RL3^3: Boosting Meta Reinforcement Learning via RL inside RL2^2

Meta reinforcement learning (meta-RL) methods such as RL$^2$ have emerged as promising approaches for learning data-efficient RL algorithms tailored to a given task distribution. However, these RL algorithms struggle with long-horizon tasks and out-of-distribution tasks since they rely on recurrent neural networks to process the sequence of experiences instead of summarizing them into general RL components such as value functions. Moreover, even transformers have a practical limit to the length of histories they can efficiently reason about before training and inference costs become prohibitive. In contrast, traditional RL algorithms are data-inefficient since they do not leverage domain knowledge, but they do converge to an optimal policy as more data becomes available. In this paper, we propose RL$^3$, a principled hybrid approach that combines traditional RL and meta-RL by incorporating task-specific action-values learned through traditional RL as an input to the meta-RL neural network. We show that RL$^3$ earns greater cumulative reward on long-horizon and out-of-distribution tasks compared to RL$^2$, while maintaining the efficiency of the latter in the short term. Experiments are conducted on both custom and benchmark discrete domains from the meta-RL literature that exhibit a range of short-term, long-term, and complex dependencies

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

Análise de empresas de médias empresas da rússia na conexão dos distritos federais e principais municípios

The article examines the trends in the number of medium-sized enterprises in Russia, in the context of federal districts and major municipalities. Detailed information is provided on the number and dynamics of medium-sized enterprises in Russia by federal districts and the largest municipalities for the period from 2008 to 2017. The indicators of the number of employees, labor efficiency and revenues of medium-sized businesses are considered. Developed by the authors and presented in the article, the map of medium-sized businesses allows you to make both management decisions to state and municipal authorities, and make investment decisions.El artículo examina las tendencias en el número de empresas medianas en Rusia, en el contexto de los distritos federales y los principales municipios. Se proporciona información detallada sobre el número y la dinámica de las medianas empresas en Rusia por los distritos federales y los municipios más grandes durante el período de 2008 a 2017. Los indicadores de la cantidad de empleados, la eficiencia laboral y los ingresos de las medianas empresas son considerados. Desarrollado por los autores y presentado en el artículo, el mapa de las medianas empresas le permite tomar decisiones de gestión ante las autoridades estatales y municipales, y tomar decisiones de inversión.O artigo examina as tendências no número de empresas de médio porte na Rússia, no contexto de distritos federais e grandes municípios. Informações detalhadas sobre o número e a dinâmica das empresas de médio porte na Rússia são fornecidas pelos distritos federais e os maiores municípios durante o período de 2008 a 2017. Os indicadores do número de funcionários, a eficiência da mão-de-obra e a renda das medianas Empresas são consideradas. Desenvolvido pelos autores e apresentado no artigo, o mapa de empresas de médio porte permite que eles tomem decisões de gestão perante as autoridades estaduais e municipais e tomem decisões de investimento

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Insuficiência renal aguda secundária à síndrome compartimental abdominal: relato de quatro casos e revisão da literatura

We report on 4 cases of abdominal compartment syndrome complicated by acute renal failure that were promptly reversed by different abdominal decompression methods. Case 1: A 57-year-old obese woman in the post-operative period after giant incisional hernia correction with an intra-abdominal pressure of 24 mm Hg. She was sedated and curarized, and the intra-abdominal pressure fell to 15 mm Hg. Case 2: A 73-year-old woman with acute inflammatory abdomen was undergoing exploratory laparotomy when a hypertensive pneumoperitoneum was noticed. During the surgery, enhancement of urinary output was observed. Case 3: An 18-year-old man who underwent hepatectomy and developed coagulopathy and hepatic bleeding that required abdominal packing, developed oliguria with a transvesical intra-abdominal pressure of 22 mm Hg. During reoperation, the compresses were removed with a prompt improvement in urinary flow. Case 4: A 46-year-old man with hepatic cirrhosis was admitted after incisional hernia repair with intra-abdominal pressure of 16 mm Hg. After paracentesis, the intra-abdominal pressure fell to 11 mm Hg.Descrevemos quatro casos de síndrome compartimental abdominal complicadas por insuficiência renal aguda e prontamente revertidas por diferentes métodos de descompressão abdominal. Caso 1: paciente obesa de 57 anos no pós-operatório de correção de hérnia incisional gigante com pressão intra-abdominal de 24 mm Hg. Após sedação e curarização, a PIA caiu para 15 mm Hg. Caso 2: paciente de 73 anos com abdômem agudo inflamatório submetida à laparotomia exploradora quando foi diagnosticado pneumoperitôneo hipertensivo. Durante a cirurgia houve melhora da diurese. Caso 3: paciente de 18 anos submetido a hepactetomia apresentou coagulopatia e sangramento hepático necessitando tamponamento com compressas, evoluindo com oligúria e PIA de 22 mm Hg. Na reoperação, após remoção das compressas houve melhora importante do fluxo urinário. Caso 4: paciente de 46 anos com cirrose hepática foi admitido após correção de hérnia incisional com pressão intra-abdominal de 16 mm Hg. Após paracentese, a pressão intra-abdominal caiu para 11 mm Hg

