Standardized maximim D-optimal designs for enzyme kineticinhibition models

Locally optimal designs for nonlinear models require a single set of nominal values for the unknown parameters.An alternative is the maximin approach that allows the user to specify a range of values for each parameter ofinterest. However, the maximin approach is difficult because we first have to determine the locally optimal designfor each set of nominal values before maximin types of optimal designs can be found via a nested optimizationprocess. We show that particle swarm optimization (PSO) techniques can solve such complex optimizationproblems effectively. We demonstrate numerical results from PSO can help find, for the first time, formulae forstandardized maximin D-optimal designs for nonlinear model with 3 or 4 parameters on the compact andnonnegative design space. Additionally, we show locally and standardized maximin D-optimal designs for inhibitionmodels are not necessarily supported at a minimum number of points. To facilitate use of such designs, wecreate a web-based tool for practitioners to find tailor-made locally and standardized maximin optimal designs

Insulin-like factor 3 and the HPG axis in the male

The hypothalamic–pituitary–gonadal (HPG) axis comprises pulsatile GnRH from the hypothalamus impacting on the anterior pituitary to induce expression and release of both LH and FSH into the circulation. These in turn stimulate receptors on testicular Leydig and Sertoli cells, respectively, to promote steroidogenesis and spermatogenesis. Both Leydig and Sertoli cells exhibit negative feedback to the pituitary and/or hypothalamus via their products testosterone and inhibin B, respectively, thereby allowing tight regulation of the HPG axis. In particular, LH exerts both acute control on Leydig cells by influencing steroidogenic enzyme activity, as well as chronic control by impacting on Leydig cell differentiation and gene expression. Insulin-like peptide 3 (INSL3) represents an additional and different endpoint of the HPG axis. This Leydig cell hormone interacts with specific receptors, called RXFP2, on Leydig cells themselves to modulate steroidogenesis, and on male germ cells, probably to synergize with androgen-dependent Sertoli cell products to support spermatogenesis. Unlike testosterone, INSL3 is not acutely regulated by the HPG axis, but is a constitutive product of Leydig cells, which reflects their number and/or differentiation status and their ability therefore to produce various factors including steroids, together this is referred to as Leydig cell functional capacity. Because INSL3 is not subject to the acute episodic fluctuations inherent in the HPG axis itself, it serves as an excellent marker for Leydig cell differentiation and functional capacity, as in puberty, or in monitoring the treatment of hypogonadal patients, and at the same time buffering the HPG output

Willingness to Continue with Software Projects: Effects of Feedback Direction and Optimism under High and Low Accountability Conditions

The willingness of managers to continue with software projects can be both beneficial and troubling. Management optimism can help bring promising projects to fruition, but can also cause valuable resources to be expended on faltering projects. This study examines three factors that can affect the willingness of managers to continue with software projects: feedback direction, feedback optimism, and accountability. Feedback direction is the objective information reflecting project prospects. Feedback optimism is the subjective mode with which the objective information has been framed. Accountability is the extent to which the manager feels responsible for project outcomes. Results of a study that manipulated these three factors showed that the effects of feedback direction and feedback optimism on willingness to continue with software projects were additive (either factor alone affected willingness to continue with software projects) when accountability was high but were interactive (both factors jointly affected willingness to continue with software projects) when accountability was low. These findings have useful implications for practice and further research

Competing with the Big Boys - Strategies for Growth for a Startup Company in the Singapore Food Industry

