bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions
Authors: Rathinakumar Ramesh , Dutta Moumita , Zhu Ping , Johnson Welkin E. , Roux Kenneth H.
Published: November 2011

The broadly neutralizing monoclonal antibodies (MAbs) 4E10, 2F5, and Z13e1 target membrane-proximal external region (MPER) epitopes of HIV-1 gp41 in a manner that remains controversial. The requirements for initial lipid bilayer binding and/or CD4 ligation have been proposed. To further investigate these issues, we probed for binding of these MAbs to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) virions with protein A-conjugated gold (PAG) nanoparticles using negative-stain electron microscopy. We found moderate levels of PAG associated with unliganded HIV-1 and SIV virions incubated with the three MAbs. Significantly higher levels of PAG were associated with CD4-liganded HIV-1 (epitope-positive) but not SIV (epitope-negative) virions. A chimeric SIV virion displaying the HIV-1 4E10 epitope also showed significantly higher PAG association after CD4 ligation and incubation with 4E10. MAbs accumulated rapidly on CD4-liganded virions and slowly on unliganded virions, although both reached similar levels in time. Anti-MPER epitope-specific binding was stable to washout. Virions incubated with an irrelevant MAb or CD4-only (no MAb) showed negligible PAG association, as did a vesicle-rich fraction devoid of virions. Preincubation with Fab 4E10 inhibited both specific and nonspecific 4E10 IgG binding. Our data provide evidence for moderate association of anti-MPER MAbs to viral surfaces but not lipid vesicles, even in the absence of cognate epitopes. Significantly greater MAb interaction occurs in epitope-positive virions following long incubation or CD4 ligation. These findings are consistent with a two-stage binding model where these anti-MPER MAbs bind first to the viral lipid bilayer and then to the MPER epitopes following spontaneous or induced exposure.
Significant Association of Multiple Human Cytomegalovirus Genomic Loci with Glioblastoma Multiforme Samples
Authors: Ranganathan Padhma , Clark Paul A. , Kuo John S. , Salamat M. Shahriar , Kalejta Robert F.
Published: November 2011

Viruses are appreciated as etiological agents of certain human tumors, but the number of different cancer types induced or exacerbated by viral infections is unknown. Glioblastoma multiforme (GBM)/astrocytoma grade IV is a malignant and lethal brain cancer of unknown origin. Over the past decade, several studies have searched for the presence of a prominent herpesvirus, human cytomegalovirus (HCMV), in GBM samples. While some have detected HCMV DNA, RNA, and proteins in GBM tissues, others have not. Therefore, any purported association of HCMV with GBM remains controversial. In most of the previous studies, only one or a select few viral targets were analyzed. Thus, it remains unclear the extent to which the entire viral genome was present when detected. Here we report the results of a survey of GBM specimens for as many as 20 different regions of the HCMV genome. Our findings indicate that multiple HCMV loci are statistically more likely to be found in GBM samples than in other brain tumors or epileptic brain specimens and that the viral genome was more often detected in frozen samples than in paraffin-embedded archival tissue samples. Finally, our experimental results indicate that cellular genomes substantially outnumber viral genomes in HCMV-positive GBM specimens, likely indicating that only a minority of the cells found in such samples harbor viral DNA. These data argue for the association of HCMV with GBM, defining the virus as oncoaccessory. Furthermore, they imply that, were HCMV to enhance the growth or survival of a tumor (i.e., if it is oncomodulatory), it would likely do so through mechanisms distinct from classic tumor viruses that express transforming viral oncoproteins in the overwhelming majority of tumor cells.
Naturally Occurring Fragments from Two Distinct Regions of the Prostatic Acid Phosphatase Form Amyloidogenic Enhancers of HIV Infection
Authors: Arnold Franziska , Schnell Jacqueline , Zirafi Onofrio , Stürzel Christina , Meier Christoph , Weil Tanja , Ständker Ludger , Forssmann Wolf-Georg , Roan Nadia R. , Greene Warner C. , Kirchhoff Frank , Münch Jan
Published: November 2011

Semen is the major vector for HIV-1 transmission. We previously isolated C-proximal fragments of the prostatic acid phosphatase (PAP) from semen which formed amyloid fibrils that potently enhanced HIV infection. Here, we used the same methodology and identified another amyloidogenic peptide. Surprisingly, this peptide is derived from an N-proximal fragment of PAP (PAP85-120) and forms, similar to the C-proximal fragments, positively charged fibrillar structures that increase virion attachment to cells. Our results provide a first example for amyloid formation by fragments of distinct regions of the same precursor and further emphasize the possible importance of amyloidogenic peptides in HIV transmission.
Genetic Informational RNA Is Not Required for Recombinant Prion Infectivity
Authors: Wang Fei , Zhang Zhihong , Wang Xinhe , Li Jiali , Zha Liang , Yuan Chong-Gang , Weissmann Charles , Ma Jiyan
Published: November 2011

