39 research outputs found

    JMASM 51: Bayesian Reliability Analysis of Binomial Model – Application to Success/Failure Data

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    Reliability data are generated in the form of success/failure. An attempt was made to model such type of data using binomial distribution in the Bayesian paradigm. For fitting the Bayesian model both analytic and simulation techniques are used. Laplace approximation was implemented for approximating posterior densities of the model parameters. Parallel simulation tools were implemented with an extensive use of R and JAGS. R and JAGS code are developed and provided. Real data sets are used for the purpose of illustration

    Action of philanthotoxin on ion channels of arthropod muscle

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    Calcium ions play an important role in many signalling pathways involved in normal cell metabolism. Pertrebations of normal Ca++ signalling may also play a pivotal role in the initiation of cell death. In these studies I have examined the influx of 45Ca++ into the extensor tibiae muscle of the locust (Schistocerca gregaria ). 45Ca++ entry could be stimulated by the addition of glutamate receptor-agonists or by activation of voltage activated calcium channels. L-glutamate, L-quisqualate and NMDA stimulated the influx of 45Ca++ while L-aspartate had only a small effect. DL-ibotenate, kainate, AMPA and glycine had no effect on 45Ca++ uptake (all agonists were tested at concentrations up to (100μM). Glycine (1μM) enhanced the 45Ca++ entry induced by NMDA and L-glutamate. Only the glycine potentiation of L-glu-stimulated responses was abolished in the presence of Mg++ (2mM) or AP5 (10μM) whereas the NMDA-stimulated response was completely abolished by these agents. These finding suggests that in the presence of glycine, L-glutamate may activate NMDA receptors and that in the absence of glycine L-glu-stimulated 45Ca++ entry occurs via activation of the qGluR. Depolarisation of the extensor tibiae muscles (50mM KCl) stimulated 45Ca++ influx by activation of voltage-sensitive calcium channels. Philanthotoxin-343 (0.1μM) had no effect on depolarisation activated calcium entry, however, nifedipine (1μM) an L-type calcium channel antagonist inhibited this Ca++ influx. Nifedipine did not inhibit L-glu-stimulated Ca++ entry suggesting that in these muscles L-type Ca++ channels are not involved in the Ca++ influx pathway following G1uR activation. Philanthotoxin-433 (PhTX-433) and many of its synthetic analogues are potent inhibitors of locust GluR. In the future these analogues may prove as useful potential neuroprotective agents or as novel pesticides. Over 100 analogues of PhTX-433 have been synthesized with changes made in the four regions of the structure, the thermospermine moiety, the tyrosyl moiety, the butyryl moiety and the terminal amino moiety. The effects of different concentrations (10-4M to 10-14M) of synthetic analogues of PhTX-433 (PhTX-343, PhTX-343-Arg, PhTX-4) were investigated in the 45Ca++ influx assay using locust extensor tibiae muscle. PhTX-343-Arg was more potent (IC50= - 7x10-9) than PhTX- 343 (IC50= - 10-8M) or PhTX-4 in blocking 45Ca H uptake. These findings were further supported by electrophysiological studies. The interaction of these synthetic analogues of philanthotoxin with GluR of locust muscle were further investigated by examining the effect of these compounds on evoked excitatory post synaptic potentials. In recent years control of ticks have been very important issue because of the social and economical damage they cause. Neuromuscular transmission is a main target site for the chemical control of many pests. Philanthotoxin and its analogues block the glutamate receptors which are involved in arthropod neuromuscular transmission and thus may prove useful as novel pesticides. The action of synthetic analogues of philanthotoxin (C7PhTX-343, DNP12-, PhTX-343 and PhTX-343) were examined on evoked excitatory postsynaptic potential in tick coxal muscle. These compounds all antagonized the evoked EPSP. C7PhTX-343 and DNP12-PhTX-343 exhibited same potency (IC50 = 10-8M) and both were more potent than PhTX-343 (IC50 ='2X10-5M). In recent years Xenopus oocyte has taken over a new role as a test tube for the study of the biogenesis, functional architecture and modulation of plasma membrane protein. Attempts were made to express mRNA from embryonic tissue of tick and locust leg muscle in to Xenopus oocyte for pharmacological studies. Xenopus oocytes failed to translate RNA faithfully and efficiently from these sources. Rat brain RNA injected oocytes used as control, expressed routinely

