bluuebunny/crossref_metadata_2025 huggingface dataset:
C-reactive protein: a poor marker of cardiovascular disease risk in HIV+ populations with a high prevalence of elevated serum transaminases
Authors: Baum M K , Rafie C , Sales S , Lai S , Duan R , Jayaweera D T , Page J B , Campa A
Published: May 2013

Summary:

Blood lipids and high-sensitivity C-reactive protein (hsCRP) are used to assess cardiovascular disease (CVD) risk. We evaluated in a cross-sectional design the relationship of hsCRP to markers of liver function (aspartate and alanine transaminases [AST and ALT, respectively]), CVD risk factors and HIV-disease progression markers in 226 HIV-1 seropositive drug users. hsCRP showed a significant inverse relationship with ALT and high-density lipoprotein, independent of age, gender, viral load, CD4 cell-count and antiretroviral (ARV) use, and was not significantly associated with HIV-disease progression markers. Serum markers of liver damage, AST and ALT, were associated with lower hsCRP, total cholesterol, low-density lipoproteins and triglycerides. Elevated liver enzymes (≥40 IU/L) were predictive of hsCRP levels that are considered a low risk for CVD. In conclusion, hsCRP may not be a reliable marker of CVD risk in populations with HIV at-risk for elevated liver enzymes due to high hepatitis B virus/hepatitis C virus prevalence and ARV use.
The use of prophylaxis against HIV after sexual exposure in pregnancy to reduce the risk of vertical transmission
Authors: Williams P M , Sherrard J , Jeffery K J M
Published: May 2013

Summary:

We present a case demonstrating the use of HIV prophylaxis post-sexual exposure in pregnancy. This has not been presented before but has certainly been discussed.
Cost effectiveness of enzyme immunoassay and immunoblot testing for the diagnosis of syphilis
Authors: Chuck Anderson , Ohinmaa Arto , Tilley Peter , Singh Ameeta , Jacobs Philip
Published: May 2013

Summary:

The burden of disease and associated healthcare costs of syphilis are significant despite widespread screening and treatment. Our objective was to conduct an economic evaluation using a simulation model when comparing enzyme immunoassay (EIA) initial testing and Inno-Lia (IL) confirmatory testing (EIA + IL) with rapid plasma reagin (RPR) initial testing and Treponema pallidum particle agglutination assay (TPPA) and fluorescent treponemal antibody absorption assay (FTA-ABS) confirmatory testing (RPR + TPPA/FTA). Estimates of prevalence, test costs and utilization of services for 2006 were derived from Alberta databases. Estimates of test characteristics were derived from the available literature. The incremental cost-effectiveness ratio was Canadian $461 per additional correct diagnosis (less costly and more effective). EIA + IL is cost-effective when compared with RPR + TPPA/FTA for screening and diagnosis of syphilis.
Patients’ reasons for attending the genitourinary medicine clinic
Authors: Markos A R
Published: May 2013

Summary:

Patients’ reasons for attending the genitourinary medicine clinic inform and dictate the range of provisions and advice that the staff should provide. The objective analysis of these reasons would better inform the process of triage, clinical services and contractual arrangements (e.g. new to follow-up ratios). Our findings indicate that almost one in every two patients is presenting first with genitourinary symptoms and the majority of the remainder either identified themselves to be at risk or were identified by the attending clinician as having medical concerns and/or risk factors. This patient group could benefit, and must be offered, tests to exclude all sexually transmitted infections (within the condition's own incubation/test window periods).
HIV transmission transcends three generations: can we prevent secondary transmission in India?
Authors: Venkatesh Kartik K , Prasad Lakshmi , Mayer Kenneth H , Kumarasamy N
Published: May 2013

Summary:

This case history documents four instances of HIV secondary transmission within a single family, which could have been stopped at multiple points by timely prevention. These cases of HIV secondary transmission that have occurred since the scale-up of HIV testing, prevention and clinical services in India raises the question whether the current HIV prevention infrastructure is sufficient and comprehensive in resource-limited settings.
Cost effectiveness of couple counselling to enhance infant HIV-1 prevention
Authors: John Francis N , Farquhar Carey , Kiarie James N , Kabura Marjory N , John-Stewart Grace C
Published: May 2013

Summary:

Data collected in the years 2001-2003 from an antenatal clinic in Nairobi, Kenya, were used to assess the benefit of couple counselling and test it as a way of increasing the uptake of interventions in the prevention of mother-to-child transmission of HIV-1. Among 2833 women enrolled, 311 (11%) received couple pretest counselling and 2100 (74%) accepted HIV-1 testing. Among those tested 314 (15%) were HIV-1 seropositive. We incorporated these and other data from the cohort study into a spreadsheetbased model and costs associated with couple counselling were compared with individual counselling in a theoretical cohort of 10,000 women. Voluntary couple counselling and testing (VCT), although more expensive, averted a greater number of infant infections when compared with individual VCT. Cost per disability-adjusted life year was similar to that of individual VCT. Sensitivity analyses found that couple VCT was more cost-effective in scenarios with increased uptake of couple counselling and higher HIV-1 prevalence.
Management of internal genital warts: do we all agree? A postal survey
Authors: Bushby S A , Chauhan M
Published: May 2013

