Computational binding mechanism of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (MurA) with inhibitors fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic aci

Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and about two million deaths are attributable to TB annually. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structural model of Mtb-MurA enzyme has been developed, for the first time, by homology modeling and molecular dynamics simulation techniques. The model provided clear insight in its structure features, i.e. substrate binding pocket, and common docking site. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E.coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structural model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives is showed best interaction compared with other inhibitor, taking in to this we also design a new efficient analogs of T6361 and T6362 which are showed even better interaction with Mtb-MurA than the parental5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing of a more specific inhibitor for Mtb-MurA enzym

Density Fluctuations in the Oscillatory Phase of Nonclassical Inflaton in FRW Universe

Using coherent and squeezed state formalisms of quantum optics for a minimally coupled non-classical inflaton in the FRW mertic is studied, in semiclassical theory of gravity. The leading order solution for the semiclassical Einstein equations in the coherent, squeezed and squeezed vacuum states are obtained perturbatively and are exhibit powerlaw expansion behaviour. The validity of the semiclassical theory is examined in the squeezed vacuum state in the oscillatory phase of the inflaton. The semiclassical theory in the oscillatory phase of the non-classical inflaton holds only if the associated squeezing parameter is much less compared to unity. Quantum fluctuations of the inflaton is also examined in coherent and squeezed state formalisms.Comment: 14 pages, 2 figures, To appear in Int.J.Mod.Phys.

Dynamical Self-assembly during Colloidal Droplet Evaporation Studied by in situ Small Angle X-ray Scattering

The nucleation and growth kinetics of highly ordered nanocrystal superlattices during the evaporation of nanocrystal colloidal droplets was elucidated by in situ time resolved small-angle x-ray scattering. We demonstrated for the first time that evaporation kinetics can affect the dimensionality of the superlattices. The formation of two-dimensional nanocrystal superlattices at the liquid-air interface of the droplet has an exponential growth kinetics that originates from interface "crushing".Comment: 4 pages, 4 figure

PREPARATION AND EVALUATION OF CYCLODEXTRIN COMPLEXES OF ANTI-TUBERCULAR DRUG RIFAMPICIN FOR IMPROVED BIOAVAILABILITY

The aim of the study was to increase the aqueous solubility, dissolution rate, stability, in vitro anti-tubercular activity and bioavailability of rifampicin by the way of inclusion complexation. Methyl B-cyclodextrin in case of rifampicin were used. Based on phase solubility studies that stoichiometry of complex of with respect to B-cyclodextrin for rifampicin was found to be 1:1 molar ratio. Different methods of preparation such as kneading and common solvent were employed to prepare the complexes. Formation of complexes In case of rifampicin, interaction of 4-methyl piperazin-1-ylimino-methyl (side chain) of rifampicin with the cyclodextrin molecule was confirmed by FTIR and 1H-NMR. The complexes prepared by different methods were subjected to solubility and in vitro dissolution studies. In case of rifampicin, in vitro anti-tubercular activity was found to be enhanced for the complexes of rifampicin indicated by a reduction in MIC of rifampicin. The oral bioavailability of rifampicin-MB-CD complex prepared by common solvent method was improved significantly. The results of stability studies revealed that stability of the drugs in solution and solid state were improved significantly due to complexation. Photostability of rifampicin is enhanced significantly by the way of complexation. Thus inclusion complexation of rifampicin with B-cyclodextrin, B-cyclodextrin derivatives and y-cyclodextrin improved its physical properties, bioavailability and in vitro activity

Magnetic and the magnetocaloric properties of Ce1-xRxFe2 and Ce(Fe1-xMx)2 compounds

We have studied selected rare earth doped and transition metal doped CeFe2 compounds by examining their structural, magnetic and magneto-thermal properties. With substitution of Ce by 5 and 10% Gd and 10% Ho, the Curie temperature can be tuned to the range of 267-318 K. Localization of Ce 4f electronic state with rare earth substitutions is attributed for the enhancement of Curie temperature. On the other hand, with Ga and Al substitution at the Fe site, system undergoes paramagnetic to ferromagnetic transition and then to an antiferromagnetic phase on cooling. The magnetocaloric effect across the transitions has been studied from both magnetization isotherms and heat capacity data. It is shown that by choosing the appropriate dopant and its concentration, the magnetocaloric effect around room temperature can be tuned.Comment: 13 pages, 6 figures, 2 table

