Radiation for Awakening the Dormant Immune System, a Promising Challenge to be Explored.

Recent advances that have been made in our understanding of cancer biology and immunology show that infiltrated immune cells and cytokines in the tumor microenvironment may play different functions that appear tightly related to clinical outcomes. Strategies aimed at interfering with the cross-talk between microenvironment tumor cells and their cellular partners have been considered for the development of new immunotherapies. These novel therapies target different cell components of the tumor microenvironment and importantly, they may be coupled and boosted with classical treatments, such as radiotherapy. In this work, we try to summarize recent data on the microenvironment impact of radiation therapy, from pre-clinical research to the clinic, while taking into account that this new knowledge will probably translate into indication and objective of radiation therapy changes in the next future.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

System failure prediction through rare-events elastic-net logistic regression

Predicting failures in a distributed system based on previous events through logistic regression is a standard approach in literature. This technique is not reliable, though, in two situations: in the prediction of rare events, which do not appear in enough proportion for the algorithm to capture, and in environments where there are too many variables, as logistic regression tends to overfit on this situations; while manually selecting a subset of variables to create the model is error- prone. On this paper, we solve an industrial research case that presented this situation with a combination of elastic net logistic regression, a method that allows us to automatically select useful variables, a process of cross-validation on top of it and the application of a rare events prediction technique to reduce computation time. This process provides two layers of cross- validation that automatically obtain the optimal model complexity and the optimal mode l parameters values, while ensuring even rare events will be correctly predicted with a low amount of training instances. We tested this method against real industrial data, obtaining a total of 60 out of 80 possible models with a 90% average model accuracy.

The Soviet legal system : post-Stalin documentation and historical commentary /

Includes bibliographies.

Management practices on public lands: hearings, Ninety-second Congress, first [and second] session[s], on S. 350, a bill to authorize the Secretary of the Interior and the Secretary of Agriculture to Institute Programs designed to reforest and restore the quality of public and private forest lands; to enhance and expand recreational opportunity on such lands; to provide financial incentives to improve management of state and private forest lands; to establish a federal forest lands management fund; to facilitate public participation in Federal Resource Management; and to enhance the quality of the environment ad the resources of the public lands; [and] S. 1734, a bill to provide for comprehensive management of the nation's forest lands through the application of sound forest practices, and for other purposes.

Frank Church, subcommittee chairman.

MULTIPRED: A computational system for prediction of promiscuous HLA binding peptides

MULTIPRED is a web-based computational system for the prediction of peptide binding to multiple molecules ( proteins) belonging to human leukocyte antigens (HLA) class I A2, A3 and class II DR supertypes. It uses hidden Markov models and artificial neural network methods as predictive engines. A novel data representation method enables MULTIPRED to predict peptides that promiscuously bind multiple HLA alleles within one HLA supertype. Extensive testing was performed for validation of the prediction models. Testing results show that MULTIPRED is both sensitive and specific and it has good predictive ability ( area under the receiver operating characteristic curve A(ROC) > 0.80). MULTIPRED can be used for the mapping of promiscuous T-cell epitopes as well as the regions of high concentration of these targets termed T-cell epitope hotspots. MULTIPRED is available at http:// antigen.i2r.a-star.edu.sg/ multipred/.

Surrogacy under Indian Legal System: Legal and Human Rights Concerns

The advancements in medical science and technology have proved to be a boon to mankind. At the same time they have raised numerous challenges before the legal systems of the world. One such advancement is that of assisted human reproductive technologies and particularly surrogacy, which have given a new meaning to the concept of procreation. These technologies have made it possible for individuals to beget a genetically related child with the help of a third party and without sexual intercourse. Among all the assisted human reproductive technologies, the practice of surrogacy, in which women agree to have their bodies used to undergo a pregnancy and give birth to a baby for another, has raised various legal and human right controversies and diverse legal responses all over the world. India has particularly become a top destination for individuals who wish to beget a child through surrogacy and hence it is imperative for the Indian government to address the challenges posed by surrogacy. This study is an attempt to examine the need and importance of surrogacy practices and the conflicting legal and human rights issues raised by surrogacy in contemporary times. It also examines the adequacy of existing legal framework in India and attempts to provide pragmatic solutions for regulating surrogacy and protecting the interests of various stakeholders involved in surrogacy.