Whether a genetic informational nucleic acid is required for the infectivity of transmissible spongiform encephalopathies is central to the debate about the infectious agent. Here we report that an infectious prion formed with bacterially expressed recombinant prion protein plus synthetic polyriboadenylic acid and synthetic phospholipid 1-palmitoyl-2-oleoylphosphatidylglycerol is competent to infect cultured cells and cause prion disease in wild-type mice. Our results show that genetic informational RNA is not required for recombinant prion infectivity.
Innate Sensing of Foamy Viruses by Human Hematopoietic Cells
Authors: Rua Réjane , Lepelley Alice , Gessain Antoine , Schwartz Olivier
Published: November 2011

Foamy viruses (FV) are nonpathogenic retroviruses that have cospeciated with primates for millions of years. FV can be transmitted through severe bites from monkeys to humans. Viral loads remain generally low in infected humans, and no secondary transmission has been reported. Very little is known about the ability of FV to trigger an innate immune response in human cells. A few previous reports suggested that FV do not induce type I interferon (IFN) in nonhematopoietic cells. Here, we examined how human hematopoietic cells sense FV particles and FV-infected cells. We show that peripheral blood mononuclear cells (PBMCs), plasmacytoid dendritic cells (pDCs), and the pDC-like cell line Gen2.2 detect FV, produce high levels of type I IFN, and express the IFN-stimulated gene MxA. Fewer than 20 FV-infected cells are sufficient to trigger an IFN response. Both prototypic and primary viruses stimulated IFN release. Donor cells expressing a replication-defective virus, carrying a mutated reverse transcriptase, induced IFN production by target cells as potently as wild-type virus. In contrast, an FV strain with
env
deleted, which does not produce viral particles, was inactive. IFN production was blocked by an inhibitor of endosomal acidification (bafilomycin A1) and by an endosomal Toll-like receptor (TLR) antagonist (A151). Silencing experiments in Gen2.2 further demonstrated that TLR7 is involved in FV recognition. Therefore, FV are potent inducers of type I IFN by pDCs and by PBMCs. This previously underestimated activation of the innate immune response may be involved in the control of viral replication in humans.
Dynamic Chromatin Environment of Key Lytic Cycle Regulatory Regions of the Epstein-Barr Virus Genome
Authors: Ramasubramanyan Sharada , Osborn Kay , Flower Kirsty , Sinclair Alison J.
Published: November 2011

The ability of Epstein-Barr virus (EBV) to establish latency allows it to evade the immune system and to persist for the lifetime of its host; one distinguishing characteristic is the lack of transcription of the majority of viral genes. Entry into the lytic cycle is coordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, and EB1), and downstream effectors, while viral genome replication requires the concerted action of Zta and six other viral proteins at the origins of lytic replication. We explored the chromatin context at key EBV lytic cycle promoters (BZLF1,BRLF1,BMRF1, andBALF5) and the origins of lytic replication during latency and lytic replication. We show that a repressive heterochromatin-like environment (trimethylation of histone H3 at lysine 9 [H3K9me3] and lysine 27 [H3K27me3]), which blocks the interaction of some transcription factors with DNA, encompasses the key early lytic regulatory regions. Epigenetic silencing of the EBV genome is also imposed by DNA methylation during latency. The chromatin environment changes during the lytic cycle with activation of histones H3, H4, and H2AX occurring at both the origins of replication and at the key lytic regulatory elements. We propose that Zta is able to reverse the effects of latency-associated repressive chromatin at EBV early lytic promoters by interacting with Zta response elements within the H3K9me3-associated chromatin and demonstrate that these interactions occurin vivo. Since the interaction of Zta with DNA is not inhibited by DNA methylation, it is clear that Zta uses two routes to overcome epigenetic silencing of its genome.
Marked Endotheliotropism of Highly Pathogenic Avian Influenza Virus H5N1 following Intestinal Inoculation in Cats
Authors: Reperant Leslie A. , van de Bildt Marco W. G. , van Amerongen Geert , Leijten Lonneke M. E. , Watson Simon , Palser Anne , Kellam Paul , Eissens Anko C. , Frijlink Hendrik W. , Osterhaus Albert D. M. E. , Kuiken Thijs
Published: November 2011

Highly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine; this is unusual since influenza viruses typically infect mammals via the respiratory tract. The dissemination of HPAIV H5N1 following intestinal entry and associated pathogenesis are largely unknown. To assess the route of spread of HPAIV H5N1 to other organs and to determine its associated pathogenesis, we inoculated infected chicken liver homogenate directly into the intestine of cats by use of enteric-coated capsules. Intestinal inoculation of HPAIV H5N1 resulted in fatal systemic disease. The spread of HPAIV H5N1 from the lumen of the intestine to other organs took place via the blood and lymphatic vascular systems but not via neuronal transmission. Remarkably, the systemic spread of the virus via the vascular system was associated with massive infection of endothelial and lymphendothelial cells, resulting in widespread hemorrhages. This is unique for influenza in mammals and resembles the pathogenesis of HPAIV infection in terrestrial poultry. It contrasts with the pathogenesis of systemic disease from the same virus following entry via the respiratory tract, where lesions are characterized mainly by necrosis and inflammation and are associated with the presence of influenza virus antigen in parenchymal, not endothelial cells. The marked endotheliotropism of the virus following intestinal inoculation indicates that the pathogenesis of systemic influenza virus infection in mammals may differ according to the portal of entry.
Melanoma Differentiation-Associated Gene 5 Is Critical for Protection against Theiler's Virus-Induced Demyelinating Disease
Authors: Jin Young-Hee , Kim Seung Jae , So Eui Young , Meng Liping , Colonna Marco , Kim Byung S.
Published: November 2011

