133 parasites/ml (interquartile range [IR], 10 to 1,048), whereas that in oral fluid specimens was 3 parasites/ml (IR, 0.41 to 92). However, there was no significant linear relationship between parasite loads assessed in the two biological samples (ρ = 0.31 and
P
= 0.06). VL diagnosis based on specific antibody detection and
Leishmania
DNA identification using oral fluid samples was equivalent in accuracy to that using blood and therefore is promising for clinical use.
First Three Reported Cases of Nosocomial Fungemia Caused by Candida auris
Authors: Lee Wee Gyo , Shin Jong Hee , Uh Young , Kang Min Gu , Kim Soo Hyun , Park Kyung Hwa , Jang Hee-Chang
Published: June 2011

Candida auris
is a newly described species whose clinical significance is not clear. Here, we describe the first three cases of nosocomial fungemia caused by
C. auris
, which confirms that it is a causative agent of bloodstream infections. All three patients presented persistent fungemia for 10 to 31 days. The isolates obtained from the three patients were misidentified as
Candida haemulonii
and
Rhodotorula glutinis
by the Vitek 2 and the API 20C systems, respectively.
C. auris
was confirmed by sequence analysis of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. The MIC ranges of amphotericin B (AMB), fluconazole (FLU), itraconazole, and voriconazole were 0.5 to 1, 2 to 128, 0.125 to 2, and 0.06 to 1 μg/ml, respectively. All isolates were susceptible to caspofungin (MIC = 0.06 μg/ml) and micafungin (MIC = 0.03 μg/ml). One patient developed breakthrough fungemia while receiving FLU therapy, and two patients who received FLU therapy followed by AMB showed therapeutic failure and fatal outcomes. Our cases show that
C. auris
fungemia can be persistent, despite FLU or AMB therapy, which emphasizes the importance of accurately identifying this species.
Prototype Foamy Virus Gag Nuclear Localization: a Novel Pathway among Retroviruses
Authors: Müllers Erik , Stirnnagel Kristin , Kaulfuss Sylvia , Lindemann Dirk
Published: June 2011

Gag nuclear localization has long been recognized as a hallmark of foamy virus (FV) infection. Two required motifs, a chromatin-binding site (CBS) and a nuclear localization signal (NLS), both located in glycine-arginine-rich box II (GRII), have been described. However, the underlying mechanisms of Gag nuclear translocation are largely unknown. We analyzed prototype FV (PFV) Gag nuclear localization using a novel live-cell fluorescence microscopy assay. Furthermore, we characterized the nuclear localization route of Gag mutants tagged with the simian vacuolating virus 40-NLS (SV40-NLS) and also dissected the respective contributions of the CBS and the NLS. We found that PFV Gag does not translocate to the nucleus of interphase cells by NLS-mediated nuclear import and does not possess a functional NLS. PFV Gag nuclear localization occurred only by tethering to chromatin during mitosis. This mechanism was found for endogenously expressed Gag as well as for Gag delivered by infecting viral particles. Thereby, the CBS was absolutely essential, while the NLS was dispensable. Gag CBS-dependent nuclear localization was neither essential for infectivity nor necessary for Pol encapsidation. Interestingly, Gag localization was independent of the presence of Pol, Env, and viral RNA. The addition of a heterologous SV40-NLS resulted in the nuclear import of PFV Gag in interphase cells, rescued the nuclear localization deficiency but not the infectivity defect of a PFV Gag ΔGRII mutant, and did not enhance FV's ability to infect G
1
/S-phase-arrested cells. Thus, PFV Gag nuclear localization follows a novel pathway among orthoretroviral Gag proteins.
Structural Analysis of Histo-Blood Group Antigen Binding Specificity in a Norovirus GII.4 Epidemic Variant: Implications for Epochal Evolution
Authors: Shanker Sreejesh , Choi Jae-Mun , Sankaran Banumathi , Atmar Robert L. , Estes Mary K. , Prasad B. V. Venkataram
Published: June 2011