Summary:

A postal survey was undertaken to determine whether there was any consensus of opinion regarding the management of internal genital warts in genitourinary medicine clinics in the UK. Overall, 110 forms were returned (57% response). The majority of clinics would refer patients with cervical warts for colposcopy especially if the patient was over the age of 25 or HIV-positive. Proctoscopy or anoscopy was performed in 60% of clinics for patients with perianal warts to determine the presence of warts within the anal canal or rectum. Only 24% of patients with intra-anal warts are referred directly to surgery for biopsy, increasing to 61% if the patient has HIV infection. Cryotherapy is the main treatment for all types of internal warts. Our findings suggest there is no consensus and we recommend that all HIV-positive patients with anal or cervical condyloma should be investigated for evidence of intraepithelial neoplasia.
A Measure-Correlation-Predict Method for Turbulence Intensity Distribution Assessment
Authors: Casella Livio
Published: May 2013

A method based on a multiple correlation analysis is proposed in this work that is able to offer a long-term assessment of turbulence intensity ( TI) distribution at a local meteorological mast using a reference wind dataset. The MCP analysis uses a joint probability distribution function which is derived from wind speed, wind direction and TI data which are simultaneously recorded at the two measurement sites.

Validation has been carried out using two met-masts which have a high level of correlation in terms of wind speeds. The algorithm properly corrects the local wind dataset, by estimating the “per sector” and “per speed” long-term distribution of TI; this was proved using different short-term data samples. Other tests, opportunely arranged using artificial wind data, help to understand the score of the method when multiple variables are used, highlighting that fine assessment can be always achieved when all the used variables are dependent on each other.
Repowering of Wind Farms — A Case Study
Authors: Nivedh B.S. , Devi R.P. Kumudini , Sreevalsan E.
Published: May 2013

The main objective of the paper is to devise a method for assessing the repowering potential and to improve the energy output from the wind farms and also to understand the impact on the power quality due to repowering. With repowering, the first-generation wind turbines can be replaced with modern multi-megawatt wind turbines. To carry-out the study an old wind farm located at Kayathar, Tamilnadu is selected. The wind farm was commissioned in 1990's with a capacity of 7.35 MW, which consists of 36 Wind Turbines each with the capacity of 200 kW and 225 kW. The present annual energy generation of the wind farm is 7350 MWhr with the plant load factor of 11.41%. The intent of this study is to predict the annual energy output of the wind farm after the repowering using WAsP (Wind Atlas Analysis Application Program). Further this study analyses the power quality issues of the various Wind Turbines. In addition, the main feeder, in which the wind farm which is taken for the study also modeled and the impact on power quality due to repowering also studied. Simulations were carried out using MATLAB.

The results are analyzed to understand the significance of repowering to overcome the energy crisis of the nation since the best locations for wind in India are occupied by old wind turbines. The following are the observations and conclusions from the above study. Plant load factor (PLF) increased to 24%, Energy yield increased to more than 4 times and the capacity of the wind farm became double. And in the view of power quality, comparing to the existing Feeder, Repowered Feeder having less reactive power consumption, and voltage variations except the harmonic distortion.
Tree-Structure Canopy: A Case Study in Design and Fabrication of Complex Steel Structures using Digital Tools
Authors: Agkathidis Asterios , Brown André
Published: May 2013

This paper describes and reflects on the design and manufacturing process of the Tree-Structure canopy for the WestendGate Tower in Frankfurt upon Main, completed early 2011. The project investigated fabrication and assembly principles of complex steel structures as well as the integration of contemporary computational design, engineering, optimization and simulation techniques in a collaborative design approach. This paper focuses on the notion of modular standardization as opposed to non standard customized components. It also engages with issues relating to digital production tools and their impact on construction cost, material performance and tolerances. In addition it examines the reconfiguration of liability during a planning and construction process, an aspect which can be strongly determined by fabrication companies rather than the architect or designer. This paper is written as a reflection on the complete building process when contemporary digital tools are used from design through to fabrication. It studies both the generation of the steel structure as well the ETFE cushion skin. It reports on a collaborative project, where the main author was responsible for the canopies design, parameterization, digitalization and fabrication, as well as for the dissemination of the outcomes and findings during the design and realization process. As such it represents an example of research through design in a contemporary and evolving field. The canopy received a design award by the Hellenic Architecture Association.
Preparation of copper nanoparticles and metal-metal bonding process using them
Authors: Kobayashi Y. , Ishida S. , Ihara K. , Yasuda Y. , Morita T.
Published: May 2013

