Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency

BACKGROUND. Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase–deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) &ggr;-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. RESULTS. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1–2.6) and granulocytes (VCN = 0.01–0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. CONCLUSION. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. TRIAL REGISTRATION. ClinicalTrials.gov NCT00794508. FUNDING. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124.
Strategies for Reversing the Effects of Metabolic Disorders Induced as a Consequence of Developmental Programming

Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioral influences, rather than genetic causes, are fueling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal, and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment.
Toward Understanding Work Characteristics in Software Engineering

Context: Work Design refers to how work is conceived, assigned across organizational levels, and structured into tasks performed by individuals or teams. Recent studies have argued that work characteristics need further investigation to improve our understanding of how to design work and tasks in this software engineering practice. Goal: The aim of this research is to explore work characteristics in software engineering research and to investigate the relationship between these characteristics and work outcomes. We expect that these results can lead us toward a proposal of an instrument for measuring work characteristics in software engineering and the understanding of how to use such measures to improve software development practice. Method: The methodological strategy to conduct this research includes a non-exact replication of two surveys performed in other fields. Further, we plan to execute the same survey, enlarging the sample and enhancing the procedures. We also intend to perform a qualitative research with a sample of the participants of the previous survey. Current status: This thesis proposal is in early stage of development. We divided this study in three phases: First, we carried out a non-exact replication of two surveys performed in other areas. Professionals of Brazilian software organizations composed our sample and this phase aimed to identify the work characteristics of software development and assess the potential relationships of these characteristics with work outcomes. The second step of this study aims to enlarge our sample by including international software professionals. We also intend to enhance the variability of software development roles of the professionals in our sample. Finally, we will perform qualitative research, which aims to triangulate data collected in the previous phases and deepen our understanding about work characteristics in software engineering
A Comparative Study of Protocols for Mouse Embryonic Stem Cell Culturing

Most stem cell laboratories still rely on old culture methods to support the expansion and maintenance of mouse embryonic stem (ES) cells. These involve growing cells on mouse embryonic fibroblast feeder cells or on gelatin in media supplemented with fetal bovine serum and leukemia inhibitory factor (LIF). However, these techniques have several drawbacks including the need for feeder-cells and/or use of undefined media containing animal derived components. Culture of stem cells under undefined conditions can induce spontaneous differentiation and reduce reproducibility of experiments. In recent years several new ES cell culture protocols, using more well-defined conditions, have been published and we have compared the standard culture protocols with two of the newly described ones: 1) growing cells in semi-adherence in a medium containing two small molecule inhibitors (CHIR99021, PD0325901) and; 2) growing cells in a spheroid suspension culture in a defined medium containing LIF and bFGF. Two feeder-dependent mouse ES (mES) cell lines and two cell lines adapted to feeder-independent growth were used in the study. The overall aim has not only been to compare self-renewal and differentiation capacity, but also ease-of-use and cost efficiency. We show that mES cells when grown adherently proliferate much faster than when grown in suspension as free-floating spheres, independent of media used. Although all the tested culture protocols could maintain sustained pluripotency after prolonged culturing, our data confirm previous reports showing that the media containing two chemical inhibitors generate more pure stem cell cultures with negligible signs of spontaneous differentiation as compared to standard mES media. Furthermore, we show that this medium effectively rescues and cleans up cultures that have started to deteriorate, as well as allow for effective adaption of feeder-dependent mES cell lines to be maintained in feeder-free conditions.
5-Fluorouracil-Induced Changes of Intestinal Integrity Biomarkers in BALB/C Mice

