Asynchronous Games over Tree Architectures

We consider the task of controlling in a distributed way a Zielonka asynchronous automaton. Every process of a controller has access to its causal past to determine the next set of actions it proposes to play. An action can be played only if every process controlling this action proposes to play it. We consider reachability objectives: every process should reach its set of final states. We show that this control problem is decidable for tree architectures, where every process can communicate with its parent, its children, and with the environment. The complexity of our algorithm is l-fold exponential with l being the height of the tree representing the architecture. We show that this is unavoidable by showing that even for three processes the problem is EXPTIME-complete, and that it is non-elementary in general

Standardized method to extract phenolic compounds from Lagerstroemia speciosa L. (Jarul) for enhanced antioxidant activity

Phenolic compounds contribute to the antioxidant property of plants and the efficient extraction of plant phenolics could enhance its antioxidant potential. Lagerstroemia speciosa (L.) Pers. has been investigated for its pharmacological activities, but comparing its antioxidant activities of phenolics derived from its various parts has a key role in developing natural antioxidants. This study was conducted to standardize the extraction of phenolics from leaves, pods and branches of L. speciosa plant, followed by determination of antioxidant activities of their solvent fractions. Phenolic compounds were extracted from the leaves, pods and branches under different parameters such as temperature, pH, type of solvent and volume of the solvent. The extracted phenolic compounds were subjected to solvent fractions and antioxidant assays were performed. Among the various extraction methods tested, the best method was 50% ethanol +1% HCl, refluxing temperature, 100 ml of solvent and 1 hour extraction time. The best solvent fractions were determined as NaHCO3 + ethyl acetate for pods and ethyl acetate alone for leaves and branches with extracted phenolics content of 150.2 mg/g, 136.2 mg/g and 82.9 mg/g, respectively. The chloroform fraction was best among the fractions with maximum ascorbic acid equivalent (ASE) in all the parts of L. speciosa tested. Ferrous ion chelating capacity indicated that butanol fraction had the highest chelation and the same was recorded in ferric ion chelating assay with an EC50 value of 28.2. Hydroxyl radical scavenging activity of the fractions indicated that NaHCO3 + EtOAc fraction of pods had potential activity. Thus, the phenolic compounds from L. speciosa are excellent sources for future investigation on potent natural antioxidant compounds

Single-strand selective monofunctional uracil-DNA glycosylase (SMUG1) deficiency is linked to aggressive breast cancer and predicts response to adjuvant therapy

Uracil in DNA is an important cause of mutagenesis. SMUG1 is a uracil DNA glycosylase that removes uracil through base excision repair. SMUG1 also processes radiation induced oxidative base damage as well as 5-fluorouracil incorporated into DNA during chemotherapy. We investigated SMUG1 mRNA expression in 249 primary breast cancers. SMUG1 protein expression was investigated in 1165 breast tumours randomised into two cohorts [training set (n=583) and test set (n=582)]. SMUG1 and chemotherapy response was also investigated in a series of 315 ER negative tumours (n=315). For mechanistic insights, SMUG1 was correlated to biomarkers of aggressive phenotype, DNA repair, cell cycle and apoptosis. Low SMUG1 mRNA expression was associated with adverse disease specific survival (p=0.008) and disease free survival (p=0.008). Low SMUG1 protein expression (25%) was associated with high histological grade (p<0.0001), high mitotic index (p<0.0001), pleomorphism (p<0.0001), glandular de-differentiation (p=0.0001), absence of hormonal receptors (ER-/PgR-/AR) (p<0.0001), presence of basal-like (p<0.0001) and triple negative phenotypes (p<0.0001). Low SMUG1 protein expression was associated with loss of BRCA1 (p<0.0001), ATM (p<0.0001) and XRCC1 (p<0.0001). Low p27 (p<0.0001), low p21 (p=0.023), mutant p53 (p=0.037), low MDM2 (p<0.0001), low MDM4 (p=0.004), low Bcl-2 (p=0.001), low Bax (p=0.003) and high MIB1 (p<0.0001) were likely in low SMUG1 tumours. Low SMUG1 protein expression was associated with poor prognosis in univariate (p<0.001) and multivariate analysis (p<0.01). In ER+ cohort that received adjuvant endocrine therapy, low SMUG1 protein expression remains associated with poor survival (p<0.01). In ER- cohort that received adjuvant chemotherapy, low SMUG1 protein expression is associated with improved survival (p=0.043). Our study suggests that low SMUG1 expression may correlate to adverse clinicopathological features and predict response to adjuvant therapy in breast cancer

