Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiretroviral therapy in a thousand patients with AIDS in Haiti.

BACKGROUND The one-year survival rate of adults and children with the acquired immunodeficiency syndrome (AIDS), without antiretroviral therapy, has been about 30 percent in Haiti. Antiretroviral therapy has recently become available in Haiti and in other developing countries. Data on the efficacy of antiretroviral therapy in developing countries are limited. High rates of coinfection with tropical diseases and tuberculosis, along with malnutrition and limited laboratory monitoring of therapy, may decrease the efficacy of antiretroviral therapy in these countries. METHODS We studied the efficacy of antiretroviral therapy in the first 1004 consecutive patients with AIDS and without previous antiretroviral therapy who were treated beginning in March 2003 in Port-au-Prince, Haiti. RESULTS During a 14-month period, three-drug antiretroviral therapy was initiated in 1004 patients, including 94 children under 13 years of age. At enrollment, the median CD4 T-cell count in adults and adolescents was 131 per cubic millimeter (interquartile range, 55 to 211 per cubic millimeter); in children, a median of 13 percent of T cells were CD4-positive (interquartile range, 8 to 20 percent). According to a Kaplan-Meier survival analysis, 87 percent of adults and adolescents and 98 percent of children were alive one year after beginning treatment. In a subgroup of 100 adult and adolescent patients who were followed for 48 to 56 weeks, 76 patients had fewer than 400 copies of human immunodeficiency virus RNA per milliliter. In adults and adolescents, the median increase in the CD4 T-cell count from baseline to 12 months was 163 per cubic millimeter (interquartile range, 77 to 251 per cubic millimeter). In children, the median percentage of CD4 T cells rose from 13 percent at baseline to 26 percent (interquartile range, 22 to 36 percent) at 12 months. Treatment-limiting toxic effects occurred in 102 of the 910 adults and adolescents (11 percent) and 5 of the 94 children (5 percent). CONCLUSIONS This report documents the feasibility of effective antiretroviral therapy in a large number of patients in an impoverished country. Overall, the outcomes are similar to those in the United States. These results provide evidence in support of international efforts to make antiretroviral therapy available to patients with AIDS in developing countries.
[Crypotanshione reduces the expression of metadherin in DU145 prostate cancer cells].

OBJECTIVE To investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells. METHODS We treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p-AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours. RESULTS CPT significantly inhibited the proliferation of the DU145 cells in a dose- and time-dependent manner (P < 0.05). After treatment with 10 µmol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 ± 4.51), (55.07 ± 5.67) and (70.84 ± 4.66)%, respectively, significantly higher than (3.1 ± 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 µmol/L CPT for 48 hours (P < 0.05). CONCLUSION CPT can inhibit the proliferation and induce the apoptosis of DU145 prostate cancer cells, which may be associated with its suppression of the downstream PI3K/AKT signaling pathway by reducing the expression of metadherin in the DU145 cells.
Reinforcement Learning for Atari Breakout

The challenges of applying reinforcement learning to modern AI applications are interesting, particularly in unknown environments in which there are delayed rewards. Classic arcade games have garnered considerable interest recently as a test bed for these kinds of algorithms. In this paper, we develop a system that is capable of teaching a computer agent how to play a custom implementation of the popular classic arcade game Breakout with variants of Q-learning and SARSA. We detail our implementation, testing, feature generation, and hyperparameter search, and eventually achieve significantly above-baseline control with SARSA. Furthermore, we investigate state-of-the-art learning techniques such as replay memory and policy gradients, finding that these techniques fail to outperform “simpler” methods. Finally, we evaluate our models through repeated gameplay, aggregate performance statistics, and parameter visualization.
A hybrid genetic algorithm for finding stable conformations of small molecules

In this work we use a hybrid genetic algorithm for finding the global minimum energy conformation of small molecules based on the Lennard-Jones potential function. Finding the global minimum of this function is very difficult because it has a large number of local minima, which may grow exponentially with molecule size. Experimental evidences show that the global minimum potential energy of a given molecule usually corresponds to its most stable conformation, which dictates the majority of its properties.
miR-29 Promotes Murine Osteoclastogenesis by Regulating Osteoclast Commitment and Migration*