Background: Intestinal mucositis is a most frequently occurring toxicity in cancer chemotherapy, and consequent malnutrition reduces tolerance to cancer therapies. Therefore it is important to lessen the severity of mucotitis and to develop complementary agents capable of reducing mucotitis-related symptoms. This study was conducted to determine 5-fluorouracil (5-FU) induced intestinal damage to understand intestinal damages due to chemotherapy and to provide information on biomarkers which can be used to screen complementary agents in future studies. Methods: BALB/c mice were divided into three experimental groups and subjected to the intraperitoneal injection of either 100 mg/kg or 200 mg/kg of 5-FU. The third group was used as PBS controls. Body weights and the consistency of the stools were recorded every day, and the animals were sacrificed on the 7th day post 5-FU administration. The expressions of intestinal tight junction proteins and mRNAs of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were determined. Results: The body weight of the animals treated with 5-FU was significantly decreased in a dose-dependent manner. However, mice given 100 mg/kg 5-FU rapidly recovered the original body weight. Symptom of diarrhea was also more severe in 200 mg/kg 5-FU treated group than that of the 100 mg/kg 5-FU treated animals. The expressions of occludin and claudin-1, not ZO-1 protein expressions in 200 mg/kg 5-FU treated animals were significantly reduced compared to those of the control group or 100 mg/kg 5-FU group. The expression of Nuclear factor-kappa B p65 (NF-κB p65) protein and TNF-α mRNA were significantly higher in 5-FU treated group compared to those of control group. No difference was observed with IL-1β expression. Conclusions: These results suggested that selected tight junction proteins and inflammatory cytokines are related to 5-FU induced mucositis, and thereby can be used as targets of developing complementary agents.
Planckian scattering effects and black hole production in low M(Pl) scenarios

We reanalyze the question of black hole creation in high energy scattering via shock wave collisions. We find that string corrections tend to increase the scattering cross section. We analyze corrections in a more physical setting, of Randall-Sundrum type and of higher dimensionality. We also analyze the scattering inside anti-de Sitter backgrounds.
Endosomal maturation by Rab conversion in Aspergillus nidulans is coupled to dynein-mediated basipetal movement

Highly motile fungal early endosomes can be easily distinguished from more static late endosomes and vacuoles, a feature that is exploited to study endosomal maturation. RabA/RabB early endosomes mature into RabSRab7 late endosomes as they move away from the tip where endocytosis predominates, augmenting their size, with concomitant loss of motility.
OMAE 2002-28604 A 40 YEARS HINDCAST OF WIND , SEA LEVEL AND WAVES IN EUROPEAN WATERS

The paper describes the initial efforts in a project whose objective is to obtain a 40-year hindcast of wind, sea level and wave climatology for European waters. The 40-year global atmospheric re-analysis carried out by the National Centre for Environmental Prediction, Washington, USA (NCEP) and the National Centre for Atmospheric Research, Boulder, Colorado, USA (NCAR) will be used as forcing of limited area atmospheric models. The fine grid atmospheric fields will be used to force state-of-the-art wave models (WAM) and sea level models (HAMSOM and TELEMAC) in regional areas around Europe so as to produce climatic information on waves, sea levels, and currents in a very large extend of the European waters, including the Mediterranean, North East Atlantic and North Sea. The available satellite data, including wind, wave and sea-level data, will be collected and will be used to be compared with the hindcast results, so as to yield uncertainty measures related to the data. Statistical analysis of the produced atmospheric, sea level and wave hindcast and remote sensed data will be performed in order to provide information about the climatological trends in the European Waters and Coastal Seas.
Prey Switching with a Linear Preference Trade-Off

In ecology, prey switching refers to a predator's adaptive change of habitat or diet in response to prey abundance. In this paper, we study piecewise-smooth models of predator-prey interactions with a linear trade-off in a predator's prey preference. We consider optimally foraging predators and derive a model for a 1 predator-2 prey interaction with a tilted switching manifold between the two sides of discontinuous vector fields. We show that the 1 predator-2 prey system undergoes a novel adding-sliding-like (center to two-part periodic orbit; “C2PO'') bifurcation in which the prey ratio transitions from constant to time-dependent. Farther away from the bifurcation point, the period of the oscillating prey ratio doubles, which suggests a possible cascade to chaos. We compare our model predictions with data on freshwater plankton, and we successfully capture the periodicity in the ratio between the predator's preferred and alternative prey types. Our study suggests that it is useful to investigate prey rat.
Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells.