Infection of dendritic and glial cells with Theiler's murine encephalomyelitis virus (TMEV) induces various cytokines via Toll-like receptor- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways. However, the involvement and role of MDA5 in cytokine gene activation and the pathogenesis of TMEV-induced demyelinating disease are largely unknown. In this study, we demonstrate that MDA5 plays a critical role in the production of TMEV-induced alpha interferon (IFN-α) during early viral infection and in protection against the development of virus-induced demyelinating disease. Our results indicate that MDA5-deficient 129SvJ mice display significantly higher viral loads and apparent demyelinating lesions in the central nerve system (CNS) accompanied by clinical symptoms compared with wild-type 129SvJ mice. During acute viral infection, MDA5-deficient mice produced elevated levels of chemokines, consistent with increased cellular infiltration, but reduced levels of IFN-α, known to control T cell responses and cellular infiltration. Additional studies with isolated CNS glial cells from these mice suggest that cells from MDA5-deficient mice are severely compromised in the production of IFN-α upon viral infection, which results in increased cellular infiltration and viral loads in the CNS. Despite inadequate stimulation, the overall T cell responses to the viral determinants were significantly elevated in MDA5-deficient mice, reflecting the increased cellular infiltration. Therefore, the lack of MDA5-mediated IFN-α production may facilitate a massive viral load and elevated cellular infiltration in the CNS during early viral infection, leading to the pathogenesis of demyelinating disease.
A systematic review of patient-reported outcome measures used to assess Achilles tendon rupture management: What's being used and should we be using it?
Authors: Kearney Rebecca S , Achten Juul , Lamb Sarah E , Plant Caroline , Costa Matthew L
Published: November 2011

Background

Currently, there is no consensus regarding the optimal management for patients following an Achilles tendon rupture. To allow comparisons between different treatments, a universally accepted outcome measure is required. However, there are currently a range of these reported within the literature.

Objective

To recommend the most suitable patient-reported outcome measure for the assessment of patients following an Achilles tendon rupture, based on a systematic review of first what is currently used and second evidence of validity.

Methods

The electronic databases MEDLINE, EMBASE and AMED were searched up to September 2010. Predefined inclusion and exclusion criteria were applied to identify what outcome measures are reported in the literature. Aspects of validity were defined and a checklist used to determine which aspects have been evaluated.

Results

Twenty-one outcome measures in 50 research papers were identified. The most commonly used was the American Orthopaedic Foot and Ankle Society hind-foot score. Of the 21 outcome measures, only 4 cited independent validation data. Of these four, only the ‘Achilles tendon Total Rupture Score’ reported evidence to support multiple facets of validity, as defined by a predetermined criteria checklist.

Conclusions

The Achilles tendon Total Rupture Score was identified as the only outcome measure which has demonstrated multiple facets of validity for use in this patient group. However, even this tool has limitations. Researchers should be aware of the limitations of the available outcome measurement tools and check on their validity before use in clinical research.
Enhancing clinical learning in the workplace: a qualitative study
Authors: Magnier K. , Wang R. , Dale V. H. M. , Murphy R. , Hammond R. A. , Mossop L. , Freeman S. L. , Anderson C. , Pead M. J.
Published: November 2011

Workplace learning (WPL) is seen as an essential component of clinical veterinary education by the veterinary profession. This study sought to understand this type of learning experience more deeply. This was done utilising observations of students on intramural rotations (IMR) and interviews with students and clinical staff. WPL was seen as an opportunity for students to apply knowledge and develop clinical and professional skills in what is generally regarded as a safe, authentic environment. Clinical staff had clear ideas of what they expected from students in terms of interest, engagement, professionalism, and active participation, where this was appropriate. In contrast, students often did not know what to expect and sometimes felt under‐prepared when entering the workplace, particularly in a new species area. With the support of staff acting as mentors, students learned to identify gaps in their knowledge and skills, which could then be addressed during specific IMR work placements. Findings such as these illustrate both the complexities of WPL and the diversity of different workplace settings encountered by the students.
Retinoids and retinoid-metabolic gene expression in mouse adipose tissues
Authors: Sima Aurelia , Manolescu Daniel-Constantin , Bhat Pangala
Published: November 2011

