Computational screening of anticancer drugs targeting miRNA155 synthesis in breast cancer

miRNAs have been identified to play a crucial role in carcinogenesis through their binding to various regulatory proteins. One such causative molecule identified as miRNA155, which when overexpressed is responsible for carcinogenesis and also leads to telomere fragility. miRNA155 levels in the blood are used for early screening of cancer. Several anticancer drugs such as doxorubicin have been identified, which act by binding to DNA and DNA binding enzymes to check their expression levels. In this study doxorubicin and its similar compounds were used to analyze their binding with miR155 DNA for inhibition of miRNA155 synthesis and their binding energies were calculated. Based on the docking, ADME, and toxicity results Morpholinyl Doxorubicin was used for molecular dynamics studies and was identified as a potential drug candidate

“Research on the "Engineering of Nano-gel for delivery of Mometasone and Itraconazole on Scalp and Beard for the Treatment of Fungal Infection"

Scalp and beard fungal infection often treated with conventional dosage form like cream, gel, emul-gel, which causes various side effects, to overcome such problems this research was conducted to develop Itraconazole and Mometsone Anti-fungal Nano-Hydro- Gel that is effective in the treatment of fungal infections of the scalp and beard. Itraconazole belongs to Azole group, which inhibit Lanosterol 14 alfa demethylase, the enzyme that converts lanosterol to ergosterol. Ergosterol is a component of yeast and fungal membranes. Nano-formulation penetrates deeper into the skin. The gel formula retains its therapeutic effect as well as the soothing effect on the hair follicles for long time. Pre-formulation studies of Itraconazole and Mometasone particles were done, and then both the API particles were converted into nano- particles through solvent diffusion method. SEM, P-XRD, IR tests were performed for characterization of Nano-Particles. Nano- Hydrogel base, prepare by using Carbopol-940, Carbopol-934, Triethanolamine and Distilled Water and engineering done by adding drug. When both Carbopol grades (934 and 940) are used together in the formulation of gel, the drug will release over a longer period of time with a smaller dose and less chance of any dose-dependent harm.Various composition were engineered an evaluated for selection of model formulation. Result- Evaluated for these parameters: Physical appearance, pH, estimation of practical yield, homogeneity, drug content uniformity, spreadability, viscosity, Statistical analysis of experimental data by ANOVA using Excel, In-vitro-drug release study, release kinetic study, Particle size analysis, (SEM), FT-IR studies. In-Vitro Anti-fungal activity tested by using Nano-gel Franz diffusion cell (Make-Orchid scientific). Amount of drug released was determined using UV- spectrophotometer at 222 nm. Conclusion- Fungal infection is most common skin condition occurs on the scalp and chin. Under these skin conditions, the hair follicles become inflamed and the affected area becomes itchy, flaky or scaly, causing redness, swelling and irritation. So this research was done with focus for pathology, pathogenesis consequently treatment of scalp and beard fungal infectio

Anorectal balloon cell melanoma: a rare variant

Balloon cell melanoma is a rare presentation of malignant melanoma, usually on the skin, with less than 100 cases reported. Mucosal BCM is even rarer, with only one case of anorectal BCM reported in English literature. The diagnosis is based on the histopathologic findings of a tumor composed of large, foamy melanocytes, with or without pigmentation, and confirmed by immunohistochemical studies showing expression for melanocytic markers. The foam cell appearance of the tumor cells and the lack of melanin pigment lead to a diagnostic dilemma, mostly when presented at an unusual location. Herein, we report a case of balloon cell melanoma at the anorectal junction in a 73-year-old male patient complaining of constipation and bleeding per rectum. Surgical resection was performed with no evidence of recurrence after three years of close follow-up. We believe this case will raise awareness among the medical community to consider this tumor a differential diagnosis in rectal masses

Cololejeunea microscopica var. exigua (A. Evans) Pócs: new to Asia

Cololejeunea microscopica var. exigua (A. Evans) Pócs has been discovered from Kodaikanal, Tamil Nadu, South India, which is a new record for the country as well as for Asia showing extended distribution of the taxon from Europe, America and Africa to Asia

Rapid and Accurate INS Transfer Alignment for Air Launched Tactical Missile Using Kalman Filter

An Inertial Navigation System (INS) independently measures the Position, Velocity, and Attitude (PVA) of thevehicle to navigate it towards the target. Since INS is a dead-reckoning system, it requires accurate initialization toprovide the navigation (PVA) solution. In the case of an air-launched tactical missile, the aircraft navigation system(Master INS) information is used to initialize accurately the missile INS (Slave INS). Rapid transfer alignment isneeded in today’s combat operation to converge slave INS initialization in the shortest possible time using aircraftnavigation information. The transfer alignment consists of first initializing the missile INS and establishing anavigation solution (PVA) using the missile IMU rates and accelerations, then a Kalman filter is used to, estimatethe errors between the Slave INS and Master INS. The proposed method’s simulation results show that a tacticalmissile INS can be aligned to an acceptable accuracy in a very short time based on the aircraft’s attitude information and with natural maneuvers experienced during aircraft take-off

Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium tuberculosis: A non-conventional hemolysin and a ribosomal RNA methyl transferase

