131 research outputs found
Stabilization of biped dynamic walking using gyroscopic couple
This paper presents a new strategy for dynamic walking where a gyroscope mounted on top of the biped is precessed to achieve balancing both in the Coronal and Sagittal planes. A gait is devised and simulation results are provided to show the feasibility of proposed balancing method.published_or_final_versio
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Analysis of Graduation Rates for Four-year Colleges: A Model of Institutional Performance Using IPEDS
Under the George W. Bush U.S. presidential administration, the federal government pushed for greater accountability among institutions of higher education for educational outcomes. Graduation rate is a key performance indicator of institutional accountability. Previous researchers of student attrition focused primarily on the effects of student level factors on student persistence/withdrawal behavior. Recently, researchers put more focus on the effects of institutional characteristics on graduation rates, but most of these studies were exploratory and based on multiple regression models. No institutional model has existed to synthesize their results within a theoretical framework. Such an institutional model is needed to explain the process of student persistence at the institutional level. The purpose of this study was to develop a model of institutional performance in graduation rate for four-year, public and private not-for-profit, Title IV institutions in the United States. This study validated the institutional model based on the IPEDS dataset using the structural equation modeling (SEM) technique. Further group comparison analyses are conducted by fitting the same SEM model to several subgroup datasets based on grouping variables such as control, geographical region and state. Benchmarking analyses were conducted to demonstrate how administrators and policy-makers can use the institutional model to compare the performance of an institution with its peers and what policy changes can they pursue to improve graduation rates
MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression
Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA was primarily via site-specific cleavage of the transgene mRNA, generating specific 5\u27 and 3\u27 mRNA fragments. Our findings promise to facilitate the development of miRNA-regulated rAAV for CNS-targeted gene delivery and other applications
Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants
Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients
Transmission dynamics, serial interval and epidemiology of COVID-19 diseases in Hong Kong under different control measures
Background: The outbreak of coronavirus disease 2019 (COVID-19) started in Wuhan, China in late December 2019, and subsequently became a pandemic. Hong Kong had implemented a series of control measures since January 2020, including enhanced surveillance, isolation and quarantine, border control and social distancing. Hong Kong recorded its first case on 23 January 2020, who was a visitor from Wuahn. We analysed the surveillance data of COVID-19 to understand the transmission dynamics and epidemiology in Hong Kong. Methods: Based on cases recorded from 23 January to 6 April 2020, we constructed the epidemic curve of daily COVID-19 incidence and used this data to estimate the time-varying reproduction number ( R t ) with the R package EpiEstim, with serial interval computed from local data. We described the demographic and epidemiological characteristics of reported cases. We computed weekly incidence by age and residential district to understand the spatial and temporal transmission of the disease. Results: COVID-19 disease in Hong Kong was characterised with local cases and clusters detected after two waves of importations, first in late January and the second one in early March. The R t increased to approximately 2 and approximately 1, respectively, following these importations; it decreased to below 1 afterwards, which coincided with the implementation, modification and intensification of different control measures. Compared to local cases, imported cases were younger (mean age: 52 years among local cases vs 35 years among imported cases), had a lower proportion of underlying disease (9% vs 5%) and severe outcome (13% vs 5%). Cases were recorded in all districts but the incidence was highest in those in the Hong Kong Island region. Conclusions: Stringent and sustained public health measures at population level could contain the COVID-19 disease at a relatively low level
Quality of life for men with metastatic castrate-resistant prostate cancer participating in an aerobic and resistance exercise pilot intervention
Background: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood. Methods: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated using self-reported questionnaires (e.g., QLQ-C30, PROMIS Fatigue, Pittsburgh Sleep Quality Index (PSQI), EPIC-26) collected at baseline and 12 weeks. Results: A total of 25 men were randomized (10 control, 8 aerobic, 7 resistance). Men were predominately white (76 %) with a median age of 71 years (range: 51 – 84) and 10.5 years (range: 0.9 – 26.3) post prostate cancer diagnosis. The men reported poor sleep quality and high levels of fatigue at enrollment. Other baseline QoL metrics were relatively high. Compared to the controls at 12 weeks, the resistance arm reported some improvements in social function and urinary irritative/obstruction symptoms while the aerobic arm reported some improvements in social function and urinary incontinence, yet worsening nausea/vomiting. Compared to the resistance arm, the aerobic arm reported worse urinary irritative/obstruction symptoms and self-rated QoL, yet some improvements in emotional function, insomnia, and diarrhea. Conclusions: The 3-month exercise intervention pilot appeared to have modest effects on QoL among mCRPC survivors on ADT. Given the feasibility, acceptability, and safety demonstrated in prior analyses, evaluation of the effect of the intervention on QoL in a larger sample and for extended duration may still be warranted
Evaluating Temporal Factors in Combined Interventions of Workforce Shift and School Closure for Mitigating the Spread of Influenza
10.1371/journal.pone.0032203PLoS ONE7
Identification of Novel Molecular Targets for Endometrial Cancer Using a Drill-Down LC-MS/MS Approach with iTRAQ
BACKGROUND: The number of patients with endometrial carcinoma (EmCa) with advanced stage or high histological grade is increasing and prognosis has not improved for over the last decade. There is an urgent need for the discovery of novel molecular targets for diagnosis, prognosis and treatment of EmCa, which will have the potential to improve the clinical strategy and outcome of this disease. METHODOLOGY AND RESULTS: We used a "drill-down" proteomics approach to facilitate the identification of novel molecular targets for diagnosis, prognosis and/or therapeutic intervention for EmCa. Based on peptide ions identified and their retention times in the first LC-MS/MS analysis, an exclusion list was generated for subsequent iterations. A total of 1529 proteins have been identified below the Proteinpilot® 5% error threshold from the seven sets of iTRAQ experiments performed. On average, the second iteration added 78% new peptides to those identified after the first run, while the third iteration added 36% additional peptides. Of the 1529 proteins identified, only 40 satisfied our criteria for significant differential expression in EmCa in comparison to normal proliferative tissues. These proteins included metabolic enzymes (pyruvate kinase M2 and lactate dehydrogenase A); calcium binding proteins (S100A6, calcyphosine and calumenin), and proteins involved in regulating inflammation, proliferation and invasion (annexin A1, interleukin enhancer-binding factor 3, alpha-1-antitrypsin, macrophage capping protein and cathepsin B). Network analyses revealed regulation of these molecular targets by c-myc, Her2/neu and TNF alpha, suggesting intervention with these pathways may be a promising strategy for the development of novel molecular targeted therapies for EmCa. CONCLUSIONS: Our analyses revealed the significance of drill-down proteomics approach in combination with iTRAQ to overcome some of the limitations of current proteomics strategies. This study led to the identification of a number of novel molecular targets having therapeutic potential for targeted molecular therapies for endometrial carcinoma
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