Радиационный анизотропный оптикотермоэлемент с боковым термостатированием

Предложены выражения для расчета характеристик и конструкция приемника, не искажающего амплитудно-фазовые характеристики проходящего лучистого потока

ANTIMYCOBACTERIAL ACTIVITY OF CRUDE EXTRACTS PRODUCED BY BACILLUS SP. ASSOCIATED WITH ENTOMOPATHOGENIC NEMATODE

Objective: The World Health Organization estimates that about 8 to 10 million new Tuberculosis (TB) cases occur annually worldwide and its incidence is currently increasing. There are two million deaths from TB each year. The global threat of tuberculosis demands the search for alternative antimycobacterial drugs. The aim of the present study was to determine the antimycobacterial activity of nine crude extracts from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) sp. Methods: The liquid media for fermentation was prepared in TSB alone, LB alone and TSB + LB (1:1) supplemented with six different carbon sources (fructose, maltose, dextrose, mannitol, sucrose and lactose) and after fermentation crude extract was extracted using ethyl acetate. The minimum inhibitory concentration (MIC) of extracts was determined using the broth dilution method on middle brook 7H11 against M. tuberculosis H37Rv. The cytotoxicity of the extracts was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay against VERO cell line. Results: Out of nine extract tested only two recorded activity and significant activity was recorded by TSB+LB+lactose, followed by TSB+LB+fructose. These two extracts were nontoxic to the normal cell line. Conclusion: Purification of these extract will get pure compounds with antimycobacterial activity in future

Role of epigenetic modifications in inhibitory immune checkpoints in cancer development and progression

A balance between co-inhibitory and co-stimulatory signals in the tumor microenvironment (TME) is critical to suppress tumor development and progression, primarily via maintaining effective immunosurveillance. Aberrant expression of immune checkpoints (ICs), including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), can create an immune-subversive environment, which helps tumor cells to evade immune destruction. Recent studies showed that epigenetic modifications play critical roles in regulating the expression of ICs and their ligands in the TME. Reports showed that the promoter regions of genes encoding ICs/IC ligands can undergo inherent epigenetic alterations, such as DNA methylation and histone modifications (acetylation and methylation). These epigenetic aberrations can significantly contribute to the transcriptomic upregulation of ICs and their ligands. Epigenetic therapeutics, including DNA methyltransferase and histone deacetylase inhibitors, can be used to revert these epigenetic anomalies acquired during the progression of disease. These discoveries have established a promising therapeutic modality utilizing the combination of epigenetic and immunotherapeutic agents to restore the physiological epigenetic profile and to re-establish potent host immunosurveillance mechanisms. In this review, we highlight the roles of epigenetic modifications on the upregulation of ICs, focusing on tumor development, and progression. We discuss therapeutic approaches of epigenetic modifiers, including clinical trials in various cancer settings and their impact on current and future anti-cancer therapies

Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer

Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited data are available on phenotypic/transcriptomic characteristics of the different MDSCs subsets in cancer. These cells include immature (I-MDSCs), monocytic (M-MDSCs), and polymorphonuclear/granulocytic (PMN-MDSCs). Phenotypic characterization of myeloid subsets from 27 colorectal cancer (CRC) patients was assessed by flow cytometric analyses. RNA-sequencing of sorted I-MDSCs, PMN-MDSCs, and antigen-presenting cells (APCs) was also performed. We found that the levels of I-MDSCs and PMN-MDSCs were increased in tumor tissues (TT), compared with normal tissues (NT) in colorectal cancer. Our functional annotation analyses showed that genes associated with histone deacetylase (HDAC) activation- and DNA methylation-mediated transcriptional silencing were upregulated, and histone acetyl transferase (HAT)-related genes were downregulated in tumor-infiltrating I-MDSCs. Moreover, pathways implicated in cell trafficking and immune suppression, including Wnt, interleukin-6 (IL-6), and mitogen-activated protein kinase (MAPK) signaling, were upregulated in I-MDSCs. Notably, PMN-MDSCs showed downregulation in genes related to DNA methylation and HDAC binding. Using an ex vivo model, we found that inhibition of HDAC activation or neutralization of IL-6 in CRC tumor tissues downregulates the expression of genes associated with immunosuppression and myeloid cell chemotaxis, confirming the importance of HDAC activation and IL-6 signaling pathway in MDSC function and chemotaxis. This study provides novel insights into the epigenetic regulations and other molecular pathways in different myeloid cell subsets within the CRC tumor microenvironment (TME), giving opportunities to potential targets for therapeutic benefits

