Hi-Val: Iterative Learning of Hierarchical Value Functions for Policy Generation

Task decomposition is effective in manifold applications where the global complexity of a problem makes planning and decision-making too demanding. This is true, for example, in high-dimensional robotics domains, where (1) unpredictabilities and modeling limitations typically prevent the manual specification of robust behaviors, and (2) learning an action policy is challenging due to the curse of dimensionality. In this work, we borrow the concept of Hierarchical Task Networks (HTNs) to decompose the learning procedure, and we exploit Upper Confidence Tree (UCT) search to introduce HOP, a novel iterative algorithm for hierarchical optimistic planning with learned value functions. To obtain better generalization and generate policies, HOP simultaneously learns and uses action values. These are used to formalize constraints within the search space and to reduce the dimensionality of the problem. We evaluate our algorithm both on a fetching task using a simulated 7-DOF KUKA light weight arm and, on a pick and delivery task with a Pioneer robot

Autoimmune Hepatitis: A Review of Current Diagnosis and Treatment

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease. Corticosteroid therapy must be instituted early and modified in an individualized fashion. Treatment decisions are often complicated by the diverse clinical manifestations, uncertainty about natural history, evolving ideas about treatment end points, and a multitude of alternative immunosuppressive agents. Achieving normal liver tests and tissue is the ideal treatment end point, but needs to be weighed against the risk of side effects. Decompensated patients may benefit from early liver transplantation. Long-term prognosis is excellent with early and aggressive initiation of therapy. Our paper discusses AIH, giving a detailed overview of its clinical presentation, risk factors, immunopathogenesis, up-to-date diagnostic criteria, current updates in therapy with a brief discussion of AIH in pregnancy, and long-term implications for cirrhosis and hepatocellular carcinoma in AIH patients

On the Design and Analysis of Parallel and Distributed Algorithms

Arrival of multicore systems has enforced a new scenario in computing, the parallel and distributed algorithms are fast replacing the older sequential algorithms, with many challenges of these techniques. The distributed algorithms provide distributed processing using distributed file systems and processing units, while network is modeled as minimum cost spanning tree. On the other hand, the parallel processing chooses different language platforms, data parallel vs. parallel programming, and GPUs. Processing units, memory elements and storage are connected through dynamic distributed networks in the form of spanning trees. The article presents foundational algorithms, analysis, and efficiency considerations.Comment: 9 page

Guided Act and Feel Indonesia (GAF-ID) – Internet-based behavioral activation intervention for depression in Indonesia: study protocol for a randomized controlled trial

Background: Depression is a leading cause of disease burden across the world. However, in low-middle income countries (LMICs), access to mental health services is severely limited because of the insufficient number of mental health professionals available. The WHO initiated the Mental Health Gap Action Program (mhGAP) aiming to provide a coherent strategy for closing the gap between what is urgently needed and what is available in LMICs. Internet-based treatment is a promising strategy that can be made available to a large number of people now that Internet access is increasing rapidly throughout the world. The present study will investigate whether such an Internet-based treatment for depression is effective in Indonesia.  Methods: An Internet-based behavioral activation treatment, with support by lay counselors who will provide online feedback on the assignments and supportive phone contact to encourage participants to work in the program (Guided Act and Feel Indonesia/GAF-ID), is compared to an online-delivered minimal psychoeducation without any support (psychoeducation/PE). Initial assessment for inclusion is based on a Patient Health Questionnaire-9 (PHQ-9) score of at least 10 and meeting criteria for major depressive disorder or persistent depressive disorder as assessed using the Structured Clinical Interview for DSM-5 (SCID-5). Participants with depression (N=312) will be recruited and randomly assigned to GAF-ID or PE. Overall assessments will be done at baseline, post intervention (10 weeks from baseline) and follow-ups (3 months and 6 months from baseline). The primary outcome is the reduction of depression symptoms as measured by the PHQ-9 after 10 weeks from baseline.  Discussion: To our knowledge, this is the first study in Indonesia that examines the effectiveness of an Internet-based intervention for depression in a randomized controlled trial. The hope is that it can serve as a starting point for bridging the mental health gap in Indonesia and other LMICs. Trial registration: Nederlands Trial Register ( www.trialregister.nl ): NTR5920 , registered on 1 July 2016

Biodegradation of Amphipathic Fluorinated Peptides Reveals a New Bacterial Defluorinating Activity and a New Source of Natural Organofluorine Compounds

Three peptides comprising mono-, di-, and tri-fluoroethylglycine (MfeGly, DfeGly, and TfeGly) residues alternating with lysine were digested by readily available proteases (elastase, bromelain, trypsin, and proteinase K). The degree of degradation depended on the enzyme employed and the extent of fluorination. Incubation of the peptides with a microbial consortium from garden soil resulted in degradation, yielding fluoride ions. Further biodegradation studies conducted with the individual fluorinated amino acids demonstrated that the degree of defluorination followed the sequence MfeGly > DfeGly > TfeGly. Enrichment of the soil bacteria employing MfeGly as a sole carbon and energy source resulted in the isolation of a bacterium, which was identified as Serratia liquefaciens. Cell-free extracts of this bacterium enzymatically defluorinated MfeGly, yielding fluoride ion and homoserine. In silico analysis of the genome revealed the presence of a gene that putatively codes for a dehalogenase. However, the low overall homology to known enzymes suggests a potentially new hydrolase that can degrade monofluorinated compounds. 19F NMR analysis of aqueous soil extracts revealed the unexpected presence of trifluoroacetate, fluoride ion, and fluoroacetate. Growth of the soil consortium in tryptone soya broth supplemented with fluoride ions resulted in fluoroacetate production; thus, bacteria in the soil produce and degrade organofluorine compounds

Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing.