    Action of philanthotoxin on ion channels of arthropod muscle

    Get PDF
    Calcium ions play an important role in many signalling pathways involved in normal cell metabolism. Pertrebations of normal Ca++ signalling may also play a pivotal role in the initiation of cell death. In these studies I have examined the influx of 45Ca++ into the extensor tibiae muscle of the locust (Schistocerca gregaria ). 45Ca++ entry could be stimulated by the addition of glutamate receptor-agonists or by activation of voltage activated calcium channels. L-glutamate, L-quisqualate and NMDA stimulated the influx of 45Ca++ while L-aspartate had only a small effect. DL-ibotenate, kainate, AMPA and glycine had no effect on 45Ca++ uptake (all agonists were tested at concentrations up to (100μM). Glycine (1μM) enhanced the 45Ca++ entry induced by NMDA and L-glutamate. Only the glycine potentiation of L-glu-stimulated responses was abolished in the presence of Mg++ (2mM) or AP5 (10μM) whereas the NMDA-stimulated response was completely abolished by these agents. These finding suggests that in the presence of glycine, L-glutamate may activate NMDA receptors and that in the absence of glycine L-glu-stimulated 45Ca++ entry occurs via activation of the qGluR. Depolarisation of the extensor tibiae muscles (50mM KCl) stimulated 45Ca++ influx by activation of voltage-sensitive calcium channels. Philanthotoxin-343 (0.1μM) had no effect on depolarisation activated calcium entry, however, nifedipine (1μM) an L-type calcium channel antagonist inhibited this Ca++ influx. Nifedipine did not inhibit L-glu-stimulated Ca++ entry suggesting that in these muscles L-type Ca++ channels are not involved in the Ca++ influx pathway following G1uR activation. Philanthotoxin-433 (PhTX-433) and many of its synthetic analogues are potent inhibitors of locust GluR. In the future these analogues may prove as useful potential neuroprotective agents or as novel pesticides. Over 100 analogues of PhTX-433 have been synthesized with changes made in the four regions of the structure, the thermospermine moiety, the tyrosyl moiety, the butyryl moiety and the terminal amino moiety. The effects of different concentrations (10-4M to 10-14M) of synthetic analogues of PhTX-433 (PhTX-343, PhTX-343-Arg, PhTX-4) were investigated in the 45Ca++ influx assay using locust extensor tibiae muscle. PhTX-343-Arg was more potent (IC50= - 7x10-9) than PhTX- 343 (IC50= - 10-8M) or PhTX-4 in blocking 45Ca H uptake. These findings were further supported by electrophysiological studies. The interaction of these synthetic analogues of philanthotoxin with GluR of locust muscle were further investigated by examining the effect of these compounds on evoked excitatory post synaptic potentials. In recent years control of ticks have been very important issue because of the social and economical damage they cause. Neuromuscular transmission is a main target site for the chemical control of many pests. Philanthotoxin and its analogues block the glutamate receptors which are involved in arthropod neuromuscular transmission and thus may prove useful as novel pesticides. The action of synthetic analogues of philanthotoxin (C7PhTX-343, DNP12-, PhTX-343 and PhTX-343) were examined on evoked excitatory postsynaptic potential in tick coxal muscle. These compounds all antagonized the evoked EPSP. C7PhTX-343 and DNP12-PhTX-343 exhibited same potency (IC50 = 10-8M) and both were more potent than PhTX-343 (IC50 ='2X10-5M). In recent years Xenopus oocyte has taken over a new role as a test tube for the study of the biogenesis, functional architecture and modulation of plasma membrane protein. Attempts were made to express mRNA from embryonic tissue of tick and locust leg muscle in to Xenopus oocyte for pharmacological studies. Xenopus oocytes failed to translate RNA faithfully and efficiently from these sources. Rat brain RNA injected oocytes used as control, expressed routinely

    Survey on synchrophasor data quality and cybersecurity challenges, and evaluation of their interdependencies

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    Synchrophasor devices guarantee situation awareness for real-time monitoring and operational visibility of smart grid. With their widespread implementation, significant challenges have emerged, especially in communication, data quality and cybersecurity. The existing literature treats these challenges as separate problems, when in reality, they have a complex interplay. This paper conducts a comprehensive review of quality and cybersecurity challenges for synchrophasors, and identifies the interdependencies between them. It also summarizes different methods used to evaluate the dependency and surveys how quality checking methods can be used to detect potential cyberattacks. This paper serves as a starting point for researchers entering the fields of synchrophasor data analytics and security

    In vitro susceptibility of typhoidal Salmonellae against newer antimicrobial agents: a search for alternate treatment options