Cancer of the uterine cervix and human papillomavirus infection

Human papillomaviruses (HPVs) have emerged as the principal sexually transmitted causal agents in the development of cancer of the uterine cervix in women. They also cause a variety of benign lesions, warts, intraepithelial neoplasia and anogenital, oral and pharyngeal papillomas. Presently, more than 100 HPV genotypes have been identified in humans, and about one-third of them have been sequenced. Of these, while HPV types 16 and 18 are considered to be the high-risk types, HPV 6 and 11 are the low-risk types in the development of cervical cancer. Evidence for causal role of HPV in the development of cervical neoplasia comes from the etiological and epidemiological observations together with the experimental findings of the molecular pathways elicited by HPV-transforming genes. Further evidence in favour of papillomavirus as the carcinoma virus comes from the findings of presence of HPV infections in cancers of oral, esophageal, larynx and nonmelanoma skin cancers. The oncogenic potentials of the virus have been attributed to its E6 and E7 genes. The products of these two genes stimulate cell proliferation by activating the cell-cycle-specific proteins and interfere with the functions of cellular growth-regulatory proteins, p53 and Rb. Identification and characterization of several human pathogenic HPV types warrant prevention of viral infection through vaccination or therapeutic intervention which could eventually control infection and expression of human pathogenic papillomaviruses

Empirical model for mean temperature for Indian zone and estimation of precipitable water vapor from ground based GPS measurements

Estimation of precipitable water (PW) in the atmosphere from ground-based Global Positioning System (GPS) essentially involves modeling the zenith hydrostatic delay (ZHD) in terms of surface Pressure (<I>P<sub>s</sub></I>) and subtracting it from the corresponding values of zenith tropospheric delay (ZTD) to estimate the zenith wet (non-hydrostatic) delay (ZWD). This further involves establishing an appropriate model connecting PW and ZWD, which in its simplest case assumed to be similar to that of ZHD. But when the temperature variations are large, for the accurate estimate of PW the variation of the proportionality constant connecting PW and ZWD is to be accounted. For this a water vapor weighted mean temperature (<I>T<sub>m</sub></I>) has been defined by many investigations, which has to be modeled on a regional basis. For estimating PW over the Indian region from GPS data, a region specific model for <I>T<sub>m</sub></I> in terms of surface temperature (<I>T<sub>s</sub></I>) is developed using the radiosonde measurements from eight India Meteorological Department (IMD) stations spread over the sub-continent within a latitude range of 8.5°–32.6° N. Following a similar procedure <I>T<sub>m</sub></I>-based models are also evolved for each of these stations and the features of these site-specific models are compared with those of the region-specific model. Applicability of the region-specific and site-specific <I>T<sub>m</sub></I>-based models in retrieving PW from GPS data recorded at the IGS sites Bangalore and Hyderabad, is tested by comparing the retrieved values of PW with those estimated from the altitude profile of water vapor measured using radiosonde. The values of ZWD estimated at 00:00 UTC and 12:00 UTC are used to test the validity of the models by estimating the PW using the models and comparing it with those obtained from radiosonde data. The region specific <I>T<sub>m</sub></I>-based model is found to be in par with if not better than a similar site-specific <I>T<sub>m</sub></I>-based model for the near equatorial station, Bangalore. A simple site-specific linear relation without accounting for the temperature effect through <I>T<sub>m</sub></I> is also found to be quite adequate for Bangalore. But for Hyderabad, a station located at slightly higher latitude, the deviation for the linear model is found to be larger than that of the <I>T<sub>m</sub></I>-based model. This indicates that even though a simple linear regression model is quite adequate for the near equatorial stations, where the temperature variations are relatively small, for estimating PW from GPS data at higher latitudes this model is inferior to the <I>T<sub>m</sub></I>-based model

Study of thyroid function in patients admitted in intensive care unit

Background: The thyroid gland produces two related hormones, tetraiodothyronine (T4) and triiodothyronine (T3) play a critical role in cell differentiation during development and maintain thermogenic and metabolic homeostasis in the adult. Critically ill patients have been defined as those that by dysfunction or failure of one or more organ system depend on survival from advanced instruments monitoring and therapy. The objective was to study the thyroid dysfunction in critically ill patients admitted in intensive care units and its relation to the mortality and severity of disease.Methods: This is a cross sectional study carried out in Dr. Pinnamaneni Siddhartha institute of medical sciences and research foundation, Chinoutpalli, Andhra Pradesh from 1st January 2022 to 30th September 2022 involving 100 patients. Patients of age above 18 years, both sexes, admitted to intensive care units with critical illness were analyzed and approved by institutional ethics committee of Dr. PSIMS and RF data were entered in MS-excel and analyzed in SPSS V22 software. Descriptive statistics, Mann-Whitney U test, logistic regression, ROC curves were applied. P values were reported for all statistical tests and a value of<0.05 was considered to be significant.Results: Out of 100 critically ill patients out of which 17 patients had sepsis, 18 had acute renal failure, 19 patients had acute respiratory failure, 19 patients had diabetic ketoacidosis, 16 patients had congestive cardiac failure, and 11 patients had stroke and their correlation with t3 hormone decrement showed positive correlation.Conclusions: Thyroid profile can be used in predicting the mortality in ICU patients