Structural heterogeneity in DNA gyrases from Gram-positive and Gram-negative bacteria

GyraseA (GyrA) subunit of DNA gyrase from mycobacteria has certain characteristics distinct from that of E. coli. Polyclonal antibodies produced against M. tuberculosis GyrA recognized GyrA from different slow and fast growing mycobacterial species and also from several Gram-positive bacteria. However, these antibodies did not cross-react with E. coli GyrA and the enzyme from other Gram-negative bacteria. The results from the present study together with multiple alignment, pairwise comparison and biochemical properties support the idea of the occurrence of two subclasses of gyrases in the bacterial kingdom, emphasizing the importance of the enzyme as a molecular target for the development of novel therapeutics

A scientific research study on the management of Manyasthamba (Cervical Spondylosis) with Nasya and Nasapana

The science of life Ayurveda, not only deals with the prevention of diseases by maintaining health but also with the alleviation of diseases. In this ultra modern era due to change in lifestyles, sedentary works and food habits, people are unable to follow the Dinacharya and Ritucharya as explained in the classics, which may lead to different diseases. Due to improper postural habits, weight bearing and other unwholesome diets and habits there are higher the chances of discomfort and disease pertaining to spinal cord. Manyasthambha is one such condition that disturbs a big population due to today’s alterations in lifestyle. Here an effort is made to study and understand the role of Nasya Karma, Nasaapana and Shamanaushadhi like Vyoshadi Guggulu in the treatment aspect of this disease. Nasya Karma and Nasaapana provided highly significant results in all the symptoms of Manyasthambha. As per the clinical data, ‘Nasaapana is found to be more effective than Nasya Karma’. So it can be concluded that better results can be obtained with Shaddharana Yoga as Amapachana, Nasaapana with Mashabaladi Kwatha followed by Vyoshadi Guggulu as Shamanoushadhi

DNA polymerase B deficiency is linked to aggressive breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts

Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12 - p11 and encodes a key DNA base excision repair protein. Pol β may be a tumour suppressor and involved in breast cancer pathogenesis. We conducted the first and the largest study to comprehensively evaluate pol β in breast cancer. We investigated pol β gene copy number changes in two cohorts (n=128 & n=1952), pol β mRNA expression in two cohorts (n=249 & n=1952) and pol β protein expression in two cohorts (n=1406 & n=252). Artificial neural network analysis for pol β interacting genes was performed in 249 tumours. For mechanistic insights, pol β gene copy number changes, mRNA and protein levels were investigated together in 1 28 tumours and validated in 1952 tumours. Low pol β mRNA expression as well as low pol β protein expression was associated high grade, lymph node positivity, pleomorphism, triple negative, basal - like phenotypes and poor survival (ps<0.001). In oestrogen receptor (ER) positive sub - group that received tamoxifen, low pol β protein remains associated with aggressive phenotype and poor survival (ps<0.001). Artificial neural network analysis revealed ER as a top pol β interacting gene. Mechanistically, there was strong positive correlation between pol β gene copy number changes and pol β mRNA expression (p<0.0000001) and between pol β mRNA and pol β protein expression (p<0.0000001). This is the first study to provide evidence that pol β deficiency is linked to aggressive breast cancer and may have prognostic and predictive significance in patients

Optimization, Characterisation and Pharmacokinetic Studies of Mucoadhesive Oral Multiple Unit Systems of Ornidazole

