Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of wall compliance on the laminar–turbulent transition of torsional Couette flow

Torsional Couette flow between a rotating disk and a stationary wall is studied experimentally. The surface of the disk is either rigid or covered with a compliant coating. The influence of wall compliance on characteristic flow instabilities and on the laminar–turbulent flow transition is investigated. Data obtained from analysing flow visualizations are discussed. It is found that wall compliance favours two of the three characteristic wave patterns associated with the transition process and broadens the parameter regime in which these patterns are observed. The results for the effects of wall compliance on the third pattern are inconclusive. However, the experiments indicate that the third pattern is not a primary constituent of the laminar–turbulent transition process of torsional Couette flow.
Drug-eluting stents in saphenous vein graft interventions: a systematic review.

AIMS A systematic review of the outcomes after drug-eluting stents (DES) implantation in saphenous vein grafts (SVGs) was performed. METHODS AND RESULTS The majority of the 33 published studies were retrospective with only two prospective randomised trials. Late loss and binary restenosis was reduced compared to bare metal stents (BMS) in all seven studies with angiographic follow-up. With the exception of one study there was no difference in mortality, myocardial infarction, or stent thrombosis between BMS and DES. The need for repeat target vessel or lesion revascularisation was lower in the DES arm in approximately half the published studies and similar in the remaining studies. CONCLUSIONS Until data from large, prospective, randomised-controlled studies become available, DES implantation in SVGs appears to be safe and, although not yet definitively proven, likely to reduce angiographic restenosis and the need for repeat target lesion revascularisation.
Pharmacological Stimulation of NADH Oxidation Ameliorates Obesity and Related Phenotypes in Mice

OBJECTIVE Nicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD+-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome. RESEARCH DESIGN AND METHODS We used β-lapachone (βL), a natural substrate of NADH:quinone oxidoreductase 1 (NQO1), to stimulate NADH oxidation. The βL-induced pharmacological effect on cellular energy metabolism was evaluated in cells derived from NQO1-deficient mice. In vivo therapeutic effects of βL on metabolic syndrome were examined in diet-induced obesity (DIO) and ob/ob mice. RESULTS NQO1-dependent NADH oxidation by βL strongly provoked mitochondrial fatty acid oxidation in vitro and in vivo. These effects were accompanied by activation of AMP-activated protein kinase and carnitine palmitoyltransferase and suppression of acetyl-coenzyme A (CoA) carboxylase activity. Consistently, systemic βL administration in rodent models of metabolic syndrome dramatically ameliorated their key symptoms such as increased adiposity, glucose intolerance, dyslipidemia, and fatty liver. The treated mice also showed higher expressions of the genes related to mitochondrial energy metabolism (PPARγ coactivator-1α, nuclear respiratory factor-1) and caloric restriction (Sirt1) consistent with the increased mitochondrial biogenesis and energy expenditure. CONCLUSIONS Pharmacological activation of NADH oxidation by NQO1 resolves obesity and related phenotypes in mice, opening the possibility that it may provide the basis for a new therapy for the treatment of metabolic syndrome.
Revisiting the Evolution of Mycobacterium bovis

ABSTRACT Though careful consideration has been placed towards genetic characterization of tubercle bacillus isolates causing disease in humans, those causing disease predominantly among wild and domesticated mammals have received less attention. In contrast to Mycobacterium tuberculosis, whose host range is largely specific to humans, M. bovis and “M bovis-like” organisms infect a broad range of animal species beyond their most prominent host in cattle. To determine whether strains of variable genomic content are associated with distinct distributions of disease, the DNA contents of M. bovis or M. bovis-like isolates from a variety of hosts were investigated via Affymetrix GeneChip. Consistent with previous genomic analysis of the M. tuberculosis complex (MTC), large sequence polymorphisms of putative diagnostic and biological consequence were able to unambiguously distinguish interrogated isolates. The distribution of deleted regions indicates organisms genomically removed from M. bovis and also points to structured genomic variability within M. bovis. Certain genomic profiles spanned a variety of hosts but were clustered by geography, while others associated primarily with host type. In contrast to the prevailing assumption that M. bovis has broad host capacity, genomic profiles suggest that distinct MTC lineages differentially infect a variety of mammals. From this, a phylogenetic stratification of genotypes offers a predictive framework upon which to base future genetic and phenotypic studies of the MTC.
A Characterization of Conserved Quantities in Non-Equilibrium Thermodynamics

The well-known Noether theorem in Lagrangian and Hamiltonian mechanics associates symmetries in the evolution equations of a mechanical system with conserved quantities. In this work, we extend this classical idea to problems of non-equilibrium thermodynamics formulated within the GENERIC (General Equations for Non-Equilibrium Reversible-Irreversible Coupling) framework. The geometric meaning of symmetry is reviewed in this formal setting and then utilized to identify possible conserved quantities and the conditions that guarantee their strict conservation. Examples are provided that demonstrate the validity of the proposed definition in the context of finite and infinite dimensional thermoelastic problems.
Expression of Vascular Endothelial Growth Factor ( VEGF )-D and Its Receptor , VEGF Receptor 3 , as a Prognostic Factor in Endometrial Carcinoma 1

