A brief survey of deep reinforcement learning

Deep reinforcement learning (DRL) is poised to revolutionize the field of artificial intelligence (AI) and represents a step toward building autonomous systems with a higherlevel understanding of the visual world. Currently, deep learning is enabling reinforcement learning (RL) to scale to problems that were previously intractable, such as learning to play video games directly from pixels. DRL algorithms are also applied to robotics, allowing control policies for robots to be learned directly from camera inputs in the real world. In this survey, we begin with an introduction to the general field of RL, then progress to the main streams of value-based and policy-based methods. Our survey will cover central algorithms in deep RL, including the deep Q-network (DQN), trust region policy optimization (TRPO), and asynchronous advantage actor critic. In parallel, we highlight the unique advantages of deep neural networks, focusing on visual understanding via RL. To conclude, we describe several current areas of research within the field

Deep Reinforcement Learning: A Brief Survey

Deep reinforcement learning (DRL) is poised to revolutionize the field of artificial intelligence (AI) and represents a step toward building autonomous systems with a higher-level understanding of the visual world. Currently, deep learning is enabling reinforcement learning (RL) to scale to problems that were previously intractable, such as learning to play video games directly from pixels. DRL algorithms are also applied to robotics, allowing control policies for robots to be learned directly from camera inputs in the real world. In this survey, we begin with an introduction to the general field of RL, then progress to the main streams of value-based and policy-based methods. Our survey will cover central algorithms in deep RL, including the deep Q-network (DQN), trust region policy optimization (TRPO), and asynchronous advantage actor critic. In parallel, we highlight the unique advantages of deep neural networks, focusing on visual understanding via RL. To conclude, we describe several current areas of research within the field

Sox9 Inhibits -Trcp-Mediated Protein Degradation To Promote Nuclear Gli1 Expression And Cancer Stem Cell Properties

The high mobility group box protein SOX9 and the GLI1 transcription factor play protumorigenic roles in pancreatic ductal adenocarcinoma (PDA). In Kras transgenic mice, each of these factors are crucial for the development of PDA precursor lesions. SOX9 transcription is directly regulated by GLI1, but how SOX9 functions downstream of GLI1 is unclear. We observed positive feedback, such that SOX9-deficient PDA cells have severely repressed levels of endogenous GLI1, attributed to loss of GLI1 protein stability. SOX9 associated with the F-box domain of the SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase component, β-TrCP (also known as F-box/WD repeat-containing protein 1A), and suppressed its association with SKP1 and GLI1, a substrate of SCF-β-TrCP. SOX9 also tethered β-TrCP within the nucleus and promoted its degradation. SOX9 bound to β-TrCP through the SOX9 C-terminal PQA/S domain that mediates transcriptional activation. Suppression of β-TrCP in SOX9-deficient PDA cells restored GLI1 levels and promoted SOX9-dependent cancer stem cell properties. These studies identify SOX9–GLI1 positive feedback as a major determinant of GLI1 protein stability and implicate β-TrCP as a latent SOX9-bound tumor suppressor with the potential to degrade oncogenic proteins in tumor cells

Kruppel-like factor 4 signals through microRNA-206 to promote tumor initiation and cell survival

Tumor cell heterogeneity poses a major hurdle in the treatment of cancer. Mammary cancer stem-like cells (MaCSCs), or tumor-initiating cells, are highly tumorigenic sub-populations that have the potential to self-renew and to differentiate. These cells are clinically important, as they display therapeutic resistance and may contribute to treatment failure and recurrence, but the signaling axes relevant to the tumorigenic phenotype are poorly defined. The zinc-finger transcription factor Kruppel-like factor 4 (KLF4) is a pluripotency mediator that is enriched in MaCSCs. KLF4 promotes RAS-extracellular signal-regulated kinase pathway activity and tumor cell survival in triple-negative breast cancer (TNBC) cells. In this study, we found that both KLF4and a downstream effector, microRNA-206 (miR-206), are selectively enriched in the MaCSC fractions of cultured human TNBC cell lines, as well as in the aldehyde dehydrogenase-high MaCSC sub-population of cells derived from xenografted human mammary carcinomas. The suppression of endogenous KLF4 or miR-206 activities abrogated cell survival and in vivo tumor initiation, despite having only subtle effects on MaCSC abundance. Using a combinatorial approach that included in silico as well as loss- and gain-of-function in vitro assays, we identified miR-206-mediated repression of the pro-apoptotic molecules programmed cell death 4 (PDCD4) and connexin 43 (CX43/GJA1). Depletion of either of these two miR-206-regulated transcripts promoted resistance to anoikis, a prominent feature of CSCs, but did not consistently alter MaCSC abundance. Consistent with increased levels of miR-206 in MaCSCs, the expression of both PDCD4 and CX43 was suppressed in these cells relative to control cells. These results identify miR-206 as an effector of KLF4-mediated prosurvival signaling in MaCSCs through repression of PDCD4 and CX43. Consequently, our study suggests that a pluripotency factor exerts prosurvival signaling in MaCSCs, and that antagonism of KLF4-miR-206 signaling may selectively target the MaCSC niche in TNBC

