Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility

Objectives: To investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility. Background: Increased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias. Methods: Following arrhythmic characterisation of the rat 4-week post-MI model (n=24), a further 27 Sprague-Dawley rats were randomised to receive rotigaptide to enhance GJ coupling (n=13) or saline control (n=14) by osmotic minipump immediately prior to, and for the first 7 days following surgical MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry. Results: Despite no detectable difference in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (Inducibility score: rotigaptide 2.40.8, control 5.00.6, p=0.02) and less heterogeneous IBZ scarring (standard deviation of IBZ Complexity Score: rotigaptide 1.10.1, control 1.40.1, p=0.04), associated with an improvement in IBZ conduction velocity (rotigaptide 43.13.4 cm/s, control 34.82.0 cm/s, p=0.04). Conclusions: Enhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches

Investigating five key predictive text entry with combined distance and keystroke modelling

This paper investigates text entry on mobile devices using only five-keys. Primarily to support text entry on smaller devices than mobile phones, this method can also be used to maximise screen space on mobile phones. Reported combined Fitt's law and keystroke modelling predicts similar performance with bigram prediction using a five-key keypad as is currently achieved on standard mobile phones using unigram prediction. User studies reported here show similar user performance on five-key pads as found elsewhere for novice nine-key pad users

Evolving concepts on the role of dyslipidemia, bioenergetics, and inflammation in the pathogenesis and treatment of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most widespread and disabling neurological conditions, accounting for half of all neuropathy cases worldwide. Despite its high prevalence, no approved disease modifying therapies exist. There is now a growing body of evidence that DPN secondary to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) represents different disease processes, with T2DM DPN best understood within the context of metabolic syndrome rather than hyperglycemia. In this review, we highlight currently understood mechanisms of DPN, along with their corresponding potential therapeutic targets. We frame this discussion within a practical overview of how the field evolved from initial human observations to murine pathomechanistic and therapeutic models into ongoing and human clinical trials, with particular emphasis on T2DM DPN and metabolic syndrome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155898/1/jns12387.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155898/2/jns12387_am.pd

Finite Element Analysis of ECAP, TCAP, RUE and CGP Processes

A finite element method was applied to study the various severe plastic deformation processes like, Equal Channel Angular Pressing (ECAP), Tubular Channel Angular Pressing (TCAP), Repetitive Upsetting and Extrusion (RUE) and Constrained Groove Pressing (CGP), considering aluminum AA-390 alloy as specimen material for all these processes. FEA simulation was carried out using AFDEX simulation tool. Effect of the various ECAP process parameters like, die corner angle, channel angle, and the coefficient of friction were analyzed. The die corner angles were divided into 2 equal parts for increasing the effectiveness of ECAP process, thereby increasing the channel number from 2 to 3 and further, their influence on ECAP process was investigated. A 3D simulation of TCAP was carried out for die shapes like triangular and trapezoidal, and variation of the generated stress and strain was plotted. In CGP, four cycle operation was carried out; wherein each cycle is composed of corrugating the specimen and subsequent straightening to original dimension. During RUE process, a maximum effective stress of 683.1 MPa was induced in the specimen after processing it for four complete cycles of RUE process; whereas the maximum strain induced during the same condition was 3.715

Ontology-Based Multimedia Presentation Generation

Multimedia data are illusory entities for the machines. Their contents include interpretable data as well as binary representations. Understanding and accessing the content-driven information for multimedia objects allow us to design an efficient multimedia querying and retrieval system. In this paper, we propose a framework to represent the multimedia information and object roles in order to generate automatic multimedia presentations. The proposed architecture attempts to represent the semantic information and the relations amongst the multimedia objects in a disclosure domain. Thus, the system is domain dependent. The represented data associates with the presentation mechanisms to create an integrated presentation generation system. A multi-layer design defines the various levels of abstraction for the proposed framework

A comparison of repetitive corrugation and straightening and high-pressure torsion using an Al-Mg-Sc alloy