Background: miR-29 is a positive regulator of osteoblastogenesis, but its role in osteoclastogenesis is undefined. Results: Expression of all miR-29 family members increased during osteoclastic differentiation. miR-29 knockdown impaired migration, osteoclast commitment, and formation. Six novel miR-29 targets were identified. Conclusion: miR-29 promotes osteoclastogenesis. Significance: These data expand our understanding of osteoclastogenesis, providing insight into miR-29 function in hematopoietic cells and other lineages. Osteoclast differentiation is regulated by transcriptional, post-transcriptional, and post-translational mechanisms. MicroRNAs are fundamental post-transcriptional regulators of gene expression. The function of the miR-29 (a/b/c) family in cells of the osteoclast lineage is not well understood. In primary cultures of mouse bone marrow-derived macrophages, inhibition of miR-29a, -29b, or -29c diminished formation of TRAP (tartrate-resistant acid phosphatase-positive) multinucleated osteoclasts, and the osteoclasts were smaller. Quantitative RT-PCR showed that all miR-29 family members increased during osteoclast differentiation, in concert with mRNAs for the osteoclast markers Trap (Acp5) and cathepsin K. Similar regulation was observed in the monocytic cell line RAW264.7. In stably transduced RAW264.7 cell lines expressing an inducible miR-29 competitive inhibitor (sponge construct), miR-29 knockdown impaired osteoclastic commitment and migration of pre-osteoclasts. However, miR-29 knockdown did not affect cell viability, actin ring formation, or apoptosis in mature osteoclasts. To better understand how miR-29 regulates osteoclast function, we validated miR-29 target genes using Luciferase 3′-UTR reporter assays and specific miR-29 inhibitors. We demonstrated that miR-29 negatively regulates RNAs critical for cytoskeletal organization, including Cdc42 (cell division control protein 42) and Srgap2 (SLIT-ROBO Rho GTPase-activating protein 2). Moreover, miR-29 targets RNAs associated with the macrophage lineage: Gpr85 (G protein-coupled receptor 85), Nfia (nuclear factor I/A), and Cd93. In addition, Calcr (calcitonin receptor), which regulates osteoclast survival and resorption, is a novel miR-29 target. Thus, miR-29 is a positive regulator of osteoclast formation and targets RNAs important for cytoskeletal organization, commitment, and osteoclast function. We hypothesize that miR-29 controls the tempo and amplitude of osteoclast differentiation.
The Dynamics of the Interest Rate in the Austrian Business Cycle Theory

This study investigates the behaviour of the interest rate over the business cycle that is predicted by the Austrian theory of economic fluctuations. The first part briefly introduces the Austrian approach and develops some of its basic tools. The second part focuses on the gap between the market rate of interest and the natural rate. The sources and consequences of this gap are studied in detail. Much emphasis is put on processes that eventually bring about a closure of this gap. Monetary policy is then identified as the main creator of this gap. Subsequent parts of the paper investigate limits of its power to keep this gap opened. The following sections find additional reasons why the market interest rate may deviate from its natural counterpart. The last section discusses the influence of the monetary policy on the natural rate itself and concludes with recommendations of great caution the central bank should follow in conducting the monetary policy.
Identifying emotional adaptation: behavioural habituation to novelty and immediate early gene expression in two inbred mouse strains

Normal anxiety is an adaptive emotional response. However, when anxiety appears to lack adaptive value, it might be defined as pathological. Adaptation in animals can be assessed for example by changes in behavioural responses over time, i.e. habituation. We hypothesize that non‐adaptive anxiety might be reflected by impaired habituation. To test our hypothesis, we repeatedly exposed male mice from two inbred strains to a novel environment, the modified hole board. BALB/cJ mice were found to be initially highly anxious, but subsequently habituated to the test environment. In contrast, 129P3/J mice initially showed less anxiety‐related behaviour compared with the BALB/cJ mice but no habituation in anxiety‐related behaviour was observed. Notably, anxiety‐related behaviour even increased during the experimental period. Complementary, 129P3/J mice did not show habituation in other parameters such as locomotor and exploratory activity, whereas significant changes appeared in these behaviours in BALB/c mice. Finally, the expression of the immediate early gene c‐fos differed between the two strains in distinct brain areas, known to regulate the integration of emotional and cognitive processes. These results suggest that 129P3/J mice might be a promising (neuro)‐behavioural animal model for non‐adaptive, i.e. pathological anxiety.
The importance of metacommunity ecology for environmental assessment research in the freshwater realm