Susceptibility to norovirus (NoV), a major pathogen of epidemic gastroenteritis, is associated with histo-blood group antigens (HBGAs), which are also cell attachment factors for this virus. GII.4 NoV strains are predominantly associated with worldwide NoV epidemics with a periodic emergence of new variants. The sequence variations in the surface-exposed P domain of the capsid protein resulting in differential HBGA binding patterns and antigenicity are suggested to drive GII.4 epochal evolution. To understand how temporal sequence variations affect the P domain structure and contribute to epochal evolution, we determined the P domain structure of a 2004 variant with ABH and secretor Lewis HBGAs and compared it with the previously determined structure of a 1996 variant. We show that temporal sequence variations do not affect the binding of monofucosyl ABH HBGAs but that they can modulate the binding strength of difucosyl Lewis HBGAs and thus could contribute to epochal evolution by the potentiated targeting of new variants to Lewis-positive, secretor-positive individuals. The temporal variations also result in significant differences in the electrostatic landscapes, likely reflecting antigenic variations. The proximity of some of these changes to the HBGA binding sites suggests the possibility of a coordinated interplay between antigenicity and HBGA binding in epochal evolution. From the observation that the regions involved in the formation of the HBGA binding sites can be conformationally flexible, we suggest a plausible mechanism for how norovirus disassociates from salivary mucin-linked HBGA before reassociating with HBGAs linked to intestinal epithelial cells during its passage through the gastrointestinal tract.
Gene N Proximal and Distal RNA Motifs Regulate Coronavirus Nucleocapsid mRNA Transcription
Authors: Mateos-Gómez Pedro A. , Zuñiga Sonia , Palacio Lorena , Enjuanes Luis , Sola Isabel
Published: June 2011

Coronavirus subgenomic mRNA (sgmRNA) transcription requires a discontinuous RNA synthesis mechanism driven by the transcription-regulating sequences (TRSs), located at the 3′ end of the genomic leader (TRS-L) and also preceding each gene (TRS-B). In transmissible gastroenteritis virus (TGEV), the free energy of TRS-L and cTRS-B (complement of TRS-B) duplex formation is one of the factors regulating the transcription of sgmRNAs. In addition, N gene sgmRNA transcription is controlled by a transcription-regulating motif, including a long-distance RNA-RNA interaction between complementary proximal and distal elements. The extension of complementarity between these two sequences increased N gene transcription. An active domain, a novel essential component of the transcription-regulating motif, has been identified. The active domain primary sequence was necessary for its activity. Relocation of the active domain upstream of the N gene TRS core sequence in the absence of the proximal and distal elements also enhanced sgmRNA N transcription. According to the proposed working model for N gene transcriptional activation, the long-distance RNA-RNA interaction relocates the distant active domain in close proximity with the N gene TRS, which probably increases the frequency of template switching during the synthesis of negative RNA. The transcription-regulating motif has been optimized to a minimal sequence showing a 4-fold activity increase in relation to the native RNA motif. Full-length TGEV infectious viruses were generated with the optimized transcription-regulating motif, which enhanced by 5-fold the transcription of the 3a gene and can be used in expression vectors based in coronavirus genomes.
Mouse Hepatitis Virus Stem-Loop 4 Functions as a Spacer Element Required To Drive Subgenomic RNA Synthesis
Authors: Yang Dong , Liu Pinghua , Giedroc David P. , Leibowitz Julian
Published: June 2011

The 5′ 140 nucleotides of the mouse hepatitis virus (MHV) 5′ untranslated region (5′UTR) are predicted to contain three secondary structures, stem-loop 1 (SL1), SL2, and SL4. SL1 and SL2 are required for subgenomic RNA synthesis. The current study focuses on SL4, which contains two base-paired regions, SL4a and SL4b. A series of reverse genetic experiments show that SL4a is not required to be base paired. Neither the structure, the sequence, nor the putative 8-amino-acid open reading frame (ORF) in SL4b is required for viral replication. Viruses containing separate deletions of SL4a and SL4b are viable. However, deletion of SL4 is lethal, and genomes carrying this deletion are defective in directing subgenomic RNA synthesis. Deletion of
131
ACA
133
just 3′ to SL4 has a profound impact on viral replication. Viruses carrying the
131
ACA
133
deletion were heterogeneous in plaque size. We isolated three viruses with second-site mutations in the 5′UTR which compensated for decreased plaque sizes, delayed growth kinetics, and lower titers associated with the
131
ACA
133
deletion. The second-site mutations are predicted to change either the spacing between SL1 and SL2 or that between SL2 and SL4 or to destabilize the proximal portion of SL4a in our model. A mutant constructed by replacing SL4 with a shorter sequence-unrelated stem-loop was viable. These results suggest that the proposed SL4 in the MHV 5′UTR functions in part as a spacer element that orients SL1, SL2, and the transcriptional regulatory sequence (TRS), and this spacer function may play an important role in directing subgenomic RNA synthesis.
Engineered Single Human CD4 Domains as Potent HIV-1 Inhibitors and Components of Vaccine Immunogens
Authors: Chen Weizao , Feng Yang , Gong Rui , Zhu Zhongyu , Wang Yanping , Zhao Qi , Dimitrov Dimiter S.
Published: June 2011