A clinicopathological and immunohistochemical study of malignant peripheral nerve sheath tumors

Background:Malignant Peripheral Nerve Sheath Tumor (MPNST) is a rare aggressive sarcoma that develops within a peripheral nerve and forms a diagnostic challenge in view of its varied histomorphology. This short series highlights the clinicopathological spectrum of 11 cases of MPNST and the incidence of neurofibromatosis 1 (NF1) association.Methods:This retrospective and descriptive study on MPNST was done in the department of pathology, Kasturba medical college Mangalore (ManipalUniversity),India over a period of three years from January 2008 to December 2010. Cases which were histopathologically diagnosed as MPNST were reviewed & immunostains was done where ever indicated to rule out the differentials.Results:A total of 11 cases of MPNST were documented with a wide age range of 17-85 years. Male:female ratio was 2.6:1. Extremities (63.64%) were found to be the most common site. Location wise most of the tumors were deep seated (63.64%) and maximum cases were high grade (54.55%). NF1 association was seen in 2 cases. Heterologous elements in the form of chondroid differentiation was seen in one case. Immunostain with S-100 was focally positive in all the cases.Conclusion:MPNST is a highly aggressive sarcoma with poor prognosis characterized by a challenge in its diagnosis as it has several mimics. Its diagnosis necessitates the incorporation of clinicopathological features and IHC with S-100 protein.

Transcriptomic analyses of myeloid-derived suppressor cell subsets in the circulation of colorectal cancer patients

Myeloid-derived suppressor cells (MDSCs) promote tumor immune evasion and favor tumorigenesis by activating various tumor-promoting downstream signals. MDSC expansion is evident in the circulation and tumor microenvironment of many solid tumors including colorectal cancer (CRC). We have recently reported the transcriptomic profiles of tumor-infiltrating MDSCs in CRC patients and uncovered pathways, which could potentially assist tumor progression. In this study, we sorted different subsets of circulating MDSCs in CRC patients and investigated their transcriptomic profiles in order to disclose pathways, which could potentially contribute to disease progression. The sorted subsets included polymorphonuclear/granulocytic MDSCs (PMN-MDSCs), immature MDSCs (I-MDSCs), and monocytic MDSCs (M-MDSCs). Our functional annotation analyses revealed that multiple pathways including DNA damage-, chemotaxis-, apoptosis-, mitogen-activated protein kinase-, transforming growth factor β-, and myeloid differentiation–related transcripts were higher in PMN-MDSCs, compared with monocytic antigen-presenting cells (APCs) or I-MDSCs. Furthermore, genes related to Janus kinase (JAK)–signal transducer and activator of transcription (STAT) were also elevated in PMN-MDSCs. These data suggest that upregulation of JAK-STAT pathway could trigger multiple downstream targets in PMN-MDSCs, which favor tumor progression. Additionally, we found that pathways including phosphatidyl inositol 3-kinase (PI3K), interleukin 6, and TGF-β in M-MDSCs and cell cycle–related pathways in I-MDSCs were upregulated, compared with monocytic APCs. Moreover, acetylation-related genes were upregulated in both PMN-MDSCs and M-MDSCs. This latter finding implicates that epigenetic modifications could also play a role in the regulation of multiple tumor-promoting genes in PMN-MDSCs and M-MDSCs. Taken together, this study reveals various signaling pathways, which regulate the function of MDSC subsets in the circulation of CRC patients. However, functional studies are warranted to support these findings

