Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells

Copyright @ 2010 Gopalakrishnan et al; licensee BioMed Central Ltd.Background The Nucleotide Excision Repair (NER) pathway specialises in UV-induced DNA damage repair. Inherited defects in the NER can predispose individuals to Xeroderma Pigmentosum (XP). UV-induced DNA damage cannot account for the manifestation of XP in organ systems not directly exposed to sunlight. While the NER has recently been implicated in the repair of oxidative DNA lesions, it is not well characterised. Therefore we sought to investigate the role of NER factors Xeroderma Pigmentosum A (XPA), XPB and XPD in oxidative DNA damage-repair by subjecting lymphoblastoid cells from patients suffering from XP-A, XP-D and XP-B with Cockayne Syndrome to hydrogen peroxide (H2O2). Results Loss of functional XPB or XPD but not XPA led to enhanced sensitivity towards H2O2-induced cell death. XP-deficient lymphoblastoid cells exhibited increased susceptibility to H2O2-induced DNA damage with XPD showing the highest susceptibility and lowest repair capacity. Furthermore, XPB- and XPD-deficient lymphoblastoid cells displayed enhanced DNA damage at the telomeres. XPA- and XPB-deficient lymphoblastoid cells also showed differential regulation of XPD following H2O2 treatment. Conclusions Taken together, our data implicate a role for the NER in H2O2-induced oxidative stress management and further corroborates that oxidative stress is a significant contributing factor in XP symptoms. Resistance of XPA-deficient lymphoblastoid cells to H2O2-induced cell death while harbouring DNA damage poses a potential cancer risk factor for XPA patients. Our data implicate XPB and XPD in the protection against oxidative stress-induced DNA damage and telomere shortening, and thus premature senescence.This research is supported by the Defence Innovative Research Programme, Defence Science and Technology Agency, Singapore (POD: 0613592) and the Academic Research Fund, Ministry of Education, Singapore (T206B3108). Supported in part by a grant from British Council, PMI2 Connect (Grant Number: RC134)

Optimal land conservation decisions for multiple species

Given an allotment of land divided into parcels, government decision-makers, private developers, and conservation biologists can collaborate to select which parcels to protect, in order to accomplish sustainable ecological goals with various constraints. In this paper, we propose a mixed-integer optimization model that considers the presence of multiple species on these parcels, subject to predator-prey relationships and crowding effects.Comment: 10 pages, 4 figures. Proceedings of the 52nd Northeast Decision Sciences Institute (NEDSI) Annual Conference, Washington, D

Efficient Solution of Portfolio Optimization Problems via Dimension Reduction and Sparsification

The Markowitz mean-variance portfolio optimization model aims to balance expected return and risk when investing. However, there is a significant limitation when solving large portfolio optimization problems efficiently: the large and dense covariance matrix. Since portfolio performance can be potentially improved by considering a wider range of investments, it is imperative to be able to solve large portfolio optimization problems efficiently, typically in microseconds. We propose dimension reduction and increased sparsity as remedies for the covariance matrix. The size reduction is based on predictions from machine learning techniques and the solution to a linear programming problem. We find that using the efficient frontier from the linear formulation is much better at predicting the assets on the Markowitz efficient frontier, compared to the predictions from neural networks. Reducing the covariance matrix based on these predictions decreases both runtime and total iterations. We also present a technique to sparsify the covariance matrix such that it preserves positive semi-definiteness, which improves runtime per iteration. The methods we discuss all achieved similar portfolio expected risk and return as we would obtain from a full dense covariance matrix but with improved optimizer performance.Comment: 14 pages, 3 figure

Decision-Making for Land Conservation: A Derivative-Free Optimization Framework with Nonlinear Inputs

Protected areas (PAs) are designated spaces where human activities are restricted to preserve critical habitats. Decision-makers are challenged with balancing a trade-off of financial feasibility with ecological benefit when establishing PAs. Given the long-term ramifications of these decisions and the constantly shifting environment, it is crucial that PAs are carefully selected with long-term viability in mind. Using AI tools like simulation and optimization is common for designating PAs, but current decision models are primarily linear. In this paper, we propose a derivative-free optimization framework paired with a nonlinear component, population viability analysis (PVA). Formulated as a mixed integer nonlinear programming (MINLP) problem, our model allows for linear and nonlinear inputs. Connectivity, competition, crowding, and other similar concerns are handled by the PVA software, rather than expressed as constraints of the optimization model. In addition, we present numerical results that serve as a proof of concept, showing our models yield PAs with similar expected risk to that of preserving every parcel in a habitat, but at a significantly lower cost. The overall goal is to promote interdisciplinary work by providing a new mathematical programming tool for conservationists that allows for nonlinear inputs and can be paired with existing ecological software.Comment: 8 pages, 2 figure

Validation of the modified Berlin questionnaire to identify patients at risk for the obstructive sleep apnoea syndrome

