Systemic Therapy in Endometrial Cancer: Recent Advances.

Endometrial cancer is a chemosensitive disease. Studies have established a clear benefit of chemotherapy in advanced stages and trials are ongoing to define its role in early stages as well. As more molecular pathways are being elucidated there is increasing role for targeted agents and future looks quite promising. We did an extensive search both online and offline for all the relevant articles including chemotherapy and targeted therapy for endometrial cancer

Improving consensus structure by eliminating averaging artifacts

<p>Abstract</p> <p>Background</p> <p>Common structural biology methods (i.e., NMR and molecular dynamics) often produce ensembles of molecular structures. Consequently, averaging of 3D coordinates of molecular structures (proteins and RNA) is a frequent approach to obtain a consensus structure that is representative of the ensemble. However, when the structures are averaged, artifacts can result in unrealistic local geometries, including unphysical bond lengths and angles.</p> <p>Results</p> <p>Herein, we describe a method to derive representative structures while limiting the number of artifacts. Our approach is based on a Monte Carlo simulation technique that drives a starting structure (an extended or a 'close-by' structure) towards the 'averaged structure' using a harmonic pseudo energy function. To assess the performance of the algorithm, we applied our approach to Cα models of 1364 proteins generated by the TASSER structure prediction algorithm. The average RMSD of the refined model from the native structure for the set becomes worse by a mere 0.08 Å compared to the average RMSD of the averaged structures from the native structure (3.28 Å for refined structures and 3.36 A for the averaged structures). However, the percentage of atoms involved in clashes is greatly reduced (from 63% to 1%); in fact, the majority of the refined proteins had zero clashes. Moreover, a small number (38) of refined structures resulted in lower RMSD to the native protein versus the averaged structure. Finally, compared to PULCHRA <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>, our approach produces representative structure of similar RMSD quality, but with much fewer clashes.</p> <p>Conclusion</p> <p>The benchmarking results demonstrate that our approach for removing averaging artifacts can be very beneficial for the structural biology community. Furthermore, the same approach can be applied to almost any problem where averaging of 3D coordinates is performed. Namely, structure averaging is also commonly performed in RNA secondary prediction <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>, which could also benefit from our approach.</p

lHuman cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis

Effector-memory T cells expressing Fas (Apo-1/CD95) are switched to an apoptotic program by cross-linking with Fas-ligand (FasL). Consequently, tumors that express FasL can induce apoptosis of infiltrating Fas-positive T lymphocytes and subdue any antitumor host immune response. Since Epstein-Barr virus (EBV)-associated tumors such as Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) express FasL, we determined whether EBV-specific cytotoxic T lymphocytes (EBV-CTLs) could be modified to resist this evasion strategy. We show that long-term down-modulation of Fas can be achieved in EBV-CTLs by transduction with small interfering RNA (siRNA) encoded in a retrovirus. Modified T cells resisted Fas/FasL-mediated apoptosis compared with control cells and showed minimal cleavage of the caspase3 substrate poly(ADP-ribose) polymerase (PARP) protein after Fas engagement. Prolonged Fas stimulation selected a uniformly Fas(low) and FasL resistant population. Removal of responsiveness to this single death signal had no other discernible effects on EBV-CTLs. In particular, it did not lead to their autonomous growth since the modified EBV-CTLs remained polyclonal, and their survival and proliferation retained dependence on antigen-specific stimulation and on the presence of other physiologic growth signals. EBV-CTLs with knocked down Fas should have a selective functional and survival advantage over unmodified EBV-CTLs in the presence of tumors expressing FasL and may be of value for adoptive cellular therapy. (c) 2005 by The American Society of Hematology

Meeting the Sustainable Development Goals leads to lower world population growth

Here we show the extent to which the expected world population growth could be lowered by successfully implementing the recently agreed-upon Sustainable Development Goals (SDGs). The SDGs include specific quantitative targets on mortality, reproductive health, and education for all girls by 2030, measures that will directly and indirectly affect future demographic trends. Based on a multidimensional model of population dynamics that stratifies national populations by age, sex, and level of education with educational fertility and mortality differentials, we translate these goals into SDG population scenarios, resulting in population sizes between 8.2 and 8.7 billion in 2100. Because these results lie outside the 95% prediction range given by the 2015 United Nations probabilistic population projections, we complement the study with sensitivity analyses of these projections that suggest that those prediction intervals are too narrow because of uncertainty in baseline data, conservative assumptions on correlations, and the possibility of new policies influencing these trends. Although the analysis presented here rests on several assumptions about the implementation of the SDGs and the persistence of educational, fertility, and mortality differentials, it quantitatively illustrates the view that demography is not destiny and that policies can make a decisive difference. In particular, advances in female education and reproductive health can contribute greatly to reducing world population growth

Figurative Language: How is it Used in Basal Readings?

