Developmental pathways and gene function in canine myxomatous mitral valve disease

Canine myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs affecting all breeds, and it shares many similarities with the equivalent human disease. From the only transcriptomic report for canine MMVD published in 2006, serotonin signalling was identified as a contributing factor and has been widely studied since. Two transcriptomic profiling studies in human MMVD have also identified oxidative stress response and bone morphogenic protein signalling contributing to disease pathology. All studies at the transcriptional level have identified a variety of biological functions in MMVD suggesting dynamic extracellular matrix (ECM) remodelling processes are on-going. Moreover, cellular changes found in MMVD are somewhat reminiscent of the events seen in early heart valve, suggesting possible re-activation of signalling pathways of which those driving development and endothelial-to-mesenchymal transition (EndoMT) are particularly interesting. EndoMT, in which endothelial cells change their identity to mesenchymal phenotype and migrate into the cardiac jelly underneath the endothelium, is a crucial mechanism in valvulogenesis. Whether or not gene regulation of EndoMT and valve development also plays a role in MMVD is unknown. In this study, the MMVD cellular changes in the Cavalier King Charles Spaniel (CKCS), a breed with the highest prevalence, earliest onset, and rapid progression of the disease, was investigated. Secondly, transcriptional profiling was conducted using the latest canine microarray chips, a single affected breed (CKCSs), stringent sample quality control and statistical thresholds, with quantitative polymerase chain reaction (Q-PCR) for data validation. After transcriptional mapping, multi-platform in silico analysis was conducted to identify relationship between differentially expressed genes and their relevant biological functions. Next, a comparison study using immunohistochemistry was performed on different severities of myxomatous valves to localize the proteins of interest. Finally, to model the transcriptional factors and their downstream targets, mitral valve endothelial cell (MVEC) clones were derived from the canine normal mitral valves for future in vitro studies. Cellular changes of MMVD between CKCS and non-CKCS populations showed no difference in their distribution, number and phenotypic markers. Global genomic expression analysis identified similar (inflammation, up-regulation of serotonin receptor and bone morphogenic protein) and novel biological functions (epithelial-to-mesenchymal transition) compared to the previous study in 2006. Key transcriptional factors and genes associated with EndoMT including SNAI1, TAGLN, ACTA2, ACTG2, HAS2, and CTNNB1 were found up-regulated, and NID1, LAMA2, CDH5 were down-regulated in the MMVD group. In myxomatous mitral valves, increased expression of HAS2 in myofibroblasts, SNAI1 expression in endothelial cells, and co-expression of CDH5 and α-smooth muscle actin (α-SMA) also suggested the presence of EndoMT compared to normal valves. Nevertheless, there is also evidence of EndoMT in normal valves (α-SMA positive endothelial cells) which might suggest contribution to life-long valve re-modelling. In addition, there was a decreased expression of microRNAs associated with modulation of extracellular matrix transcripts, including miR-23, miR-29, and miR-218, indicating epigenetic regulation in MMVD. Based on the cellular changes, MMVD in CKCS appears to be representative of MMVD in all breeds and the early-onset of MMVD in that breed does not lead to different end-stage pathology. Novel biological functions such as EndoMT, were identified by transcriptional profiling, and by using powerful bioinformatic tools providing insight into understanding gene regulation in MMVD. Furthermore, a relationship between developmental biology processes and MMVD pathogenesis was established, with a likely important role for epigenetics in disease pathogenesis

SOFTWARE-AS-A-SERVICE (SAAS) INNOVATION IN THE CONTEXT OF SOFTWARE INDUSTRY: A RESOURCE ORCHESTRATION PERSPECTIVE

Cloud computing brings a paradigm shift in the software industry and changes the business model of software vendors (SV). Software as a service (SaaS), the most popular form of cloud computing, has been recognized as the fundamental change in the delivery, utilization, and management of software. While the transformation to SaaS requires changes within the organization, SVs must actively take action to attract customers to accept the SaaS business model, the so-called pull strategy. Drawing on the resource orchestration view, we propose that the antecedents (i.e., structuring cloud resources, developing service bundling capability, and leveraging cloud ecosystem) are related to the likelihood of an innovative SaaS, which, in turn, is associated with SaaS attractiveness to users. Our proposed research framework provides a guideline for SV to attract and persuade customers to adopt SaaS solutions actively

Comparison of clinical outcomes and toxicity in endometrial cancer patients treated with adjuvant intensity-modulated radiation therapy or conventional radiotherapy

PurposeTo evaluate the treatment outcomes and toxicity in endometrial cancer patients treated with hysterectomy and adjuvant intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).MethodsThere were 101 patients with stage IA-IIIC2 endometrial carcinoma treated with hysterectomy and adjuvant radiotherapy. In total, 36 patients received adjuvant CRT and 65 were treated with adjuvant IMRT. The endpoints were overall survival, local failure-free survival, and disease-free survival. Patients were assessed for acute toxicity weekly according to the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema.ResultsThe 5-year overall survival, local failure-free survival, and disease-free survival for the CRT group and the IMRT group were 82.9% versus 93.5% (p = 0.26), 93.7% versus 89.3% (p = 0.68), and 88.0% versus 82.8% (p = 0.83), respectively. Four (11.1%) patients had Grade 3 or greater acute gastrointestinal (GI) toxicity and three (8.3%) patients had Grade 3 or greater acute genitourinary (GU) toxicity in the CRT group, whereas four (6.2%) patients had Grade 3 or greater acute GI toxicity in the IMRT group and no patient had severe GU toxicity. There was one (2.8%) patient who had Grade 3 or greater late GI toxicity and one (2.8%) patient had Grade 3 or greater late GU toxicity in the CRT group, whereas no patient had severe GI or GU toxicity in the IMRT group.ConclusionAdjuvant IMRT for endometrial cancer patients had comparable clinical outcomes with CRT and had less acute and late toxicity