This work describes a metal-metal bonding process by the use of Cu nanoparticles as a filler material. The Cu particles used were prepared by reduction of Cu2+ with hydrazine in the presence of cetyltrimethylammonium bromide as a dispersing agent (uncoated Cu particles). Polypyrrole (PPy)-coated Cu nanoparticles were also used as the filler. Strong bonding for Cu discs was not obtained by using the PPy-coated particles. For the uncoated Cu particles, a shear strength required for separating the discs bonded by annealing at 400°C in H2 gas was as large as 18.1 MPa.
Cold field emission electrode as a local probe of proximal microscopes: Investigation of defects in monocrystalline silicon solar cells
Authors: Tománek P. , Škarvada P. , Dallaeva D. , Grmela L. , Macků R. , Smith S.
Published: May 2013

Monocrystalline silicon is still very interesting material for solar cells fabrication due to its quality and external efficiency. Nevertheless during a tailoring of eligible silicon wafers, some inhomogeneities or irregularities emerge and provide defects which give trouble to good operation of solar panels. Generally, there are two classes of defects in silicon wafer: material defects due to imperfections or irregularity in crystal structure (point, line, square or volume defects), and defects induced by wafer processing. To avoid a use of damaged cells, macroscopic and microscopic measurement techniques must be applied. In this paper we present a microscopic method combining electrical noise measurements with scanning probe localization of luminous micro-spots defects. The paper brings experimental results showing local electric and optical investigations of defects in etched monocrystalline silicon solar cells and a use of cold field emission tungsten electrode as a local probe for apertureless scanning near-field optical microscope.
Enhancement of flow behavior of polypropylene composite via LMW and HMW flow promoters
Authors: Singh Neelam , Dutta Santanu
Published: May 2013

This paper discusses how melt flow indices and flow behavior data can be used to predict polymer flow in real industrial processes. The ability to simulate flow behavior can help us establish a robust process that has a large processing window and which accommodates a natural variation. The effect of shear rate on viscosity is of far greater significance. It is therefore important to find the Newtonian region of the curve and set the process parameters in this region for a specified mould thickness. This paper also aims at modifying the flow behavior of polypropylene blends using various lubricants and flow promoters both low molecular weight and polymeric flow promoters.
Calculating rupture of pile under static loading by method of analysis
Authors: Benyaghla Hacène , Meksaouine Mohamed , Mokrani Larbi , Belabed Lazhar
Published: May 2013

The theoretical study, presented here, deals with the problem of interaction pile soil, thus making a contribution in determining the resistance and friction edge side for a single stake sought by a charge axial static. The theoretical tool used is the theorem cinematic theory analysis limit, in the case of a material Coulomb, developing a model in three dimensions. The aim of this research is to determine the limit load massive breakdown by the model proposed using the computer code mathcad. The calculation program takes into account physical phenomena, ie the expansion and contraction of soil under a load static. The results, calculated by the proposed model are compared with experimental results made in the laboratory 3SR Grenoble (France) and the results of conventional methods used in the calculations of this type of constructions.
The adhibition research of filling paste preparation system based on fuzzy PID control algorithm
Authors: Wang G. , Guo K. , Zhang B.
Published: May 2013

The filling paste blending system is the core part in a paste backfill mining scheme. Its precision directly determines the flow properties and condensation curing performance of the filling slurry, thus it affects the filling effect of the underground mining working face. The research fuzzy PID control algorithm is introduced into the filling paste blending automatic control system in order to achieve a better control effect (Geng, 2007). Detailed introduces fuzzy PID controller design process, through the simulation experiment shows that fuzzy PID controller improves the system of external disturbance, and adapt to the internal parameters change robustness, ensure the precision of the burden system.
Manufacturing and characteristics analysis of PU/MWNT film for electrosatic dissipation
Authors: Kim Seung-Jin , Park Jun-Hyeong , Kim Jeong-hyun
Published: May 2013

This study surveys the characteristics of the nanocomposite film for PU/MWNT. For this purpose, several kinds of PU/MWNT nanocomposite films were prepared with four kinds of MWNT, MWNT contents and two kinds of dispersion times and ESD (Electrostatic Dissipation) films composed with polyurethane (PU) block copolymer and selected multi-walled carbon nanotube (MWNT) were also prepared by disperse processing with various MWNT contents and dispersion times, and their mechanical and chemical properties were investigated with electrical conductivity. The tensile properties and chemical properties of PU/MWNT nanocomposite films were measured using UV-visible spectrometer and discussed with the manufacturing conditions of nanocomposite film. Furthermore, the PU/MWNT films were made by dispersing with five kinds of CNT content and six kinds of dispersion time under the DMF (dimethylformamide) solution, and the mechanical properties of the PU/MWNT films were analyzed by Instron and discussed with various dispersion conditions.
Case Report: Laparoscopic trocar management of a giant paraovarian cyst: a case report
Authors: Kandil Mohamed , Sayyed Tarek , Zakaria Mohamed
Published: May 2013