Entrepreneurship provides the basis for satisfying of personal goals and possibly profit maximization; Singapore has a good infrastructure in place to facilitate new business setup and other business functions. Being one of the first few industries that have promoted trade and main revenue drivers, the Singapore Food Industry is in its mature state and entrenched with established big-name global, regional and national players with long histories. But because of its ability to innovate, and with consumers constantly looking for new refreshing tastes, the Food industry continues to be earmarked by the government as the few pillars of growth and therefore has an abundance of opportunities for the entrepreneurially adventurous and hungry (Tan 2002). But with only a small market of 4.9 million local dwellers, competitive environment in the Food Industry is not for the faint hearted (Ranken, Kill & Baker 1997), while increasingly sophisticated consumers are demanding improved services, varieties, quality and value from food companies. New niche players would thus still be able to carve out a space and enjoy a fairly lucrative amount of return with Singapore’s robust and fairly resilient economy. This study involves a particular new entrant to the food landscape, Preferred Choice Food Company (PCFC). Supporting only institutional customers, PCFC manages and caters to staff or employee cafeterias, creating a niche for itself in small to medium sized companies, choosing not to go head on with established competitors. Since its inception in 2008, it has steadily increased its food service portfolio to 5 cafeteria outlets and recently expanded its operations to serve the Muslim clientele which makes up about 10% of the overall staff community. With a stable operational footing and resource base, PCFC is now positioned to take the next step forward, focusing on growth and expansion opportunities in the vast food service industry. But being a new startup, immediate growth priorities would have to be conservative, organic and the most natural; which is to be able to maximize current resource capabilities to achieve a competitive advantage in a market that will incur low investment outlay but yet provide good return on investment. PCFC’s competitive environment was evaluated and through SWOT and Value Chain Analysis, PCFC core competencies of pre-packed sauces, value added activities and ability to keep overheads low was found to have led to its competitive advantage. Added capability requirements were also identified to provide sustained competitive advantage. Expansion opportunities in the food industry from service provision to manufacturing were applied to a competitive analysis matrix derived from Michael Porter’s 5 forces, opportunities were subsequently ranked to determine the most promising path of growth to follow (Tan 2002). Based on the findings, commercial catering for consumers was the most obvious short term growth plan while packed condiments manufacturing and direct food retail would provide vast and promising opportunities for the longer term. As any startup where preservation of capital and speed of inflow of revenues is the key, the implementation strategy for immediate expansion plans would have to consider activities with the lowest outlay but with the greatest possible return (Ranken, Kill & Baker 1997). Plans for implementation include the most applicable marketing mix, operational and financial requirements for the added capabilities and resources required. Finally this study provides information on the future steps that PCFC may embark on that could pave the way for sustainable and continued growth required in the Singapore Food Industry

Detection of medically important Candida species by absolute quantitation real-time polymerase chain reaction

Background: Chronic obstructive pulmonary disease (COPD) is one of the most important causes of disability and mortality in the world. Although cigarette smoking and environmental pollutants have been recognized as the major causes of COPD, the role of infection in the pathogenesis and progression of COPD has also been reported. Objectives: The aim of the present study was to find the relationship between Helicobacter Pylori infection and COPD through anti H. pylori IgG serology, real time PCR of bronchoalveolar lavage and trans bronchial biopsy urease tests. Patients and Methods: This descriptive cross-sectional study was carried out on 60 adults with COPD. After obtaining the patient’s history, physical examination, spirometry and confirmation of COPD diagnosis by pulmonologist, subjects were selected through convenience sampling. In order to determine the severity and prognosis of disease, the global initiative for chronic obstructive lung disease (GOLD) criteria and BODE index were used. Subjects underwent bronchoscopy for obtaining bronchoalveolar lavage (BAL) samples and biopsy was performed. Biopsy and BAL samples were investigated respectively by urease test and real time PCR. Moreover, patients’ serum samples were serologically studied for detection of anti H. pylori IgG. Results: Mean age of the participants was 60.65 ± 9.15 years, and 25% were female and 75% were male. The prevalence rate of H. pylori in COPD patients was 10% according to real time PCR, 88.3% according to the serology test and 0% based on the urease test. According to the results of PCR and considering the severity of disease based on the GOLD criteria, from those with a positive PCR, one patient (16.6%) had very severe obstruction, three (50%) had severe obstruction and two patients (33.3%) had moderate obstruction. The relationship between H. pylori presence (based on PCR) and disease severity and prognosis was not statistically significant. Conclusions: These findings can justify the hypothesis of direct injury and chronic inflammation via inhalation and aspiration resulting in H. pylori colonization. In fact, it is thought that H. Pylori infection, beside the host genetic vulnerability and other environmental risk factors might make the patient susceptible to COPD or lead to COPD worsening. Although we found H. pylori infection in some patients with COPD, the results of this study, could not explain the pathogenic mechanisms of COPD

Cloning and expression of a Vi mimotope of Salmonella enterica serovar Typhi through nucleotide-nucleotide hybridization approach.l

A recombinant His-Vi protein of Salmonella enterica serovar Typhi was successfully constructed and cloned into an expression vector through a nucleotide-nucleotide hybridization approach. After transformation of the construct into Escherichia coli, the recombinant His-Vi protein with a size of approximately 4 kDa was successfully produced and proven by Western blot analysis. This recombinant protein can be used to detect specific anti-Vi antibody produced by typhoid patients. Overall, the His-Vi recombinant protein could serve as a potential diagnostic reagent to detect S. Typhi infection in an individual

