In search of no-loss strategies for the game of Tic-tac-toe using a customized genetic algorithm

The game of Tic-tac-toe is one of the most commonly known games. This game does not allow one to win all the time and a significant proportion of games played results in a draw. Thus, the best a player can hope is to not lose the game. This study is aimed at evolving a number of no-loss strategies using genetic algorithms and comparing them with existing methodologies. To efficiently evolve no-loss strategies, we have developed innovative ways of representing and evaluating a solution, initializing the GA population, developing GA operators including an elite preserving scheme. Interestingly, our GA implementation is able to find more than 72 thousands no-loss strategies for playing the game. Moreover, an analysis of these solutions has given us insights about how to play the game to not lose it. Based on this experience, we have developed specialized efficient strategies having a high win-to-draw ratio. The study and its results are interesting and can be encouraging for the techniques to be applied to other board games for finding efficient strategies

Tuberculosis of bilateral sacroiliac joints with bilateral psoas abscess: an unusual presentation

Infectious diseases usually affect the sacroiliac joint unilaterally. Out of all tuberculosis cases, bone tuberculosis is reported in 3-5% of cases. The purpose of this case report is to draw attention to the diagnostic challenge of bilateral tuberculous sacroiliitis with psoas abscess, as this clinical picture is very rare. Tuberculosis of the sacroiliac joint is often missed due to vague symptoms. More often, patients are examined in the supine position, thereby overlooking the sacroiliac joint. Involvement of the sacroiliac joint is rare, but exact numbers are not available. Our case report shows a complication of skeletal Tb that a psoas abscess may develop, causing nonspecific symptoms.

A Correlation Technique to Reduce the Number of Predictors to Estimate the Survival Time of HIV/ AIDS Patients on ART

Till now, many research papers have been published which aims to estimate the survivle time of the HIV/AIDS patients taking into consideration all the predictors viz, Age, Sex, CD4, MOT, Smoking, Weight, HB, Coinfection, Time, BMI, Location Status, Marital Status, Drug etc, although all the predictors need not to be included in the model. Since some of the predictors may be correlated/ associated and may have some influence on the outcome variable, therefore, instead of taking both the significantly correlated/ associated predictors, we may take only one of the two. In this way, we may be able to reduce the number of predictors without affecting the estimated survival time. In this paper we have tried to reduce the number of predictors by determining the highly positively correlated predictors and then evaluating the effect of correlation/ association on the survival time of HIV/AIDS patients. These predictors that we have considered in the starting are Age, Sex, State, Smoking, Alcohol, Drugs, Opportunistic Infections (OI), Living Status (LS), Occupation (OC), Marital Status (MS) and Spouse for the data collected from 2004 to 2014 of AIDS patients in an ART center of Delhi, India. We have performed one – way ANOVA to test the association between a quantitative and a categorical variable and Chi-square test to test between two categorical variables. To select one of the two highly correlated/ associated predictors, a suitable model is fitted keeping one predictor independent at a time and other dependent and the model having the smaller AIC is considered and the independent variable in the model is included in the modified model. The fitted models are logistic, linear and multinomial logistic depending on the type of the independent variable to be fitted. Then the true model (having all the predictors) and the modified model (with reduced number of predictors) are compared on the basis of their AICs and the model having minimum AIC is chosen. In this way we could reduce the number of predictors by almost 50% without affecting the estimated survival time with a reduced standard error

Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Author Posting. © American Society for Clinical Investigation, 2006. This article is posted here by permission of American Society for Clinical Investigation for personal use, not for redistribution. The definitive version was published in Journal of Clinical Investigation 116 (2006): 1668-1674, doi:10.1172/JCI22466.Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding protein, to purified InsP3R type 1 (InsP3R1) increased the channel activity in both a calcium-dependent and -independent manner. In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway. To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders. Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder.This work was supported by a grant from the NIH (GM63496 to B.E. Ehrlich), German National Merit Foundation scholarships (C. Schlecker and W. Boehmerle), and a National Kidney Foundation Fellowship (A. Varshney)

OECD-407 Driven 28-day-repeated-dose non-clinical safety evaluation of Tinospora cordifolia (Giloy) stem aqueous extract in Sprague-Dawley rats under GLP compliance

Introduction:Tinospora cordifolia (Wild.) Hook.f. & Thomson (Giloy), has been widely used in the Ayurvedic system of medicine. However, some sporadic under-powered case studies have recently reported Tinospora cordifolia associated toxicity. Thus, following OECD 407 guidelines, a 28-day-repeated-dose-14-day-recovery toxicological evaluation of the aqueous extract of T. cordifolia stem (TCWE) was conducted under good laboratory practice (GLP), in Sprague-Dawley (SD) rats.Methods: 100, 300, and 1000 mg/kg/day of TCWE was given orally to designated treatment groups of either sex. Two separate 14-day recovery satellite groups received either vehicle control or 1000 mg/kg/day of TCWE.Results: In this study, TCWE was found safe up to a dose of 1000 mg/kg/day with no mortality or related toxicological manifestation in terms of clinical signs, ocular effects, hematology, urinalysis, clinical chemistry parameters, or macro- or microscopic changes in any organs. The satellite group did not show any adverse effect after 14-day recovery period. Thus, the No-Observed-Adverse-Effect-Level (NOAEL) of TCWE was determined to be 1000 mg/kg/day.Discussion: In conclusion, this study established the non-clinical safety of the aqueous extract of T. cordifolia stem, which confirms the age-old safe medicinal use of this herb, and also paves the path for future clinical research on formulations containing Tinospora cordifolia

