Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Methylation of the BsuRI (5′-GGCC-3′) Sites in the E2a Region of Adenovirus Type 2 DNA Does Not Affect Expression in Xenopus laevis Oocytes

The early region 2a (E2a) of adenovirus type 2 (Ad2) DNA codes for a 72,000-dalton DNA-binding protein and is expressed in the Ad2-transformed hamster cell line HE1 but not in cell lines HE2 and HE3 (H. Esche, J. Virol. 41:1076-1082, 1982; K. Johansson et al., J. Virol. 27:628-639, 1978). An inverse correlation between DNA methylation at the 5′-CCGG-3′ sites of the E2a region and of gene expression in these cell lines has been observed (L. Vardimon et al., Nucleic Acids Res. 8:2461-2473, 1980). When the cloned E2a region of Ad2 DNA is methylated in vitro at the 5′-CCGG-3′ sites, the gene is not transcribed after being injected into the nuclei of Xenopus laevis oocytes, whereas unmethylated DNA is expressed (L. Vardimon et al., Eur. J. Cell Biol. 25:13-15, 1981; L. Vardimon et al., Proc. Natl. Acad. Sci. U.S.A. 79:1073-1077, 1982). These data demonstrate that DNA methylation is directly involved in the shut-off of transcription. In the present communication we investigated in detail the control region of the gene for the DNA-binding protein in Ad2-transformed cell lines and showed that the first late control region (map coordinate 72 on the viral DNA) of the E2a region is present in its entirety in cell lines HE1, HE2, and HE3. The HaeIII sites (5′-GGCC-3′) in the E2a region in all three cell lines were not methylated. When the DNA methyltransferase BsuRI was used, all 5′-GGCC-3′ sites in the cloned E2a region of Ad2 DNA were methylated in vitro. It was shown that methylation of these sites did not inhibit the expression of this viral gene in X. laevis oocytes. Thus, for methylation to affect gene expression in the E2a region it has to occur at specific sites (e.g., 5′-CCGG-3′) which may be different for other genes.
Assessment of Foot Trajectory for Human Gait Phase Detection Using Wireless Ultrasonic Sensor Network

This paper presents a new highly accurate gait phase detection system using wearable wireless ultrasonic sensors, which can be used in gait analysis or rehabilitation applications. The gait phase detection system uses the foot displacement information during walking to extract the following gait phases: heel-strike, heel-off, toe-off, and mid-swing. The displacement of foot-mounted ultrasonic sensor is obtained from several passive anchors placed at known locations by employing local spherical positioning technique, which is further enhanced by the combination of recursive Newton-Gauss method and Kalman Filter. The algorithm performance is examined by comparing with a commercial optical motion tracking system with ten healthy subjects and two foot injured subjects. Accurate estimates of gait cycle (with an error of -0.02 ±0.01 s), stance phase(with an error of 0.04±0.03 s), and swing phase (with an error of -0.05±0.03 s) compared to the reference system are obtained. We have also investigated the influence of walking velocities on the performance of the proposed gait phase detection algorithm. Statistical analysis shows that there is no significant difference between both systems during different walking speeds. Moreover, we have tested and discussed the possibility of the proposed system for clinical applications by analyzing the experimental results for both healthy and injured subjects. The experiments show that the estimated gait phases have the potential to become indicators for sports and rehabilitation engineering.
Speed: too much of a good thing?

Time-based strategy has become the latest key to competitive advantage. However, the implicit assumption that speed has a linear relationship with project success lacks examination. Several perspectives including time compression diseconomies resulting from the limits of the capacity for human information processing, bounded rationality of decision making, "absorptive capability" of organizations, and organizational learning, are applied to the study of new product development (NPD) teams. We argue that uncertainty is a critical contingency for understanding speed in NPD. We propose that whether speed has a linear or curvilinear relationship with success will depend upon the degree of uncertainty. Our results show that the relationship is curvilinear when either technology uncertainty or market turbulence is high but linear when such uncertainty is low. In contrast, we find a curvilinear relationship under conditions of low market newness but not under conditions of high market newness. An important implication is that it is necessary to analyze the source and degree of uncertainty of a project before a time-based strategy is selected. The limitations and future research related to these results are discussed.
Molecular pathogenesis of Waldenström’s macroglobulinemia

Waldenström’s macroglobulinemia is an indolent, lymphoproliferative disease, characterized by a heterogeneous lymphoplasmacytic bone marrow infiltrate and high immunoglobulin M production. While technological advances over the past several decades have dramatically improved the possibilities of studying the molecular basis of Waldenström’s macroglobulinemia, the pathogenesis of the disease remains fragmented. Undoubtedly, research has been successful in uncovering underlying aberrations and deregulated mechanisms in this disease, providing useful information for identifying biomarkers for disease diagnosis, risk stratification and therapeutic intervention, but there is still a long way to go before the pathogenesis of Waldenström’s macroglobulinemia is fully revealed. In addition, the low number of in vitro or in vivo models significantly challenges extensive analysis. In this manuscript, we review the molecular basis of this disease.
The police-based crisis intervention team (CIT) model: I. Effects on officers' knowledge, attitudes, and skills.