How much attention do editors of basal readers give to figurative language? What is the most common figure of speech found in basal readers? What is the least common figure of speech bound in basal readers? These were the questions the authors sought to answer through their research

Antibacterial and antifungal activities of methanol extracts of Desmodium adscendens root and Bombax buonopozense leaves

In-vitro antibacterial and antifungal activities of methanol extracts of Desmodium adscendens (Sw.) DC root and Bombax buonopozense P. Beauv. leaves against some bacterial and fungal isolates implicated in oro-dental, urogenital and other opportunistic infections were investigated using standard microbiological methods. The extracts of D. adscendens exhibited significant inhibitory action against all twelve organisms tested at a concentration of 2.00 mg/ml, while that of B. buonopozense inhibited nine organisms at the same concentration and conditions. The minimum inhibitory concentration (MIC) exhibited by extract of D. adscendens ranged between 0.0625 and 0.25 mg/ml while that of B. buonopozense ranged between 0.125 and 0.50 mg/ml. Phytochemical analysis of the two plant extracts revealed the presence of tannins and saponins while D. adscendens has alkaloids and flavonoids in addition. Between 92 and 100% of Staphylococcus aureus SA 1199 were killed within 120 minutes of contact time with a concentration of 0.25 - 0.50 mg/ml, while 98 - 100% of Candida albicans ATCC 90029 were killed within the same period and  concentration by the same extract (D. adscendens). Therefore, this study justified the antimicrobial properties of these plants, hence the plants could be recommended for use as source of new drugs for fungal and bacterial infections. © 2013 International Formulae Group. All rights reserved.Keywords: Desmodium adscendens, Bombax buonopozense, antibacterial, antifungal, Minimum Inhibitory Concentratio

Mathematical Model: Comparative Study of Thermal Effects of Laser in Corneal Refractive Surgeries

Lasers have been widely used in ophthalmology. Refractive errors are some of the most common ophthalmic abnormalities worldwide. Laser refractive surgery was developed to correct refractive errors myopia, hyperopia and astigmatism. Two types of laser surgical techniques: lamellar and thermal are available to reshape the corneal curvature. Ultraviolet (UV) emitting argon fluoride (ArF) excimer laser is used to sculpt cornea in lamellar procedures, whereas, infrared (IR) emitting holmium yttrium aluminum garnet (Ho: YAG) laser is used to shrink cornea in thermal procedure. Tissue heating is common in all types of laser surgical techniques. Hence, in this paper, a finite element model is developed to investigate the temperature distribution of cornea in different laser refractive surgeries. Characteristics of optical and thermal processes and influence of the parameters of radiation and tissues on the results of laser action are investigated. The results of mathematical modeling in different surgical techniques are discussed, compared, and validated with experimental results

Diversity Analysis and Physico-Morphlogical Characteritics of Indigenous Germplasm of Lablab Bean

Germplasm characterization is an important component of crop breeding program. In characterizing indigenous beans lablab which is used for vegetables as well pulses in Nepal. Twenty three lablab beans germplasm were evaluated for different qualitative and quantitive physico-morphological charecteristics for two years during 2011 and 2012 at Horticulture Research Station, Malepatan, Pokhara. The germplasm showed considerable variations in most of the qualitative and quantitative traits. Leaf size, vine color, flower color, pod color, pod shape, pod type and seed color varied among the genotypes. Variation was also observed in yield attributing characters eg, pod length and width, 10 fresh pod weight, seeds per pod and 100-seed weight. Days to 50% flowering ranged from 81 to 130 days indicating the presence of early varieties. Fresh pod weight of 10 pods was ranged from 45.0 g to 162.5 g. Multivariate analysis indicated four groups in these genotypes, among with ML-02 and ML-10 were distinct in comparioson with other genotypes. Simple selection may be considered to develop high yielding, early type varieties from these gentopypes