Vitamin A and its analogs (retinoids) regulate adipocyte differentiation. Recent investigations have demonstrated a relationship among retinoids, retinoid-binding-protein 4 (RBP4) synthesized in adipose tissues, and insulin-resistance status. In this study, we measured retinoid levels and analyzed the expression of retinoid homeostatic genes associated with retinol uptake, esterification, oxidation, and catabolism in subcutaneous (Sc) and visceral (Vis) mouse fat tissues. Both Sc and Vis depots were found to contain similar levels of all-trans retinol. A metabolite of retinol with characteristic ultraviolet absorption maxima for 9-cis retinol was observed in these 2 adipose depots, and its level was 2-fold higher in Sc than in Vis tissues. Vis adipose tissue expressed significantly higher levels of RBP4, CRBP1 (intracellular retinol-binding protein 1), RDH10 (retinol dehydrogenase), as well as CYP26A1 and B1 (retinoic acid (RA) hydroxylases). No differences in STRA6 (RBP4 receptor), LRAT (retinol esterification), CRABP1 and 2 (intracellular RA-binding proteins), and RALDH1 (retinal dehydrogenase) mRNA expressions were discerned in both fat depots. RALDH1 was identified as the only RALDH expressed in both Sc and Vis adipose tissues. These results indicate that Vis is more actively involved in retinoid metabolism than Sc adipose tissue.
Calculating anisotropic physical properties from texture data using the MTEX open-source package
Authors: Mainprice David , Hielscher Ralf , Schaeben Helmut
Published: November 2011

This paper presents the background for the calculation of physical properties of an aggregate from constituent crystal properties and the texture of the aggregate in a coherent manner. Emphasis is placed on the important tensor properties of 2nd and 4th rank with applications in rock deformation, structural geology, geodynamics and geophysics. We cover texture information that comes from pole figure diffraction and single orientation measurements (electron backscattered diffraction or EBSD, electron channelling pattern, Laue pattern, optical microscope universal-stage). In particular, we provide explicit formulae for the calculation of the averaged tensor from individual orientations or from an orientation distribution function (ODF). For the latter we consider numerical integration and an approach based on the expansion into spherical harmonics. This paper also serves as a reference paper for the mathematical tensor capabilities of the texture analysis software MTEX, which is a comprehensive, freely available MatLab toolbox that covers a wide range of problems in quantitative texture analysis, for example, ODF modelling, pole figure to ODF inversion, EBSD data analysis and grain detection. MTEX offers a programming interface which allows the processing of involved research problems as well as highly customizable visualization capabilities; MTEX is therefore ideal for presentations, publications and teaching demonstrations.
Posttranslational modifications control FoxO3 activity during denervation
Authors: Bertaggia Enrico , Coletto Luisa , Sandri Marco
Published: November 2011

Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes, and renal failure, often aggravating pathological progression. The atrophy process is controlled by a transcriptional program that regulates the expression of a subset of genes named atrophy-related genes. The Forkhead Box O (FoxO) family of transcription factors plays a critical role in the atrophy program being sufficient and necessary for the expression of rate-limiting enzymes of ubiquitin-proteasome and autophagy-lysosome systems. Therefore, a fine regulation of FoxOs is critical to avoid excessive proteolysis and cachexia. FoxO activity can be modulated by different mechanisms including phosphorylation, acetylation, ubiquitination, and glycosylation. Here we show that FoxO3 is progressively acetylated during denervation and concomitantly atrogin-1, the bona fide FoxO3 target, is downregulated. FoxO3 interacts with the histone acetyl-transferase p300, and its acetylation causes cytosolic relocalization and degradation. Several lysine residues of FoxOs are known to be acetylated. To identify which lysines are critical for FoxO3 activity we have generated different FoxO3 mutants that either mimic or prevent lysine acetylation. We found that FoxO3 mutants that mimic acetylation show a decrease of transcriptional activity and cytosolic localization. Importantly, acetylation induces FoxO3 degradation via proteasome system. Between the different lysines, lysine 262 is critical for translocation of FoxO3. In conclusion, we provide evidence that FoxO3 activity is negatively modulated by acetylation and ubiquitination in a time-dependent and coordinated manner. This fine-tuning mechanism of FoxO3 regulation may be important to prevent excessive muscle loss and can be used as a therapeutic approach to counteract muscle wasting.
Antiplasmodial Properties and Bioassay-Guided Fractionation of Ethyl Acetate Extracts fromCarica papayaLeaves
Authors: Melariri Paula , Campbell William , Etusim Paschal , Smith Peter
Published: November 2011

We investigated the antiplasmodial properties of crude extracts fromCarica papayaleaves to trace the activity through bioassay-guided fractionation. The greatest antiplasmodial activity was observed in the ethyl acetate crude extract.C. papayashowed a high selectivity forP. falciparumagainst CHO cells with a selectivity index of 249.25 and 185.37 in the chloroquine-sensitive D10 and chloroquine-resistant DD2 strains, respectively.Carica papayaethyl acetate extract was subjected to bioassay-guided fractionation to ascertain the most active fraction, which was purified and identified using high-pressure liquid chromatography (HPLC) and GC-MS (Gas chromatography-Mass spectrometry) methods. Linoleic and linolenic acids identified from the ethyl acetate fraction showed IC50of 6.88 μg/ml and 3.58 μg/ml, respectively. The study demonstrated greater antiplasmodial activity of the crude ethyl acetate extract ofCarica papayaleaves with an IC50of2.96±0.14 μg/ml when compared to the activity of the fractions and isolated compounds.
Conversion of Tumors into Autologous Vaccines by Intratumoral Injection ofα-Gal Glycolipids that Induce Anti-Gal/α-Gal Epitope Interaction
Authors: Galili Uri
Published: November 2011