Most bioassessment programs rest on the assumption that species have different niches, and that abiotic environmental conditions and changes therein determine community structure. This assumption is thus equivalent to the species sorting perspective (i.e. that species differ in their responses to environmental variation) in metacommunity ecology. The degree to which basing bioassessment on the species sorting perspective is reasonable is likely to be related to the spatial extent of a study and the characteristics of the organism groups (e.g. dispersal ability) with which the effects of anthropogenic changes are assessed. Recent findings in metacommunity research have stressed that community structure is determined not only by local abiotic environmental conditions but also by biotic interactions and dispersal‐related effects. For example, dispersal limitation may prevent community structure recovery from the effects of a putative stressor, as organisms may not be able to disperse to all sites in a region. Mass effects (i.e. the presence of species in environmentally suboptimal sites due to high dispersal rates from environmentally suitable sites) may, in turn, obscure the effects of a stressor, as dispersal from source sites (e.g. an unaltered site) allows persistence at sink sites (e.g. an anthropogenically altered site). Better bioassessment should thus take both niche‐ and dispersal‐related processes simultaneously into consideration, which can be accomplished by explicitly modelling spatial location as a proxy for dispersal effects. Such an integrated approach should be included in bioassessment programs using general multivariate approaches, predictive modelling, and multimetric indices.
Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal

Background and Purpose Anticoagulant-associated intracranial hemorrhage (aaICH) presents with larger hematoma volumes, higher risk of hematoma expansion, and worse outcome than spontaneous intracranial hemorrhage. Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of anticoagulation after aaICH. Given the lack of randomized controlled trial evidence of efficacy, and the potential for thrombotic complications, we aimed to determine outcomes in patients with aaICH treated with PCC. Methods We conducted a prospective multicenter registry of patients treated with PCC for aaICH in Canada. Patients were identified by local blood banks after the release of PCC. A chart review abstracted clinical, imaging, and laboratory data, including thrombotic events after therapy. Hematoma volumes were measured on brain CT scans and primary outcomes were modified Rankin Scale at discharge and in-hospital mortality. Results Between 2008 and 2010, 141 patients received PCC for aaICH (71 intraparenchymal hemorrhages). The median age was 78 years (interquartile range, 14), 59.6% were male, and median Glasgow Coma Scale was 14. Median international normalized ratio was 2.6 (interquartile range, 2.0) and median parenchymal hematoma volume was 15.8 mL (interquartile range, 31.8). Median post-PCC therapy international normalized ratio was 1.4: 79.5% of patients had international normalized ratio correction (<1.5) within 1 hour of PCC therapy. Patients with intraparenchymal hemorrhage had an in-hospital mortality rate of 42.3% with median modified Rankin Scale of 5. Significant hematoma expansion occurred in 45.5%. There were 3 confirmed thrombotic complications within 7 days of PCC therapy. Conclusions PCC therapy rapidly corrected international normalized ratio in the majority of patients, yet mortality and morbidity rates remained high. Rapid international normalized ratio correction alone may not be sufficient to alter prognosis after aaICH.
Earnings Management and Capital Resource Allocation: Evidence from China's Accounting‐Based Regulation of Rights Issues

From 1996 to 1998, listed companies in China were required to achieve a minimum return on equity (ROE) of 10 percent in each of the previous three years before they could apply for permission to issue additional shares. As a result of this rule, there was a heavy concentration of ROEs in the area just above 10 percent. We show that the Chinese regulators appear to have scrutinized firms using excess amounts of nonoperating income to reach the 10 percent hurdle. In addition, their ability to do so seems to have improved over time, which allows them to be better able to identify firms that subsequently performed better. However, many firms were still able to gain rights issue approval through excess nonoperating income. We show that these firms subsequently underperformed other approved firms that did not use the same practice, indicating that the Chinese regulators' objective of guiding capital resources toward the well‐performing sectors is partially compromised by earnings management.
Shift of the Cellular Oxidation‐Reduction Potential in Neural Cells Expressing Bcl‐2