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    OBJECTIVES: To determine the minimum inhibitory concentrations (MICs) of ceftriaxone, azithromycin, pefloxacin, cefipime and imipenem for Salmonella Typhi (S. Typhi) and Paratyphi. METHODS: One hundred and fifty four isolates of Salmonella Typhi and S. Paratyphi A, B and C growing in blood culture were selected. MICs of ceftriaxone, azithromycin, pefloxacin, cefipime and imipenem were performed by agar dilution method as recommended by clinical laboratory standard institutes. RESULTS: MIC90 of azithromycin and pefloxacin was 8 microg/ml, cefipime was 0.06 microg/ml and imipenem was 0.5 microg/ml. None of the strains were found to be resistant to ceftriaxone but 3 isolates showed higher MIC value of 2 microg/ml. CONCLUSION: Azithromycin appears a suitable alternate for the treatment of typhoid in the community. Imipenem and cefipime are good options in complicated cases to be treated in hospital settings. Pefloxacin cannot be used as MICs are higher. Presence of isolates with higher MIC of ceftriaxone is serious and stresses upon continuous laboratory surveillance to guide clinicians appropriately

    Journey from black to pink gums: management of melanin induced physiological gingival hyper pigmentation

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    Abstract Smile is an expression of happiness, self-confidence, kindness and beauty. Along with teeth and lips, gingiva is also a vital component of smile. Melanin induced gingival hyper pigmentation may appear un-aesthetic especially when it is associated with high smile line, upper anterior labial segment and is uneven in appearance. It affects individuals from all races. Generally, it is believed that melanin induced gingival hyper pigmentation is confined to individuals from dark races. But studies have shown that Iranian, Indian, Italian, Arabian, Greek. German, French, Japanese, Chinese, Jewish, Thai, Malaysian and other ethnic groups also display clinical gingival pigmentation.1 Gingival hyper pigmentation may result in psychological distress especially when the appearance is of utmost importance for the individuals. This article aims to focus on the physiology, clinical appearance and treatment options available for the melanin induced gingival hyper pigmentation along with the reported recurrence in the light of current literature

    Myths and fallacies about epilepsy among residents of a Karachi slum area

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    Misconceptions about epilepsy may explain the considerable stigma accompanying it. We aimed to identify such fallacies through questionnaire-based interviews of 487 adult residents of a slum area in Karachi, Pakistan. Of those interviewed, 25% believed that epilepsy was caused by evil spirits, black magic and envy by others those without a school education were more likely to hold these views (P \u3c 0.05). Perceived complications included impotence and cancer. Shoe-sniffing was considered a treatment modality by 13%. It appears that misconceptions abound regarding epilepsy\u27s causes, complications and methods of treatment. However, those who had received a school education were less likely to link epilepsy with supernatural phenomena

    Prevalence of Self-Medication of Psychoactive Stimulants and Antidepressants among Undergraduate Pharmacy Students in Twelve Pakistani Cities

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    Purpose: To evaluate the prevalence of self-medication of psychoactive stimulants and antidepressants among pharmacy students of Pakistan.Methods: A cross-sectional survey on self-medication of psychoactive stimulants and antidepressants among pharmacy students was conducted with a structured and validated questionnaire distributed to a total of 2981 final year undergraduate pharmacy students in 12 major Pakistani cities (Karachi, Lahore, Islamabad, Rawalpindi, Sargodha, Dera Ismail Khan, Abbottabad, Bahawalpur, Hyderabad, Faisalabad, Multan and Peshawar) of Pakistan. Out of this, 2516 (718 male and 1798 female) students completed and returned the questionnaire.Results: Prevalence of self-medication of psychoactive stimulants was 1.31 (1.13 – 1.75 for 95% CI) and antidepressants was 8.34 (8.03 – 8.85 for 95% CI). A majority of the students (63 %) identified academic competition as a driving force for indulging in self-medication of psychoactive stimulants while nearly all the students (96 %)admitted using antidepressants to obtain relief from the pressure of studies (p < 0.05).Conclusion: Pakistani pharmacy students, despite being aware of the hazards of psychoactive stimulants, indulge in self-medication. Prevalence of self-medication with antidepressants is very high among the students due to the pressure of studies. Primarily, academic competition is the major driving force for the use of psychoactive stimulants.Keywords: Self-medication, Psychoactive stimulants, Antidepressants, Pharmacy students, Academicpressur

    CMS physics technical design report : Addendum on high density QCD with heavy ions

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