Soluble forms of the HIV-1 receptor CD4 (sCD4) have been extensively characterized for more than 2 decades as promising inhibitors and components of vaccine immunogens. However, they were mostly based on the first two CD4 domains (D1D2), and numerous attempts to develop functional, high-affinity, stable soluble one-domain sCD4 (D1) have not been successful because of the strong interactions between the two domains. We have hypothesized that combining the power of structure-based design with sequential panning of large D1 mutant libraries against different HIV-1 envelope glycoproteins (Envs) and screening for soluble mutants could not only help solve the fundamental stability problem of isolated D1, but may also allow improvement of D1 affinity while preserving its cross-reactivity. By using this strategy, we identified two stable monomeric D1 mutants, mD1.1 and mD1.2, which were significantly more soluble and bound Env gp120s more strongly (50-fold) than D1D2, neutralized a panel of HIV-1 primary isolates from different clades more potently than D1D2, induced conformational changes in gp120, and sensitized HIV-1 for neutralization by CD4-induced antibodies. mD1.1 and mD1.2 exhibited much lower binding to human blood cell lines than D1D2; moreover, they preserved a β-strand secondary structure and stability against thermally induced unfolding, trypsin digestion, and degradation by human serum. Because of their superior properties, mD1.1 and mD1.2 could be potentially useful as candidate therapeutics, components of vaccine immunogens, and research reagents for exploration of HIV-1 entry and immune responses. Our approach could be applied to other cases where soluble isolated protein domains are needed.
Alcohol involvement in aggression between intimate partners in New Zealand: a national cross-sectional study
Authors: Connor Jennie L , Kypri Kypros , Bell Melanie L , Cousins Kimberly
Published: June 2011

Objectives

To examine the role of alcohol at the time of aggressive incidents between intimate partners in the general population by gender, by estimating (1) prevalence and severity of aggression, and drinking at the time, (2) associations of drinking at the time of the aggression with reported severity, anger and fear, and (3) association of usual drinking patterns with partner aggression.

Design

A national survey of 18–70-year-olds using an electoral roll sample obtained self-reported alcohol consumption, partner's alcohol consumption and details of the most severe partner aggression by the respondent and towards the respondent in the past 2 years. The mean scores for associated severity, anger and fear were analysed by gender and alcohol involvement. Multinomial models estimated associations of drinking patterns with aggression to and from the respondent.

Results

The response rate was 49% (n=1925). Men and women reported similar prevalence of victimisation and perpetration of aggression (11–15%). Alcohol was involved in more than 25% of incidents, and reported more by women than by men, particularly male-only drinking when the respondent was the victim. Women reported greater severity, anger and fear with victimisation than men, and drinking was associated with greater reported severity. Heavy episodic drinking by respondents was associated with a threefold increase in victimisation and doubling of perpetration of aggression involving alcohol. Heavy episodic drinking by either partner was also associated with drinking being involved in reported aggression.

Conclusions

The experience of intimate-partner aggression in a cross-section of households differs by gender and the involvement of alcohol, and ‘counts’ of aggressive acts in a population-based survey do not reflect the reality of gender differences. Heavy episodic drinking patterns are associated with more aggression involving alcohol within relationships, and alcohol involvement is associated with increased severity.
AXIOMATIZATIONS AND FACTORIZATIONS OF SUGENO UTILITY FUNCTIONS
Authors: COUCEIRO MIGUEL , WALDHAUSER TAMÁS
Published: June 2011

In this paper we consider a multicriteria aggregation model where local utility functions of different sorts are aggregated using Sugeno integrals, and which we refer to as Sugeno utility functions. We propose a general approach to study such functions via the notion of pseudo-Sugeno integral (or, equivalently, pseudo-polynomial function), which naturally generalizes that of Sugeno integral, and provide several axiomatizations for this class of functions.