Anti-Gal is the most abundant antibody in humans, constituting 1% of immunoglobulins. Anti-Gal binds specificallyα-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). Immunogenicity of autologous tumor associated antigens (TAA) is greatly increased by manipulating tumor cells to expressα-gal epitopes and bind anti-Gal. Glycolipids withαgal epitopes (α-gal glycolipids) injected into tumors insert into the tumor cell membrane. Anti-Gal binding to the multiple α-gal epitopesde novopresented on the tumor cells results in targeting of these cells to APC via the interaction between the Fc portion of the bound anti-Gal and Fcγ; receptors on APC. The APC process and present immunogenic TAA peptides and thus, effectively activate tumor specific CD4+ helper T cells and CD8+ cytotoxic T cells which destroy tumor cells in micrometastases. The induced immune response is potent enough to overcome immunosuppression by Treg cells. A phase I clinical trial indicated thatα-gal glycolipid treatment has no adverse effects. In addition to achieving destruction of micrometastases in cancer patients with advance disease,α-gal glycolipid treatment may be effective as neo-adjuvant immunotherapy. Injection ofα-gal glycolipids into primary tumors few weeks prior to resection can induce a protective immune response capable of destroying micrometastases expressing autologous TAA, long after primary tumor resection.
An Unusual Case of Spontaneous Bladder Perforation with Associated Autodialysis of the Ensuing Urinary Ascites
Authors: Aber A. , Hyder S. A. , Arumuham V.
Published: November 2011

Spontaneous rupture of the urinary bladder is a rare occurrence, and when encountered it is a diagnostic challenge. We present an unusual case of urinary bladder rupture in a patient with severe cerebral palsy who initially presented with localized abdominal pain and during admission developed generalized peritonitis caused by bladder rupture. In this case, the patient had none of risk factors associated with urinary bladder.
The Bioactivated Interfacial Behavior of the Fluoridated Hydroxyapatite-Coated Mg-Zn Alloy in Cell Culture Environments
Authors: Li Jianan , Cao Lei , Song Yang , Zhang Shaoxiang , Zhao Changli , Zhang Fan , Zhang Xiaonong
Published: November 2011

A partially fluorine substituted hydroxyapatite- (FHA-) coated Mg-Zn alloy was prepared to investigate the interfacial behavior of degradable Mg-based biomaterials with degradable bioactive coatings in a cell culture environment. Peaks from the results of X-ray diffraction (XRD) were characterized and compared before and after cell culture. It was found that Ca-P, including poorly crystalline ion-substituted Ca-deficient HA (CDHA), was formed in greater amounts on the interface of coated samples compared with the uncoated ones. A thermodynamic mechanism for Ca-P formation on biodegradable Mg alloys in a cell culture environment is proposed. Combined with improved cell calcification, the-FHA coated Mg alloys have the ability to promote CDHA formation, as expected thermodynamically. It is suggested that the specific cell culture environment and the bone-like FHA coatings together facilitate the observed behavior. Moreover, cell culture environment probably increased the biomineralization to a detectable level by affecting the kinetics of apatite formation.
Contractive Mapping in Generalized, Ordered Metric Spaces with Application in Integral Equations
Authors: Gholizadeh L. , Saadati R. , Shatanawi W. , Vaezpour S. M.
Published: November 2011

We consider the concept of Ω‐distance on a complete, partially ordered G‐metric space and prove some fixed point theorems. Then, we present some applications in integral equations of our obtained results.
Central and Peripheral GABAAReceptor Regulation of the Heart Rate Depends on the Conscious State of the Animal
Authors: Bentzen Bo Hjorth , Grunnet Morten
Published: November 2011

Intuitively one might expect that activation of GABAergic inhibitory neurons results in bradycardia. In conscious animals the opposite effect is however observed. GABAergic neurons in nucleus ambiguus hold the ability to control the activity of the parasympathetic vagus nerve that innervates the heart. Upon GABA activation the vagus nerve will be inhibited leaving less parasympathetic impact on the heart. The picture is however blurred in the presence of anaesthesia where both the concentration and type of anaesthetics can result in different effects on the cardiovascular system. This paper reviews cardiovascular outcomes of GABA activation and includes own experiments on anaesthetized animals and isolated hearts. In conclusion, the impact of changes in GABAergic input is very difficult to predict in these settings, emphasizing the need for experiments performed in conscious animals when aiming at determining the cardiovascular effects of compounds acting on GABAergic neurons.
An Initial Investigation of the Generalization of a School-Based Social Competence Intervention for Youth with High-Functioning Autism
Authors: Schmidt Carla , Stichter Janine P. , Lierheimer Kristin , McGhee Stephanie , O'Connor Karen V.
Published: November 2011

