Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Mechanical Strain on the Cardiomyogenic Differentiation of Periodontal Ligament Derived Stem Cells

of a dissertation at the University of Miami. Dissertation supervised by Professor Herman S. Cheung. No. of pages in text. (124) The application of cellular therapies for the treatment of myocardial infarction has proven to be an invaluable tool in the recent years and the functional recovery observed in these studies, while not complete, provides encouraging evidence for the possibility of cellular therapies to completely restore normal heart function. However, questions still remain as to what are the optimal cell source, pre-conditioning methods and delivery techniques for such an application. Employing a tissue engineering approach to the problem, we hope to develop therapies that can act upon all aspects necessary to cardiomyogenic recovery. These aspects include recovery of stromal cell microenvironment, activation and recruitment of local progenitor and stem cell niches and active contribution to the myocardium itself. Here I propose the use of a unique population of stem cells arising from the embryonic neural crest, which is known to be essential for the viable and correct development of the heart. These cells were shown to express neural crest markers as well as pluripotency-associated markers. Furthermore, the cells were shown to express proteins essential to the formation of gap junctions and to possess a cardiomyogenic differentiation potential by several means. Similarly, the concept of cell preconditioning prior to their introduction in-vivo is not a new one and has been tried by different techniques with carrying degrees of success. Here I propose the investigation into the effect of mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for the better engraftment of the cells while in the heart. Mechanical strain was shown to elicit a cardiomyogenic response from the cells following just a couple of hours of stimulation. Dynamic mechanical strain was shown to activate transcription factors essential to the cardiomyogenic differentiation of the cells and was also shown to contribute to the correct morphological presentation of several key cardiac proteins. The mode in which mechanical strain elicited these responses was demonstrated to be via the mediation of the reactive oxygen species (ROS) pathways and elimination of elevated ROS levels by free-radical scavengers was shown to completely abolish the cardiomyogenic response of the cells. Finally, prior mechanical strain exposure was shown to increase the cellular adhesion and retention on membranes subjected to a second mechanical stress stimulation. Given the results presented here, the use of these periodontal ligament-derived stem cells (PDLSC) in combination with mechanical strain preconditioning of the cells prior to their delivery into the heart may pose a valuable alternative for the treatment of myocardial infarction and merits further exploration for its capacity to augment the already observed beneficial effects of cellular therapies.
Three Cases of Viridans Group Streptococcal Bacteremia in Children with Febrile Neutropenia and Literature Review

Three cases of viridans group streptococcal bacteremia in 2 children with brain tumours and in 1 with autoimmune neutropenia are presented. All children were neutropenic. The 2 patients with malignancy also had mucositis. The isolated strains of viridans group streptococci showed considerable resistance to antibiotics. All patients were empirically treated with third generation cephalosporins and amikacin, before antibiotic sensitivities were available and recovered without complications. Viridans group streptococcal bacteremia should be suspected in neutropenic children, especially in the presence of mucositis. Prospective, randomized clinical trials of mouth antiseptics are needed to clarify the usefulness, if any, of such measures in the reduction of viridans group streptococcal bacteremia in this group of patients.
Maternal and fetal deaths after gastric bypass surgery for morbid obesity.

To the Editor: Antiobesity operations, particularly the Roux-en-Y gastric bypass, are increasingly common. In the United States, 103,000 such operations were performed in 2003.1 We report a complication of a gastric bypass procedure that resulted in the death of a pregnant woman and of her fetus. At 31 weeks' gestation, a 41-year-old woman (gravida 1) presented at her community hospital with midepigastric pain, nausea, and vomiting that had begun 30 minutes after she had ingested a fatty meal. She had undergone Roux-en-Y gastric bypass surgery 18 months previously but still weighed 199.6 kg (440 lb). Initial evaluation revealed a tender .
Kinesin-related proteins required for assembly of the mitotic spindle