The role of acidic glycosphingolipids in cell growth and differentiation was investigated using the multipotent leukemia cell line K562. When GM3 was added to cell culture media, the growth of K562 cells was remarkably inhibited and the cells were shown to have megakaryocytoid morphology. Ultrastructural study demonstrated that K562 cells treated with GM3 had platelet peroxidase-positive structures, which were considered to be the specific marker of megakaryocyte. Furthermore, AP-3 directed against an epitope present on membrane glycoprotein IIIa reacted with the GM3-treated cells. Free N-acetylneuraminic acid, GM1, GM2, GD1a, and a mixture of bovine brain gangliosides containing GD1a and GT1b did not affect growth of K562 cells or show morphological changes. According to chemical analyses, GM3 content increased in megakaryocytoid differentiation induced by tetradecanoylphorbol-13-acetate, whereas GM3 decreased in erythroid differentiation induced by hemin. Enzymatic analysis showed that the GM3 increase during megakaryocytoid differentiation was a result of the sialyltransferase activation. These results indicated that exogenous GM3 induced differentiation of K562 cells into a "GM3-rich" lineage, i.e., mainly megakaryocytoid lineage, and that GM3 accumulation in the GM3-rich lineage was the result of the activation of GM3 synthase. These findings strongly suggested that GM3 ganglioside, a minor membrane component, has a crucial role in not only the differentiation induction but also the determination of the differentiation direction in pluripotent K562 cells.
Seedlings in the Theory of Shortest Paths

This article explores three developments that arise from the fundamental theorem of Beardwood, Halton, and Hammersley on the asymptotic behavior of the shortest path through n random points. The first development concerns the role of martingales in the theory of shortest paths, especially their role in large deviation inequalities. The second development concerns the use of Lipschitz spacefilling curves to obtain analytical bounds in the theory of the TSP, and it provides some bounds that refine those of Bartholdi and Platzman on the worst case performance of the spacefilling heuristic for the TSP. The final topic addresses the relationship between Karp’s partitioning heuristic and the BHH theorem.
Cellular basis for singing motor pattern generation in the field cricket (Gryllus bimaculatus DeGeer)

The singing behavior of male crickets allows analyzing a central pattern generator (CPG) that was shaped by sexual selection for reliable production of species‐specific communication signals. After localizing the essential ganglia for singing in Gryllus bimaculatus, we now studied the calling song CPG at the cellular level. Fictive singing was initiated by pharmacological brain stimulation. The motor pattern underlying syllables and chirps was recorded as alternating spike bursts of wing‐opener and wing‐closer motoneurons in a truncated wing nerve; it precisely reflected the natural calling song. During fictive singing, we intracellularly recorded and stained interneurons in thoracic and abdominal ganglia and tested their impact on the song pattern by intracellular current injections. We identified three interneurons of the metathoracic and first unfused abdominal ganglion that rhythmically de‐ and hyperpolarized in phase with the syllable pattern and spiked strictly before the wing‐opener motoneurons. Depolarizing current injection in two of these opener interneurons caused additional rhythmic singing activity, which reliably reset the ongoing chirp rhythm. The closely intermeshing arborizations of the singing interneurons revealed the dorsal midline neuropiles of the metathoracic and three most anterior abdominal neuromeres as the anatomical location of singing pattern generation. In the same neuropiles, we also recorded several closer interneurons that rhythmically hyper‐ and depolarized in the syllable rhythm and spiked strictly before the wing‐closer motoneurons. Some of them received pronounced inhibition at the beginning of each chirp. Hyperpolarizing current injection in the dendrite revealed postinhibitory rebound depolarization as one functional mechanism of central pattern generation in singing crickets.
Risk factors for heart failure in a cohort of patients with newly diagnosed myocardial infarction: a matched, case-control study in Iran

