Syntheses and conformational analyses of some cyclohexane-based 1,3-dipodands and 1,3,5-tripodands

A series of dipodands (2, 4 and 9) as well as tripodands (13, 18, 20, 26 and 31) have been synthesized and characterized. The general synthetic methodology followed involves alkylation of the cyclohexane-based alcohols with the arm tosylates.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI). The conformational aspects governing the complexation of these podands with alkali metal ions were studied by \sp1H NMR, \sp{13}C NMR and \sp{13}C dynamic NMR supported by complementary molecular mechanics studies. The relative complexing abilities of 2 and comformationally biased 9 have been measured by \sp{13}C NMR competition experiments. Lipophilic podand 18 and model 13 were studied for the possibility of micellar behavior of these molecules. The relative complexing abilities of podands 37, 13, 18 and 2 were compared by competition experiments. Extra long arm podands 26 and 31 were found to be capable of complexing two Na\sp+ ions. The Na\sp+--Na\sp+ distance was estimated by CPK models to be approximately 3.2 A\sp{\rm o}. A concentration dependence study of 1:1 mixture of complex to free ligand was done in CDCl\sb3 by \sp{13}C dynamic NMR. (Abstract shortened with permission of author.)

Role of Doppler indices in prediction of perinatal outcome in preeclampsia

Background: Preeclampsia is a major cause of maternal and perinatal mortality and morbidity worldwide, particularly in developing countries. The objective of the study was to study Doppler indices in pregnancies with preeclampsia and to correlate Doppler indices with perinatal outcome.Methods: This was a prospective study conducted within a period of September 2012 to August 2014 where 100 singleton preeclampsia patients attending tertiary care hospital were recruited. These patients were followed by serial Doppler assessment and the result of the last Doppler examination within 10 days of delivery was considered in the subsequent correlation with perinatal outcomes. Perinatal outcome was studied under major and minor adverse outcome.Results: In this study out of total population 54% were primigravida patients. 43.75% caesarean sections done for fetal distress with abnormal Doppler. Bilateral uterine artery diastolic notch and umbilical artery S/D ratio have better sensitivity (72.55%) for prediction of minor adverse outcome while uterine artery diastolic notch has better sensitivity (86.67%) for major adverse outcome. Umbilical artery and middle cerebral artery RI have better specificity and positive predictive value  for prediction of both major and minor adverse outcome. Bilateral uterine artery notch and umbilical artery S/D ratio have better negative predictive value for prediction of both major and minor adverse outcome.Conclusions: In this study it is concluded that Doppler analysis helps not only earlier detection of uteroplacental and fetoplacental changes associated with the disease but also help to take decision for early intervention. Doppler technology has provided the best opportunity for repetitive non-invasive haemodynamic monitoring in pregnancy for fetal well-being evaluation and predicting perinatal outcome

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

Study Protocol: insulin and its role in cancer

<p>Abstract</p> <p>Background</p> <p>Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.</p> <p>Methods/Design</p> <p>Based on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.</p> <p>Discussion</p> <p>Well controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.</p

Can multinational companies foster institutional change and sustainable development in emerging countries? A case study.

Emerging countries present institutional necessities that hinder their sustainable development. In the face of this challenge, companies, and in particular multinational companies (MNCs), can foster sustainable development through their corporate social responsibility (CSR) initiatives. This study focuses on the role of institutional change in transforming CSR into sustainable development in emerging countries. To this end, we propose a view of CSR focused on its institutional determinants and outcomes from a social and developmental perspective. By using quantitative and qualitative data, we analyse the case of three MNCs from different industries based in Europe and operating in Mexico. The case study shows how firms can stimulate institutional change in developing economies and contribute to their sustainable development as measured by the sustainable development goals. Various mechanisms about how this process is made are devised: institutional entrepreneurship, multistakeholder initiatives, interconnection of different institutional dimensions, and subsidiary entrepreneurship. The case study highlights the interaction among MNCs, developing countries, and institutions and how firms' sustainable actions scale up to the macro level.post-print399 K

Peak effect in a superconducting DyBa2Cu3O7-y film at microwave frequencies

We report the observation of a peak in the microwave (9.55 GHz) surface resistance in an epitaxial DyBa2Cu3O7-y superconducting film in magnetic fields (parallel to the c axis) ranging between 0.2 to 0.9 Tesla. Such a peak is absent in the measurements done in zero-field. The temperature and field dependence of the peak suggests that this peak could be associated with the peak effect phenomenon reflecting the order-disorder transformation in the flux-line lattice. A strong dependence of this peak effect at frequencies close to the depinning frequency of the flux line lattice is observed.Comment: 1 text, 4 figures (all postscript) to be published in Phys. Rev.

Controlled Synthesis, Characterization, and Flow Properties of Ethylene–Diene Copolymers

The flow response of branched entangled resins is dominated by the branching topology of the constituent molecules, a property that is not directly accessible using experimental analytical tools for industrially relevant complex resins. In this paper, the controlled terpolymerization of ethylene, 1,9-decadiene, and either hexene or octene in a continuous stirred tank reactor with a metallocene catalyst, is reported. The synthesized samples are characterized extensively with various analytical tools and their rheological properties are measured with small amplitude oscillatory shear and start-up uniaxial extension experiments. A model is developed for the polymerization process with the mass balance during synthesis providing strong constraints on the rate constants. In silico ensembles of molecules, generated via Monte Carlo sampling, are used to reproduce the experimental results. The computer model allows us to infer the detailed branching structure of the molecules and to predict the optimum range of reactor conditions for this synthesis

The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins

The Ku-binding motif (KBM) is a short peptide module first identified in APLF that we now show is also present in Werner syndrome protein (WRN) and in Modulator of retrovirus infection homologue (MRI). We also identify a related but functionally distinct motif in XLF, WRN, MRI and PAXX, which we denote the XLF-like motif. We show that WRN possesses two KBMs; one at the N terminus next to the exonuclease domain and one at the C terminus next to an XLF-like motif. We reveal that the WRN C-terminal KBM and XLF-like motif function cooperatively to bind Ku complexes and that the N-terminal KBM mediates Ku-dependent stimulation of WRN exonuclease activity. We also show that WRN accelerates DSB repair by a mechanism requiring both KBMs, demonstrating the importance of WRN interaction with Ku. These data define a conserved family of KBMs that function as molecular tethers to recruit and/or stimulate enzymes during NHEJ