Assessment of the direct and indirect effects of MPP+ and dopamine on the human proteasome: implications for Parkinson's disease aetiology

Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson’s disease (PD), linked recently to proteasomal dysfunction. Our study analysed how these factors influence the various activities of the proteasome in human SH-SY5Y neuroblastoma cells treated with the PD mimetics MPP+ (a complex 1 inhibitor) or dopamine. Treatment with these toxins led to dose- and time-dependent reductions in ATP and glutathione and also chymotrypsin-like and post-acidic like activities; trypsin-like activity was unaffected. Antioxidants blocked the effects of dopamine, but not MPP+, suggesting that oxidative stress was more important in the dopamine-mediated effects. With MPP+, ATP depletion was a prerequisite for loss of proteasomal activity. Thus in a dopaminergic neuron with complex 1 dysfunction both oxidative stress and ATP depletion will contribute independently to loss of proteasomal function. We show for the first time that addition of MPP+ or dopamine to purified samples of the human 20S proteasome also reduced proteasomal activities; with dopamine being most damaging. As with toxin-treated cells, chymotrypsin-like activity was most sensitive and trypsin-like activity the least sensitive. The observed differential sensitivity of the various proteasomal activities to PD mimetics is novel and its significance needs further study in human cells

Medical students' preference for choice of clinical specialties: A multicentre survey in Nigeria

Background: The important goal of undergraduate medical training is to train doctors who would undergo further training to become specialists in various fields of clinical medicine. The admission into the specialty training programame depends largely on the pool of undergraduate medical students who have passed qualifications exams and are willing to choose and undergo training in a given clinical specialty. There are many factors considered by medical students when they make up their minds to choose a clinical specialty. This study seeks to determine the medical student preference for the clinical specialty and the factors that they consider in making such choice.Methods: This is a cross-sectional questionnaire based multicentre study in 3 accredited medical training institutions in Nigeria. Final year medical students who were willing to participate in the study filled out the questionnaires for fifteen minutes.  Information on their age, gender, specialty of preference and reason for choosing a particular clinical specialty were sought.Results: A total of 187 final year students took part in the study. Most of the students where in 21 – 30 year age range. Obstetrics and Gynaecology (24.9%), Surgery (18.9%), Internal medicine (14.1%) and Paediatics (8.1%), where the top clinical specialties preferred by the respondents. The less preferred specialties where Pathology  (2.7%), radiology (1.1%) ophthalmology (4.3%), ENT (0%). Personal liking  (51.9%), society perception (13.0%), financial reward (8.1%); where the most considered reasons for the choice of specialty.Conclusion:Medical students prefer to choose core-clinical specialty based on personal liking, financial reward and society perception.Keyword: Medical Students' Preference; Clinical Specialties; Nigeri

Cross-sectional analysis of critical risk factors for PPP water projects in China

© 2014 American Society of Civil Engineers. During the past decades in China, the traditional state monopoly has experienced difficulties in meeting the huge demand for new infrastructure and improvement in service levels, engendering the growth of different forms and degrees of private sector involvement. Since the 1990s, China has started experimenting with the public-private partnership (PPP) delivery method in the water supply sector. However, many problems stemming from unsuccessful risk management have been encountered in PPP applications that have eventually led to project failure. This paper aims to identify and evaluate typical risks associated with PPP projects in the Chinese water supply sector. A literature review, a Delphi survey, and face-to-face interviews were used to achieve these objectives. Finally, a register of 16 critical risk factors (CRFs) of water PPP projects in China was established. The findings revealed that completion risk, inflation, and price change risk have a higher impact on Chinese water PPP projects, whereas government corruption, an imperfect law and supervision system, and a change in market demand have a lower impact on the water supply sector. The findings can help project stakeholders to improve the efficiency of privatization in public utility service and provide private investors with a better understanding while they participate in the enormous Chinese water market through the PPP mode

Summarizing Review Scores of "Unequal" Reviewers

A frequently encountered problem in decision making is the following review problem: review a large number of objects and select a small number of the best ones. An example is selecting conference papers from a large number of submissions. This problem involves two sub-problems: assigning reviewers to each object, and summarizing reviewers ’ scores into an overall score that supposedly reflects the quality of an object. In this paper, we address the score summarization sub-problem for the scenario where a small number of reviewers evaluate each object. Simply averaging the scores may not work as even a single reviewer could influence the average significantly. We recognize that reviewers are not necessarily on an equal ground and propose the notion of “leniency” to model this difference of reviewers. Two insights underpin our approach: (1) the “leniency ” of a reviewer depends on how s/he evaluates objects as well as on how other reviewers evaluate the same set of objects, (2) the “leniency” of a reviewer and the “quality ” of objects evaluated exhibit a mutual dependency relationship. These insights motivate us to develop a model that solves both “leniency ” and “quality” simultaneously. We study the effectiveness of this model on a real-life dataset

RecipeGPT: Generative pre-training based cooking recipe generation and evaluation system

National Research Foundation (NRF) Singapore under International Research Centres in Singapore Funding Initiativ