OBJECTIVE Individuals with serious mental illnesses are very likely to interact with police officers. The crisis intervention team (CIT) model is being widely implemented by police departments across the United States to improve officers' responses. However, little research exists on officer-level outcomes. The authors compared officers with or without CIT training on six key constructs related to the CIT model: knowledge about mental illnesses, attitudes about serious mental illnesses and treatments, self-efficacy for deescalating crisis situations and making referrals to mental health services, stigmatizing attitudes, deescalation skills, and referral decisions. METHODS The sample included 586 officers, 251 of whom had received the 40-hour CIT training (median of 22 months before the study), from six police departments in Georgia. In-depth, in-person assessments of officers' knowledge, attitudes, and skills were administered. Many measures were linked to two vignettes, in written and video formats, depicting typical police encounters with individuals with psychosis or with suicidality. RESULTS CIT-trained officers had consistently better scores on knowledge, diverse attitudes about mental illnesses and their treatments, self-efficacy for interacting with someone with psychosis or suicidality, social distance stigma, deescalation skills, and referral decisions. Effect sizes for some measures, including deescalation skills and referral decisions pertaining to psychosis, were substantial (d=.71 and .57, respectively, p<.001). CONCLUSIONS CIT training of police officers resulted in sizable and persisting improvements in diverse aspects of knowledge, attitudes, and skills. Research should now address potential outcomes at the system level and for individuals with whom officers interact.
Microenvironment and Dose-Delivery-Dependent Response after Exposure to Ionizing Radiation in Human Colorectal Cancer Cell Lines

A significant body of knowledge about radiobiology is based on studies of single dose cellular irradiation, despite the fact that conventional clinical applications using dose fractionation. In addition, cellular radiation response strongly depends on cell–cell and cell–extracellular matrix (ECM) interactions, which are poorly established in cancer cells grown under standard 2D cell culture conditions. In this study, we investigated the response of human colorectal carcinoma (CRC) DLD1 and HT29 cell lines, bearing distinct p53 mutations, to a single 2 or 10 Gy dose or fractionated 5 × 2 Gy doses of radiation using global transcriptomics analysis. To examine cellular response to radiation in a cell–ECM-interaction-dependent manner, CRC cells were grown under laminin-rich ECM 3D cell culture conditions. Microarray data analysis revealed that, overall, a total of 1,573 and 935 genes were differentially expressed (fold change >1.5; P < 0.05) in DLD1 and HT29 cells, respectively, at 4 h postirradiation. However, compared to a single dose of radiation, fractionated doses resulted in significantly different transcriptomic response in both CRC cell lines. Furthermore, pathway enrichment analysis indicated that p53 pathway and cell cycle/DNA damage repair or immune response functional categories were most significantly altered in DLD1 or HT29 cells, respectively, after fractionated irradiations. Novel observations of radiation-response-mediated activation of pro-survival pathways in CRC cells grown under lr-ECM 3D cell culture conditions using fractionated doses provide new directions for the development of more efficient radiotherapy strategies. Our results also indicated that cell line specific radiation response with or without activation of the conventional p53 pathway is ECM dependent, suggesting that the ECM is a key component in cellular radiation response.
Nutritional Markers in Liver Allograft Recipients

Background. Malnutrition is common in patients with end-stage liver disease considered for transplantation, but it is unclear whether this affects the outcome after transplantation. Aim. To determine whether the severity of malnutrition in liver transplant candidates affects outcome after transplantation. Methods. We did a prospective study of 61 patients with chronic liver disease accepted for transplantation. Findings. The Child-Pugh and Model for End-Stage Liver Disease (MELD) score correlated significantly but weakly with the mid-arm circumference (MAC) (&rgr;=−0.34 and -0.31, P=0.015 and 0.025, respectively) but not with hand-grip strength, triceps skin-fold thickness (TSFT), or mid-arm muscle circumference. The Child-Pugh score but not the MELD was significantly associated with intensive therapy unit stay but not eventual outcome; there was a weak but statistically significant correlation between death and MAC (&rgr;=+0.29, P=0.04) and TSFT (&rgr;=+0.25, P=0.02). Conclusions. These findings suggest that nutritional parameters and markers of disease severity do not correlate well with outcomes after transplantation.
Adaptive Group Sparse Multitask Learning via Trace Lasso Sulin

