Microwave-assisted synthesis of 3-aminobenzo[b]thiophene scaffolds for the preparation of kinase inhibitors

Microwave irradiation of 2-halobenzonitriles and methyl thioglycolate in the presence of triethylamine in DMSO at 130 °C provides rapid access to 3-aminobenzo[b]thiophenes in 58–96% yield. This transformation has been applied in the synthesis of the thieno[2,3-b]pyridine core motif of LIMK1 inhibitors, the benzo[4,5]thieno[3,2-e][1,4]diazepin-5(2H)-one scaffold of MK2 inhibitors and a benzo[4,5]thieno[3,2-d]pyrimidin-4-one inhibitor of the PIM kinases

Economic Change and Change in Well-Being in the Czech Republic, with Comparisons to Married Women in the United States

Examines the effects of economic change on individual well-being for a panel of married Czech women compared with a US sample from IA (N = 192 & 386, respectively, in 1990/91). Questionnaire data show that respondents who were forced to make economic adjustments reducing their standard of living also reported increased health problems & depressive symptoms. Contrary to some US findings the relationship between economic adjustments & change in depressive symptoms was strongest among those who reported having the strongest sense of personal control (mastery) & the highest perceived social support. Compared with the US sample, married Czech women reported more depressive symptoms, had more health problems, & were lower in feelings of mastery. In addition, Czech women recorded significantly stronger paths linking education to changes in health conditions & depressive symptoms, whereas US women had significantly stronger paths linking actual economic conditions to subsequent economic adjustments. Data suggest that the US stress-distress model applies in the Czech Republic as well, but further understanding of the differentiated role of social support & mastery for Czech & US women is necessray to more completely interpret the observed interactions

Lower bounds for the first eigenvalue of the magnetic Laplacian

We consider a Riemannian cylinder endowed with a closed potential 1-form A and study the magnetic Laplacian with magnetic Neumann boundary conditions associated with those data. We establish a sharp lower bound for the first eigenvalue and show that the equality characterizes the situation where the metric is a product. We then look at the case of a planar domain bounded by two closed curves and obtain an explicit lower bound in terms of the geometry of the domain. We finally discuss sharpness of this last estimate.Comment: Replaces in part arXiv:1611.0193

If cooperation is likely punish mildly: Insights from economic experiments based on the snowdrift game

Punishment may deter antisocial behavior. Yet to punish is costly, and the costs often do not offset the gains that are due to elevated levels of cooperation. However, the effectiveness of punishment depends not only on how costly it is, but also on the circumstances defining the social dilemma. Using the snowdrift game as the basis, we have conducted a series of economic experiments to determine whether severe punishment is more effective than mild punishment. We have observed that severe punishment is not necessarily more effective, even if the cost of punishment is identical in both cases. The benefits of severe punishment become evident only under extremely adverse conditions, when to cooperate is highly improbable in the absence of sanctions. If cooperation is likely, mild punishment is not less effective and leads to higher average payoffs, and is thus the much preferred alternative. Presented results suggest that the positive effects of punishment stem not only from imposed fines, but may also have a psychological background. Small fines can do wonders in motivating us to chose cooperation over defection, but without the paralyzing effect that may be brought about by large fines. The later should be utilized only when absolutely necessary.Comment: 15 pages, 6 figures; accepted for publication in PLoS ON

Arteriography during ex vivo renal perfusion A complication

A case of bilateral renal-cell carcinoma unsuccessfully treated with bench surgery is reported. The reason for failure was apparently the toxicity of the contrast media used during the ex vivo arteriographic studies. © 1973

Continuum removal in H\alpha\ extragalactic measurements

We point out an important source of error in measurements of extragalactic H-alpha emission and suggest ways to reduce it. The H-alpha line, used for estimating star formation rates, is commonly measured by imaging in a narrow band and a wide band, both which include the line. The image analysis relies on the accurate removal of the underlying continuum. We discuss in detail the derivation of the emission line's equivalent width and flux for extragalactic extended sources, and the required photometric calibrations. We describe commonly used continuum-subtraction procedures, and discuss the uncertainties that they introduce. Specifically, we analyse errors introduced by colour effects. We show that the errors in the measured H-alpha equivalent width induced by colour effects can lead to underestimates as large as 40% and overestimates as large as 10%, depending on the underlying galaxy's stellar population and the continuum-subtraction procedure used. We also show that these errors may lead to biases in results of surveys, and to the underestimation of the cosmic star formation rate at low redshifts (the low z points in the Madau plot). We suggest a method to significantly reduce these errors using a single colour measurement.Comment: 8 pages, 3 figures, MNRAS in pres

Dynamical robustness of biological networks with hierarchical distribution of time scales

We propose the concepts of distributed robustness and r-robustness, well adapted to functional genetics. Then we discuss the robustness of the relaxation time using a chemical reaction description of genetic and signalling networks. First, we obtain the following result for linear networks: for large multiscale systems with hierarchical distribution of time scales the variance of the inverse relaxation time (as well as the variance of the stationary rate) is much lower than the variance of the separate constants. Moreover, it can tend to 0 faster than 1/n, where n is the number of reactions. We argue that similar phenomena are valid in the nonlinear case as well. As a numerical illustration we use a model of signalling network that can be applied to important transcription factors such as NFkB

An Evolutionary Sequence of Expanding Hydrogen Shells in Galaxy Discs

Large HI shells, with diameters of hundreds of pc and expansion velocities of 10-20kms-1 are well observed features of local gas rich galaxies. These shells could well be predicted as a result of the impact of OB associations on the ISM, but doubt has been cast on this scenario by the apparent absence of OB stars close to the centres of a large fraction of these shells in recent observations of the SMC. Using Fabry-Perot scanned Halpha emission line mapping of nearby galaxy discs we have detected, in all the HII regions where the observations yield sufficient angular resolution and S:N ratio, dominant Halpha shells with radii a few tens of pc, expanding at velocities of 50-100kms-1. We have applied a simple dynamically consistent framework in which we can extrapolate the properties of the observed Halpha shells to a few 10^7yr after the formation of the OB stars. The framework includes the dynamical inputs of both winds and SNe on the surrounding ISM. The results give quantitative statistical support to the hypothesis that the Halpha emitting shells are generic progenitors of the HI shells. During the time taken for an expanding shell to reach the size of a typical HI shell, the OB association may well lose its most luminous stars so the absence of such stars near the centres of many of the HI shells is well explained in this scenario.Comment: 8 pages, 4 figures, accepted for publication in Astronomy and Astrophysic