This study evaluated the impact of generalization of the Social Competence Intervention-Adolescent (SCI-A) curriculum in a school setting for individuals with high-functioning autism or Asperger's Syndrome (). This study examined to what degree the generalization of the SCI-A curriculum could be measured when delivered in a school setting. Across the six participants preliminary results suggest improvement on teacher reports of social skills and executive functioning. Some improvements were also evident in direct measures of facial-expression recognition. Data collected in the nonintervention settings indicated that some generalization of social interaction skills may have occurred for all six participants. Future research directions are discussed.
Phase 4 Pharmacovigilance Trial of Paromomycin Injection for the Treatment of Visceral Leishmaniasis in India
Authors: Sinha Prabhat K. , Jha T. K. , Thakur Chandreshwar P. , Nath Devendra , Mukherjee Supriyo , Aditya Amrendra Kumar , Sundar Shyam
Published: November 2011

Background. A phase 3 study demonstrated the safety and efficacy of paromomycin (paromomycin IM injection) for treatment of VL in an inpatient setting.Methods. This phase 4 study was conducted to assess the safety and efficacy of paromomycin in children and adults in an outpatient setting in Bihar, India.Results. This study enrolled 506 adult and pediatric patients. Of the 494 patients in the intent-to-treat (ITT) population, 98% received a full course of treatment. The overall study completion rate was 94% (462/494) for the ITT population and 96% (461/479) for the efficacy-evaluable (EE) population. Initial clinical cure was 99.6%, and final clinical cure 6 months after treatment was 94.2%. Grade 3 or 4 adverse events occurred in 5% of patients; events with a frequency of ≥1% were increases in alanine aminotransferase and aspartate aminotransferase.Conclusions. This study confirms the safety and efficacy of paromomycin to treat VL in an outpatient setting.
Diabetic Peripheral Microvascular Complications: Relationship to Cognitive Function
Authors: Ba-Tin Lorraine , Strike Paul , Tabet Naji
Published: November 2011

Peripheral microvascular complications in diabetes are associated with concurrent cerebrovascular disease. As detailed cognitive assessment is not routinely carried out among diabetic patients, the aim was to establish whether the presence of clinical “peripheral” microvascular disease can identify a subgroup of patients with early evidence of cognitive impairment. Detailed psychometric assessment was performed in 23 diabetic patients with no microvascular complications (Group D), 27 diabetic patients with at least one microvascular complication: retinopathy, neuropathy, and/or nephropathy (Group DC), and 25 healthy controls (Group H). Groups D and DC participants had significantly lower scores on reaction time (P=0.003and 0.0001, resp.) compared to controls. Similarly, groups D and DC participants had significantly lower scores on rapid processing of visual information (P=0.034and 0.001, resp.) compared to controls. In contrast, there was no significant difference between Groups D and DC on any of the cognitive areas examined. The results show that diabetes, in general, is associated with cognitive dysfunction, but the additional presence of peripheral microvascular disease does not add to cognitive decline. The study, however, indirectly supports the notion that the aetiology of cognitive impairment in diabetes may not be restricted to vascular pathology.
A New Method for Detecting the Time‐Varying Nonlinear Damping in Nonlinear Oscillation Systems: Nonparametric Identification
Authors: Jang T. S. , Baek Hyoungsu , Kim M. C. , Moon B. Y.
Published: November 2011

This paper presents an original method that can be used for identifying time‐varying nonlinear damping characteristics of a nonlinear oscillation system. The method developed involves the nonparametric identification, in which only the system responses, namely, displacement and velocity need to be known for the identification. However, the method is concerned with a Volterra‐type integral equation of the first kind, which leads to an instability of numerical solutions. That is, the solutions identified lack stability properties. In order to overcome the difficulty, a stabilization technique is applied to the identification process. A numerical example comprising a highly nonlinear system is examined to demonstrate the workability of the proposed method for the time‐varying damping identification.
Successful Renal Replacement Therapy for a Patient with Severe Hemophilia after Surgical Treatment of Intracranial Hemorrhage and Hydrocephalus
Authors: Kato Noriko , Chin-Kanasaki Masami , Tanaka Yuki , Yasuda Mako , Yokomaku Yukiyo , Sakaguchi Masayoshi , Isshiki Keiji , Araki Shin-ichi , Ohta Shigeru , Uzu Takashi
Published: November 2011

A 21-year-old Japanese male with severe hemophilia A was developed end-stage renal failure. He was placed on combination therapy with peritoneal dialysis (PD) and hemodialysis (HD). Eight months later, he developed a hypertensive cerebral hemorrhage. After emergency surgery, he was managed with PD without HD to avoid cerebral edema. One month later, his renal replacement therapy was switched to HD (three times a week) from PD, since a ventriculoperitoneal shunt catheter was placed to treat his hydrocephalus. HD could be performed safety without anticoagulant agents on condition that factor VIII is given after every HD.
Parametric Evaluations of the Rogers‐Ramanujan Continued Fraction
Authors: Bagis Nikos
Published: November 2011

In this paper with the help of the inverse function of the singular moduli we evaluate the Rogers‐Ranmanujan continued fraction and its first derivative.
Leiomyosarcoma of Bone: A Case Report
Authors: Frings Andreas , Leithner Andreas , Liegl-Atzwanger Bernadette
Published: November 2011

