Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

BackgroundMajor histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy.Hypothesis/objectivesTo determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM.AnimalsTwenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]).MethodsImmunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed.ResultsSarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles.Conclusions and clinical importanceDeficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates

Green communication in energy renewable wireless mesh networks: routing, rate control, and power allocation

PublishedJournal Article© 2014 IEEE. The increasing demand for wireless services has led to a severe energy consumption problem with the rising of greenhouse gas emission. While the renewable energy can somehow alleviate this problem, the routing, flow rate, and power still have to be well investigated with the objective of minimizing energy consumption in multi-hop energy renewable wireless mesh networks (ER-WMNs). This paper formulates the problem of network-wide energy consumption minimization under the network throughput constraint as a mixed-integer nonlinear programming problem by jointly optimizing routing, rate control, and power allocation. Moreover, the min-max fairness model is applied to address the fairness issue because the uneven routing problem may incur the sharp reduction of network performance in multi-hop ER-WMNs. Due to the high computational complexity of the formulated mathematical programming problem, an energy-aware multi-path routing algorithm (EARA) is also proposed to deal with the joint control of routing, flow rate, and power allocation in practical multi-hop WMNs. To search the optimal routing, it applies a weighted Dijkstra's shortest path algorithm, where the weight is defined as a function of the power consumption and residual energy of a node. Extensive simulation results are presented to show the performance of the proposed schemes and the effects of energy replenishment rate and network throughput on the network lifetime

Cerebral malaria: Gamma-interferon redux

There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma (IFN-?). In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by IFN-? in the pathogenesis of this often fatal and debilitating condition. © 2014 Hunt, Ball, Hansen, Khaw, Guo, Bakmiwewa, Mitchell, Combes and Grau

Superconducting ECR ion source: From 24-28 GHz SECRAL to 45 GHz fourth generation ECR.

The development of superconducting ECR source with higher magnetic fields and higher microwave frequency is the most straight forward path to achieve higher beam intensity and higher charge state performance. SECRAL, a superconducting third generation ECR ion source, is designed for 24-28 GHz microwave frequency operation with an innovative magnet configuration of sextupole coils located outside the three solenoids. SECRAL at 24 GHz has already produced a number of record beam intensities, such as 40Ar12+ 1.4 emA, 129Xe26+ 1.1 emA, 129Xe30+ 0.36 emA, and 209Bi31+ 0.68 emA. SECRAL-II, an upgraded version of SECRAL, was built successfully in less than 3 years and has recently been commissioned at full power of a 28 GHz gyrotron and three-frequency heating (28 + 45 + 18 GHz). New record beam intensities for highly charged ion production have been achieved, such as 620 eμA 40Ar16+, 15 eμA 40Ar18+, 146 eμA 86Kr28+, 0.5 eμA 86Kr33+, 53 eμA 129Xe38+, and 17 eμA 129Xe42+. Recent beam test results at SECRAL and SECRAL II have demonstrated that the production of more intense highly charged heavy ion beams needs higher microwave power and higher frequency, as the scaling law predicted. A 45 GHz superconducting ECR ion source FECR (a first fourth generation ECR ion source) is being built at IMP. FECR will be the world's first Nb3Sn superconducting-magnet-based ECR ion source with 6.5 T axial mirror field, 3.5 T sextupole field on the plasma chamber inner wall, and 20 kW at a 45 GHz microwave coupling system. This paper will focus on SECRAL performance studies at 24-28 GHz and technical design of 45 GHz FECR, which demonstrates a technical path for highly charged ion beam production from 24 to 28 GHz SECRAL to 45 GHz FECR

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

International students and further education colleges in England: The context, policy tensions, and some aspects of practice

This chapter sets out the context of publicly funded further education colleges in England, outlining the position and development of these complex institutions within the broader educational structure. This is followed by discussion of some tensions and contradictions which arise from government policies partially driven by anxieties derived from debates surrounding levels of immigration together with recognition of the imperatives and opportunities arising from globalisation. The benefits of the internationalisation of education have been expounded whilst simultaneously enforcing visa regulations which impede the efforts of colleges to make inroads in the international student market. In particular, disparities between the treatment of the further and higher education sectors are highlighted. The paper also provides an account of practices which have emerged in a single FE college in England over a decade of working with international students following an access to HE course. The chapter indicates some of the many benefits which have been brought to FE by international students as well as the ways in which a college has developed its practices in response to their needs

Synthesis and Photoluminescence Properties of Porous Silicon Nanowire Arrays

Herein, we prepare vertical and single crystalline porous silicon nanowires (SiNWs) via a two-step metal-assisted electroless etching method. The porosity of the nanowires is restricted by etchant concentration, etching time and doping lever of the silicon wafer. The diffusion of silver ions could lead to the nucleation of silver nanoparticles on the nanowires and open new etching ways. Like porous silicon (PS), these porous nanowires also show excellent photoluminescence (PL) properties. The PL intensity increases with porosity, with an enhancement of about 100 times observed in our condition experiments. A “red-shift” of the PL peak is also found. Further studies prove that the PL spectrum should be decomposed into two elementary PL bands. The peak at 850 nm is the emission of the localized excitation in the nanoporous structure, while the 750-nm peak should be attributed to the surface-oxidized nanostructure. It could be confirmed from the Fourier transform infrared spectroscopy analyses. These porous SiNW arrays may be useful as the nanoscale optoelectronic devices

Interrogating Institutionalized Establishments: Urban-Rural Inequalities in China’s Higher Education

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Comprehensive analysis of human microRNA target networks

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) mediate posttranscriptional regulation of protein-coding genes by binding to the 3' untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation, depending on the degree of sequence complementarity. In general, a single miRNA concurrently downregulates hundreds of target mRNAs. Thus, miRNAs play a key role in fine-tuning of diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. However, it remains to be fully elucidated whether a set of miRNA target genes regulated by an individual miRNA in the whole human microRNAome generally constitute the biological network of functionally-associated molecules or simply reflect a random set of functionally-independent genes.</p> <p>Methods</p> <p>The complete set of human miRNAs was downloaded from miRBase Release 16. We explored target genes of individual miRNA by using the Diana-microT 3.0 target prediction program, and selected the genes with the miTG score ≧ 20 as the set of highly reliable targets. Then, Entrez Gene IDs of miRNA target genes were uploaded onto KeyMolnet, a tool for analyzing molecular interactions on the comprehensive knowledgebase by the neighboring network-search algorithm. The generated network, compared side by side with human canonical networks of the KeyMolnet library, composed of 430 pathways, 885 diseases, and 208 pathological events, enabled us to identify the canonical network with the most significant relevance to the extracted network.</p> <p>Results</p> <p>Among 1,223 human miRNAs examined, Diana-microT 3.0 predicted reliable targets from 273 miRNAs. Among them, KeyMolnet successfully extracted molecular networks from 232 miRNAs. The most relevant pathway is transcriptional regulation by transcription factors RB/E2F, the disease is adult T cell lymphoma/leukemia, and the pathological event is cancer.</p> <p>Conclusion</p> <p>The predicted targets derived from approximately 20% of all human miRNAs constructed biologically meaningful molecular networks, supporting the view that a set of miRNA targets regulated by a single miRNA generally constitute the biological network of functionally-associated molecules in human cells.</p