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium tuberculosis </it>is a virulent bacillus causing tuberculosis, a disease responsible for million deaths each year worldwide. In order to understand its mechanism of pathogenesis in humans and to help control tuberculosis, functions of numerous <it>Mycobacterium tuberculosis </it>genes are being characterized. In this study we report the dual functionality of <it>tlyA </it>gene product of <it>Mycobacterium tuberculosis </it>annotated as Rv1694, a 268 amino acid long basic protein.</p> <p>Results</p> <p>The recombinant purified Rv1694 protein was found to exhibit hemolytic activity <it>in vitro</it>. It showed concentration and time-dependent hemolysis of rabbit and human erythrocytes. Multiple oligomeric forms (dimers to heptamers) of this protein were seen on the membranes of the lysed erythrocytes. Like the oligomers of conventional, well-known, pore-forming toxins, the oligomers of Rv1694 were found to be resistant to heat and SDS, but were susceptible to reducing agents like β-mercaptoethanol as it had abolished the hemolytic activity of Rv1694 indicating the role of disulfide bond(s). The Rv1694 generated <it>de novo </it>by <it>in vitro </it>transcription and translation also exhibited unambiguous hemolysis confirming the self assembly and oligomerization properties of this protein. Limited proteolytic digestion of this protein has revealed that the amino terminus is susceptible while in solution but is protected in presence of membrane. Striking feature of Rv1694 is its presence on the cell wall of <it>E. coli </it>as visualized by confocal microscopy. The surface expression is consistent with the contact dependent haemolytic ability of <it>E. coli </it>expressing this protein. Also, immune serum specific to this protein inhibits the contact dependent hemolysis. Moreover, Rv1694 protein binds to and forms stable oligomers on the macrophage phagosomal membranes. In addition to all these properties, <it>E. coli </it>expressing Rv1694 was found to be susceptible to the antibiotic capreomycin as its growth was significantly slower than mock vector transformed <it>E. coli</it>. The S30 extract of <it>E. coli </it>expressing the Rv1694 had poor translational activity in presence of capreomycin, further confirming its methylation activity. Finally, incorporation of methyl group of [³H]-S-adenosylmethionine in isolated ribosomes also confirmed its methylation activity.</p> <p>Conclusions</p> <p>The Rv1694 has an unusual dual activity. It appears to contain two diverse functions such as haemolytic activity and ribosomal RNA methylation activity. It is possible that the haemolytic activity might be relevant to intra-cellular compartments such as phagosomes rather than cell lysis of erythrocytes and the self-assembly trait may have a potential role after successful entry into macrophages by <it>Mycobacterium tuberculosis</it>.</p

Sum-Rate Maximization of IRS-Aided SCMA System

We study an intelligent reflecting surface (IRS)-aided downlink sparse code multiple access (SCMA) system for massive connectivity in future machine -type communication networks. Our objective is to maximize the system sum-rate subject to the constraint of minimum user data rate, the total power of base station, SCMA codebook structure, and IRS channel coefficients. To this end, a joint optimization problem involving IRS phase vector, factor graph matrix assignment, and power allocation problem is formulated, which is non-convex in nature. This problem is solved by developing an alternating optimization (AO) algorithm. A key idea is to first divide the formulated non-convex problem into three subproblems (i.e., factor graph matrix assignment, power allocation, and phase vector of IRS) and then tackle them iteratively. The validity of the proposed schemes is shown using the simulation results. Moreover, compared to the SCMA system without IRS, a significant performance improvement in the IRS-aided SCMA system is shown in terms of achievable sum-rate

Membrane Bound Monomer of Staphylococcal α-Hemolysin Induces Caspase Activation and Apoptotic Cell Death despite Initiation of Membrane Repair Pathway

BACKGROUND: Wild type Staphylococcal alpha-hemolysin (alpha-HL) assembly on target mammalian cells usually results in necrotic form of cell death; however, caspase activation also occurs. The pathways of caspase activation due to binding/partial assembly by alpha-HL are unknown till date. RESULTS: Cells treated with H35N (a mutant of alpha-HL that remains as membrane bound monomer), have been shown to accumulate hypodiploid nuclei, activate caspases and induce intrinsic mitochondrial apoptotic pathway. We have earlier shown that the binding and assembly of alpha-HL requires functional form of Caveolin-1 which is an integral part of caveolae. In this report, we show that the caveolae of mammalian cells, which undergo a continuous cycle of 'kiss and run' dynamics with the plasma membrane, have become immobile upon the binding of the monomer. The cells treated with H35N were unable to recover despite activation of membrane repair mechanism involving caspase-1 dependent activation of sterol regulatory element binding protein-1. CONCLUSIONS: This is for the first time we show the range of cellular changes and responses that take place immediately after the binding of the monomeric form of staphylococcal alpha-hemolysin

Resource Allocation for Sum-Rate Maximization in Multi-UAV SCMA Networks

This work investigates a sparse code multiple access (SCMA) assisted multiple unmanned aerial vehicles (UAVs) downlink communication network for improved data services to multiple ground users. Our objective is to maximize the sum-rate of the multi-UAV SCMA network by optimizing the SCMA factor graph matrix used for resource allocation, considering the inter-UAV and intra-UAV interference components. The formulated problem is non-convex in nature and is subject to the SCMA codebook constraints. We propose a factor graph matrix assignment algorithm to solve this optimization problem. Our simulation results demonstrate the superiority of the proposed scheme in terms of rate performance over the benchmark schemes. Thus, compared with orthogonal multiple access strategies, SCMA emerge as a promising candidate for next generation multiple access (NGMA) techniques