The aim of this paper is to present clinicopathologic features and immunohistochemical findings of a primary leiomyosarcoma of bone occurring in the proximal femur of a 46-year-old Caucasian male patient. Each case report on this exceedingly rare entity contributes to the notion of this disease.
Dietary Supplementation with Omega-3-PUFA-Rich Fish Oil Reduces Signs of Food Allergy in Ovalbumin-Sensitized Mice
Authors: de Matos Olívia Gonçalves , Amaral Sylvia Stella , Pereira da Silva Pedro Elias Marques , Perez Denise Alves , Alvarenga Débora Moreira , Ferreira Adaliene Versiani Matos , Alvarez-Leite Jacqueline , Menezes Gustavo Batista , Cara Denise Carmona
Published: November 2011

We investigated the effect of dietary supplementation with n-3 PUFA (fish oil source) in an experimental model of food allergy. Mice were sensitized (allergic group) or not (nonallergic group) with OVA and were fed with OVA diet to induce allergy signals. Mice were fed with regular diet in which 7% of lipid content was provided by soybean (5% of n-3 PUFA) or fish (25% of n-3 PUFA) oil. Allergic group mice had increased serum levels of antiovalbumin IgE and IgG1 and changes in small intestine, characterized by an increased edema, number of rolling leukocytes in microcirculation, eosinophil infiltration, mucus production, and Paneth cell degranulation, in comparison to non-allergic group. All these inflammatory parameters were reduced in mice fed high-n-3-PUFA diet. Our data together suggest that diet supplementation with n-3 PUFA from fish oil may consist of a valid adjuvant in food allergy treatment.
The Feasibility of Reducing and Measuring Sedentary Time among Overweight, Non-Exercising Office Workers
Authors: Kozey-Keadle Sarah , Libertine Amanda , Staudenmayer John , Freedson Patty
Published: November 2011

This study examined the feasibility of reducing free-living sedentary time (ST) and the convergent validity of various tools to measure ST. Twenty overweight/obese participants wore the activPAL (AP) (criterion measure) and ActiGraph (AG; 100 and 150 count/minute cut-points) for a 7-day baseline period. Next, they received a simple intervention targeting free-living ST reductions (7-day intervention period). ST was measured using two questionnaires following each period. ST significantly decreased from 67% of wear time (baseline period) to 62.7% of wear time (intervention period) according to AP (n= 14,P<0.01). No other measurement tool detected a reduction in ST. The AG measures were more accurate (lower bias) and more precise (smaller confidence intervals) than the questionnaires. Participants reduced ST by ~5%, which is equivalent to a 48_min reduction over a 16-hour waking day. These data describe ST measurement properties from wearable monitors and self-report tools to inform sample-size estimates for future ST interventions.
Juvenile Angiofibroma: Evolution of Management
Authors: Nicolai Piero , Schreiber Alberto , Bolzoni Villaret Andrea
Published: November 2011

Juvenile angiofibroma is a rare benign lesion originating from the pterygopalatine fossa with distinctive epidemiologic features and growth patterns. The typical patient is an adolescent male with a clinical history of recurrent epistaxis and nasal obstruction. Although the use of nonsurgical therapies is described in the literature, surgery is currently considered the ideal treatment for juvenile angiofibroma. Refinement in preoperative embolization has provided significant reduction of complications and intraoperative bleeding with minimal risk of residual disease. During the last decade, an endoscopic technique has been extensively adopted as a valid alternative to external approaches in the management of small-intermediate size juvenile angiofibromas. Herein, we review the evolution in the management of juvenile angiofibroma with particular reference to recent advances in diagnosis and treatment.
The Prevalence of Fibromyalgia in Other Chronic Pain Conditions
Authors: Yunus Muhammad B.
Published: November 2011

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.
MRI Texture Analysis in Multiple Sclerosis
Authors: Zhang Yunyan
Published: November 2011

Multiple sclerosis (MS) is a complicated disease characterized by heterogeneous pathology that varies across individuals. Accurate identification and quantification of pathological changes may facilitate a better understanding of disease pathogenesis and progression and help identify novel therapies for MS patients. Texture analysis evaluates interpixel relationships that generate characteristic organizational patterns in an image, many of which are beyond the ability of visual perception. Given its promise detecting subtle structural alterations texture analysis may be an attractive means to evaluate disease activity and evolution. It may also become a new tool to assess therapeutic efficacy if technique issues are resolved and pathological correlates are further confirmed. This paper describes the concept, strategies, and considerations of MRI texture analysis; summarizes applications of texture analysis in MS as a measure of tissue integrity and its clinical relevance; then discusses potentially future directions of texture analysis in MS.
Diversity of Human Leukemia Xenograft Mouse Models: Implications for Disease Biology
Authors: Meyer Lüder Hinrich , Debatin Klaus-Michael
Published: November 2011