In multi-task learning (MTL), tasks are learned jointly so that information among related tasks is shared and utilized to help improve generalization for each individual task. A major challenge in MTL is how to selectively choose what to share among tasks. Ideally, only related tasks should share information with each other. In this paper, we propose a new MTL method that can adaptively group correlated tasks into clusters and share information among the correlated tasks only. Our method is based on the assumption that each task parameter is a linear combination of other tasks’ and the coefficients of the linear combination are active only if there is relatedness between the two tasks. Through introducing trace Lasso penalty on these coefficients, our method is able to adaptively select the subset of coefficients with respect to the tasks that are correlated to the task. Our model frees the process of determining task clustering structure as used in the literature. Efficient optimization method based on alternating direction method of multipliers (ADMM) is developed to solve the problem. Experimental results on both synthetic and real-world datasets demonstrate the effectiveness of our method in terms of clustering related tasks and generalization performance.
Transient calcium elevation in polymorphonuclear leukocytes triggered by thrombin‐activated platelets

Abstract: The effect of thrombin‐activated platelets and their release products on the intracellular free calcium concentration ([Ca2+]i) of human polymorphonuclear leukocytes (PMNs) was studied by loading PMNs with a fluorescent indicator of calcium, fura‐2. [Ca2+]i of PMNs was transiently elevated by thrombin‐activated platelets. The supernatant of thrombin‐activated platelets also elicited a transient elevation of [Ca2+]i in PMNs. Pretreatment of the supernatant with hexokinase caused a decrease in the transient [Ca2+]i elevation of PMNs, while hexokinase abrogated the [Ca2+]i elevation of PMNs elicited by 80 μmol/1 adenosine triphosphate (ATP). Pretreatment of the supernatant with trypsin also decreased the magnitude of the elevation, while trypsin had no effect on the response to ATP. These findings suggest that thrombin‐activated platelets induce a transient [Ca2+]i elevation in PMNs by releasing ATP and some trypsin‐sensitive factor(s).
Self-medication: A current challenge

Self-medication is a global phenomenon and potential contributor to human pathogen resistance to antibiotics. The adverse consequences of such practices should always be emphasized to the community and steps to curb it. Rampant irrational use of antimicrobials without medical guidance may result in greater probability of inappropriate, incorrect, or undue therapy, missed diagnosis, delays in appropriate treatment, pathogen resistance and increased morbidity. This review focused on the self-medication of allopathic drugs, their use, its safety and reason for using it. It would be safe, if the people who are using it, have sufficient knowledge about its dose, time of intake, side effect on over dose, but due to lack of information it can cause serious effects such as antibiotic resistance, skin problem, hypersensitivity and allergy. There is need to augment awareness and implement legislations to promote judicious and safe practices. Improved knowledge and understanding about self-medication may result in rationale use and thus limit emerging microbial resistance issues. Articles which were published in peer reviewed journals, World Self-Medication Industry and World Health Organization websites relating to self-medication reviewed.
Dopamine enhances terminal excitability of hippocampal-accumbens neurons via D2 receptor: role of dopamine in presynaptic inhibition

The effects of dopamine on the axonal terminals of hippocampal-nucleus accumbens (HIPP-ACC) neurons were investigated in urethane-anesthetized rats using extracellular single-unit recording techniques. Antidromic responses recorded in the ventral subiculum of the hippocampus were evoked by stimulation of the medial accumbens. Baseline terminal excitability of these neurons, established by threshold stimulation of the accumbens, was markedly enhanced by conditioning stimulation (10 Hz) of the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic neurons. Iontophoretic application of sulpiride, a selective D2 antagonist, onto the HIPP-ACC terminals attenuated the increased terminal excitability of these neurons produced by conditioning VTA stimulation, while intraperitoneal injection of SCH23390, a selective D1 antagonist, failed to attenuate this effect. Iontophoretic application of dopamine or its selective D2 agonist, LY171555, onto the terminals of the HIPP-ACC neurons mimicked the prolonged enhancement of the terminal excitability produced by VTA stimulation, whereas SKF38393, a D1 agonist, had no effect. The effects of VTA stimulation, dopamine and LY171555 application were similar after the accumbens had been pretreated with ibotenic acid, suggesting a direct action of dopamine on the axonal terminals of HIPP-ACC neurons, and that changes in terminal excitability were not mediated via interneurons or feedback pathways from the accumbens to the hippocampus. Since iontophoretic application of potassium, a depolarizing agent, also enhanced the terminal excitability of the HIPP- ACC neurons, it appears that dopamine depolarized, via D2 receptors, the axonal terminals of HIPP-ACC neurons. (ABSTRACT TRUNCATED AT 250 WORDS)
Migration and health in Canada: health in the global village

