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Ring hypothesis is one of the pieces of the theoretical polynomial math that has been thoroughly used in pictures. Nevertheless, ring hypothesis has not been associated with picture division. In this paper, we propose another rundown of similarity among pictures using rings and the entropy work. This new record was associated as another stopping standard to the Mean Shift Iterative Calculation with the goal to accomplish a predominant division. An examination on the execution of the calculation with this new ending standard is finished. In spite of the fact that ring hypothesis and class hypothesis from the start sought after assorted direction it turned out during the 1970s – that the investigation of functor groupings furthermore reveals new plots for module hypothesis.

Twitter is a ubiquitous, socially engaging and a rapid communication medium. To filter the relevant information like news, hashtags, links, followers, retweets for better user experience recommender systems have been extensively used on Twitter. Uncertainty in user preference, fuzziness in the rating process and the imprecision associated with the voluminous and varied Twitter data are some of the difficulties associated which impede enhanced recommendations. This research put forwards an Adaptive Neuro-Fuzzy Inference System (ANFIS) based tweet recommender model to handle the uncertainty, impreciseness and vagueness in item features and user’s behavior. The proposed hybrid content-based and collaborative filtering based recommended model learns the interests of source and target users to categorize tweets. The users are characterized as source user and target user to whom the tweet is to be recommended. The interests of the source and target user are extracted and the correlation between user interests is established which along with the category of the target tweet are then used to build the neuro-fuzzy model. The results show that the proposed model predicts the recommendation score correctly most of the time with the satisfactory Root Mean Square Error (RMSE) value indicating the fitness of the designed ANFIS model.

Background and objectives MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria. Methods and results Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells. Conclusion These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription.

Alginates are natural anionic carbohydrates found in the cell wall of brown algae and several bacterial strains. Alginate is easily degradable, bioactive, cost-effective, and less-toxic anionic polymer. This polymer is quite abundant in nature and is regularly being used in dentistry due to its extraordinary properties like biocompatibility, elasticity, nontoxicity. The selection of materials used in dentistry is based upon the consistency of their chemical, physical, and biological properties; susceptibility of their exquisite qualities; and operator’s inclinations, and also depends on the type of treatment being provided. For a long time, impression material from alginates has been a principal of many dental processes. This chapter comprises an overview of the uses of alginate-based bionanocomposites in the field of dentistry and a complete outlook of how the best alginate impressions are being prepared.

Isothermal low cycle fatigue (LCF) properties of Cu-Cr-Zr-Ti alloy were evaluated at different temperatures (300 °C, 450 °C and 600 °C) in high purity argon atmosphere. The cyclic stress response (CSR) was highly dependent on the test temperature. CSR at 300 °C showed primary hardening and secondary hardening at lower strain amplitudes from 0.25% to 0.8% and primary hardening followed by continuous softening at 1.2% strain amplitude. At 450 °C, the alloy exhibited a higher degree of primary hardening followed by saturation of stress. Transmission electron microscopic observations made on the samples tested upto different number of cycles indicate that precipitation of fine Cr precipitates was the main reason for the secondary hardening at 300 °C and extensive primary hardening at 450 °C. Even though precipitation was assisted by mechanical working during cycling, it is observed that the secondary hardening occurred almost at the same time irrespective of the strain amplitude used in the tests. At 450 °C and higher strain amplitudes, precipitates nucleated at the dislocations within a few initial cycles causing pinning of the dislocations thereby increasing the stress response. CSR at 600 °C showed continuous softening without any hardening. It is found that the precipitates nucleated during heating and soaking at the test temperature itself before the start of the strain cycling and coarsening of precipitates as well as loss of coherency with the matrix caused continuous softening at 600 °C. With an increase in test temperature, a reduction in fatigue life is observed and the life reduction is significant at higher strain amplitudes. Microstructural observations and fractographic studies indicated that cracks initiated predominantly at surface and propagated inward. Intergranular cracking was observed at higher strain amplitudes at all temperatures.