A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole antifungal drugs. Whole-genome sequencing (WGS) was performed for high-resolution single-nucleotide polymorphism (SNP) analysis of 24 A. fumigatus isolates, including azole-resistant and susceptible clinical and environmental strains obtained from India, the Netherlands, and the United Kingdom, in order to assess the utility of WGS for characterizing the alleles causing resistance. WGS analysis confirmed that TR34/L98H (a mutation comprising a tandem repeat [TR] of 34 bases in the promoter of the cyp51A gene and a leucine-to-histidine change at codon 98) is the sole mechanism of azole resistance among the isolates tested in this panel of isolates. We used population genomic analysis and showed that A. fumigatus was panmictic, with as much genetic diversity found within a country as is found between continents. A striking exception to this was shown in India, where isolates are highly related despite being isolated from both clinical and environmental sources across >1,000 km; this broad occurrence suggests a recent selective sweep of a highly fit genotype that is associated with the TR34/L98H allele. We found that these sequenced isolates are all recombining, showing that azole-resistant alleles are segregating into diverse genetic backgrounds. Our analysis delineates the fundamental population genetic parameters that are needed to enable the use of genome-wide association studies to identify the contribution of SNP diversity to the generation and spread of azole resistance in this medically important fungus. IMPORTANCE: Resistance to azoles in the ubiquitous ascomycete fungus A. fumigatus was first reported from clinical isolates collected in the United States during the late 1980s. Over the last decade, an increasing number of A. fumigatus isolates from the clinic and from nature have been found to show resistance to azoles, suggesting that resistance is emerging through selection by the widespread usage of agricultural azole antifungal compounds. Aspergillosis is an emerging clinical problem, with high rates of treatment failures necessitating the development of new techniques for surveillance and for determining the genome-wide basis of azole resistance in A. fumigatus

Inherent-Structure Dynamics and Diffusion in Liquids

The self-diffusion constant D is expressed in terms of transitions among the local minima of the potential (inherent structure, IS) and their correlations. The formulae are evaluated and tested against simulation in the supercooled, unit-density Lennard-Jones liquid. The approximation of uncorrelated IS-transition (IST) vectors, D_{0}, greatly exceeds D in the upper temperature range, but merges with simulation at reduced T ~ 0.50. Since uncorrelated IST are associated with a hopping mechanism, the condition D ~ D_{0} provides a new way to identify the crossover to hopping. The results suggest that theories of diffusion in deeply supercooled liquids may be based on weakly correlated IST.Comment: submitted to PR

Increased yield of smear positive pulmonary TB cases by screening patients with >2 weeks cough, compared to >3 weeks and adequacy of 2 sputum smear examinations for diagnosis

Background RNTCP recommends examining three sputum smears for AFB from Chest Symptomatics (CSs) with cough of >3 weeks for diagnosis of Pulmonary TB (PTB). A previous multi-centric study from Tuberculosis Research centre (TRC) has shown that the yield of sputum positive cases can be increased if duration of cough for screening was reduced to >2 weeks. Other studies have shown that two smear examinations are adequate for diagnosis of smear positive PTB . To validate the above findings, a cross sectional multi-centric study was repeated in different settings in five geographical areas in India. Methods Three primary and secondary level health facilities with high out-patient attendance were selected from two Tuberculosis Units (TU) in each of the 15 selected districts to screen about 10,000 new adult outpatients from each state. For patients who did not volunteer history of cough, symptoms were elicited using a structured simple questionnaire. All the CSs were referred for sputum examination. Results A total of 96,787 out-patients were registered. Among them 69,209 (72%) were new adult out-patients. Using >2 weeks of cough instead of > 3 weeks as the criterion for screening, there was an overall increase of 58% in CS and 23% increase in the detection of smear-positive cases. Among 211 patients, 210 were positive at least by one smear from the initial two specimens. Increase in the work-load if 2 smears were done for patients with cough of >2 weeks cough were 2 specimens (i.e.13 to 15) per day for an adult OPD of 150. Conclusion The yield of sputum positive PTB cases can be improved by screening patients with >2 weeks cough and two specimens are adequate for diagnosis

The Potential Energy Landscape and Mechanisms of Diffusion in Liquids

The mechanism of diffusion in supercooled liquids is investigated from the potential energy landscape point of view, with emphasis on the crossover from high- to low-T dynamics. Molecular dynamics simulations with a time dependent mapping to the associated local mininum or inherent structure (IS) are performed on unit-density Lennard-Jones (LJ). New dynamical quantities introduced include r2_{is}(t), the mean-square displacement (MSD) within a basin of attraction of an IS, R2(t), the MSD of the IS itself, and g_{loc}(t) the mean waiting time in a cooperative region. At intermediate T, r2_{is}(t) posesses an interval of linear t-dependence allowing calculation of an intrabasin diffusion constant D_{is}. Near T_{c} diffusion is intrabasin dominated with D = D_{is}. Below T_{c} the local waiting time tau_{loc} exceeds the time, tau_{pl}, needed for the system to explore the basin, indicating the action of barriers. The distinction between motion among the IS below T_{c} and saddle, or border dynamics above T_{c} is discussed.Comment: submitted to pr