A Distributed Computational Architecture for Integrating Multiple Biomolecular Pathways

Biomolecular pathways are building blocks of cellular biochemical function. Computational biology is in rapid transition from diagrammatic representation of pathways to quantitative and predictive mathematical models, which span time-scales, knowledge domains and spatial-scales. This transition is being accelerated by high-throughput experimentation which isolates reactions and their corresponding rate constants. A grand challenge of systems biology is to model the whole cell by integrating these emerging quantitative biomolecular pathway models. Current integration approaches do not scale. A new parallel and distributed computational architecture, CytoSolve, directly addresses this scalability issue. Results are presented in the solution of a concrete biological model: the Epidermal Growth Factor Receptor (EGFR) pathway model published by Kholodenko. The EGFR pathway is selected since known solutions exist for this problem, enabling direct confirmation of the CytoSolve approach. Results from this effort demonstrate that CytoSolve provides a core platform for addressing a grand challenge of systems biology to model the whole cell by integrating multiple biomolecular pathway models.Singapore-MIT Alliance (SMA

Evaluating Model Testing and Model Checking for Finding Requirements Violations in Simulink Models

Matlab/Simulink is a development and simulation language that is widely used by the Cyber-Physical System (CPS) industry to model dynamical systems. There are two mainstream approaches to verify CPS Simulink models: model testing that attempts to identify failures in models by executing them for a number of sampled test inputs, and model checking that attempts to exhaustively check the correctness of models against some given formal properties. In this paper, we present an industrial Simulink model benchmark, provide a categorization of different model types in the benchmark, describe the recurring logical patterns in the model requirements, and discuss the results of applying model checking and model testing approaches to identify requirements violations in the benchmarked models. Based on the results, we discuss the strengths and weaknesses of model testing and model checking. Our results further suggest that model checking and model testing are complementary and by combining them, we can significantly enhance the capabilities of each of these approaches individually. We conclude by providing guidelines as to how the two approaches can be best applied together.Comment: 10 pages + 2 page reference

Extended-spectrum beta-lactamases-producing <i>Escherichia coli</i> in common vampire bats <i>Desmodus rotundus</i> and livestock in Peru

Antibiotic resistance mediated by bacterial production of extended‐spectrum beta‐lactamase (ESBL) is a global threat to public health. ESBL resistance is most commonly hospital‐acquired; however, infections acquired outside of hospital settings have raised concerns over the role of livestock and wildlife in the zoonotic spread of ESBL‐producing bacteria. Only limited data are available on the circulation of ESBL‐producing bacteria in animals. Here, we report ESBL‐producing Escherichia coli in wild common vampire bats Desmodus rotundus and livestock near Lima, Peru. Molecular analyses revealed that most of this resistance resulted from the expression of blaCTX‐M‐15 genes carried by plasmids, which are disseminating worldwide in hospital settings and have also been observed in healthy children of Peru. Multilocus sequence typing showed a diverse pool of E. coli strains carrying this resistance that were not always host species‐specific, suggesting sharing of strains between species or infection from a common source. This study shows widespread ESBL resistance in wild and domestic animals, supporting animal communities as a potential source of resistance. Future work is needed to elucidate the role of bats in the dissemination of antibiotic‐resistant strains of public health importance and to understand the origin of the observed resistance

Surgical management of vaginal agenesis using a modified Mc Indoe’s technique: VIMS experience

Background: Mullerian agenesis is a challenge to reconstructive surgeons. In order to create a new vagina that mimic the normal one in size, lining and appearance, multiple techniques have been designed; among these techniques Mc Indoe’s vaginoplasty represents the simplest one with good results. Mc Indoe’s operation which involves the creation of a space between bladder and rectum, insertion of a mould covered with split-thickness skin graft into that neo-vaginal space, and use of postoperative vaginal mould for dilation and to avoid stenosis. However, many modifications have been introduced in time in an attempt to increase the success rates. The purpose of vaginal agencies treatment is to create an adequate passage for penetration during sexual intercourse.Methods: Between Jan 2010 to June 2017, ten patients with vaginal agenesis were admitted to Dept of Obstetrics and Gynaecology, VIMS Ballari for vaginal reconstruction. All cases underwent a modified Mc Indoe’s technique, and follow up was done for one year.Results: All ten cases of vaginal agenesis underwent vaginal reconstruction by modified Mc Indoe's technique. Post-operative vaginal length varied from 5 to 7 cm in patients who used mould regularly. Successful skin graft take was achieved in 6 cases. one case of perforation of rectum and one case of vaginal stricture was noted.Conclusions: To optimize sexual comfort, the clinical management of women with vaginal agenesis must be multidisciplinary and individually tailored. Our findings suggest that the modified Mc Indoe’s technique is a simple, effective procedure for the treatment of vaginal agenesis, but proper mould usage after surgery remains the cornerstone of the treatment