A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation

STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under normal physiological conditions, the activation of STATs is tightly regulated. In cancer, by contrast, STAT proteins, particularly STAT3 and STAT5, become activated constitutively, thereby driving the malignant phenotype of cancer cells. Since these proteins are largely dispensable in the function of normal adult cells, STATs represent a potentially important target for cancer therapy. Although transcription factors have traditionally been viewed as suboptimal targets for pharmacological inhibition, chemical biology approaches have been particularly fruitful in identifying compounds that can modulate this pathway through a variety of mechanisms. STAT inhibitors have notable anti-cancer effects in many tumor systems, show synergy with other therapeutic modalities, and have the potential to eradicate tumor stem cells. Furthermore, STAT inhibitors identified through the screening of chemical libraries can then be employed in large scale analyses such as gene expression profiling, RNA interference screens, or large-scale tumor cell line profiling. Data derived from these studies can then provide key insights into mechanisms of STAT signal transduction, as well as inform the rational design of targeted therapeutic strategies for cancer patients

A Survey on Menopausal Symptoms in relation to Prakruti

Menopause is a universal phenomenon and an unavoidable physiological transition process in a women’s life, which marks the end of women’s reproductive capacity. It is caused by the depletion of ovarian function followed by the cessation of menstruation. In Ayurveda literature, the term Rajonivṛtti (menopause) is used for menopause and it considered as a sign of aging or Jarā. As a result of change in hormones after menopause certain psychological and biological changes affect women’s health and degrade her quality of life. Ācāryā Vāgbhaṭa had mentioned that in Kaphaprakṛti (body type) individual, and women who are having a habit of taking ghee (Vātapitta Prasamana - pacify Vata Pitta humors) and milk (Jeevaniya), and who are having a pleasant mind in those subjects the Ārtava (menstruation) retains long . The aim of the study was to assess the menopausal symptoms that is mentioned in the menopausal rating scale (MRS) in relation to Prakruti of an individual. For that a survey study is conducted in 250 menopausal women in Sakthikulangara village (Kollam district) who satisfy the inclusion and exclusion criteria. It was observed that out of the 11 menopausal symptoms 9 symptoms shows statistically significant association with Vātapittaprakṛti

Chromosome stability of callus cultures of Crocus sativus

Two year old canus cultures, raised from corm explants of Crocus sativus, showed an unusual chromosome number stability when maintained on MS medium supplemented with 2,4-D (2 mg/l) and kinetin (0.5 mg/l). Such studies may give an insight into the po·ssible origin of somaclonal variants. &nbsp

Marine Ecosystem Challenges & Opportunities (MECOS 3)

The Marine Biological Association of India (MBAI), established in 1958, is proud to gear up for MECOS3, the third symposium on Marine Ecosystems- Challenges and Opportunities during 7-10 January, 2020. The MBAI besides organising MECOS1 (2009) and MECOS2 (2014) has inculcated active interest and participation among its members by handling several national and international symposia/seminars, since its formation. The MBAI has 794 life members and 20 institutional members. The mandate of the MBAI is promotion of scientific research in the field of marine biology and allied sciences

Closed incision negative pressure therapy:international multidisciplinary consensus recommendations

Surgical site occurrences (SSOs) affect up to or over 25% of patients undergoing operative procedures, with the subset of surgical site infections (SSIs) being the most common. Commercially available closed incision negative pressure therapy (ciNPT) may offer surgeons an additional option to manage clean, closed surgical incisions. We conducted an extensive literature search for studies describing ciNPT use and assembled a diverse panel of experts to create consensus recommendations for when using ciNPT may be appropriate. A literature search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials using key words \u2018prevention\u2019, \u2018negative pressure wound therapy (NPWT)\u2019, \u2018active incisional management\u2019, \u2018incisional vacuum therapy\u2019, \u2018incisional NPWT\u2019, \u2018incisional wound VAC\u2019, \u2018closed incisional NPWT\u2019, \u2018wound infection\u2019, and \u2018SSIs\u2019 identified peer-reviewed studies published from 2000 to 2015. During a multidisciplinary consensus meeting, the 12 experts reviewed the literature, presented their own ciNPT experiences, identified risk factors for SSOs and developed comprehensive consensus recommendations. A total of 100 publications satisfied the search requirements for ciNPT use. A majority presented data supporting ciNPT use. Numerous publications reported SSI risk factors, with the most common including obesity (body mass index 6530 kg/m2); diabetes mellitus; tobacco use; or prolonged surgical time. We recommend that the surgeon assess the individual patient's risk factors and surgical risks. Surgeons should consider using ciNPT for patients at high risk for developing SSOs or who are undergoing a high-risk procedure or a procedure that would have highly morbid consequences if an SSI occurred

A CFD Investigation into the Flow Distribution on a Car passing by a Truck

Abstract The flow distribution occurring on a car when it is passing by a truck is investigated using three dimensiona

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations

SummaryAccumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly “drug-tolerant” cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.PaperCli

Synthesis, Spectroscopic Characterization and Molecular Docking Studies of 2-Butyl-4-Chloro-5-Formylimidazole Thiosemicarbazone Cobalt (II) Complex

A novel 2-Butyl-4-chloro-5-formylimidazole thiosemicarbazonecobalt (II) complex is synthesized and characterized by using spectroscopic techniques like elemental analysis, FT-IR, HRMS, electronic spectral analysis and Powder-X-ray diffraction. The Co(II) complex is found to be highly efficient in inhibiting the growth of human pathogens likeS. aureusand B. megaterium with MIC value 12.0 μg/mL whose inhibition zones are almost comparable with the standard antibiotic. The synthesized complex well occupies in the active site of β- ketoacyl-acyl carrier protein synthase III enzyme (PDB: 1MZS), in consists of catalytic triad and adenine-binding site, so the designed compoundis promising for to treat bacterial infection. © 2019 Author(s)

Planar reorientation maneuvers of space multibody systems using internal controls

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77104/1/AIAA-11411-971.pd

Numerical evaluation of inflationary 3-point functions on curved field space

We extend the public CppTransport code to calculate the statistical properties of fluctuations in multiple-field inflationary models with curved field space. Our implementation accounts for all physical effects at tree-level in the 'in-in' diagrammatic expansion. This includes particle production due to time-varying masses, but excludes scenarios where the curvature perturbation is generated by averaging over the decay of more than one particle. We test our implementation by comparing results in Cartesian and polar field-space coordinates, showing excellent numerical agreement and only minor degradation in compute time. We compare our results with the PyTransport 2.0 code, which uses the same computational approach but a different numerical implementation, finding good agreement. Finally, we use our tools to study a class of gelaton-like models which could produce an enhanced non-Gaussian signal on equilateral configurations of the Fourier bispectrum. We show this is difficult to achieve using hyperbolic field-space manifolds and simple inflationary potentials