Study on the algal flora as indicator of organic pollution in Darna River, Nasik (M.S.)

The algal flora i.e. algal bio indicators can be used for assessing the status, magnitude of the deterioration of the fresh water bodies; Moreover, aquatic algae can act as good indicators of water quality i.e. certain algal forms grow in a specific type of polluted water. These provide information of kind of organic pollution for that particular fresh water ecosystem. In the present research paper, PalmerÂ’ s algal genus and species pollution index (1969) was used to determine the tolerance of algal species towards an organic pollution in the Darna River. Thus the algal genera that are most tolerant to organic pollution can be identified. The Palmers algal index is simply calculated by summing up the scores of all relevant algal taxa present within the collected water samples from the Darna River

Diversity-oriented synthesis of a library of substituted tetrahydropyrones using oxidative carbon-hydrogen bond activation and click chemistry

Eighteen (2RS,6RS)-2-(4-methoxyphenyl)-6-(substituted ethyl)dihydro- 2Hpyran-4(3H)ones were synthesized via a DDQ-mediated oxidative carbon-hydrogen bond activation reaction. Fourteen of these tetrahydropyrans were substituted with triazoles readily assembled via azide-alkyne click-chemistry reactions. Examples of a linked benzotriazole and pyrazole motif were also prepared. To complement the structural diversity, the alcohol substrates were obtained from stereoselective reductions of the tetrahydropyrone. This library provides rapid access to structurally diverse non-natural compounds to be screened against a variety of biological targets. © 2011 by the authors

Artificial neural network predication and validation of optimum suspension parameters of a passive suspension system

This paper presents the modeling and optimization of quarter car suspension system using Macpherson strut. A mathematical model of quarter car is developed, simulated and optimized in Matlab/Simulink® environment. The results are validated using test rig. The suspension system parameters are optimized using a genetic algorithm for objective functions viz. vibration dose value (VDV), frequency weighted root mean square acceleration (hereafter called as RMS acceleration), maximum transient vibration value, root mean square suspension space and root mean square tyre deflection. ISO 2631-1 standard is adopted to assess ride and health criterion. Results shows that optimum parameters provide ride comfort and health criterions over classical design. The optimization results are experimentally validated using quarter car test setup. The genetic algorithm optimization results are further extended to the artificial neural network simulation and prediction model. Artificial neural network model is carried out in Matlab/Simulink® environment and Neuro Dimensions. Simulation, experimental and predicted results are in close correlation. The optimized system reduces the values of VDV by 45%. Also, RMS acceleration is reduced by 47%. Thus, the optimized system improved ride comfort by reducing RMS acceleration and improved health criterion by reducing the VDV. Finally ANN can be used for predicting the optimum suspension parameters values with good agreement

Insomnia and restless leg syndrome in patients undergoing chronic hemodialysis in Rafsanjan ali ibn abitaleb hospital

Background: Sleep is one of the most fundamental human needs; without any doubt sleep is even more essential for sick patients, especially for patients with chronic illnesses. Sleep disturbance may lead to anxiety and reduced quality of life. Restless leg syndrome (RLS) is a sensory-motor disorder accompanied by a strong desire to move the legs or other parts of the body, which can cause sleep disturbance. Its etiology is unknown, but increased urea and creatinine levels before dialysis, iron deficiency due to kidney failure and end-stage renal disease (ESRD) are mentioned as causes. Objectives: This study is designed to examine the prevalence of insomnia and restless leg syndrome in patients undergoing chronic hemodialysis in Rafsanjan Ali Ibn Abitaleb Hospital. Patients and Methods: In this study we used two questionnaires to evaluate the presence of RLS and insomnia in ESRD patients who were undergoing hemodialysis treatment as kidney replacement therapy. Results: According to our results, 54.5 of patients were diagnosed with RLS, and of those 65.2 and 42.9 were women and men, respectively. RLS is seen more often among patients with blood group type A, but this result was not statistically significant. There was a statistically significant correlation between RLS and a positive family history of RLS, between RLS and the number of hemodialysis treatments per week and also between RLS and the Insomnia Severity Index. Unlike previous studies, in this study we did not find any statistically significant correlation between RLS and biochemical factors such as serum iron, TIBC, BUN, creatinine, potassium, calcium and phosphorous levels. Conclusions: The frequency of RLS among our patients was remarkable and we conclude that all patients who are undergoing hemodialysis should be screened for RLS, which can assist in providing proper attention and treatment. © 2016, Nephrology and Urology Research Center

Monotherapy efficacy of blood-brain barrier permeable small molecule reactivators of protein phosphatase 2A in glioblastoma