We identified two new Saccharomyces cerevisiae kinesin-related genes, KIP1 and KIP2, using polymerase chain reaction primers corresponding to highly conserved regions of the kinesin motor domain. Both KIP proteins are expressed in vivo, but deletion mutations conferred no phenotype. Moreover, kip1 kip2 double mutants and a triple mutant with kinesin- related kar3 had no synthetic phenotype. Using a genetic screen for mutations that make KIP1 essential, we identified another gene, KSL2, which proved to be another kinesin-related gene, CIN8. KIP1 and CIN8 are functionally redundant: double mutants arrested in mitosis whereas the single mutants did not. The microtubule organizing centers of arrested cells were duplicated but unseparated, indicating that KIP1 or CIN8 is required for mitotic spindle assembly. Consistent with this role, KIP1 protein was found to colocalize with the mitotic spindle.
Toward improved drought tolerance in bioenergy crops: QTL for carbon isotope composition and stomatal conductance in Populus

Dedicated non-food bioenergy crops like poplar are needed as sustainable, low-input feedstocks for renewable energy in a future drier climate, where they can be grown on marginal soils. Such plants should have a low water, carbon, and chemical footprint. Capturing natural variation in traits associated with water use efficiency (WUE) is the first step to developing trees that require less water and may be adapted to drier environments. We have assessed stomatal conductance (gs) and leaf carbon isotope composition (δ13C, an indirect indicator of leaf WUE) in two Populus species, P. deltoides and P. trichocarpa and their F2 progeny, grown in the United Kingdom and in Italy. Populus deltoides leaves showed lower δ13C than P. trichocarpa, suggesting a higher WUE in P. trichocarpa, although without drought preconditioning, gs of P. trichocarpa was less responsive to dehydration and abscisic acid treatment than P. deltoides, suggesting that leaf anatomy may also contribute to δ13C in Populus. Quantitative trait loci (QTL) were identified for δ13C on eight linkage groups (LG) and two QTL for gs. From these. QTL and differential gene expression in response to drought from microarray data, we focused on three hotspots and identified 23 novel candidate genes on LG VI, X, and XVI. We have begun to unravel the genetic basis of WUE in bioenergy Populus revealing important underpinning data for breeding and improvement in poplar genotypes for a future drier climate.
Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes.

BACKGROUND Aging is associated with increased cardiovascular risk and endothelial dysfunction. Since exercise can improve endothelium-dependent vasodilation, in the present study we tested whether long-term physical activity could prevent aging-related endothelial dysfunction. METHODS AND RESULTS In 12 young and elderly (age 26.9+/-2.3 and 62.9+/-5.8 years, respectively) healthy sedentary subjects and 11 young and 14 elderly matched athletes (age 27.5+/-1.9 and 66.4+/-6.1 years, respectively), we studied (with strain-gauge plethysmography) forearm blood flow modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator, at baseline, during infusion of N(G)-monomethyl-L-arginine (L-NMMA) (100 microg/100 mL forearm tissue per minute), a nitric oxide-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), an antioxidant, and finally under simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In young athletes and sedentary subgroups, vasodilation to acetylcholine was inhibited by L-NMMA and was not changed by vitamin C. In elderly subjects, vasodilation to acetylcholine was blunted as compared with young subjects in both control subjects and athletes, whereas the response to sodium nitroprusside was similar. Moreover, in elderly athletes, vitamin C did not change the vasodilation to acetylcholine. In contrast, in elderly sedentary subjects, the response to acetylcholine was resistant to L-NMMA. In this subgroup, vitamin C increased the vasodilation to acetylcholine and restored the inhibiting effect of L-NMMA. CONCLUSIONS These results suggest that regular physical activity can at least in part prevent the age-induced endothelial dysfunction, probably the restoration of nitric oxide availability consequent to prevention of production of oxidative stress.
Open Access Journal of Sports Medicine Dovepress Factors Affecting the Regulation of Pacing: Current Perspectives