Moreover, we address and solve the problem of factorizing a Sugeno utility function as a composition q(φ1(x1),…,φn(xn)) of a Sugeno integral q with local utility functions φi, if such a factorization exists.
COUPLED MAGNETIC FIELD AND VISCOELASTICITY OF FERROGEL
Authors: HAN YI , HONG WEI , FAIDLEY LEANN
Published: June 2011

Composed of a soft polymer matrix and magnetic filler particles, ferrogel is a smart material responsive to magnetic fields. Due to the viscoelasticity of the matrix, the behaviors of ferrogel are usually rate-dependent. Very few models with coupled magnetic field and viscoelasticity exist in the literature, and even fewer are capable of reliable predictions. Based on the principles of non-equilibrium thermodynamics, a field theory is developed to describe the magneto-viscoelastic property of ferrogel. The theory provides a guideline for experimental characterizations and structural designs of ferrogel-based devices. A specific material model is then selected and the theory is implemented in a finite element code. Through numerical examples, the responses of a ferrogel in uniform and non-uniform magnetic fields are analyzed. The dynamic response of a ferrogel to cyclic magnetic fields is also studied, and the prediction agrees with our experimental results. In the reversible limit, our theory recovers existing models for elastic ferrogel, and is capable of capturing some instability phenomena.
THE INFLUENCE OF MICROSTRUCTURE ON BOUNDARY LAYER INTERACTIONS IN IONIC POLYMER TRANSDUCERS
Authors: DAVIDSON JACOB D. , GOULBOURNE N. C.
Published: June 2011

Ionic polymer transducers (IPTs), also known as ionic polymer-metal composites (IPMCs), are smart sensors and actuators which operate through a coupling of micro-scale chemical, mechanical, and electrical interactions. It is known that ion movement, when a voltage is applied, causes stresses which lead to a net bending movement of a cantilevered transducer towards the anode. However, it is not well understood how these stresses arise, and it is not known how the material microstructure affects the observed macroscopic bending response. In this work, we apply a micromechanics modeling framework to analyze how assumptions of the material microstructure of an IPT affect local interactions and the resulting boundary layer stresses which lead to actuation. In the micromechanics framework, local equilibrium consists of a balance between internal cluster pressure and the stress developed in the polymer backbone. Here, we derive a generalized expression for the electrostatic cluster pressure and show how it depends on microstructure and microstructural evolution in the boundary layers. It is proposed that the boundary layer stiffness varies locally with changes in solvent uptake and charge density; this relationship is defined from micromechanics equilibrium conditions and includes effects of the generalized electrostatic cluster pressure. By assuming a relationship between ion and solvent movement, we then examine how boundary layer stresses are affected by assumptions of the material microstructure. The results and implications of the model are compared with recent experimental observations as well as other models of IPT actuation.
Role of astrocytes and altered regulation of spinal glutamatergic neurotransmission in stress-induced visceral hyperalgesia in rats
Authors: Bradesi Sylvie , Golovatscka Viktoriya , Ennes Helena S. , McRoberts James A. , Karagiannidis Iordanes , Bakirtzi Kyriaki , Pothoulakis Charalabos , Mayer Emeran A.
Published: June 2011

Glutamate (Glu) is the primary excitatory neurotransmitter in the central nervous system and plays a critical role in the neuroplasticity of nociceptive networks. We aimed to examine the role of spinal astroglia in the modulation of glutamatergic neurotransmission in a model of chronic psychological stress-induced visceral hyperalgesia in male Wistar rats. We assessed the effect of chronic stress on different glial Glu control mechanisms in the spinal cord including N-methyl-d-aspartate receptors (NMDARs), glial Glu transporters (GLT1 and GLAST), the Glu conversion enzyme glutamine synthetase (GS), and glial fibrillary acidic protein (GFAP). We also tested the effect of pharmacological inhibition of NMDAR activation, of extracellular Glu reuptake, and of astrocyte function on visceral nociceptive response in naive and stressed rats. We observed stress-induced decreased expression of spinal GLT1, GFAP, and GS, whereas GLAST expression was upregulated. Although visceral hyperalgesia was blocked by pharmacological inhibition of spinal NMDARs, we observed no stress effects on NMDAR subunit expression or phosphorylation. The glial modulating agent propentofylline blocked stress-induced visceral hyperalgesia, and blockade of GLT1 function in control rats resulted in enhanced visceral nociceptive response. These findings provide evidence for stress-induced modulation of glia-controlled spinal Glu-ergic neurotransmission and its involvement in chronic stress-induced visceral hyperalgesia. The findings reported in this study demonstrate a unique pattern of stress-induced changes in spinal Glu signaling and metabolism associated with enhanced responses to visceral distension.
Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology
Authors: Kenna Kelly , De Matteo Robert , Hanita Takushi , Rees Sandra , Sozo Foula , Stokes Victoria , Walker David , Bocking Alan , Brien James , Harding Richard
Published: June 2011