Propanil Exposure Induces Delayed but Sustained Abrogation of Cell-Mediated Immunity through Direct Interference with Cytotoxic T-Lymphocyte Effectors

The postemergent herbicide propanil (PRN; also known as 3,4-dichloropropionanilide) is used on rice and wheat crops and has well-known immunotoxic effects on various compartments of the immune system, including T-helper lymphocytes, B lymphocytes, and macrophages. It is unclear, however, whether PRN also adversely affects cytotoxic T lymphocytes (CTLs), the primary (1°) effectors of cell-mediated immunity. In this study we examined both the direct and indirect effects of PRN exposure on CTL activation and effector cell function to gauge its likely impact on cell-mediated immunity. Initial experiments addressed whether PRN alters the class I major histocompatibility complex (MHC) pathway for antigen processing and presentation by antigen-presenting cells (APCs), thereby indirectly affecting effector function. These experiments demonstrated that PRN does not impair the activation of CTLs by PRN-treated APCs. Subsequent experiments addressed whether PRN treatment of CTLs directly inhibits their activation and revealed that 1° alloreactive CTLs exposed to PRN are unimpaired in their proliferative response and only marginally inhibited in their lytic activity. Surprisingly, secondary stimulation of these alloreactive CTL effectors, however, even in the absence of further PRN exposure, resulted in complete abrogation of CTL lytic function and a delayed but significant long-term effect on CTL responsiveness. These findings may have important implications for the diagnosis and clinical management of anomalies of cell-mediated immunity resulting from environmental exposure to various herbicides and other pesticides

Physical education as Olympic education

Introduction In a recent paper (Parry, 1998, p. 64), I argued that the justification of PE activities lies in their capacity to facilitate the development of certain human excellences of a valued kind. Of course, the problem now lies in specifying those ‘human excellences of a valued kind’, and (for anyone) this task leads us into the area of philosophical anthropology. I suggested that the way forward for Physical Education lies in the philosophical anthropology (and the ethical ideals) of Olympism, which provide a specification of a variety of human values and excellences which: •have been attractive to human groups over an impressive span of time and space •have contributed massively to our historically developed conceptions of ourselves •have helped to develop a range of artistic and cultural conceptions that have defined Western culture. •have produced a range of physical activities that have been found universally satisfying and challenging. Although physical activities are widely considered to be pleasurable, their likelihood of gaining wide acceptance lies rather in their intrinsic value, which transcends the simply hedonic or relative good. Their ability to furnish us with pleasurable experiences depends upon our prior recognition in them of opportunities for the development and expression of valued human excellences. They are widely considered to be such opportunities for the expression of valued human excellences because, even when as local instantiations, their object is to challenge our common human propensities and abilities. I claimed that Olympic ideals may be seen not merely as inert ‘ideals’, but living ideas which have the power to remake our notions of sport in education, seeing sport not as mere physical activity but as the cultural and developmental activity of an aspiring, achieving, well-balanced, educated and ethical individual. This paper seeks to make good that claim by trying to develop a case for Physical Education as Olympic Education. I begin by setting out various accounts and conceptions of the Olympic Idea; then I suggest a unifying and organising account of the philosophical anthropology of Olympism; and this is followed by the practical application of that account in two examples of current ethical issues. Finally, I seek to present an account of Physical Education as Olympic Education

Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol.

Emerging evidence suggests that patient-reported outcome (PRO)-specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best-practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported.Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points.Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO-specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion.The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r)

X-ray Spectral Survey of WGACAT Quasars, II: Optical and Radio Properties of Quasars with Low Energy X-ray Cut-offs

We have selected quasars with X-ray colors suggestive of a low energy cut-off, from the ROSAT PSPC pointed archive. We examine the radio and optical properties of these 13 quasars. Five out of the seven quasars with good optical spectra show associated optical absorption lines, with two having high delta-v candidate systems. Two other cut-off quasars show reddening associated with the quasar. We conclude that absorption is highly likely to be the cause of the X-ray cut-offs, and that the absorbing material associated with the quasars, not intervening along the line-of-sight. The suggestion that Gigahertz Peaked Sources are associated with X-ray cut-offs remains unclear with this expanded sample.Comment: 17 pages, LaTeX, including 2 Tables and 1 figure. Ap.J. in pres