Background: Immigration has been and remains an important force shaping Canadian demography and identity. Health characteristics associated with the movement of large numbers of people have current and future implications for migrants, health practitioners and health systems. We aimed to identify demographics and health status data for migrant populations in Canada. Methods: We systematically searched Ovid MEDLINE (1996–2009) and other relevant web-based databases to examine immigrant selection processes, demographic statistics, health status from population studies and health service implications associated with migration to Canada. Studies and data were selected based on relevance, use of recent data and quality. Results: Currently, immigration represents two-thirds of Canada’s population growth, and immigrants make up more than 20% of the nation’s population. Both of these metrics are expected to increase. In general, newly arriving immigrants are healthier than the Canadian population, but over time there is a decline in this healthy immigrant effect. Immigrants and children born to new immigrants represent growing cohorts; in some metropolitan regions of Canada, they represent the majority of the patient population. Access to health services and health conditions of some migrant populations differ from patterns among Canadian-born patients, and these disparities have implications for preventive care and provision of health services. Interpretation: Because the health characteristics of some migrant populations vary according to their origin and experience, improved understanding of the scope and nature of the immigration process will help practitioners who will be increasingly involved in the care of immigrant populations, including prevention, early detection of disease and treatment.
Essays on monetary policy in open economies

EZEQUIEL R. CABEZON: ESSAYS ON MONETARY POLICY IN OPEN ECONOMIES. (Under the direction of Richard Froyen.) This dissertation studies whether monetary policy has short run effects on output in emerging economies and characterizes the mechanisms of transmission of the monetary policy. Specifically it focuses on the real effects of the monetary policy in Brazil, where policymakers introduced structural reforms earlier than other emerging economies. Chapter I identifies the effects of monetary policy in Brazil using a vector autoregressive model. It finds that monetary policy has short run effects on output and nearly none on prices. This contrasts with the policy wisdom that monetary policy in EMEs can only affect prices. Chapter II, studies the interest rate channel of monetary policy in Brazil. It finds that surprise changes in the monetary policy interest rates have larger effects on the market interest rate during expansions than in recessions. This is attributed to the larger expected duration of expansion over recesions. Chapter III, uses a Dynamic Stochastic General Equilibrium model to study the effects of monetary policy when firms borrow to finance their working capital in an open economy. This issue is crucial in cases like Brazil where working capital credit explains half of the firms’ borrowing and it quadrupled in the last 15 years. A monetary policy tightening has two effects: i) It discourages consumption (the traditional demand channel) and ii) It increases the production cost (known as the working capital channel). The final effect on inflation is unclear as these effects work in opposite directions. The model concludes that in an open economy where there is working capital borrowing, the aggregate demand channel dominates the working capital channel. This is due to the strong response of consumption to the exchange rate.
The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement.

OBJECTIVE To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE). METHODS Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic. RESULTS The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%. CONCLUSION PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.
Primary cutaneous follicular lymphoma: an assessment of clinical, histopathologic, immunophenotypic, and molecular features.

PURPOSE Unlike nodal follicular lymphoma (NFL), Primary cutaneous follicular lymphomas (PCFLs) rarely express Bcl-2 protein or t(14;18)(q32;q21) (Bcl-2/IgH). The aim of this study was to further characterize PCFL in a large series from North America. PATIENTS AND METHODS Clinical data and archival formalin-fixed, paraffin-embedded tissue were obtained from 32 patients. PCFL was defined as follicular lymphoma limited to the skin at the time of diagnosis and within the first 6 months after diagnosis. Specimens were analyzed for the expression of CD3, CD10, CD20, Bcl-2, and Bcl-6 proteins by immunohistochemistry as well as for the presence of t(14;18)(q32;q21) by polymerase chain reaction. RESULTS The male-to-female ratio was 1.5:1, with a median age of 60 years. Twenty-four patients had lesions on the head and neck, five had lesions on the trunk, and three had lesions on both head and trunk. Follow-up data were available in all cases, with a mean length of 35.8 months. The majority of the patients were treated with radiation therapy. All patients were alive at last follow-up except one. Recurrence was noted in seven patients (22%), after a mean disease-free survival time of 17.7 months. CD10 and Bcl-6 expression were seen in 29 (91%) of 32 and 31 (97%) of 32 cases, respectively. Bcl-2 expression was noted in 13 (41%) of 32 cases. PCR results for t(14;18)(q32;q21) were positive in 11 (34%) of 32 patients and showed correlation with Bcl-2 protein expression. The sequencing of the t(14;18)(q32;q21) amplicons confirmed unique breakpoints in each of the seven tested cases. Comparison between the Bcl-2 and/or t(14;18)(q32;q21)-positive and t(14;18)(q32;q21)-negative cases revealed no significant difference in age, site, clinical course, or outcome. CONCLUSION We demonstrated Bcl-2 protein expression and t(14;18)(q32;q21) in a significant minority of cases, suggesting a relationship with NFL. It remains to be seen whether, on longer follow-up, there is any clinical difference in cases with and without t(14;18)(q32;q21).