Blood-brain barrier opening in a large animal model using closed-loop microbubble cavitation-based feedback control of focused ultrasound sonication

Focused ultrasound (FUS) in combination with microbubbles has been established as a promising technique for noninvasive and localized Blood-brain barrier (BBB) opening. Real-time passive cavitation detection (PCD)-based feedback control of the FUS sonication is critical to ensure effective BBB opening without causing hemorrhage. This study evaluated the performance of a closed-loop feedback controller in a porcine model. Calibration of the baseline cavitation level was performed for each targeted brain location by a FUS sonication in the presence of intravenously injected microbubbles at a low acoustic pressure without inducing BBB opening. The target cavitation level (TCL) was defined for each target based on the baseline cavitation level. FUS treatment was then performed under real-time PCD-based feedback controller to maintain the cavitation level at the TCL. After FUS treatment, contrast-enhanced MRI and ex vivo histological staining were performed to evaluate the BBB permeability and safety. Safe and effective BBB opening was achieved with the BBB opening volume increased from 3.8 ± 0.7 to 53.6 ± 23.3 m

Emotion and Concentration Integrated System: Applied to the Detection and Analysis of Consumer Preference

With the expansion of consumer market, the appearance becomes an important issue when consumers make decisions under the situation of similar qualities and contents. Accordingly, to attract consumers, companies cost and take much attention on product appearance. Compared to using questionnaires individually, obtaining humans’ thoughts directly from their brains can accurately grasp the actual preference of consumers, which can provide effective and precious decisions for companies. \ In this study, consumers’ brainwaves which are related to concentration and emotion are extracted by wearing a portable and wireless Electroencephalography (EEG) device. The extracted EEG data are then trained by using perceptron learning algorithm (PLA) to make the judgments of concentration and emotion work well with each subject. They are then applied to the detection and analysis of consumer preference. Finally, the questionnaires are also performed and used as the reference on training process. They are integrated with brainwaves data to create one prediction model which can improve the accuracy significantly. The Partial Least Squares is used to compare the correlation between different factors in the model, to ensure the test can accurately meet consumers’ thoughts

Strategic Optimization of Water Reuse in Wafer Fabs via Multi-Constraint Linear Programming Technique

The risk of water shortage has been posing as a threat to water demanding industries in Taiwan, including the high-tech industries where ultrapure water is needed for the production of microchips. Such risks are especially unpredictable in the age of climate change, where more frequent extreme climate events such as prolonged droughts have sent these industries scrambling for securing water supply at a very high cost. The national policy also mandates strict water recycling standards for these high-tech plants, while the risk of water supply shortage also forces the industry to be water-conscious. However, most plants set their water recycling strategies based on experience or ‘‘rules of thumb” practices, without implementing optimization tools that can help making decisions in a more scientific approach. In this study we applied linear programming technique to optimize the water recovery path for a microchip assembly plant. A water balance diagram was formulated and completed to determine the existing water recycling performance, and the data was converted to a water flow network. The water flow network was then derived with a mathematical model to formulate a linear optimization problem. The proposed linear programming model is composed of mass balance constraints, unit specification constraints, capacity constraints as well as water quality constraints (discharge limits). The linear programming method was effectively applied to improve the efficiency of water reuse. With the installation of the regeneration units, an increase of 40.1% in the volume of reused water was predicted. The results from water cost structure also indicated that, at higher water tariff, water reuses through reclaiming and generating spent effluents can alleviate the overall water consumption costs

CFTR Mutation Analysis of a Caucasian Father with Congenital Bilateral Absence of Vas Deferens, a Taiwanese Mother, and Twins Resulting from ICSI Procedure

Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is one of the most common autosomal recessive diseases in Caucasians. We screened for the CFTR gene mutation in a Caucasian father with congenital bilateral absence of the vas deferens (CBAVD), a Taiwanese mother, and twins resulting from an intracytoplasmic single sperm injection (ICSI) procedure. DNA fragments that showed abnormal banding patterns on temporal temperature gradient gel electrophoresis analysis followed by analysis of DNA sequence was used. The Caucasian father with CBAVD had ΔF508 and p.L375F mutations. The two children were heterozygous for the ΔF508 and p.L375F mutations, respectively. Mutation analysis of the CFTR gene should always be recommended for infertile couples seeking ICSI. The possibility of the children resulting from ICSI being a victim or carrier of CBAVD or CF, especially when the father is Caucasian with CBAVD, should be discussed during genetic counseling

Interpersonal Relationships among University Safety Professionals: The Impact of a Safety Departmentf

PresentationForming strong interpersonal relationships enables an organization or individual to achieve more favorable outcomes. The objectives of this study were to examine the frequency of interpersonal interactions among safety professionals (SPs) employed at Taiwanese universities and the factors that affected this frequency. To accomplish these objectives, we mailed questionnaires to a simple random sampling of 200 university SPs. Moreover, an interpersonal relationship scale was developed in this study; exploratory factor and internal consistency analyses revealed that the scale was valid and reliable. Results derived from the questionnaire revealed that in SP interpersonal relationships, general affairs department personnel, laboratory or internship unit supervisors, and teaching staff ranked highest in frequency of interactions. Multivariate analysis of variance results showed that establishing a safety department exerted a statistically significant effect on SP interpersonal relationships. SPs employed by universities with safety departments interacted more frequently with both internal and external relationships. Therefore, we suggest that universities without a safety department establish such a department to strengthen the labor safety and health structure, thereby benefitting SPs in fulfilling responsibilities to promote safety and health management