Airway management in polytrauma patients can create unanticipated challenges, particularly in the presence of tracheal injury. A 24-year-old male who suffered a road traffic accident was diagnosed with complete tracheal disruption with a gap of 3.5 cm with minimal external signs of injury. Initial intubation attempts revealed resistance at 18 cm from the angle of the mouth with the endotracheal tube creating a visible contour just below the skin in the midline of the neck. Associated palpable crepitus in the neck led to the suspicion of tracheal disruption. The patient was then intubated using a bougie. The tube was pushed into the bronchus distal to the suspected gap and then withdrawn to lie just above the carina, thereby providing adequate ventilation and preventing further development of subcutaneous emphysema. Associated injuries were managed by multidisciplinary consultations. Prompt thinking and quick clinical decisions with respect to the airway proved to be life-saving for the patient.

Aeromonas hydrophila, a gram negative bacterium is a major fish pathogen and causes major economic losses to aquaculture industry. Outer membrane proteins play a significant role in its survival during different environmental conditions and bacterial pathogenesis. The outer membrane protein R (OmpR) is a member of the two-component regulatory system of Aeromonas hydrophila which differentially regulates the expression of OmpF or OmpC depending on the osmolarity conditions. Role of OmpR has been demonstrated in its virulence in other infectious bacteria and it is found to be a potential drug target/vaccine candidate. However, the OmpR of A. hydrophila has not been characterized. In the present study, we report recombinant expression, purification of the OmpR of A. hydrophila strain Ah17 in salt inducible E. coli GJ1158 cells. Leaky expression of rOmpR was confirmed by Western blot analysis using anti-6 × His antibody. The histidine tagged recombinant OmpR (rOmpR) (~29 kDa) was purified using Ni-NTA affinity chromatography from the soluble fraction of induced E. coli cells. The rOmpR was found to be highly immunogenic with end point titres of greater than 1:80,000. The anti-rOmpR antisera were capable of agglutinating live A. hydrophila cells, thus showing vaccine potential of the rOmpR.

The etiology of cardiac fibrogenesis is quite diverse, but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined. Myocardin-related transcription factor A facilitates the transcription of cytoskeletal genes by serum response factor during fibrosis; therefore, its specific role in cardiac EndMT might be of importance. Activation of activating transcription factor 3 (ATF-3) during cardiac EndMT is speculative, since ATF-3 responds to a transforming growth factor β (TGF-β) stimulus and controls the expression of the primary epithelial-to-mesenchymal transition markers Snail, Slug, and Twist. Although the role of TGF-β in EndMT-mediated cardiac fibrosis has been established, targeting of the TGF-β ligand has not proven to be a viable anti-fibrotic strategy owing to the broad functional importance of this ligand. Thus, targeting of downstream transcriptional mediators may be a useful therapeutic approach in attenuating cardiac fibrosis. Here, we discuss some of the transcription factors that may regulate EndMT-mediated cardiac fibrosis and their involvement in type 2 diabetes.

Noscapine, an opium-derived 'kinder-gentler' microtubule-modulating drug is in Phase I/II clinical trials for cancer chemotherapy. However, its limited water solubility encumbers its development into an oral anticancer drug with clinical promise. Here we report the synthesis of 9 third-generation, water-soluble noscapine analogs with negatively charged sulfonato and positively charged quaternary ammonium groups using noscapine, 9-bromonoscapine and 9-aminonoscapine as scaffolds. The predictive free energy of solvation was found to be lower for sulfonates (6a-c; 8a-c) compared to the quaternary ammonium-substituted counterparts, explaining their higher water solubility. In addition, sulfonates showed higher charge dispersability, which may effectively shield the hydrophobicity of isoquinoline nucleus as indicated by hydrophobicity mapping methods. These in silico data underscore efficient net charge balancing, which may explain higher water solubility and thus enhanced antiproliferative efficacy and improved bioavailability. We observed that 6b, 8b and Sc strongly inhibited tubulin polymerization and demonstrated significant antiproliferative activity against four cancer cell lines compared to noscapine. Molecular simulation and docking studies of tubulin-drug complexes revealed that the brominated compound with a four-carbon chain (4b, 6b, and 8b) showed optimal binding with tubulin heterodimers. Interestingly, 6b, 8b and Sc treated PC-3 cells resulted in preponderance of mitotic cells with multipolar spindle morphology, suggesting that they stall the cell cycle. Furthermore, in vivo pharmacokinetic evaluation of 6b, 8b and Sc revealed at least 1-2-fold improvement in their bioavailability compared to noscapine. To our knowledge, this is the first report to demonstrate novel water-soluble noscapine analogs that may pave the way for future pre-clinical drug development. (C) 2014 Elsevier Inc. All rights reserved.