Improving phylogeny reconstruction at the strain level using peptidome datasets

Typical bacterial strain differentiation methods are often challenged by high genetic similarity between strains. To address this problem, we introduce a novel in silico peptide fingerprinting method based on conventional wet-lab protocols that enables the identification of potential strain-specific peptides. These can be further investigated using in vitro approaches, laying a foundation for the development of biomarker detection and application-specific methods. This novel method aims at reducing large amounts of comparative peptide data to binary matrices while maintaining a high phylogenetic resolution. The underlying case study concerns the Bacillus cereus group, namely the differentiation of Bacillus thuringiensis, Bacillus anthracis and Bacillus cereus strains. Results show that trees based on cytoplasmic and extracellular peptidomes are only marginally in conflict with those based on whole proteomes, as inferred by the established Genome-BLAST Distance Phylogeny (GBDP) method. Hence, these results indicate that the two approaches can most likely be used complementarily even in other organismal groups. The obtained results confirm previous reports about the misclassification of many strains within the B. cereus group. Moreover, our method was able to separate the B. anthracis strains with high resolution, similarly to the GBDP results as benchmarked via Bayesian inference and both Maximum Likelihood and Maximum Parsimony. In addition to the presented phylogenomic applications, whole-peptide fingerprinting might also become a valuable complementary technique to digital DNA-DNA hybridization, notably for bacterial classification at the species and subspecies level in the future.This research was funded by Grant AGL2013-44039-R from the Spanish “Plan Estatal de I+D+I”, and by Grant EM2014/046 from the “Plan Galego de investigación, innovación e crecemento 2011-2015”. BS was recipient of a Ramón y Cajal postdoctoral contractfrom the Spanish Ministry of Economyand Competitiveness. This work was also partially funded by the [14VI05] Contract-Programme from the University of Vigo and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273).The research leading to these results has also received funding from the European Union’s Seventh Framework Programme FP7/REGPOT-2012-2013.1 under grant agreement n˚ 316265, BIOCAPS. This document reflects only the authors’ views and the European Union is not liable for any use that may be made of the information contained herein. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Concurrent Oral 1 - Therapy of rheumatic disease: OP4. Effectiveness of Rituximab in Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register (BSRBR)

Background: Rituximab (RTX) in combination with methotrexate (MTX) has been licensed since 2006 for the management of severe active rheumatoid arthritis (RA) in patients who have failed at least one anti-tumour necrosis factor (anti-TNF) therapy. Published clinical trials have demonstrated the efficacy of RTX in improving both clinical symptoms and patients' physical function. This study aimed to assess the effectiveness of RTX in RA patients treated in routine clinical practice by examining clinical and patient reported outcomes six months after receiving a first course of RTX. Methods: The analysis involved 550 RA patients registered with the BSRBR, who were starting RTX and were followed up for at least 6 months. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical response while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients 6 months after starting RTX. The change in DAS28 and HAQ was compared between seronegative and seropositive patients and anti-TNF naïve patients versus anti-TNF failures. The response was also compared between patients receiving RTX in combination with MTX, other non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) or no nbDMARDs. Results: The mean (s.d.) age of the cohort was 59 (12) years and 78% of the patients were females. The patients had a mean (s.d.) of 15 (10) years of disease duration. 16% were biologic naïve while 84% were anti-TNF failures. 32% of the patients were seronegative and 68% were seropositive. The mean (95% CI) DAS28 at baseline was 6.2 (6.1, 6.3) which decreased to 4.8 (4.7, 4.9) at 6 months of follow up. 16% were EULAR good responders, 43% were moderate responders and 41% were non responders. The mean (95% CI) change in HAQ was −0.1 (−0.2, −0.1) (Table 1). The mean change in DAS28 was similar in seropositive and seronegative patients (p = 0.18) while the anti-TNF naïve patients showed a greater reduction in DAS28 scores than anti-TNF failures (p = 0.05). Patients receiving RTX in combination with MTX showed similar changes in DAS28 and HAQ compared to patients receiving RTX alone or with other nbDMARDs. Conclusions: RTX has proven to be effective in the routine clinical practice. Anti-TNF naïve patients seem to benefit more from RTX treatment than anti-TNF failures. Disclosure statement: The authors have declared no conflicts of interes