High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ∼145 DGA). Maternal and fetal arterial blood was sampled at 131–133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (∼0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal PaCO2, or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.
The cerebral critical oxygen threshold of ventilated preterm lambs and the influence of antenatal inflammation
Authors: Andersen C. C. , Pillow J. J. , Gill A. W. , Allison B. J. , Moss T. J. M. , Hooper S. B. , Nitsos I. , Kluckow M. , Polglase G. R.
Published: June 2011

Perinatal inflammation is associated with adverse neurodevelopmental outcomes, which may be partly due to changes in the cerebral oxygen delivery/consumption relationship. We aimed to determine the critical oxygen delivery threshold of the brain of preterm, ventilated lambs and to determine whether the critical threshold is affected by exposure to inflammation in utero. Pregnant ewes received intra-amniotic injection of lipopolysaccharide or saline at 125 or 127 days of gestation. Pulmonary and systemic flow probes and catheters were surgically positioned in the fetus immediately before delivery at 129 days of gestation. After delivery, lambs were ventilated for 90 min using a positive end-expiratory pressure recruitment strategy. Cardio-respiratory variables and blood gases were measured regularly. Systemic and cerebral oxygen delivery, consumption (Fick), and extraction were calculated, and the relationship between cerebral delivery and consumption analyzed. Linear regression was used to define the transition or “critical” oxygen threshold as the point at which the slope of the oxygen delivery/consumption curve changed to be >10°. Four subgroups were defined according to the calculated critical threshold. A total of 150 measurements were recorded in 18 lambs. Fetal cerebral oxygen consumption was increased by antenatal lipopolysaccharide ( P < 0.05). The postnatal critical oxygen threshold was 3.6 ml·kg−1·min−1, corresponding to cerebral oxygen consumption of 0.73 ml·kg−1·min−1. High oxygen delivery and consumption were associated with increased pulmonary and carotid blood flow and systemic extraction compared with low oxygen delivery and consumption. No postnatal effect of antenatal inflammation was observed. Inflammation in utero increases fetal, but not postnatal, cerebral oxygen consumption. Adverse alterations to pulmonary blood flow can result in reduced cerebral blood flow, oxygen delivery, and consumption. Regardless of exposure to inflammation, there is a consistent postnatal relationship between cerebral oxygen delivery and consumption.
Muscle damage alters the metabolic response to dynamic exercise in humans: a31P-MRS study
Authors: Davies Rosemary C. , Eston Roger G. , Fulford Jonathan , Rowlands Ann V. , Jones Andrew M.
Published: July 2011

We used31P-magnetic resonance spectroscopy to test the hypothesis that exercise-induced muscle damage (EIMD) alters the muscle metabolic response to dynamic exercise, and that this contributes to the observed reduction in exercise tolerance following EIMD in humans. Ten healthy, physically active men performed incremental knee extensor exercise inside the bore of a whole body 1.5-T superconducting magnet before (pre) and 48 h after (post) performing 100 squats with a load corresponding to 70% of body mass. There were significant changes in all markers of muscle damage [perceived muscle soreness, creatine kinase activity (434% increase at 24 h), and isokinetic peak torque (16% decrease at 24 h)] following eccentric exercise. Muscle phosphocreatine concentration ([PCr]) and pH values during incremental exercise were not different pre- and post-EIMD ( P > 0.05). However, resting inorganic phosphate concentration ([Pi]; pre: 4.7 ± 0.8; post: 6.7 ± 1.7 mM; P < 0.01) and, consequently, [Pi]/[PCr] values (pre: 0.12 ± 0.02; post: 0.18 ± 0.05; P < 0.01) were significantly elevated following EIMD. These mean differences were maintained during incremental exercise ( P < 0.05). Time to exhaustion was significantly reduced following EIMD (519 ± 56 and 459 ± 63 s, pre- and post-EIMD, respectively, P < 0.001). End-exercise pH (pre: 6.75 ± 0.04; post: 6.83 ± 0.04; P < 0.05) and [PCr] (pre: 7.2 ± 1.7; post: 14.5 ± 2.1 mM; P < 0.01) were higher, but end-exercise [Pi] was not significantly different (pre: 19.7 ± 1.9; post: 21.1 ± 2.6 mM, P > 0.05) following EIMD. The results indicate that alterations in phosphate metabolism, specifically the elevated [Pi] at rest and throughout exercise, may contribute to the reduced exercise tolerance observed following EIMD.
Quick phases control ocular torsion during smooth pursuit
Authors: Hess Bernhard J. M. , Thomassen Jakob S.
Published: June 2011