Background & Objectives: Awareness regarding obstructive sleep apnoea (OSA) among general public as well as practicing physicians is low in India. The present study was undertaken to test the utility of modified Berlin questionnaire for risk categorization of OSA in Indian setting. Methods: The modified Berlin questionnaire was administered in 180 middle aged adults (of 320 screened), of whom, 104 underwent overnight polysomnograhy, in a cross-sectional study at a tertiary care, referral center in north India. Questionnaire addressed the presence of frequency of snoring, wake time sleepiness, fatigue, obesity and hypertension. Subjects with persistent and frequent symptoms in any two of these three domains were considered in high risk category for obstructive sleep apnoea. Overnight polysomnograhy was performed to measure apnoea and hypopnoea index (AHI). Results: Questions about the symptoms demonstrated internal consistency (Cronbach alpha correlations 0.92-0.96). Of the 180 respondents to the screening questions, 80 were in the high risk and the rest were in low risk group. For 104 subjects who underwent polysomnograhy, risk grouping was useful in prediction of AHI. High risk category predicted an AHI > 5 with a sensitivity of 86 per cent, specificity of 95 per cent, positive and negative predictive values of 96 and 82 per cent respectively. These results were comparable to Berlin questionnaire study done in the western population for validation. Interpretation & Conclusion: On the basis of the findings of present study it is concluded that administration of modified Berlin questionnaire prior to a polysomnography study can identify high risk subjects and can thus avoid unnecessary polysomnography studies especially in resource-limited settings. To identify subjects at risk for OSA syndrome in general population, this questionnaire can be applied. However, the findings of the present study need to be confirmed further in a large number of subjects in a community-based setting

Designing of a comprehensive format for the analysis of Deha Prakruti

Prevalence of life style disorders has reached alarming proportions among Indians in the recent years. So prevention of life style disorders is a challenge now a days. Ayurveda provides a definite ray of hope for this. Prakruti in Ayurveda is the expression of person in context of morphology, Physiology, behavior and relation to ecology. To provide such guidelines on individual basis consideration of Deha Prakruti is important parameter. So it is a need of Ayurveda practitioner to have a precise format for diagnosis of exact Deha Prakruti in short period for convenience of OPD patients. Present study is effort to design a concise format for Deha Prakruti analysis

The fundamental study of the principle Rogan Rutujan Na Jatu in the treatment of Pittaj Shirahshul (headache) w.s.r. to Virechanopakrama

To prevent the recurrence of seasonal disorders Rutuvat Shodhanopakrama (Seasonal detoxification) is the ideal pathway. So in Varsharutu (Rainy season), Bastikarma (Enema therapy); Sharadrutu (Autumn season), Virechankarma (Purgation therapy) and in Vasantrutu (Spring sea- son), Vaman karma (Emesis therapy) is best for Shodhan (detoxification) of vitiated Vatadosha, Pittadosha and Kapha dosha respectively to avoid occurrence of seasonal disorders. Study is conducted only on Virechana karma (Purgation therapy) in Sharad Rutu (Autumn season) on sample size of 30 patients suffering from Pittaj Shirahshul (Headache). The chief symptoms of the disease are Shirodaha (Burning sensation in head), Shirovedana (Headache), Chakshudaha (Burning sensation in eyes), Trushna (Thirst), Bhrama (Giddiness) and Swedpravrutti (Sweating). Sharadkalin Trivrutadi Virechana yoga (purgative formulation used in Autumn) is most efficacious which acts as Pittaghna (reduces Pitta) and Rechana (purgative) which could be the beneficial line of treatment for Pittaj Shirahshul (Headache). Hence Virechana karma (Purgation ther- apy) should be carried out furthermore in every Sharad rutu (autumn season) to reduce the risk of relapse and to prevent rutujanya pittaj shirahshul (headache due to vitiated Pitta)

Post COVID-19 Guillain Barre syndrome with syndrome of inappropriate secretion of antidiuretic hormone

Guillain Barre syndrome (GBS) is a rare but potentially fatal immune mediated disorder of peripheral nerves and nerve roots usually triggered by infections characterized by ascending paralysis with or without sensory symptoms, hyporeflexia to areflexia. Usually preceded by gastrointestinal or respiratory infection. Post COVID-19 neurological manifestation include GBS, transverse myelitis etc., occur at varying incidence rates at various places. Here we report a 42-year-old lady who had COVID-19 recovered presented with quadriparesis with absent deep tendon reflexes with electro-diagnostically proven AMSAN variety of GBS treated successfully with IVIg. Patient was having hyponatremia which was diagnosed to be due to SIADH and was successfully treated with fluid restriction and tolvaptan. This case is being reported due to combination of COVID-19, COVID vaccination shortly before GBS and hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) which is quite rare combination

Performance evaluation of Bragg coherent diffraction imaging

In this study, we present a numerical framework for modeling three-dimensional (3D) diffraction data in Bragg coherent diffraction imaging (Bragg CDI) experiments and evaluating the quality of obtained 3D complex-valued real-space images recovered by reconstruction algorithms under controlled conditions. The approach is used to systematically explore the performance and the detection limit of this phase-retrieval-based microscopy tool. The numerical investigation suggests that the superb performance of Bragg CDI is achieved with an oversampling ratio above 30 and a detection dynamic range above 6 orders. The observed performance degradation subject to the data binning processes is also studied. This numerical tool can be used to optimize experimental parameters and has the potential to significantly improve the throughput of Bragg CDI method