Awareness of computer vision syndrome and related factors among information technology professionals

Background: Extensive use of computers for both professional and personal purpose has led to an increase in computer related health problems. Aim of this study was to evaluate the awareness regarding symptoms and the related factors in computer vision syndrome (CVS) among a group of information technology (IT) professionals.Methods: This study was conducted among 300 IT employees. After obtaining informed consent, structured questionnaire was given and data collected and analyzed.Results: Out of 300 respondents, 194 (64.7%) were males and 106 (35.3%) females. Mean age was 30.5 years.48.3% had more than eight years of computer usage and 77.3% used computers on an average of 8-12 hours per day. About 201 (67%) of the participants had at least one ocular symptom, most common was dryness (96%). 94.7% reported eyestrain and 86.3% reported redness and itching. Dryness and eyestrain were more in males (p<0.05). Dryness, eyestrain and redness were more in those who used computers for more than eight years duration and for 8-12 hours/day (p<0.05). 253 (84.3%) were aware about this syndrome, the main source being internet. The main relief measure adopted was to take a break in between the work hours. Only 51.3% consulted a doctor for their symptoms.  Conclusions: In our study though 84.3% of IT professionals were aware of CVS and 67% had at least one ocular symptom, only 51.3% took professional advice for their problems. There is a definite need for awareness about corrective measures and treatment methods to be adopted for CVS among IT professionals

Surveys without Questions: A Reinforcement Learning Approach

The 'old world' instrument, survey, remains a tool of choice for firms to obtain ratings of satisfaction and experience that customers realize while interacting online with firms. While avenues for survey have evolved from emails and links to pop-ups while browsing, the deficiencies persist. These include - reliance on ratings of very few respondents to infer about all customers' online interactions; failing to capture a customer's interactions over time since the rating is a one-time snapshot; and inability to tie back customers' ratings to specific interactions because ratings provided relate to all interactions. To overcome these deficiencies we extract proxy ratings from clickstream data, typically collected for every customer's online interactions, by developing an approach based on Reinforcement Learning (RL). We introduce a new way to interpret values generated by the value function of RL, as proxy ratings. Our approach does not need any survey data for training. Yet, on validation against actual survey data, proxy ratings yield reasonable performance results. Additionally, we offer a new way to draw insights from values of the value function, which allow associating specific interactions to their proxy ratings. We introduce two new metrics to represent ratings - one, customer-level and the other, aggregate-level for click actions across customers. Both are defined around proportion of all pairwise, successive actions that show increase in proxy ratings. This intuitive customer-level metric enables gauging the dynamics of ratings over time and is a better predictor of purchase than customer ratings from survey. The aggregate-level metric allows pinpointing actions that help or hurt experience. In sum, proxy ratings computed unobtrusively from clickstream, for every action, for each customer, and for every session can offer interpretable and more insightful alternative to surveys.Comment: The Thirty-Third AAAI Conference on Artificial Intelligence (AAAI-19

Anti-cancer natural products inducing cross-talk between apoptosis and autophagy mutual proteins to regulate cancer cell death: design of future green anticancer therapies

The present letter concerns anti-cancer natural products inducing cross-talk between apoptosis and autophagy mutual proteins to regulate cancer cell death for future cancer green therapeutic approaches. The course of cancer advancement has always been attributed to the defectiveness in cell death mechanisms (Du et al., 2013; Hematulin et al., 2014). These defects act as a shield in protecting tumor cells from drugs and therapies, all at the same time, maintaining a longer life span and prompting their dispersion procedures. Autophagy and apoptosis safeguards cells from cellular damages and maintains proliferation and homeostasis by deporting outgrowth and controlling differentiation of pernicious cells. The autophagic proteins are conventionally found in hindering apoptosis whereas vice versa accounts had been reported for apoptotic-intermediates in preventing autophagic responses