During prolonged dynamic and rhythmic exercise, muscular pain and discomfort arises as a result of an increased concentration of deleterious metabolites. Sensed by peripheral nociceptors and transmitted via afferent feedback to the brain, this provides important information regarding the physiological state of the muscle. These sensations ultimately contribute to what is termed " exercise-induced pain ". Despite being well recognized by athletes and coaches, and suggested to be integral to exercise performance, this construct has largely escaped attention in experimental work. This perspective article highlights the current understanding of pacing in endurance performance, and the causes of exercise-induced pain. A new perspective is described, which proposes how exercise-induced pain may be a contributing factor in helping individuals to regulate their work rate during exercise and thus provides an important construct in pacing.
Systematic review of the impact of erythropoiesis-stimulating agents on fatigue in dialysis patients.

BACKGROUND One of the cardinal symptoms of anemia in chronic kidney disease (CKD) patients is fatigue. Recently, results from Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) raised questions about the role of erythropoiesis-stimulating agents (ESAs) in improving fatigue and the appropriate hemoglobin (Hb) target in anemic patients with CKD. These discussions should be considered with all available evidence to determine the level of benefits and risks associated with ESA therapy on fatigue among both early-stage CKD patients and end-stage renal disease patients on dialysis. METHODS The study was a systematic review of the literature on fatigue in adults on maintenance dialysis therapy. The requirement for inclusion in the review was the measurement of fatigue before and after ESA treatment. Outcomes that were assessed were fatigue as measured by the Kidney Disease Questionnaire, the 36-item Short-Form general health survey, the Nottingham Health Profile, the Profile of Mood States or the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Several different measures of fatigue were used in the studies. RESULTS Fifteen articles met the criteria for inclusion, including 10 distinct studies and one extension study. There was one placebo-controlled randomized clinical trial (RCT) and one extension, five single-arm, three high versus low, one intravenous versus subcutaneous and one switch from epoetin alfa to darbepoetin alfa. The only placebo-controlled RCT found a 22-26% improvement in fatigue. Single-arm cohort studies demonstrated a reduction in fatigue after a substantial increase in Hb. Studies with a baseline Hb <10 g/dL and partial correction to a minimum Hb ≥ 10 g/dL showed an average improvement in fatigue of 34.6%. Studies with a baseline Hb ≥ 11 g/dL and full correction to a minimum Hb ≥ 12 g/dL showed an average improvement in fatigue of 5.5%, while studies with no change in Hb (either placebo or control group) showed a decline of 0.7% in fatigue outcomes. CONCLUSION Partial correction of anemia with ESA results in improvement of fatigue among patients on dialysis, most strikingly in those patients with baseline Hb levels <10 g/dL.
Correction: Budding Yeast Pch2, a Widely Conserved Meiotic Protein, Is Involved in the Initiation of Meiotic Recombination

Budding yeast Pch2 protein is a widely conserved meiosis-specific protein whose role is implicated in the control of formation and displacement of meiotic crossover events. In contrast to previous studies where the function of Pch2 was implicated in the steps after meiotic double-strand breaks (DSBs) are formed, we present evidence that Pch2 is involved in meiotic DSB formation, the initiation step of meiotic recombination. The reduction of DSB formation caused by the pch2 mutation is most prominent in the sae2 mutant background, whereas the impact remains mild in the rad51 dmc1 double mutant background. The DSB reduction is further pronounced when pch2 is combined with a hypomorphic allele of SPO11. Interestingly, the level of DSB reduction is highly variable between chromosomes, with minimal impact on small chromosomes VI and III. We propose a model in which Pch2 ensures efficient formation of meiotic DSBs which is necessary for igniting the subsequent meiotic checkpoint responses that lead to proper differentiation of meiotic recombinants. Citation: Farmer S, Hong E-JE, Leung W-K, Argunhan B, Terentyev Y, et al. (2012) Budding Yeast Pch2, a Widely Conserved Meiotic Protein, Is Involved in the Initiation of Meiotic Recombination. PLoS ONE 7(6): e39724. doi:10.1371/journal.pone. 0039724 Editor: Michael Lichten, National Cancer Institute, United States of America Received April 20, 2012; Accepted May 25, 2012; Published June 22, 2012 Copyright: 2012 Farmer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The Tsubouchi lab is supported by Marie Curie Cancer Care and Biotechnology and Biological Sciences Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: EEH is currently employed by ImmunoGen Inc. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials. * E-mail: h.tsubouchi@sussex.ac. uk . These authors contributed equally to this work. ¤ Current address: School of Life and Medical Sciences, University College London, London, United Kingdom
Assessing the Refactorability of Software Clones