Intracellular Ca2+ Signaling and Human Disease The Hunt Begins with Huntington's

AbstractHuntingtin, a protein altered by polyglutamine expansion in Huntington's disease (Httexp), forms a signaling complex with the InsP3R, an intracellular calcium channel, and Htt-associated protein 1A (HAP1A). The addition of Httexp increases the InsP3R sensitivity to InsP3, which subsequently makes neurons hyperresponsive to stimulation and presumably more prone to neurodegenerative processes

Elevated testosterone induces apoptosis in neuronal cells

Testosterone plays a crucial role in neuronal function, but elevated concentrations can have deleterious effects. Here we show that supraphysiological levels of testosterone (micromolar range) initiate the apoptotic cascade. We used three criteria, annexin V labeling, caspase activity, and DNA fragmentation, to determine that apoptotic pathways were activated by testosterone. Micromolar, but not nanomolar, testosterone concentrations increased the response in all three assays of apoptosis. In addition, testosterone induced different concentration-dependent Ca2+ signaling patterns: at low concentrations of testosterone (100 nM), Ca2+ oscillations were produced, whereas high concentrations (1-10 μM) induced a sustained Ca2+ increase. Elevated testosterone concentrations increase cell death, and this effect was abolished in the presence of either inhibitors of caspases or the inositol 1,4,5-trisphosphate receptor (InsP 3R)-mediated Ca2+ release. Knockdown of InsP3R type 1 with specific s

Thyrogrit, supplemented with a sub-optimal dose of levothyroxine, restores thyroid function in rat model of propylthiouracil-induced hypothyroidism

Abstract Background Hypothyroidism is a common endocrine ailment, whose current standard of care is hormonal replacement therapy with levothyroxine (LT4). There is a medical need for alternative and safer therapies as LT4 is associated with special treatment considerations and adverse effects. Thyrogrit (THY) is a polyherbal formulation indicated for the treatment of hypothyroidism. The present study, describes the characterization of the phytocompounds present in THY and its in-vivo efficacy in rat model of hypothyroidism, in combination with a sub-optimal dose of LT4. Methods Ultra High Performance Liquid chromatography was employed for the identification of the phytocompounds present in THY. For the evaluation of its in-vivo efficacy, female Wistar rats were administered THY orally, 15-days prior to disease induction, and continued throughout the experiment. Subsequently, hypothyroidism was induced by oral administration of propylthiouracil (PTU). From day 45 onwards, animals were administered orally with a sub-optimal dose of LT4 (2 μg/kg) till the end of the study. On day 79, animals were euthanized, blood was collected for measurement of thyroid hormones and other clinical chemistry parameters. Weights of liver, kidney and thyroid were recorded. Finally, the thyroid was subjected to histopathological evaluation through hematoxylin and eosin (H&E staining), immunohistochemistry as well as immunofluorescence. Results The principal phyto-components detected in THY by Ultra High Performance Liquid Chromatography included gallic acid, protocatechuic acid, corilagin, ellagic acid, piperine, guggulsterone E and Z, which are documented to exerted beneficial effects on thyroid function. In the in-vivo study, THY when supplemented with a low dose of levothyroxine restored the PTU-induced reduction in the serum levels of T3 and T4 and improved PTU-induced renal impairment. THY treatment ameliorated the hallmark histopathological changes associated with hypothyroidism and C-cell hyperplasia. Further, co-administration of THY and LT4 did not show any major non-clinical safety concerns even after the administration for more than twelve weeks. Conclusion This study has demonstrated that co-administration of THY and LT4 improves the PTU-evoked alterations in the thyroid ultrastructure and function, abrogates hypothyroidism-associated renal impairment and exhibits an acceptable basic safety profile. Graphical abstrac

The energy-irrigation nexus in Bangladesh: implications of rapid rural electrification on informal groundwater markets

This brief provides a summary of research and findings on the impacts of rapid rural electrification in Bangladesh on the informal water markets during the last decade and how these markets in turn have affected irrigation access among smallholder farmers. The note emphasizes the importance of energy sources in determining the nature of groundwater access in Bangladesh, where groundwater remains central to irrigated agriculture and food production

Withania somnifera (L.) Dunal whole-plant extract demonstrates acceptable non-clinical safety in rat 28-day subacute toxicity evaluation under GLP-compliance

Abstract Withania somnifera (L.) Dunal (Ashwagandha) is widely used in Ayurveda, Unani and Siddha systems of medicines due to its therapeutic application in numerous ailments. Traditionally, the medications prepared from the plant employ only its roots and based on the currently available scientific literature, their efficacy and safety is well established. Apart from the roots, the aerial parts also contain bioactive components and correspondingly certain marketed preparations also employ the leaves of the plant. Accordingly, Ministry of Ayush, Government of India has lately issued an advisory emphasizing the need for extensive efficacy and safety profiling of leaf-based products. Consequently, we have conducted the present GLP-driven study, in which the non-clinical safety of a hydromethanolic extract of the whole plant of Withania somnifera (WSWPE) has been assessed according to OECD guideline 407. In this study Sprague Dawley rats of either sex were orally administered with WSWPE for 28-consecutive days at the doses of 100, 300 and 1000 mg/kg/day. The study also included a satellite group of animals that received WSWPE for 28-days followed by a 14-days recovery period. Withania somnifera Whole Plant Extract was found to be safe up to the dose level of 1000 mg/kg/day as no toxicologically relevant findings could be detected