We have recently demonstrated that hydroxychavicol is a major constituent and the most active biophenolic of Piper betel leaves with significant antiproliferative activity in the micro molar range. Herein we present the design, synthesis and evaluation of fifteen novel hydroxychavicol analogs with varying antiproliferative activities in cancer cell lines from two representative tissue types, namely, the prostate and cervix that show very encouraging results compared to the parent compounds. Our long range goal is to develop a structure–activity guided relationship to gain mechanistic insights into novel molecular targets of this class of bioactive molecules for rational drug development. Cytotoxicity-guided experimentation on these novel analogs yielded the following structural factors as the key activity regulators: 1) unlike the hydroxyl substituent at position-4, the position-3 hydroxyl is vital for enhanced activity 2) acetoxyl groups are dispensable for activity as corroborated earlier by others 3) allylic double bonds at 2′C–3′C serve to positively influence antiproliferative activity 4) long saturated side chains at 1′-position negatively regulate antiproliferative activity and 5) maneuvering position-4 with a benzyl group positively impacted the biological activity profile. Most amphiphilic compounds showed moderate to good therapeutic potential as expected on the basis of medicinal chemistry principles. Intriguingly, the most active compound with ten-fold higher activity than the parent molecule was realized by sheer serendipity to employ a silica gel based rearrangement that was further explored using nuclear magnetic resonance spectroscopy and density functional theory calculations. This is the first report to describe strategies for optimal synthesis of a novel series of 15 analogs based upon hydroxychavicol, a simple phytochemical of immense anticancer potential.

Mycobacterium avium subspecies paratuberculosis, the cause of granulomatous enteritis in ruminants, has also been associated with Inflammatory Bowel disease or Crohn’s disease in human population. Present study aimed to investigate bio-presence of MAP in suspected and confirmed cases of Type 1 Diabetes in clinical samples (blood and serum) of human beings from Chattarpur district of Madhya Pradesh. Screening of 88 serum samples for the presence of MAP using ‘Indigenous ELISA’, 34 (38.6%) were positive for MAP infection. Whereas of the 71 blood samples screened, 28 (39.4%) were positive in IS900 PCR. Screening of 19 serum and 16 blood samples from 20 confirmed patients of ‘Type 1 diabetes’, 31.5 and 43.7% were positive by ‘Indigenous ELISA’ and IS900 PCR, respectively. Comparison of Indigenous ELISA and IS900 PCR revealed fair agreement between the two tests. Bio-typing of DNA of 8 positive blood samples by IS1311 PCR-RE revealed presence of ‘Indian Bison type’ biotype. Presence of MAP bacterimia in the patients suffering from Type 1 Diabetes added to the existing knowledge that MAP may provide foundation for establishing diabetes in human subjects. This is the first report of presence of MAP in human Type 1 Diabetes patients from India. ‘Indian Bison Type’ biotype in domestic livestock suggests a link and interspecies transmission through food chain.

0.3C-CrMoV(ESR) steel is an ultra-high strength low alloy steel indigenously developed by ISRO for space applications. The steel is used in the form of rings of 2.8 m diameter also. In this paper, the effect of tempering temperature on ring rolled steel for the best combination of fracture toughness and strength properties is studied. The tensile properties and fracture toughness of the steel were evaluated in the as quenched and tempered conditions through the specimens drawn in radial direction of the ring segment. Five tempering temperatures were used in the study: 200, 450, 475, 500 and 510°C. Tensile strength of the steel showed continuous decrease with increasing tempering temperature, but yield strength increased reaching maximum when tempered at 450°C and further decreased with increasing tempering temperature. The elongation was higher for higher tempering temperature. The strain hardening exponent decreased with increasing tempering temperature. The fracture toughness test results showed that tempering between 475 and 510°C exhibited better combination of fracture toughness and strength.