FEE EXPENSES CORRELATION IN THE FIELD OF LAW AND OTHER EXPENSES ON FINANCIAL RESULT OF THE RUSSIAN ENTERPRISES

Purpose: to determine features of interrelation and influence of expenses by fee in the field of law and other expenses on financial result of the Russian enterprises. Methods: general-logical methods of knowledge, correlation and regression analysis, comparative analysis, graphic analysis. Results: in article features of interrelation and influence of fee expenses in the field of law and other expenses on financial result of the Russian enterprises are investigated. The general characteristic of subject relevance is given. The modern scientific works considering questions of interrelation and various factors influence on financial result are analyzed. Despite rather large number of publications on the matter, we revealed lack of works of the expenses of the enterprises on external legal services considering influence on their financial result. For elimination of this gap, as the first of steps, we generalized data on proceeds from sales, profits before the taxation, prime costs, fee expenses in the field of law, fee expenses of science, fee of education, fee expenses of audit organizations. Specific weight of the presented expenses in prime cost is calculated. This statistics is presented from 2011 for 2016 in a section of the federal districts of Russia. Further the coefficients of correlation and factors which are most closely interconnected with revenue and profit were defined. The regression model of the resulting sign (proceeds from sales) and factorial signs is constructed (fee expenses in the field of law and fee expenses of science). An assessment of quality of the received regression equation is in conclusion given. Scientific novelty: in article on the basis of the regression analysis an assessment of interrelation and to influence of fee expenses in the field of law for proceeds from sales is given. Practical importance: the main results, provisions and conclusions of article can be used when developing strategy of the enterprises, at decision-making in the field of management of expenses. The data obtained in article will be useful to scientists-economists, scientific and pedagogical workers to expansion and better understanding of subject domain. The methodological base of article can act as an example when forming research competences of students, undergraduates and graduate students

ОСНОВЫ УПРАВЛЕНИЯ СОЦИАЛЬНЫМИ ПРОЕКТАМИ БИЗНЕСА

In article on wide material the author opens basic approaches to formation of the theoretical base of management of social projects of business.The purpose of work is generalization of theoretical bases of project management of business which have social character. The logic of a statement of material is under construction as follows. In water part of article authors do the assumption that at the heart of an object of research three basic elements are put: project management, social management and management of social projects. Proceeding from this assumption in work further reasonings are under construction. The main part of article contains three subsections. In the fi rst subsection of article defi nition of the concept «project management» is formulated and methodological approaches to project management (PRINCE2, PERT, the Model Agile, Lean Management, BRM) are generalized. In the second subsection the author's understanding of entity of social management is presented and the main techniques of social management are considered, and also the characteristic of methodology of management of social projects is given. In the third subsection the author's concept of entity of management of social projects of business is formulated. In fi nal part of article authors draw a conclusion about the importance of management of social projects of business. This article, fi rst of all, has theoretical and methodological value for formation of eff ective methods and instruments of management of social projects of business, and also for development of the theory and practice of corporate social responsibility.В статье авторы раскрывают основные подходы к формированию теоретического фундамента управления социальными проектами бизнеса. Целью работы является обобщение теоретических основ управления проектами бизнеса, которые носят социальный характер. Логика изложения материала строится следующим образом. В водной части статьи авторы делают предположение о том, что в основе предмета исследования заложены три основных элемента: управление проектами, социальное управление и управление социальными проектами. Исходя из этого предположения в работе строятся дальнейшие рассуждения. Основная часть статьи содержит три подраздела. В первом подразделе статьи сформулировано определение понятия «управление проектами» и обобщены методологические подходы к управлению проектами (PRINCE2, PERT, Модель Agile, Лин-менеджмент, BRM). Во втором подразделе представлено авторское понимание сущности социального управления и рассмотрены основные методики социального управления, а также дана характеристика методологии управления социальными проектами. В третьем подразделе сформулирована авторская концепция сущности управления социальными проектами бизнеса. В заключительной части статьи авторы делают вывод о значимости управления социальными проектами бизнеса. Данная статья, в первую очередь, имеет теоретическое и методологическое значение для формирования эффективных методов и инструментов управления социальными проектами бизнеса, а также для развития теории и практики корпоративной социальной ответственности