A 17-year-old woman had undergone exploratory laparotomy because of a huge cystic pelviabdominal mass equivalent of 36 weeks' gestation. A closed system drainage maneuver was applied via using a laparoscopic trocar to drain a revealed large left paraovarian cyst. This maneuver was found to be a simple and effective method to safely aspirate giant paraovarian cysts; thus allowing their total excision.
Psychodrama in Taiwan: Recent Developments and History
Authors: Lai Nien-Hwa
Published: May 2013

Psychodrama has evolved significantly in Taiwan in the last forty years. At present, the method is being adapted to the needs of our culture. We are proceeding with research on culture-related theories. This may also have implications for the entrance of psychodrama in other countries in Asia.
Choosing the Unchosen: Counteracting the Sociodynamic Effect Using Complementary Sharing
Authors: Korshak Shelley J. , Shapiro Marianne
Published: May 2013

When Moreno says that our subject of inquiry is nothing less than healing the whole of mankind, he challenges us to embrace differences. This article explores diversity, and describes using complementary sharing in a forced choice action sociogram. This technique enhances the diversity and cohesion of the group by helping the participants discover the wisdom of those not chosen.
Current State of Knowledge on Oral Anticoagulant Reversal Using Procoagulant Factors
Authors: Nitzki-George Diane , Wozniak Izabela , Caprini Joseph A
Published: May 2013

OBJECTIVE:

To discuss current trends and challenges in the use of procoagulants for treating bleeding caused by use of oral anticoagulants.

DATA SOURCES:

Literature searches of PubMed (MEDLINE), Google, and Medscape were conducted in February 2013. There were no date limitations. Search terms included anticoagulation agents, anticoagulation reversal, anticoagulation reversal agents, apixaban, clinical studies, dabigatran, 3-factor PCCs, 4-factor PCCs, FEIBA, fresh frozen plasma, human studies, pharmacology, prescribing information, rFVIIa, rivaroxaban, vitamin K, and warfarin.

DATA SYNTHESIS:

Warfarin has been the mainstay for the treatment and prevention of primary and secondary thrombosis in patients with cardiovascular disorders such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and stroke. Three oral anticoagulants have recently become available in the US: a direct thrombin inhibitor, dabigatran etexilate, and 2 direct factor Xa inhibitors, rivaroxaban and apixaban. Reversal strategies for anticoagulant-associated bleeding are well established for warfarin; however, strategies to stop bleeding in a patient who has taken one of the newer anticoagulants are less clear. In the US, agents available for oral anticoagulant reversal include activated prothrombin complex concentrate (APCC), 3-factor PCCs, and recombinant activated factor VII (rFVIIa). Few studies have evaluated the 3-factor PCCs, and current evidence for APCC and rFVIIa as reversal agents for dabigatran and rivaroxaban is based primarily on laboratory or animal studies, or on small studies in healthy humans and case reports.

CONCLUSIONS:

Patients contemplating using the new oral anticoagulants should be informed about specific clinical situations that could pose a bleeding risk such as the need for emergency surgery because no reliable antidote is available to stop the bleeding, which could prove fatal.
Local Authority Liability in Tort to Owners of Defective Buildings: The New Zealand Position
Authors: Tobin Rosemary
Published: May 2013

In New Zealand since the late 1970s, an action has been available against the local authority for any negligence on its part in the course of construction of a building. The duty of care is imposed on local authorities in respect of the issue of building consents, inspection during the course of the building's construction and the issue of any final certificate. The duty became known as the Hamlin principle, and was confirmed by the Privy Council in respect of a single residential dwelling. However, the building environment changed in the 1990s and this change led to a leaky home crisis affecting thousands of homes. It led inevitably to a challenge to the Hamlin principle. Recently, however, the Supreme Court confirmed the Hamlin principle in respect of both residential and commercial properties, whether single buildings or multi-unit properties. This article considers the evolution of local authority liability for the construction of buildings in New Zealand.
Confessions and the Criminal Justice Act 2003
Authors: Stockdale Michael , Clough Joanne
Published: May 2013

The admissibility of hearsay evidence in criminal proceedings in England and Wales is now governed by provisions of the Criminal Justice Act 2003, a result of Law Commission reform proposals. The Law Commission's Report left several issues concerning the admissibility of confessions in the context of its proposed hearsay regime unclear, some of which have not yet been clarified by the post-2003 Act jurisprudence. In particular, whilst the authorities have established that confessions made by third parties may be admissible in exceptional circumstances, the courts have not yet engaged with s. 128(2) of the 2003 Act which limits the extent to which confessions made by defendants may be admissible under the 2003 Act's provisions. Moreover, whilst the Court of Appeal has recognised both that certain confessions may exist outside the 2003 Act's statutory framework and that the admissibility of such a confession for the prosecution when made by a defendant is governed by s. 76 of the Police and Criminal Evidence Act 1984, other issues concerning the admissibility of such confessions have not yet been resolved.
Cystatin C– and Creatinine-Based Estimates of Renal Function and Their Value for Risk Prediction in Patients with Acute Coronary Syndrome: Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study
Authors: Åkerblom Axel , Wallentin Lars , Larsson Anders , Siegbahn Agneta , Becker Richard C , Budaj Andrzej , Himmelmann Anders , Horrow Jay , Husted Steen , Storey Robert F , Åsenblad Nils , James Stefan K
Published: May 2013

BACKGROUND

The estimated glomerular filtration rate (eGFR) independently predicts cardiovascular death or myocardial infarction (MI) and can be estimated by creatinine and cystatin C concentrations. We evaluated 2 different cystatin C assays, alone or combined with creatinine, in patients with acute coronary syndrome.

