Automatic Goal Discovery in Subgoal Monte Carlo Tree Search

Monte Carlo Tree Search (MCTS) is a heuristic search algorithm that can play a wide range of games without requiring any domain-specific knowledge. However, MCTS tends to struggle in very complicated games due to an exponentially increasing branching factor. A promising solution for this problem is to focus the search only on a small fraction of states. Subgoal Monte Carlo Tree Search (S-MCTS) achieves this by using a predefined subgoal-predicate that detects promising states called subgoals. However, not only does this make S-MCTS domain-dependent, but also it is often difficult to define a good predicate. In this paper, we propose using quality diversity (QD) algorithms to detect subgoals in real-time. Furthermore, we show how integrating QD-algorithms into S-MCTS significantly improves its performance in the Physical Travelling Salesmen Problem without requiring any domain-specific knowledge

The morbidity of urethral stricture disease among male Medicare beneficiaries

<p>Abstract</p> <p>Background</p> <p>To date, the morbidity of urethral stricture disease among American men has not been analyzed using national datasets. We sought to analyze the morbidity of urethral stricture disease by measuring the rates of urinary tract infections and urinary incontinence among men with a diagnosis of urethral stricture.</p> <p>Methods</p> <p>We analyzed Medicare claims data for 1992, 1995, 1998, and 2001 to estimate the rate of dual diagnoses of urethral stricture with urinary tract infection and with urinary incontinence occurring in the same year among a 5% sample of beneficiaries. Male Medicare beneficiaries receiving co-incident ICD-9 codes indicating diagnoses of urethral stricture and either urinary tract infection or urinary incontinence within the same year were counted.</p> <p>Results</p> <p>The percentage of male patients with a diagnosis of urethral stricture who also were diagnosed with a urinary tract infection was 42% in 2001, an increase from 35% in 1992. Eleven percent of male Medicare beneficiaries with urethral stricture disease in 2001 were diagnosed with urinary incontinence in the same year. This represents an increase from 8% in 1992.</p> <p>Conclusions</p> <p>Among male Medicare beneficiaries diagnosed with urethral stricture disease in 2001, 42% were also diagnosed with a urinary tract infection, and 11% with incontinence. Although the overall incidence of stricture disease decreased over this time period, these rates of dual diagnoses increased from 1992 to 2001. Our findings shed light into the health burden of stricture disease on American men. In order to decrease the morbidity of stricture disease, early definitive management of strictures is warranted.</p

Non-global logarithms and jet algorithms in high-pT jet shapes

We consider jet-shape observables of the type proposed recently, where the shapes of one or more high-pT jets, produced in a multi-jet event with definite jet multiplicity, may be measured leaving other jets in the event unmeasured. We point out the structure of the full next-to-leading logarithmic resummation specifically including resummation of non-global logarithms in the leading-Nc limit and emphasising their properties. We also point out differences between jet algorithms in the context of soft gluon resummation for such observables.Comment: 22 pages, 4 figures. Title and a few words changed. Several typos corrected. Version accepted by JHE

Effects of selected food phytochemicals in reducing the toxic actions of TCDD and p,p′-DDT in U937 macrophages

To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p′-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT–PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells. We tested auraptene on DDT-induced reactive oxygen species (ROS) formation in U937 macrophages and found that auraptene is a powerful agent antagonizing this action of DDT. To confirm the significance of these actions of zerumbone and auraptene at the cellular level, we assessed their influence on TCDD-induced apoptosis resistance in intact U937 macrophages and found that they are capable of reversing this action of TCDD. In conclusion, zerumbone and auraptene were identified to be the most effective agents in protecting U937 macrophages from developing these cell toxic effects of TCDD and DDT

Owning an overweight or underweight body: distinguishing the physical, experienced and virtual body

Our bodies are the most intimately familiar objects we encounter in our perceptual environment. Virtual reality provides a unique method to allow us to experience having a very different body from our own, thereby providing a valuable method to explore the plasticity of body representation. In this paper, we show that women can experience ownership over a whole virtual body that is considerably smaller or larger than their physical body. In order to gain a better understanding of the mechanisms underlying body ownership, we use an embodiment questionnaire, and introduce two new behavioral response measures: an affordance estimation task (indirect measure of body size) and a body size estimation task (direct measure of body size). Interestingly, after viewing the virtual body from first person perspective, both the affordance and the body size estimation tasks indicate a change in the perception of the size of the participant’s experienced body. The change is biased by the size of the virtual body (overweight or underweight). Another novel aspect of our study is that we distinguish between the physical, experienced and virtual bodies, by asking participants to provide affordance and body size estimations for each of the three bodies separately. This methodological point is important for virtual reality experiments investigating body ownership of a virtual body, because it offers a better understanding of which cues (e.g. visual, proprioceptive, memory, or a combination thereof) influence body perception, and whether the impact of these cues can vary between different setups

Exploring forest structural complexity by multi-scale segmentation of VHR imagery