Abstract: Expression of the protooncogene bcl‐2 inhibits both apoptotic and in some cases necrotic cell death in many cell types, including neural cells, and in response to a wide variety of inducers. The mechanism by which the Bcl‐2 protein acts to prevent cell death remains elusive. One mechanism by which Bcl‐2 has been proposed to act is by decreasing the net cellular generation of reactive oxygen species. To evaluate this proposal, we measured activities of antioxidant enzymes as well as levels of glutathione and pyridine nucleotides in control and bcl‐2 transfectants in two different neural cell lines—rat pheochromocytoma PC12 and the hypothalamic GnRH cell line GT1‐7. Both neural cell lines overexpressing bcl‐2 had elevated total glutathione levels when compared with control transfectants. The ratios of oxidized glutathione to total glutathione in PC12 and GT1‐7 cells overexpressing bcl‐2 were significantly reduced. In addition, the NAD+/NADH ratio of bcl‐2‐expressing PC12 and GT1‐7 cells was two‐ to threefold less than that of control cell lines. GT1‐7 cells overexpressing bcl‐2 had the same level of glutathione peroxidase, catalase, superoxide dismutase, and glutathione reductase activities as control cells. PC12 cells overexpressing bcl‐2 had a twofold increase in superoxide dismutase and catalase activity when compared with matched control transfected cells. The levels of glutathione peroxidase and glutathione reductase in PC12 cells overexpressing bcl‐2 were similar to those of control cells. These results indicate that the overexpression of bcl‐2 shifts the cellular redox potential to a more reduced state, without consistently affecting the major cellular antioxidant enzymes.
MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma.

CONTEXT MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome. OBJECTIVE To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome. DESIGN, SETTING, AND PATIENTS MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort. MAIN OUTCOME MEASURES MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. RESULTS Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome. CONCLUSIONS Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome.
Hepatic stem cells in liver regeneration

The concept that the liver contains epithelial cells that share some of the major properties of stem cells of the well‐characterized, stem cell‐fed lineages found in bone marrow, intestinal epithelium, and epidermis is now well supported. Nevertheless, the population dynamics of the major types of liver epithelial cells, hepatocytes, and bile epithelia display a striking difference from the population dynamics of the classic stem cell systems. The focus of this review is on recent studies of the activation and expansion of liver stem cells in vivo and the role these cells may play in regeneration of the liver. The requirement for a selective and sustained expression of growth factors during the early stages of stem cell activation is highlighted. In addition, results are presented supporting the hypothesis that after loss of liver mass, both the quiescent stem cells as well as the residual differentiated hepatocytes and bile duct epithelial cells are activated to proliferate. However, significant contribution of the stem cells to the regeneration process only occurs under circumstances in which the residual differentiated cells are functionally compromised and/or cannot proliferate. —Thorgeirsson, S. S. Hepatic stem cells in liver regeneration FASEB J. 10, 1249‐1256 (1996)
Summary of: Essential and insightful narratives from teacher candidates: Challenges with an equity initiative in teacher education

This article aims to share the too often silenced or missing voices of teacher candidates’ accounts in a university-school based equity initiative. The Diverse Schools (DS) Initiative is a one year long university-school based equity initiative that took place in a Canadian university which offers a Bachelor of Education program. The partnership occurred between the local school board and the university in the hopes that this initiative would benefit associate teachers, teacher candidates, and ultimately the students in the public school. The DS initiative is founded upon the simultaneous teaching that took place in a one yearlong required course in the Bachelor of Education entitled School and Society, and in eight professional development seminars for associate teachers. What is unique about this initiative is that the course instructors for School and Society also designed and led the professional seminars for associate teachers. The associate teachers were given release time from their school board to attend these professional development seminars that facilitated dialogue around similar themes and topics that were explored in the course. The School and Society course had approximately 70 teacher candidates and the professional seminars had approximately 20 associate teachers in attendance. It is important to note that the DS Initiative only involved 10 teacher candidates and their respective 10 associate teachers. All the participants volunteered to participate in this DS Initiative, which extended outside the regular practicum experience. The particular cohort that took up the DS Initiative was the Equity Option which was designed to address inner city schools’ diverse students’ needs. The associate teachers at the professional development seminars taught at inner city schools and self-identified as urban educators, some of whom had been paired with teacher candidates in the second academic term. Originally, ten associate teachers signed up to do the research interviews; however, during the research process two of them withdrew their participation for personal reasons. As a result, this study is based upon the experiences of ten teacher candidates and eight of their respective associate teachers. The theoretical underpinning of the DS Initiative is based upon the blended theories of culturally responsive teaching and culturally relevant pedagogy. The amalgamation of these two theories has been renamed ‘culturally responsive and relevant pedagogy’ (CRRP) by Ryan and Lina, who are the developers and instructors of the DS Initiative. According to Ryan and Lina, the purpose of CRRP was to create a common language in order to promote an equity dialogue between