METHODS

We analyzed plasma cystatin C, measured with assays from Gentian and Roche, and serum creatinine in 16 279 patients from the PLATelet Inhibition and Patient Outcomes (PLATO) trial. We evaluated Pearson correlation and agreement (Bland–Altman) between methods, as well as prognostic value in relation to cardiovascular death or MI during 1 year of follow up by multivariable logistic regression analysis including clinical variables, biomarkers, c-statistics, and relative integrated discrimination improvement (IDI).

RESULTS

Median cystatin C concentrations (interquartile intervals) were 0.83 (0.68–1.01) mg/L (Gentian) and 0.94 (0.80–1.14) mg/L (Roche). Overall correlation was 0.86 (95% CI 0.85–0.86). The level of agreement was within 0.39 mg/L (2 SD) (n = 16 279).

The areas under the curve (AUCs) in the multivariable risk prediction model with cystatin C (Gentian, Roche) or Chronic Kidney Disease Epidemiology Collaboration eGFR (CKD-EPI) added were 0.6914, 0.6913, and 0.6932. Corresponding relative IDI values were 2.96%, 3.86%, and 4.68% (n = 13 050). Addition of eGFR by the combined creatinine–cystatin C equation yielded AUCs of 0.6923 (Gentian) and 0.6924 (Roche) with relative IDI values of 3.54% and 3.24%.

CONCLUSIONS

Despite differences in cystatin C concentrations, overall correlation between the Gentian and Roche assays was good, while agreement was moderate. The combined creatinine–cystatin C equation did not outperform risk prediction by CKD-EPI.
Retailers’ Use of Partially Comparative Pricing: From Across-Category to Within-Category Effects
Authors: Miniard Paul W. , Mohammed Shazad Mustapha , Barone Michael J. , Alvarez Cecilia M.O.
Published: May 2013

Prior research suggests that partially comparative pricing—in which a retailer provides price comparisons for some, but not all, of its products—is a double-edged sword. On the one hand, such pricing improves beliefs about the retailer's competitive price advantage on comparatively priced products for which its prices are compared with a competitor. On the other hand, it has been shown to damage perceptions of the retailer's noncomparatively priced products relative to those charged by the competition. However, this latter outcome is based on evidence examining the influence of partially comparative pricing across different product categories. The authors propose and demonstrate in five studies that price comparisons may actually improve relative price beliefs about the noncomparatively priced brands within the same product category. They further show this improvement to be attenuated as the number of price comparisons increase or when the price comparison is attached to a brand perceived as less typical of the product category. The authors conclude by drawing managerial implications and offer suggestions for further research.
Advertising in a Competitive Market: The Role of Product Standards, Customer Learning, and Switching Costs
Authors: Anderson Eric T. , Simester Duncan
Published: May 2013

Standard models of competition predict that firms will sell less when competitors target their customers with advertising. This is particularly true in mature markets with many competitors that sell relatively undifferentiated products. However, the authors present findings from a large-scale randomized field experiment that contrast sharply with this prediction. The field experiment measures the impact of competitors' advertising on sales at a private label apparel retailer. Surprisingly, for a substantial segment of customers, the competitors' advertisements increased sales at this retailer. This robust effect was obtained through experimental manipulation and by measuring actual purchases from large samples of randomly assigned customers. The effect size is also large, with customers ordering more than 4% more items in some categories in the treatment condition (vs. the control). The authors examine how these positive spillovers vary across product categories to illustrate the importance of product standards, customer learning, and switching costs. The findings have the potential to change our understanding of competition in mature markets.
Triheteromeric NMDA Receptors at Hippocampal Synapses
Authors: Tovar Kenneth R. , McGinley Matthew J. , Westbrook Gary L.
Published: May 2013