The presence of duplicated code in software systems is significant and several studies have shown that clones can be potentially harmful with respect to the maintainability and evolution of the source code. Despite the significance of the problem, there is still limited support for eliminating software clones through refactoring, because the unification and merging of duplicated code is a very challenging problem, especially when software clones have gone through several modifications after their initial introduction. In this work, we propose an approach for automatically assessing whether a pair of clones can be safely refactored without changing the behavior of the program. In particular, our approach examines if the differences present between the clones can be safely parameterized without causing any side-effects. The evaluation results have shown that the clones assessed as refactorable by our approach can be indeed refactored without causing any compile errors or test failures. Additionally, the computational cost of the proposed approach is negligible (less than a second) in the vast majority of the examined cases. Finally, we perform a large-scale empirical study on over a million clone pairs detected by four different clone detection tools in nine open-source projects to investigate how refactorability is affected by different clone properties and tool configuration options. Among the highlights of our conclusions, we found that (a) clones in production code tend to be more refactorable than clones in test code, (b) clones with a close relative location (i.e., same method, type, or file) tend to be more refactorable than clones in distant locations (i.e., same hierarchy, or unrelated types), (c) Type-1 clones tend to be more refactorable than the other clone types, and (d) clones with a small size tend to be more refactorable than clones with a larger size.
Mortality and morbidity in high risk infants during a six year follow-up.

OBJECTIVE To study the mortality and morbidity in high risk infants after discharge from the hospital. DESIGN Prospective, 6 year follow up. SETTING High Risk Clinic (HRC). METHODS Infants discharged from a Neonatal Special Care Unit were identified for follow up using predetermined risk criteria. Home visits were made by the social worker, if appointments to HRC were missed. Verbal autopsy was performed in case of home deaths. Intercurrent illnesses and rehospitalizations were recorded. At six years, the children who had come for the final assessment at 30 months on the Bayley Scales, were recalled for assessment of the intelligence quotient, by Stanford-Binet Scale. RESULTS Four hundred and four high risk infants and eighty six controls were enrolled. There were 40 deaths in the study period, out of which 38 occurred in the first year of life, sixty per cent of these occurring in the first three months. The mortality was significantly higher in the VLBW group. Out of the 22 hospital deaths, 72.7% were due to infection. There was a significant difference (p < 0.001) in the mortality rate between the group which attended the HRC regularly (6.4%) as compared to that of the defaulters (27.6%). Ninety five children had rehospitalization in the High Risk group as compared to two in the control group (p < 0.001). In the 286 children who were assessed at 6 years, the incidence of borderline intelligence was 14.6% as compared to 5.6% in the controls (p < 0.05). CONCLUSION Mortality and rehospitalization rate is high in high risk infants, after discharge from the hospital. Children who appear to have normal development in the third year, may show a high incidence (14.6%) of borderline intelligence at six years.
Learning, planning, and control for quadruped locomotion over challenging terrain