Glioblastoma is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumour suppressors has not been thoroughly studied as yet as a glioblastoma therapeutic strategy. Tumour suppressor protein phosphatase 2A is inhibited by non-genetic mechanisms in glioblastoma, and thus, it would be potentially amendable for therapeutic reactivation. Here, we demonstrate that small molecule activators of protein phosphatase 2A, NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood–brain barrier, and in vivo partition to mouse brain tissue after oral dosing. In vitro, small molecule activators of protein phosphatase 2A exhibit robust cell-killing activity against five established glioblastoma cell lines, and nine patient-derived primary glioma cell lines. Collectively, these cell lines have heterogeneous genetic background, kinase inhibitor resistance profile and stemness properties; and they represent different clinical glioblastoma subtypes. Moreover, small molecule activators of protein phosphatase 2A were found to be superior to a range of kinase inhibitors in their capacity to kill patient-derived primary glioma cells. Oral dosing of either of the small molecule activators of protein phosphatase 2A significantly reduced growth of infiltrative intracranial glioblastoma tumours. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested glioblastoma cell lines, also significantly increased survival of mice bearing orthotopic glioblastoma xenografts. In summary, this report presents a proof-of-principle data for blood–brain barrier—permeable tumour suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background. These results also provide the first indications that protein phosphatase 2A reactivation might be able to challenge the current paradigm in glioblastoma therapies which has been strongly focused on targeting specific genetically altered cancer drivers with highly specific inhibitors. Based on demonstrated role for protein phosphatase 2A inhibition in glioblastoma cell drug resistance, small molecule activators of protein phosphatase 2A may prove to be beneficial in future glioblastoma combination therapies.</p

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

Seasonal Variation of Physicochemical Parameters and Fresh Water Algae in Pashan Lake

Pashan lake is situated northwest to Pune railway station on NDA road. It is about 3 km from University of Pune Railway Station. The lake was screened for different physicochemical parameters of water and different form of algae during the year 2001-2002. Periodic collections have been made from selecting sampling points of the lake at an interval of a fortnight during January 2001-December 2002. The water samples have been collected in bottles and characterized for different physiochemical parameters the algal forms were observed preserved in 4% formalin and Lugol's solution for detail studies. The live as well as preserved forms were observed under phase contract microscope and identifies with the help of Philipose, Smith, Fritsch and Prescott. Individual algal form or colony was micro photographed in Department of Botany, University of Pune, Pune-411007. The result revealed that the water temperature varied from 16-36oC, where as pH ranged from 6.5 to 7.4 . A marked variation in total alkalinity was observed during summer season. The dissolved oxygen content was high during summer season Nitrate level varied from 1.02 2.532 mg /L. Lowest concentration of nitrate, phosphate, chloride, carbonate, sulphate, calcium and magnesium were recorded during the pre-monsoon seasons. The results on fresh water algae indicated that most of the algae forms were planktonic, free floating and epiphytic. The algae forms belong to different genera of Cyanophyceae, Chlorophyceae, Bacillariophyceae, Dinophyceae, Chrysophyceae and Euglenophyceae. The results on seasonal variations in algal forms revealed that the members of Cyanophyceae were abundant in monsoon while members of Chlorophyceae were increased during the post monsoon to winter season. On the other hand diatoms were found abundant throughout the year except in October-November. The result of the present investigation revealed that physicochemical parameters of lake water significantly influenced the algae vegetation

Optimization of nonlinear quarter car suspension–seat–driver mod

In this paper a nonlinear quarter car suspension–seat–driver model was implemented for optimum design. A nonlinear quarter car model comprising of quadratic tyre stiffness and cubic stiffness in suspension spring, frame, and seat cushion with 4 degrees of freedom (DoF) driver model was presented for optimization and analysis. Suspension system was aimed to optimize the comfort and health criterion comprising of Vibration Dose Value (VDV) at head, frequency weighted RMS head acceleration, crest factor, amplitude ratio of head RMS acceleration to seat RMS acceleration and amplitude ratio of upper torso RMS acceleration to seat RMS acceleration along with stability criterion comprising of suspension space deflection and dynamic tyre force. ISO 2631-1 standard was adopted to assess ride and health criterions. Suspension spring stiffness and damping and seat cushion stiffness and damping are the design variables. Non-dominated Sort Genetic Algorithm (NSGA-II) and Multi-Objective Particle Swarm Optimization – Crowding Distance (MOPSO-CD) algorithm are implemented for optimization. Simulation result shows that optimum design improves ride comfort and health criterion over classical design variables

Potential of Vitex negundo roots in the treatment of ulcerative colitis in mice

Objective: The present work was undertaken to validate its folk use in the treatment of ulcerative colitis (UC) by using the method of acetic acid-induced colitis in mice