OBJECTIVES: Risk factors for heart failure (HF) have not yet been studied in myocardial infarction (MI) patients in Iran. This study was conducted to determine these risk factors. METHODS: In this nationwide, hospital-based, case-control study, the participants were all new MI patients hospitalized from April 2012 to March 2013 in Iran. The data on 1,691 new cases with HF (enrolled by census sampling) were compared with the data of 6,764 patients without HF as controls. We randomly selected four controls per one case, matched on the date at MI and HF diagnosis, according to incidence density sampling. Using conditional logistic regression models, odds ratios (ORs) with a 95% confidence interval (CI) were calculated to identify potential risk factors. RESULTS: The one-year in-hospital mortality rate was 18.2% in the cases and higher than in the controls (12.1%) (p<0.05). Significant risk factors for HF were: right bundle branch block (RBBB) (OR, 2.86; 95% CI, 1.95 to 4.19), stroke (OR, 2.00; 95% CI, 1.39 to 2.89), and coronary artery bypass grafting (CABG) (OR, 2.03; 95% CI, 1.34 to 3.09). Diabetes, hypertension, percutaneous coronary intervention (PCI), atrial fibrillation, ventricular tachycardia, and age were determined to be the factors significantly associated with HF incidence (p<0.05). The most important factor in women was diabetes (OR, 1.41; 95% CI, 1.05 to 1.88). Age, hypertension, PCI, CABG, and RBBB were the most important factors in men. CONCLUSIONS: Our findings may help to better identify and monitor the predictive risk factors for HF in MI patients. The pattern of risk factors was different in men and women.
Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials

Background Intra-articular injection of hyaluronic acid is a common, yet controversial, therapeutic option for patients with knee osteoarthritis (OA). The purpose of this research was to determine the safety and efficacy of US-approved viscosupplements for symptomatic knee OA. Methods We searched MedLine and EMBase for randomized, sham-controlled trials evaluating safety and/or clinical efficacy of US-approved viscosupplements in patients with symptomatic knee OA. Knee pain severity and knee joint function were assessed at 4 to 13 weeks and 14 to 26 weeks. Safety outcomes included serious adverse events, treatment-related serious adverse events, patient withdrawal, and adverse event-related patient withdrawal occurring at any time during follow-up. Results A total of 29 studies representing 4,866 unique patients (active: 2,673, control: 2,193) were included. All sham-controlled trials used saline injections as a control. Viscosupplementation resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to preinjection values, with standardized mean difference values ranging from 1.07 to 1.37 (all P<0.001). Compared to controls, standardized mean difference with viscosupplementation ranged from 0.38 to 0.43 for knee pain and 0.32 to 0.34 for knee function (all P<0.001). There were no statistically significant differences between viscosupplementation and controls for any safety outcome, with absolute risk differences of 0.7% (95% confidence interval [CI]: −0.2 to 1.5%) for serious adverse events, 0% (95% CI: −0.4 to 0.4%) for treatment-related serious adverse events, 0% (95% CI: −1.6 to 1.6%) for patient withdrawal, and 0.2% (95% CI: −0.4 to 0.8%) for adverse event-related patient withdrawal. Conclusion Intra-articular injection of US-approved viscosupplements is safe and efficacious through 26 weeks in patients with symptomatic knee OA.
Association Between a Novel 11–Base Pair Deletion Mutation in the Promoter Region of the Scavenger Receptor Class B Type I Gene and Plasma HDL Cholesterol Levels in Taiwanese Chinese

Objective—Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels. Methods and Results—We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp CCCCGCCCC GT deletion mutation from positions −140 to −150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a C →T substitution at position −142. Twenty-six of 690 unrelated subjects were heterozygous for the −140 to −150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the −140 to −150 deletion mutation was significantly associated with increased HDL-C levels and explained ≈0.5% of the variation in HDL-C levels in this population. Conclusions—A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population.
Analysis of physical inactivities and sedentary behaviors of adolescents in Guangzhou

Objective To study the condition of physical exercise related behaviors among Guangzhou adolescents,and to provide scientific evidence for intervention.Methods A "Questionnaire of Health Related Behaviors among Adolescents in China" was used among 11 939 students in 66 schools in Guangzhou.Results In the past 7 days,the rate of students whose sports days were less than 3 days was 48.61%,and the rate of students who participated in moderate-intensity exercise less than three days was 62.14%,the rates for girls were higher than those for boys,and they gradually increased with grade.The rate of students watched TV more than 2 hours every day was 45.13%,which was the highest in middle school than other schools,and was gradually decreased with the education level of their mother.The rate of students playing video or computer games more than 2 hours every day was 45.13%,which was the highest in vocational school than other schools.The rate of students doing homework more than 4 hours every day was 15.23%,which was higher in girls than in boys,higher in urban than in rural,highest in high school.Conclusion Among adolescents,incidence of physical activity-absent behaviors is prevailing,and exercise is not enough.It is necessary to adopt scientific measures to improve their exercise level.