A comparative study was conducted to evaluate the influence of two different severe plastic deformation (SPD) processes: repetitive corrugation and straightening (RCS) and high-pressure torsion (HPT). Samples of an Al-3Mg-0.25Sc alloy with an initial grain size of ∼150 μm were processed by RCS through 8 passes at room temperature either without any rotation during processing or with a rotation of 90° around the longitudinal axis between each pass. Thin discs of the alloy were also processed for up to 5 turns by HPT at room temperature. The results show that both procedures introduce significant grain refinement with average grain sizes of ∼0.6–0.7 μm after RCS and ∼95 nm after HPT. Measurements of the Vickers microhardness gave values of ∼128 after RCS and ∼156 after HPT. The results demonstrate that processing by HPT is the optimum processing technique in achieving both high strength and microstructural homogeneity

Rapid microsphere‐assisted peptide screening (MAPS) of promiscuous MHCII‐binding peptides in Zika virus envelope protein

Despite promising developments in computational tools, peptide‐class II MHC (MHCII) binding predictors continue to lag behind their peptide‐class I MHC counterparts. Consequently, peptide–MHCII binding is often evaluated experimentally using competitive binding assays, which tend to sacrifice throughput for quantitative binding detail. Here, we developed a high‐throughput semiquantitative peptide–MHCII screening strategy termed microsphere‐assisted peptide screening (MAPS) that aims to balance the accuracy of competitive binding assays with the throughput of computational tools. Using MAPS, we screened a peptide library from Zika virus envelope (E) protein for binding to four common MHCII alleles (DR1, DR4, DR7, DR15). Interestingly, MAPS revealed a significant overlap between peptides that promiscuously bind multiple MHCII alleles and antibody neutralization sites. This overlap was also observed for rotavirus outer capsid glycoprotein VP7, suggesting a deeper relationship between B cell and CD4+ T cell specificity which can facilitate the design of broadly protective vaccines to Zika and other viruses.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154342/1/aic16697.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154342/2/aic16697_am.pd

Experimental arthritis is dependent on mouse mast cell protease-5

© 2017 by The American Society for Biochemistry and Molecular Biology, Inc. The constitutive heparin+ (HP) mast cells (MCs) in mice express mouseMCprotease (mMCP)-5 and carboxypeptidaseA (mMC-CPA). The amino acid sequence ofmMCP-5is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralisinfected mice. In contrast, the constitutive HP+ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis ofmMCP-5from theMCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wildtype mice in two disease models

Cross-cultural validation of the Cardiac Depression Scale in Iran

Background. The Cardiac Depression Scale (CDS) is a disease-specific instrument for measuring depression in cardiac patients. This study was designed to validate the CDS in an Iranian population. Methods. Translation and back-translation of the 26-item CDS scale was performed using recommended procedures. The Iranian translation of the CDS (I-CDS) was administered to 261 individuals in Iran, concurrently with the Beck Depression Inventory. The factor structure of the I-CDS was examined using exploratory factor analysis procedures to enable comparison with previous psychometric evaluation ofthe CDS. Receiver operating characteristic curves were used to examine the ability of the I-CDS to discriminate between categories of depression. Results. First-order exploratory factor analysis uncovered two robust factors, consistent with the second-order dimensions originally reported by the developers of this instrument. Cronbach's alpha was .88 for the total 26-item I-CDS, indicating satisfactory internal consistency of the I-CDS. Intercorrelation between the total scores for the I-CDS and BDI was .62 (p < .001). For the I-CDS cut-off of 90, the sensitivity was 85%, and specificity was 61% with a computed area under the curve (AUC) of 0.81 (95% CI, 0.76-0.87). For the I-CDS cut-off of 100, the sensitivity was 81%, and specificity was 63% with a computed AUC of 0.81 (95% CI, 0.76-0.87). Conclusion. This validation study of the Iranian version of theCDSdemonstrated that it is an acceptable, reliable, and valid measure of depression in people with heart disease.Copyright © The British Psychological Society