Forests are complex ecological systems, characterised by multiple-scale structural and dynamical patterns which are not inferable from a system description that spans only a narrow window of resolution; this makes their investigation a difficult task using standard field sampling protocols. We segment a QuickBird image covering a beech forest in an initial stage of old-growthness – showing, accordingly, a good degree of structural complexity – into three segmentation levels. We apply field-based diversity indices of tree size, spacing, species assemblage to quantify structural heterogeneity amongst forest regions delineated by segmentation. The aim of the study is to evaluate, on a statistical basis, the relationships between spectrally delineated image segments and observed spatial heterogeneity in forest structure, including gaps in the outer canopy. Results show that: some 45% of the segments generated at the coarser segmentation scale (level 1) are surrounded by structurally different neighbours; level 2 segments distinguish spatial heterogeneity in forest structure in about 63% of level 1 segments; level 3 image segments detect better canopy gaps, rather than differences in the spatial pattern of the investigated structural indices. Results support also the idea of a mixture of macro and micro structural heterogeneity within the beech forest: large size populations of trees homogeneous for the examined structural indices at the coarser segmentation level, when analysed at a finer scale, are internally heterogeneous; and vice versa. Findings from this study demonstrate that multiresolution segmentation is able to delineate scale-dependent patterns of forest structural heterogeneity, even in an initial stage of old-growth structural differentiation. This tool has therefore a potential to improve the sampling design of field surveys aimed at characterizing forest structural complexity across multiple spatio-temporal scales.L'articolo è disponibile sul sito dell'editore www.sciencedirect.co

FUS-DDIT3 Prevents the Development of Adipocytic Precursors in Liposarcoma by Repressing PPARγ and C/EBPα and Activating eIF4E

FUS-DDIT3 is a chimeric protein generated by the most common chromosomal translocation t(12;16)(q13;p11) linked to liposarcomas, which are characterized by the accumulation of early adipocytic precursors. Current studies indicate that FUS-DDIT3- liposarcoma develops from uncommitted progenitors. However, the precise mechanism whereby FUS-DDIT3 contributes to the differentiation arrest remains to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we have characterized the adipocyte regulatory protein network in liposarcomas of FUS-DITT3 transgenic mice and showed that PPARgamma2 and C/EBPalpha expression was altered. Consistent with in vivo data, FUS-DDIT3 MEFs and human liposarcoma cell lines showed a similar downregulation of both PPARgamma2 and C/EBPalpha expression. Complementation studies with PPARgamma but not C/EBPalpha rescued the differentiation block in committed adipocytic precursors expressing FUS-DDIT3. Our results further show that FUS-DDIT3 interferes with the control of initiation of translation by upregulation of the eukaryotic translation initiation factors eIF2 and eIF4E both in FUS-DDIT3 mice and human liposarcomas cell lines, explaining the shift towards the truncated p30 isoform of C/EBPalpha in liposarcomas. Suppression of the FUS-DDIT3 transgene did rescue this adipocyte differentiation block. Moreover, eIF4E was also strongly upregulated in normal adipose tissue of FUS-DDIT3 transgenic mice, suggesting that overexpression of eIF4E may be a primary event in the initiation of liposarcomas. Reporter assays showed FUS-DDIT3 is involved in the upregulation of eIF4E in liposarcomas and that both domains of the fusion protein are required for affecting eIF4E expression. CONCLUSIONS/SIGNIFICANCE: Taken together, this study provides evidence of the molecular mechanisms involve in the disruption of normal adipocyte differentiation program in liposarcoma harbouring the chimeric gene FUS-DDIT3.Research in ISG group is supported partially by FEDER and by MEC (SAF2006-03726), Junta de Castilla y León (CSI03A05), FIS (PI050087, PI050116), Fundación de Investigación MMA, Federación de Cajas de Ahorro Castilla y León (I Convocatoria de Ayudas para Proyectos de Investigación Biosanitaria con Células Madre), CDTEAM project (CENIT-Ingenio 2010) and MEC Consolider-Ingenio 2010 (Ref. CSD2007-0017).Research in ISG group is supported partially by FEDER and by MEC (SAF2006-03726 and PETRI N° 95-0913.OP), Junta de Castilla y León (CSI03A05), FIS (PI050087, PI050116), Fundación de Investigación MMA, Federación de Cajas de Ahorro Castilla y León (I Convocatoria de Ayudas para Proyectos de Investigación Biosanitaria con Células Madre), CDTEAM project (CENIT-Ingenio 2010) and MEC Consolider-Ingenio 2010 (Ref. CSD2007-0017). MSM is supported by the Ramon y Cajal Scientific Spanish Program, Fondo Investigacion Sanitaria (FIS PI04-1271), Junta de Castilla y León (SA085A06) and Fundación Manuel Solorzano, University of Salamanca.Peer reviewe

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area: two modes of decreasing release probability

<p>Abstract</p> <p>Background</p> <p>Synaptic burst activation feeds back as a short-term depression of release probability at hippocampal CA3-CA1 synapses. This short-term synaptic plasticity requires functional astrocytes and it affects both the recently active (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses (transient heterosynaptic depression). The aim of this study was to investigate and compare the components contributing to the depression of release probability in these two different scenarios.</p> <p>Results</p> <p>When tested using paired-pulses, following a period of inactivity, the transient heterosynaptic depression was expressed as a reduction in the response to only the first pulse, whereas the response to the second pulse was unaffected. This selective depression of only the first response in a high-frequency burst was shared by the homosynaptic post-burst depression, but it was partially counteracted by augmentation at these recently active synapses. In addition, the expression of the homosynaptic post-burst depression included an astrocyte-mediated reduction of the pool of release-ready primed vesicles.</p> <p>Conclusions</p> <p>Our results suggest that activated astrocytes depress the release probability via two different mechanisms; by depression of vesicular release probability only at inactive synapses and by imposing a delay in the recovery of the primed pool of vesicles following depletion. These mechanisms restrict the expression of the astrocyte-mediated depression to temporal windows that are typical for synaptic burst activity.</p