NMDA receptors are composed of two GluN1 (N1) and two GluN2 (N2) subunits. Constituent N2 subunits control the pharmacological and kinetic characteristics of the receptor. NMDA receptors in hippocampal or cortical neurons are often thought of as diheteromeric, meaning that they contain only one type of N2 subunit. However, triheteromeric receptors with more than one type of N2 subunit also have been reported, and the relative contribution of diheteromeric and triheteromeric NMDA receptors at synapses has been difficult to assess. Because wild-type hippocampal principal neurons express N1, N2A, and N2B, we used cultured hippocampal principal neurons from N2A and N2B knock-out mice as templates for diheteromeric synaptic receptors. However, summation of N1/N2B and N1/N2A EPSCs could not account for the deactivation kinetics of wild-type EPSCs. To make a quantitative estimate of NMDA receptor subtypes at wild-type synapses, we used the deactivation kinetics and the effects of the competitive antagonist NVP-AAM077. Our results indicate that three types of NMDA receptors contribute to wild-type EPSCs, with at least two-thirds being triheteromeric receptors. Functional isolation of synaptic triheteromeric receptors revealed deactivation kinetics and pharmacology that were distinct from either diheteromeric receptor subtype. Because of differences in open probability, synaptic triheteromeric receptors outnumbered N1/N2A receptors by 5.8 to 1 and N1/N2B receptors by 3.2 to 1. Our results suggest that triheteromeric NMDA receptors must either be preferentially assembled or preferentially localized at synapses.
Promoted Interaction of Nuclear Factor-κB with Demethylated Cystathionine-β-Synthetase Gene Contributes to Gastric Hypersensitivity in Diabetic Rats
Authors: Zhang Hong-Hong , Hu Ji , Zhou You-Lang , Hu Shufen , Wang Yong-Meng , Chen Wei , Xiao Ying , Huang Li-Yen Mae , Jiang Xinghong , Xu Guang-Yin
Published: May 2013

Patients with long-standing diabetes frequently demonstrate gastric hypersensitivity with an unknown mechanism. The present study was designed to investigate roles for nuclear factor-κB (NF-κB) and the endogenous H2S-producing enzyme cystathionine-β-synthetase (CBS) signaling pathways by examiningcbsgene methylation status in adult rats with diabetes. Intraperitoneal injection of streptozotocin (STZ) produced gastric hypersensitivity in female rats in response to gastric balloon distention. Treatment with the CBS inhibitor aminooxyacetic acid significantly attenuated STZ-induced gastric hypersensitivity in a dose-dependent fashion. Aminooxyacetic acid treatment also reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI in diabetic rats. Conversely, the H2S donor NaHS enhanced neuronal excitability of gastric DRG neurons. Expression of CBS and p65 were markedly enhanced in gastric DRGs in diabetic rats. Blockade of NF-κB signaling using pyrrolidine dithiocarbamate reversed the upregulation of CBS expression. Interestingly, STZ treatment led to a significant demethylation of CpG islands in thecbsgene promoter region, as determined by methylation-specific PCR and bisulfite sequencing. STZ treatment also remarkably downregulated the expression of DNA methyltransferase 3a and 3b. More importantly, STZ treatment significantly enhanced the ability ofcbsto bind DNA at the p65 consensus site, as shown by chromatin immunoprecipitation assays. Our findings suggest that upregulation ofcbsexpression is attributed tocbspromoter DNA demethylation and p65 activation and that the enhanced interaction of thecbsgene and p65 contributes to gastric hypersensitivity in diabetes. This finding may guide the development and evaluation of new treatment modalities for patients with diabetic gastric hypersensitivity.
BDNF-Dependent Recycling Facilitates TrkB Translocation to Postsynaptic Density during LTP via a Rab11-Dependent Pathway
Authors: Huang Shu-Hong , Wang Jue , Sui Wen-Hai , Chen Bing , Zhang Xiao-Yan , Yan Jing , Geng Zhao , Chen Zhe-Yu
Published: May 2013

Brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function via tropomyosin related kinase B (TrkB) receptor activation. However, whether BDNF could regulate TrkB levels at synapse during long-term potentiation (LTP) is still unknown. We show in cultured rat hippocampal neurons that chemical LTP (cLTP) stimuli selectively promote endocytic recycling of BDNF-dependent full-length TrkB (TrkB-FL) receptors, but not isoform T1 (TrkB.T1) receptors, via a Rab11-dependent pathway. Moreover, neuronal-activity-enhanced TrkB-FL recycling could facilitate receptor translocation to postsynaptic density and enhance BDNF-induced extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation and rat hippocampal neuron survival. Finally, we found that cLTP could stimulate the switch of Rab11 from an inactive to an active form and that GTP-bound Rab11 could enhance the interaction between TrkB-FL and PSD-95. Therefore, the recycling endosome could serve as a reserve pool to supply TrkB-FL receptors for LTP maintenance. These findings provide a mechanistic link between Rab11-dependent endocytic recycling and TrkB modulation of synaptic plasticity.
Balance of Calcineurin Aα and CDK5 Activities Sets Release Probability at Nerve Terminals
Authors: Kim Sung Hyun , Ryan Timothy A.
Published: May 2013