The objective of the present study was to investigate the applicability of matrix type mucoadhesive oral multiple unit systems (MUS) for sustaining the release of ornidazole in the gastrointestinal tract (GIT). The MUS were prepared by ionotropic gelation method using chitosan and hydroxypropyl methyl cellulose K4M (HPMC K4M) according to 32 factorial designs and were evaluated in vitro and in vivo. The particle size length ranged from 0.78 to 1.30 mm and breadth from 0.76 to 1.30 mm, respectively. The entrapment efficiency was in range of 80 to 96%. The rapid wash-off test was observed faster at intestinal pH 6.8 as compared to acidic pH 1.2. The fluoroscopic study revealed the retention of MUS in GIT for more than 5 hours. The pharmacokinetic parameters Cmax, Tmax, mean residence time (MRT) and area under curve (AUC) of developed MUS were found to be improved significantly (p<0.05) when compared with marketed immediate release tablets each containing 500 mg of drug. This study demonstrates that the MUS could be a good alternative to immediate release tablets to deliver ornidazole and expected to be less irritant to gastric and intestinal mucosa

FORMULATION AND EVALUATION OF BILAYERED FELODIPINE TRANSDERMAL PATCHES: IN VITRO AND EX VIVO CHARACTERIZATION

Objective: Felodipine (FD) is an effective Biopharmaceutics Classification System Class II calcium channel blocker mainly used in the management of hypertension and angina pectoris. It has poor solubility and low oral bioavailability (15%). To overcome these disadvantages and to maintain constant plasma concentration for maximum therapeutic activity, there is a need to design an alternative route, that is, transdermal route. The pharmacokinetic parameters make FD a suitable candidate for transdermal delivery. The present investigation consists of the study of in vitro and ex vivo skin flux of FD from bilayered transdermal patches. Methods: The patches were fabricated by solvent casting method using hydrophilic and hydrophobic polymer with different composition. Tween 80 incorporated as solubilizer, polyethylene glycol 600 as plasticizer, menthol, eucalyptus oil, and lemongrass oil used as permeation enhancers, respectively. The prepared transdermal drug delivery system was extensively evaluated for in vitro release, ex vivo permeation through pig ear skin, moisture content, moisture absorption, water vapor transmission, and mechanical properties. The physicochemical interaction between FD and polymers was investigated by Fourier-transform infrared (FTIR) spectroscopy. Results: All the formulations exhibited satisfactory physicochemical and mechanical characteristics. A flux of 35.2 μg/cm2 h, 27.9 μg/cm2 h, and 25.25 μg/cm2 h was achieved for optimized formulations containing lemongrass oil, eucalyptus oil, and menthol, respectively, permeation enhances. Values of tensile strength (0.0652±0.034 kg/mm²) and elongation at break (0.8749±0.0.0029% mm²) revealed that formulation F9 was strong but not brittle. Drug and excipients compatibility studies showed no evidence of interaction between the active ingredient and polymers. Conclusion: Bilayered FD transdermal patches could be prepared with required flux and suitable mechanical properties

Utilisation of Ram Air Turbine on a Fighter Platform for Energy Extraction Failure Mode Study

Aircraft electrical system needs to be robust enough to cater for electrical power requirements of all the systems of the aircraft and all the safety/degraded mission critical systems in failure modes. Designing such a robust electrical system for a developmental aircraft program is a challenge. A developmental aircraft during its various phases would involve integration of additional systems and new weapons (in case of fighter aircraft). Integration of newer systems imposes fresh challenges in managing the electrical system architecture especially in failure modes. Weapon integration in a prototype fighter program is dynamic as newer contemporary weapons are developed at faster pace and ever evolving. Power crisis through existing on-board power generation systems in failure mode was felt during an indigenous aircraft development program. A novel idea of introducing a Ram Air Turbine and utilize the power generated during main alternator failure for critical systems was studied. The intention of this paper is to cover the details of the study carried out towards utlisation of such a Ram Air Turbine in landing phase for extraction of energy in case of main alternator failure