Summary Aim Cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Altered expression of several genes and their regulation by microRNAs has been reported in hypertrophied failing hearts. This study aims to examine the role of Cdc42, Pak1, and miR-30c in the pathogenesis of cardiac hypertrophy in DCM. Methods DCM was induced in Wistar rats by low-dose streptozotocin-high-fat diet for 12 weeks. Cardiac expression of Cdc42, Pak1 and miR-30c, and hypertrophy markers (ANP and β-MHC) was studied in DCM vs control rats and in high-glucose (HG)-treated H9c2 cardiomyocytes. Results Diabetic rats showed cardiomyocyte hypertrophy, increased heart-to-body weight ratio, and an increased expression of ANP and β-MHC. Cardiac expression of Cdc42 and Pak1 genes was increased in diabetic hearts and in HG-treated cardiomyocytes. miR-30c was identified to target Cdc42 and Pak1 genes, and cardiac miR-30c expression was found to be decreased in DCM rats, patients with DCM, and in HG-treated cardiomyocytes. miR-30c overexpression decreased Cdc42 and Pak1 genes and attenuated HG-induced cardiomyocyte hypertrophy, whereas miR-30c inhibition increased Cdc42 and Pak1 gene expression and myocyte hypertrophy in HG-treated cardiomyocytes. Conclusion Downregulation of miR-30c mediates prohypertrophic effects of hyperglycemia in DCM by upregulation of Cdc42 and Pak1 genes.

An austenitic stainless steel tank used for storing liquid nitrogen tetroxide (N 2 O 4 ) had shown leaks while in service. The repair welding of the tank could not extend the life of the tank much. The leaked portion was subject to detailed failure analysis using standard metallographic techniques. The results revealed that the failure was mainly due to stress corrosion cracking.

It is appreciated far and wide that increased and regular consumption of fruits and vegetables is linked with noteworthy anticancer benefits. Extensively consumed as a spice in foods and beverages worldwide, ginger (Zingiber officinale Roscoe) is an excellent source of several bioactive phenolics, including non-volatile pungent compounds such as gingerols, paradols, shogaols and gingerones. Ginger has been known to display anti-inflammatory, antioxidant and antiproliferative activities, indicating its promising role as a chemopreventive agent. Here, we show that whole ginger extract (GE) exerts significant growth-inhibitory and death-inductory effects in a spectrum of prostate cancer cells. Comprehensive studies have confirmed that GE perturbed cell-cycle progression, impaired reproductive capacity, modulated cell-cycle and apoptosis regulatory molecules and induced a caspase-driven, mitochondrially mediated apoptosis in human prostate cancer cells. Remarkably, daily oral feeding of 100 mg/kg body weight of GE inhibited growth and progression of PC-3 xenografts by approximately 56 % in nude mice, as shown by measurements of tumour volume. Tumour tissue from GE-treated mice showed reduced proliferation index and widespread apoptosis compared with controls, as determined by immunoblotting and immunohistochemical methods. Most importantly, GE did not exert any detectable toxicity in normal, rapidly dividing tissues such as gut and bone marrow. To the best of our knowledge, this is the first report to demonstrate the in vitro and in vivo anticancer activity of whole GE for the management of prostate cancer.

Aeromonas hydrophila is a major pathogen both of aquatic and terrestrial organisms, including humans. Infection with A. hydrophila results in severe economic losses to the aquaculture industry. In humans, Aeromonas hydrophila infections are known to cause gastroenteritis and wound infections. Investigations for developing a potential vaccine for its control are underway. The availability of the complete sequence information of A. hydrophila strain ATCC 7966T genome has made it possible to carry out the in silico analysis of its genome for various aspects of its biology. Keeping in view the possible risks that A. hydrophila poses to humans, in silico analysis of the A. hydrophila genome was carried out for the identification of potential vaccine and drug targets. Our study revealed 2097 genes which are non-homologous to human genome. Screening these genes using the Database of Essential Genes (DEG) resulted in the identification of 379 genes as essential genes of the bacteria. Further analysis of the identified essential genes, using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways database, revealed 87 enzymes of A. hydrophila that may be used as drug targets, as they are not present in humans. Of these, 15 enzymes belong to pathways present only in the bacteria, whereas 72 enzymes are from the pathways that are common to both human and the bacteria. These can be used as a platform for further investigation to develop effective drugs against A. hydrophila.