The control of neurotransmitter release at nerve terminals is of profound importance for neurological function and provides a powerful control system in neural networks. We show that the balance of enzymatic activities of the α isoform of the phosphatase calcineurin (CNAα) and the kinase cyclin-dependent kinase 5 (CDK5) has a dramatic influence over single action potential (AP)-driven exocytosis at nerve terminals. Acute or chronic loss of these enzymatic activities results in a sevenfold impact on single AP-driven exocytosis. We demonstrate that this control is mediated almost entirely through Cav2.2 (N-type) voltage-gated calcium channels as blocking these channels with a peptide toxin eliminates modulation by these enzymes. We found that a fraction of nerve terminals are kept in a presynaptically silent state with no measurable Ca2+influx driven by single AP stimuli attributable to the balance of CNAα and CDK5 activities because blockade of either CNAα or CDK5 activity changes the proportion of presynaptically silent nerve terminals. Thus, CNAα and CDK5 enzymatic activities are key determinants of release probability.
Accumulation of Abnormal Adult-Generated Hippocampal Granule Cells Predicts Seizure Frequency and Severity
Authors: Hester Michael S. , Danzer Steve C.
Published: May 2013

Accumulation of abnormally integrated, adult-born, hippocampal dentate granule cells (DGCs) is hypothesized to contribute to the development of temporal lobe epilepsy (TLE). DGCs have long been implicated in TLE, because they regulate excitatory signaling through the hippocampus and exhibit neuroplastic changes during epileptogenesis. Furthermore, DGCs are unusual in that they are continually generated throughout life, with aberrant integration of new cells underlying the majority of restructuring in the dentate during epileptogenesis. Although it is known that these abnormal networks promote abnormal neuronal firing and hyperexcitability, it has yet to be established whether they directly contribute to seizure generation. If abnormal DGCs do contribute, a reasonable prediction would be that the severity of epilepsy will be correlated with the number or load of abnormal DGCs. To test this prediction, we used a conditional, inducible transgenic mouse model to fate map adult-generated DGCs. Mossy cell loss, also implicated in epileptogenesis, was assessed as well. Transgenic mice rendered epileptic using the pilocarpine-status epilepticus model of epilepsy were monitored continuously by video/EEG for 4 weeks to determine seizure frequency and severity. Positive correlations were found between seizure frequency and (1) the percentage of hilar ectopic DGCs, (2) the amount of mossy fiber sprouting, and (3) the extent of mossy cell death. In addition, mossy fiber sprouting and mossy cell death were correlated with seizure severity. These studies provide correlative evidence in support of the hypothesis that abnormal DGCs contribute to the development of TLE and also support a role for mossy cell loss.
Reduced Serotonin Transporter Availability Decreases Prefrontal Control of the Amygdala
Authors: Volman Inge , Verhagen Lennart , den Ouden Hanneke E. M. , Fernández Guillén , Rijpkema Mark , Franke Barbara , Toni Ivan , Roelofs Karin
Published: May 2013

After a threatening event, the risk of developing social psychopathologies is increased in short-allele (s) carriers of the serotonin transporter gene. The amygdala becomes overresponsive to emotional stimuli, an effect that could be driven by local hypersensitivity or by reduced prefrontal regulation. This study distinguishes between these two hypotheses by using dynamic causal modeling of fMRI data acquired in a preselected cohort of human s-carriers and homozygous long-allele carriers. Increased amygdala activity in s-carriers originates from reduced prefrontal inhibitory regulation when social emotional behavior needs to be controlled, suggesting a mechanism for increased vulnerability to psychopathologies.
A Novel Transgenic Rat Model for Spinocerebellar Ataxia Type 17 Recapitulates Neuropathological Changes and SuppliesIn VivoImaging Biomarkers
Authors: Kelp Alexandra , Koeppen Arnulf H. , Petrasch-Parwez Elisabeth , Calaminus Carsten , Bauer Claudia , Portal Esteban , Yu-Taeger Libo , Pichler Bernd , Bauer Peter , Riess Olaf , Nguyen Huu Phuc
Published: May 2013

Spinocerebellar ataxia 17 (SCA17) is an autosomal-dominant, late-onset neurodegenerative disorder caused by an expanded polyglutamine (polyQ) repeat in the TATA-box-binding protein (TBP). To further investigate this devastating disease, we sought to create a first transgenic rat model for SCA17 that carries a full human cDNA fragment of theTBPgene with 64 CAA/CAG repeats (TBPQ64). In line with previous observations in mouse models for SCA17, TBPQ64 rats show a severe neurological phenotype including ataxia, impairment of postural reflexes, and hyperactivity in early stages followed by reduced activity, loss of body weight, and early death. Neuropathologically, the severe phenotype of SCA17 rats was associated with neuronal loss, particularly in the cerebellum. Degeneration of Purkinje, basket, and stellate cells, changes in the morphology of the dendrites, nuclear TBP-positive immunoreactivity, and axonal torpedos were readily found by light and electron microscopy. While some of these changes are well recapitulated in existing mouse models for SCA17, we provide evidence that some crucial characteristics of SCA17 are better mirrored in TBPQ64 rats. Thus, this SCA17 model represents a valuable tool to pursue experimentation and therapeutic approaches that may be difficult or impossible to perform with SCA17 transgenic mice. We show for the first time positron emission tomography (PET) and diffusion tensor imaging (DTI) data of a SCA animal model that replicate recent PET studies in human SCA17 patients. Our results also confirm that DTI are potentially useful correlates of neuropathological changes in TBPQ64 rats and raise hope that DTI imaging could provide a biomarker for SCA17 patients.
Salient Sounds Activate Human Visual Cortex Automatically
Authors: McDonald John J. , Störmer Viola S. , Martinez Antigona , Feng Wenfeng , Hillyard Steven A.
Published: May 2013

Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, this study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2–4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of colocalized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task.
“Throw That Junk!” The Art of the Movie in Citizen Kane
Authors: Knapp Jeffrey
Published: May 2013

“Junk” is the final word spoken in Hollywood’s most famous art project, Citizen Kane. This essay focuses on three different registers in Kane for understanding the film’s persistent intermingling of art and junk. The first is Charles Foster Kane’s dual career as a newspaper publisher and an art collector; the second, Kane’s cross-class marriage to the shopgirl Susan Alexander; and the third is the film’s signature visual motif, which the essay calls a scatterform. Comparing these features of Kane with similar features in a more conventional Hollywood film, My Best Girl, the essay shows how the peculiar texture of Kane derives from its attempt to think its way out of a theoretical double bind generated by the contemporary insistence that the only way a movie could rival traditional art forms was to reject them as models for emulation. That is why Citizen Kane ties its own artistic bravura to such mass-produced junk as a store-bought snow globe and a sled whose brand name is “Rosebud.”
Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells
Authors: Hescot Ségolène , Slama Abdelhamid , Lombès Anne , Paci Angelo , Remy Hervé , Leboulleux Sophie , Chadarevian Rita , Trabado Séverine , Amazit Larbi , Young Jacques , Baudin Eric , Lombès Marc
Published: May 2013

Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane is the most effective medical therapy for adrenocortical carcinoma, but its molecular mechanism of action remains poorly understood. Although mitotane is known to have mitochondrial (mt) effects, a direct link to mt dysfunction has never been established. We examined the functional consequences of mitotane exposure on proliferation, steroidogenesis, and mt respiratory chain, biogenesis and morphology, in two human adrenocortical cell lines, the steroid-secreting H295R line and the non-secreting SW13 line. Mitotane inhibited cell proliferation in a dose- and a time-dependent manner. At the concentration of 50 μM (14 mg/l), which corresponds to the threshold for therapeutic efficacy, mitotane drastically reduced cortisol and 17-hydroxyprogesterone secretions by 70%. This was accompanied by significant decreases in the expression of genes encoding mt proteins involved in steroidogenesis (STAR,CYP11B1, andCYP11B2). In both H295R and SW13 cells, 50 μM mitotane significantly inhibited (50%) the maximum velocity of the activity of the respiratory chain complex IV (cytochromecoxidase (COX)). This effect was associated with a drastic reduction in steady-state levels of the whole COX complex as revealed by blue native PAGE and reduced mRNA expression of both mtDNA-encoded COX2 (MT-CO2) and nuclear DNA-encoded COX4 (COX4I1) subunits. In contrast, the activity and expression of respiratory chain complexes II and III were unaffected by mitotane treatment. Lastly, mitotane exposure enhanced mt biogenesis (increase in mtDNA content andPGC1α(PPARGC1A) expression) and triggered fragmentation of the mt network. Altogether, our results provide first evidence that mitotane induced a mt respiratory chain defect in human adrenocortical cells.
Whole-Genome Sequences of DA and F344 Rats with Different Susceptibilities to Arthritis, Autoimmunity, Inflammation and Cancer
Authors: Guo Xiaosen , Brenner Max , Zhang Xuemei , Laragione Teresina , Tai Shuaishuai , Li Yanhong , Bu Junjie , Yin Ye , Shah Anish A , Kwan Kevin , Li Yingrui , Jun Wang , Gulko Pércio S
Published: May 2013

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease.
Ab initio based large-scale screening of hypothetical MOFs for carbon capture application
Authors: Daff Thomas D. , Woo Tom K.
Published: May 2013

Metal organic frameworks (MOFs) are porous solids that are potential high performance carbon capture materials. We have mined a hypothetical MOF database for structures that have exceptional low-pressure CO2 adsorption properties. We have applied the REPEAT method to generate accurate atomic charges that regenerate the ab initio electrostatic potential. We show that large scale screening at high accuracy is feasible for thousands of structures. We identify promising synthesis targets, like a simple combination of chrysene linker and vanadium inorganic unit, and examine in detail structural features that make better performing MOFs from those that would not be synthesisable. We find that, although screening large numbers of hypothetical structures is necessary to provide experimental targets, there are limitations to the suggestion of using the this database directly for synthesis targets and propose improvements and constraints that should be incorporated into the design of further generations of such a building-block algorithm to reach the accuracy required for high-quality CO2 adsorption simulation.