Citizens across the country are demanding an end to the generations of violence and suppression faced by hundreds of millions of Indian women and girls - from rape and domestic abuse, to lower pay ...and no right to property. The following Indian Womanifesto is a six-point plan critical to the freedom, safety, equality and flourishing of India's women and girls. Devaki Jain, Suneeta Dhar, Ruth Manorama, Uma Chakravarti, Lalita Ramdas, Vibhuti Patel, Rohini Hensman, National Federation of Dalit Women, National Alliance of Women, Stree Mukti Sangathana, Women's Voice, All India Progressive Women's Association and other organisations and individuals.
Distant recurrences occurring years after removal of the primary tumor arise from disseminated tumor cells (DTCs) that lie dormant (quiescent/asymptomatic) until they emerge to overt metastases. ...These quiescent DTCs are resistant to conventional treatments. Hence, to date there is no available treatment which targets dormant DTCs before they form overt metastases. Therefore, understanding the biology of dormant DTCs and the mechanisms of their reactivation is vital in our pursuit to develop therapies to prevent cancer from ever recurring.
This review will address the striking similarities between the biology of DTCs and the biology of cancer stem cells (CSCs) or CSC-like cells including cancer progenitor-like cells. These similarities are related to intrinsic mechanisms of survival and quiescence, and their cross-talk with mediators, produced in their surrounding niches that may support either dormancy or outgrowth. Unraveling these similarities may provide us with exciting opportunities to either mitigate the survival of residing dormant DTCs/CSCs or maintain them in a dormant state. Whether the stemness properties of CSCs/cancer progenitor-like cells already comprising the recurring tumor can be exploited in order to differentiate them, and thus promote their dormancy, will be explored as well. Overall, these emerging concepts may provide us with new opportunities to prevent lethal recurrences.
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•Security is an intangible quality of the built environment that can be quantified.•Evaluating security affects the way we behave, perceive, and use the built environment.•Evaluating ...security allows planners to assess the risks before design decisions are made.•Urban morphology relating to security can predict the possibility of crime.
Designing secured urban spaces is one of the main ambitions of urban planners during the planning and design process. People usually travel by foot through safe routes and urban spaces in the built environment as they are perceived as safe areas, such as: lighted paths, walking on the livable side of a sidewalk instead of walking beside a sealed façade, or away from unsecured building entrances. The way people use and interact in their built environment involves their cognitive perception, which depends upon the urban fabric details. Therefore, planners and decision makers aimed in understanding the way the components of the built environment affect unsecured environments so as to assess the risks before design decisions are made. However, they lack new approaches and models with which to evaluate a qualitative sense of security that is understandable on a human-scale in the built environment. This research deals with this gap in information and measures one unmeasurable qualitative aspect of the built environment, the sense of security, in quantitative terms based on a geo-spatial system, and then relate it to human-scale urban form. The Security Rating Index (SRI) establishes a GIS-based, quantifiable system to identify and rate insecure urban spaces to be used by urban planners and city decision makers to evaluate and improve urban resilience. The system is based on measurements of urban elements that influence the sense of security in the built environment, and can be used to identify characteristics and hot spots of unsecured spaces in a city. The SRI is demonstrated on several case studies on different scales.
Glycosylation is one of the most common posttranslational modifications to occur in protein biosynthesis, yet its effect on the thermodynamics and kinetics of proteins is poorly understood. A ...minimalist model based on the native protein topology, in which each amino acid and sugar ring was represented by a single bead, was used to study the effect of glycosylation on protein folding. We studied in silico the folding of 63 engineered SH3 domain variants that had been glycosylated with different numbers of conjugated polysaccharide chains at different sites on the protein's surface. Thermal stabilization of the protein by the polysaccharide chains was observed in proportion to the number of attached chains. Consistent with recent experimental data, the degree of thermal stabilization depended on the position of the glycosylation sites, but only very weakly on the size of the glycans. A thermodynamic analysis showed that the origin of the enhanced protein stabilization by glycosylation is destabilization of the unfolded state rather than stabilization of the folded state. The higher free energy of the unfolded state is enthalpic in origin because the bulky polysaccharide chains force the unfolded ensemble to adopt more extended conformations by prohibiting formation of a residual structure. The thermodynamic stabilization induced by glycosylation is coupled with kinetic stabilization. The effects introduced by the glycans on the biophysical properties of proteins are likely to be relevant to other protein polymeric conjugate systems that regularly occur in the cell as posttranslational modifications or for biotechnological purposes.
Metastases are the major cause of cancer patients' mortality and can occur years and even decades following apparently successful treatment of the primary tumor. Early dissemination of cancer cells, ...followed by a protracted period of dormancy at distant sites, has been recently recognized as the clinical explanation for this very-long latency. The mechanisms that govern tumor dormancy at distant sites and their reactivation to proliferating metastases are just beginning to be unraveled. Tumor cells, that survive the immune surveillance and hemodynamic forces along their journey in the circulation and successfully colonize and adopt to the new and "hostile" microenvironment and survive in a quiescent dormant state for years before emerging to proliferative state, must display high plasticity. Here we will discuss whether the plasticity of dormant tumor cells is required for their long-term survival and outgrowth. Specifically, we will focus on whether epithelial mesenchymal transition and acquisition of stem-like properties can dictate their quiescent and or their proliferative fate. Deeper understanding of these intertwining processes may facilitate in the future the development of novel therapies.
We revisit certain aspects of thermalization in 2D conformal field theory (CFT). In particular, we consider similarities and differences between the time dependence of correlation functions in ...various states in rational and non-rational CFTs. We also consider the distinction between global and local thermalization and explain how states obtained by acting with a diffeomorphism on the ground state can appear locally thermal, and we review why the time-dependent expectation value of the energy-momentum tensor is generally a poor diagnostic of global thermalization. Since all 2D CFTs have an infinite set of commuting conserved charges, generic initial states might be expected to give rise to a generalized Gibbs ensemble rather than a pure thermal ensemble at late times. We construct the holographic dual of the generalized Gibbs ensemble and show that, to leading order, it is still described by a Banados-Teitelboim-Zanelli black hole. The extra conserved charges, while rendering c<1 theories essentially integrable, therefore seem to have little effect on large-c conformal field theories.
Abstract This article analyzes the effect of grade retention in high school on later school outcomes in Italy. Grade retention is a strong signal of poor performance, so retained students should ...revise downwards their perceived probability of success in school. Grade retention also implies an increase in costs. Therefore, we expect a negative effect on future educational careers. However, the evidence from the existing literature is mixed. Using longitudinal administrative data, we propose a matching strategy to assess the impact of grade retention on institutional settings with considerable leeway in promotion/retention decisions. Following this strategy, we can interpret our results as estimates of the impact for students close to the threshold between retention and promotion. Our results add to the existing evidence that grade retention in high school has a negative impact on student’s educational outcomes by dramatically increasing dropout rates. Consistent with the compensatory advantage hypothesis, the negative effects are stronger for students with low educated or immigrant parents. Our findings suggest that alternatives to grade retention should be found to address underachievement.
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