We present a control architecture for fast quadruped locomotion over rough terrain. We approach the problem by decomposing it into many sub-systems, in which we apply state-of-the-art learning, planning, optimization, and control techniques to achieve robust, fast locomotion. Unique features of our control strategy include: (1) a system that learns optimal foothold choices from expert demonstration using terrain templates, (2) a body trajectory optimizer based on the Zero-Moment Point (ZMP) stability criterion, and (3) a floating-base inverse dynamics controller that, in conjunction with force control, allows for robust, compliant locomotion over unperceived obstacles. We evaluate the performance of our controller by testing it on the LittleDog quadruped robot, over a wide variety of rough terrains of varying difficulty levels. The terrain that the robot was tested on includes rocks, logs, steps, barriers, and gaps, with obstacle sizes up to the leg length of the robot. We demonstrate the generalization ability of this controller by presenting results from testing performed by an independent external test team on terrain that has never been shown to us.
Sequential settlement and site dependence in a migratory raptor

Habitat selection models, such as the ideal free, ideal despotic, site-dependent, and conspecific cuing models, are of great importance to behavioral ecologists given their capability to predict habitat distributions and to link individual behavior to population processes. However, there have been relatively few field tests of their predictions. We tested the 4 models by studying the process of sequential settlement on territory in 2 distant populations of a migratory raptor, the black kite Milvus migrans. Results were mainly consistent with the site-dependent model: on arrival, kites settled on progressively lower quality territories, and earlier arriving individuals were older, larger, and in better body condition than later arriving ones, leading to a state-dependent arrival sequence also predicted by a previous theoretical model of settlement pattern. Occupation of superior territories by superior phenotypes resulted in cascading advantages for earlier arriving individuals in terms of subsequent reproductive performance. At the population level, the populations expanded/retracted from lower quality sites during population increases/declines. The above scenario was consistent across the 2 populations, and a review of the literature uncovered a remarkably consistent picture of state-dependent arrival, progressive monopolization of best quality sites, and cascading effects on subsequent breeding performance. We propose as a general paradigm of sequential settlement the following process: 1) arrival date is a reliable surrogate of phenotype quality, 2) early-arriving individuals have preferential access to the best quality sites and partners, 3) the above conditions cascade into a number of benefits ultimately related to higher fitness for earlier arriving individuals. Copyright 2007, Oxford University Press.
Effect of peginterferon alfa‐2b and ribavirin on hepatocellular carcinoma prevention in older patients with chronic hepatitis C

The population of patients chronically infected with hepatitis C virus (HCV) is aging, and the number of older patients with HCV‐related hepatocellular carcinoma (HCC) is increasing. The purpose of this study was to elucidate the effects of peginterferon and ribavirin combination therapy on prevention of HCC in older patients with chronic hepatitis C (CH‐C).
Does Ketamine Have Preemptive Effects in Women Undergoing Abdominal Hysterectomy Procedures?

Ketamine may produce “preemptive” analgesia when administered before surgically induced trauma. Therefore, we hypothesized that pre- versus postincisional administration of ketamine would improve pain control after abdominal hysterectomy procedures. Eighty-nine patients were randomly assigned to one of three treatment groups according to a placebo-controlled, double-blinded protocol: Group 1 (placebo) received saline 0.04 mL/kg IV immediately before and after surgery; Group 2 (preincision), received ketamine 0.4 mg/kg IV before skin incision and saline at the end of the operation; and Group 3 (postincision), received saline before skin incision, and ketamine 0.4 mg/kg IV was given after skin closure. The general anesthetic technique was standardized in all three treatment groups. During the first postoperative hour, Group 3 experienced significantly less pain than Groups 1 and 2, as assessed by using both visual analog and verbal rating scales. There were no significant differences between Groups 1 and 2 with respect to pain scores, postoperative opioid analgesic requirements, and incidence of postoperative nausea and vomiting. We conclude that a single dose of ketamine 0.4 mg/kg IV fails to produce preemptive analgesic effects. Implications Even though ketamine 0.4 mg/kg IV has short-lasting acute analgesic effects, it failed to produce a preemptive effect when given before abdominal hysterectomy procedures.