Over the past decade, xenografting human leukemia cells into mice with different levels of immunodeficiency, with or without preconditioning, has provided an important tool to study various aspects of leukemia biology and to identify distinct clinical risk groups for evaluation of novel therapeutic strategies, as well as the possibility of amplifying human leukemia cells in vivo. Interestingly, these models using human acute lymphoblastic leukemia and acute myeloid leukemia cells as xenografts recapitulate many clinical features of the disease. Similar to the human environment (for example, in the bone marrow), transplanted leukemia cells in the murine setting are exposed to both favorable and unfavorable conditions for engraftment that may exert a distinct pressure for selection of subclones. Thus, results obtained in these models may vary depending on the experimental setup. The impact of in vivo growth of human leukemia cells on the background of a more or less hostile murine environment for leukemia biology and the course of the disease in patients are discussed in the context of the diversity of xenograft models. Cancer Res; 71(23); 7141–4. ©2011 AACR.
Anti-EGFR Antibody Cetuximab Enhances the Cytolytic Activity of Natural Killer Cells toward Osteosarcoma
Authors: Pahl Jens H.W. , Ruslan S. Eriaty N. , Buddingh Emilie P. , Santos Susy J. , Szuhai Karoly , Serra Massimo , Gelderblom Hans , Hogendoorn Pancras C.W. , Egeler R. Maarten , Schilham Marco W. , Lankester Arjan C.
Published: November 2011

Purpose: Osteosarcoma and Ewing's sarcoma are the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease have a poor prognosis, illustrating the need for alternative therapies. Sarcoma cells are susceptible to the cytolytic activity of resting natural killer (NK) cells which can be improved by interleukin (IL)-15 stimulation. In this study, we explored whether the cytolytic function of resting NK cells can be augmented and specifically directed toward sarcoma cells by antibody-dependent cellular cytotoxicity (ADCC).

Experimental Design: Epidermal growth factor receptor (EGFR) expression was examined on osteosarcoma and Ewing's sarcoma cell lines by flow cytometry and in osteosarcoma biopsy and resection specimens by immunohistochemistry. Cetuximab-mediated ADCC by NK cells from osteosarcoma patients and healthy controls was measured with 4-hour 51Cr release assays.

Results: EGFR surface expression was shown on chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cells (12/12), most primary osteosarcoma cultures (4/5), and few Ewing's sarcoma cell lines (2/7). In the presence of cetuximab, the cytolytic activity of resting NK cells against all EGFR-expressing sarcoma cells was substantially increased and comparable with that of IL-15–activated NK cells. Surface EGFR expression on primary osteosarcoma cultures correlated with EGFR expression in the original tumor. The cytolytic activity of osteosarcoma patient-derived NK cells against autologous tumor cells was as efficient as that of NK cells from healthy donors.

Conclusion: Our data show that the cytolytic potential of resting NK cells can be potentiated and directed toward osteosarcoma cells with cetuximab. Therefore, cetuximab-mediated immunotherapy may be considered a novel treatment modality in the management of advanced osteosarcoma. Clin Cancer Res; 18(2); 432–41. ©2011 AACR.
Colchicine Reduces Postoperative Atrial Fibrillation
Authors: Imazio Massimo , Brucato Antonio , Ferrazzi Paolo , Rovere Maria Elena , Gandino Anna , Cemin Roberto , Ferrua Stefania , Belli Riccardo , Maestroni Silvia , Simon Caterina , Zingarelli Edoardo , Barosi Alberto , Sansone Fabrizio , Patrini Davide , Vitali Ettore , Trinchero Rita , Spodick David H. , Adler Yehuda ,   for the COPPS Investigators
Published: November 2011

Background—

Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery.

Methods and Results—

The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively;
P
=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days;
P
=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days;
P
=0.009). Side effects were similar in the study groups.

Conclusion—

Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
.
Unique identifier: NCT00128427.
Ability Sorting and the Importance of College Quality to Student Achievement: Evidence from Community Colleges
Authors: Stange Kevin
Published: November 2011

This article examines the effect of institutional quality on the educational attainment of community college students, a large group that has been mostly overlooked in previous work. The effect of institutional quality is generally difficult to separate from that of student ability because more capable students usually sort into better colleges. A detailed analysis of student sorting reveals this not to be the case among community college students, for whom college quality is effectively determined by factors other than their aptitude. This facilitates identification of school quality effects. I find that community college quality (as measured by instructional expenditure per student and several other measures) has no impact on community college students' educational attainment. States and colleges should seek to identify other factors that may be more influential.
Algorithms as Scores: Coding Live Music
Authors: Magnusson Thor
Published: November 2011

The author discusses live coding as a new path in the evolution of the musical score. Live-coding practice accentuates the score, and whilst it is the perfect vehicle for the performance of algorithmic music it also transforms the compositional process itself into a live event. As a continuation of 20th-century artistic developments of the musical score, live-coding systems often embrace graphical elements and language syntaxes foreign to standard programming languages. The author presents live coding as a highly technologized artistic practice, shedding light on how non-linearity, play and generativity will become prominent in future creative media productions.
Social Composition: Musical Data Systems for Expressive Mobile Music
Authors: Hamilton Robert , Smith Jeffrey , Wang Ge
Published: November 2011

This article explores the role of symbolic score data in the authors' mobile music-making applications, as well as the social sharing and community-based content creation workflows currently in use on their on-line musical network. Web-based notation systems are discussed alongside in-app visual scoring methodologies for the display of pitch, timing and duration data for instrumental and vocal performance. User-generated content and community-driven ecosystems are considered alongside the role of cloud-based services for audio rendering and streaming of performance data.