Psychological impact of noise exposure among machine and non-machine operators in construction industry

Noise hazard is reported as a serious issue among the construction industry in Malaysia. The aim of the study is to determine the personal noise exposure level and the prevalence of psychological health effect symptoms among the machine and non-machine operators on construction site in Malaysia. Sixty-one (61) construction workers were participated as respondents and categorized into machine and non-machine operators group. All respondents were monitored for 8 hours working time using personal noise dosimeter for personal noise monitoring. Questionnaires and interviewed sessions were used to determine the prevalence of psychological health effect symptoms. The results obtained reveal that the construction workers have high personal noise exposure level where machine operators are significantly higher compared to non-machine operators. The prevalence of psychological health effect symptoms among machine operators is 89% higher than the non-machine operators. Lastly, there is a significant positive relationship between the personal noise exposure level and the prevalence of psychological health effect symptoms among the construction workers

Population data and forensic evaluation of six alu insertions in indigenous groups from Sabah, Malaysia

Background and aim: The present study is the first to report the genetic relatedness of indigenous populations of Sabah, Malaysia, using a set of Indel markers (HS4.32, TPA25, APO, PV92, B65 and HS3.23). The primary aim was to assess the genetic relationships among these populations and with populations from other parts of the world by examining the distribution of these markers. Subjects and methods: A total of 504 volunteers from the three largest indigenous groups, i.e. Kadazan-Dusun, Bajau and Rungus, were recruited for the study. Six Alu insertions were typed by PCR with specific primer sets. Results: All insertions were found to present at different frequencies, ranging from 0.170–0.970. The heterozygosity of most of the markers was high (.0.4), with the exception of HS3.23 and APO. A genetic differentiation study revealed that these populations are closely related to each other (GST ¼0.006). A principle component plot showed that these populations have higher affinity to Mainland South East Asia/East Asia populations, rather than Island Southeast Asia (ISEA) populations. Conclusion: In summary, these indigenous groups were closely associated in terms of their genetic composition. This finding also supports the colonization model of ISEA, which suggests that the inhabitants of this region were mostly descendants from Southern Chin

Maternal exposure to dibutyl phthalate (Dbp) or diethylstilbestrol (des) leads to long-term changes in hypothalamic gene expression and sexual behavior

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8–12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior

Health System for Dengue Control in Singapore

Dengue fever/dengue haemorrhagic fever (DF/DHF) first appeared in Singapore in an outbreak in 1960. In 1966, the Ministry of Health established the Vector Control Unit which was charged with the responsibility of controlling the dengue vector mosquitoes, Aedes aegypti and Aedes albopictus. The Unit immediately launched an Aedes control programme based on source reduction and public health education. To obtain reliable statistics on disease incidence, DF/DHF was made administratively notifiable in 1966, and finally, legally notifiable in 1977. It was also recognized early in the control programme that long-term and active participation by the community was essential for its implementation. A new legislation called the Destruction of Disease-Bearing Insects Act was thus enacted in 1968. The Act empowers vector control officers to enter and examine houses for mosquito breeding, to take appropriate control measures, and to serve offenders with orders and summonses which carry a fine or imprisonment by the court. With the new legislation in force, the Aedes control programme adopted an integrated approach of source reduction, public health education and law enforcement. When the new Ministry of the Environment was formed in 1972 to take over the responsibility of environmental health, its Vector Control and Research Department and the Quarantine & Epidemiology Department became responsible for the surveillance and control of DF/DHF in the country. Surveillance of disease incidence and Aedes vectors is important in the prevention and control of DF/DHF outbreaks. Disease surveillance is conducted by officers of the Quarantine & Epidemiology Department based on notifications on clinically diagnosed cases as well as on the number of blood specimens submitted by hospitals, clinics, and private practitioners to the Virology Division of the Department of Pathology in the Ministry of Health and the Department of Microbiology of the National University of Singapore for laboratory confirmation of dengue infection. Aedes surveillance depends on regular surveys of mosquito larvae and adults in designated DF/DHF-sensitive areas. In addition to destruction of breeding habitats, fogging is carried out when the Aedes house index is 2% and above, or when a potential outbreak situation arises such as the occurrence of a focus of two or more DF/DHF cases in an area