One of the open questions in oculomotor control of visually guided eye movements is whether it is possible to smoothly track a target along a curvilinear path across the visual field without changing the torsional stance of the eye. We show in an experimental study of three-dimensional eye movements in subhuman primates ( Macaca mulatta) that although the pursuit system is able to smoothly change the orbital orientation of the eye's rotation axis, the smooth ocular motion was interrupted every few hundred milliseconds by a small quick phase with amplitude <1.5° while the animal tracked a target along a circle or ellipse. Specifically, during circular pursuit of targets moving at different angular eccentricities (5°, 10°, and 15°) relative to straight ahead at spatial frequencies of 0.067 and 0.1 Hz, the torsional amplitude of the intervening quick phases was typically around 1° or smaller and changed direction for clockwise vs. counterclockwise tracking. Reverse computations of the eye rotation based on the recorded angular eye velocity showed that the quick phases facilitate the overall control of ocular orientation in the roll plane, thereby minimizing torsional disturbances of the visual field. On the basis of a detailed kinematic analysis, we suggest that quick phases during curvilinear smooth tracking serve to minimize deviations from Donders' law, which are inevitable due to the spherical configuration space of smooth eye movements.
Diagrammatics for Soergel Categories
Authors: Elias Ben , Khovanov Mikhail
Published: June 2011

The monoidal category of Soergel bimodules can be thought of as a categorification of the Hecke algebra of a finite Weyl group. We present this category, when the Weyl group is the symmetric group, in the language of planar diagrams with local generators and local defining relations.
Validation of Farmer Perceived Soil Fertility Improving Tree Species in Agropastoral Communities of Bushenyi District
Authors: Muzoora Albert. K. , Turyahabwe Nelson , Majaliwa Jackson G. M.
Published: June 2011

In sub-Saharan Africa, including Uganda, there is declining soil fertility and limited on-farm use of inorganic fertilizers due to poverty and limited subsidies for inorganic fertilizer use. Thus, integration of soil fertility improving tree species (SFITs) in farming systems remains a plausible option to sustaining soil productivity. However, knowledge of the effects of many of the locally growing farmer perceived soil fertility enhancing tree species on to soil chemical and nutrient contents are thus still lacking, and this has constrained decisions on their adoption and scaling up. The objectives of this paper were to identify farmers' preferred soil fertility improving tree species in agropastoral communities of Kyeizooba subcounty Bushenyi district, and characterize their litter content and assess their effect on selected soil chemical properties. Semistructured questionnaires were administered to 333 randomly selected agropastoral farmers. Litter and soils under canopy soils were sampled from three different environments: Under canopy radius (A), canopy edge (B), open pasture land up to thrice the canopy radius (C). Results revealedEucalyptusas the most common tree species on livestock farms, followed byErythrina abyssinica. The highest litter content was recorded forMarkhamia lutea(240 g/cm2under its canopy) followed byCroton macrostachyus(90 g/cm2), and 19 g/cm2Erythrina abyssinica. Nitrogen was higher (P=.02) inErythrina abyssinicalitter, K and carbon inCroton macrostachyuslitter (P=.03). These results give evidence that of soil improversErythrina abyssinica,Croton macrostachyus, andMarkhamia luteamay positively affect soil fertility. Farmers' indigenous knowledge and or valuation of important tree species can be relied on, and thus, their indigenous knowledge need to be incorporated during identification of tree species for promotion in farming systems.