Purpose: To evaluate the prognostic value of vascular endothelial growth factor (VEGF)-D and VEGF receptor (VEGFR)-3 in endometrial carcinoma. Experimental Design: We assessed the levels of immunoreactivity for VEGF-D and VEGFR-3 in 71 endometrial carcinomas, 14 complex atypical endometrial hyperplasias, and 16 normal endometria by immunohistochemistry. Results: VEGF-D was stained in both tumor cells and adjacent stromal cells. VEGFR-3 was stained in both tumor cells and adjacent endothelial cells. Immunoreactivity for VEGF-D in tumor cells and adjacent stromal cells became significantly stronger as lesions progressed from normal endometrium to advanced carcinoma. Similarly, immunoreactivity for VEGFR-3 in tumor cells and adjacent endothelial cells was significantly greater as lesions progressed from normal endometrium to advanced carcinoma. A strong correlation was found between high levels of VEGF-D immunoreactivity in carcinoma cells and VEGFR-3 in both carcinoma cells and adjacent endothelial cells. Similarly, high levels of VEGF-D immunoreactivity in stromal cells were significantly correlated with those of VEGFR-3 in both carcinoma cells and endothelial cells. High levels of VEGF-D in carcinoma cells and stromal cells, as well as those of VEGFR-3 in carcinoma cells and endothelial cells, were significantly related to myometrial invasion and lymph node metastasis. A strong correlation was found between poor survival and high levels of VEGF-D in both carcinoma cells and stromal cells and between poor survival and high levels of VEGFR-3 in carcinoma cells. Moreover, the high levels of VEGF-D in stromal cells and VEGFR-3 in carcinoma cells were independent prognostic factors in endometrial carcinoma. Conclusions: The presence of VEGF-D and VEGFR-3 in endometrial carcinoma may predict myometrial invasion and lymph node metastasis and may prospectively identify patients who are at increased risk for poor outcome. In addition, VEGF-D and VEGFR-3 may be promising targets for new therapeutic strategies in endometrial carcinoma.
Breaking the Negative Cycle: The Formation of Self-Efficacy Beliefs in the Arts. A Focus on Professional Experience in Pre-Service Teacher Education

ACCORDING TO THE NATIONAL Education and the Arts Statement (Ministerial Council on Education, Employment, Training and Youth Affairs, 2007), all children and young people should have a high-quality arts education. To achieve this teachers require a high level of skill and training, and the belief that they are self-efficacious in the teaching of arts education (Andrews, 2004). This points to the role of pre-service teacher education to develop the capability to teach arts education. This study utilises Bandura's (1997) model of self-efficacy beliefs. Novice early childhood teachers were invited to reflect on their professional practice experience during pre-service teacher education to provide insights into how this has contributed to the formation of their self-efficacy beliefs in the arts. Findings confirm that novice teachers develop beliefs about arts education during professional experience that shape their future beliefs towards teaching arts in the early years. These beliefs are likely to be negative, thereby contributing to the formation of negative emotional association and low self-efficacy beliefs for teaching arts. Furthermore, three main themes emerged from the data about the impact of professional experience: 1) supervising teacher practice (vicarious experience); 2) supervising teacher feedback (verbal persuasion); and 3) the profile of arts as a subject experienced by the respondent (vicarious experience). The implications of these findings are considered in terms of pre-service teacher education and ongoing professional learning for teachers.
Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion

Estrogens play a pivotal role in the development and progression of prostate cancer (PCa). Their actions are mediated by estrogen receptors (ERs), particularly ERβ in the prostate epithelium. With the discovery of ERβ isoforms, data from previous studies that focused principally on the wild-type ERβ (ERβ1) may not be adequate in explaining the still controversial role of ERβ(s) in prostate carcinogenesis. In this study, using newly generated isoform-specific antibodies, immunohistochemistry (IHC) was performed on a tumor microarray comprised of 144 specimens. IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERβ1, ERβ2, and ERβ5 in PCa. ERβ2 was commonly found in the cytoplasm and was the most abundant isoform followed by ERβ1 localized predominantly in the nucleus, and ERβ5 was primarily located in the cytoplasm. Logistic regression analyses demonstrated that nuclear ERβ2 (nERβ2) is an independent prognostic marker for prostate specific antigen (PSA) failure and postoperative metastasis (POM). In a Kaplan–Meier analysis, the combined expression of both nERβ2 and cytoplasmic ERβ5 identified a group of patients with the shortest POM-free survival. Cox proportional hazard models revealed that nERβ2 predicted shorter time to POM. In concordance with IHC data, stable, ectopic expression of ERβ2 or ERβ5 enhanced PCa cell invasiveness but only PCa cells expressing ERβ5 exhibited augmented cell migration. This is the first study to uncover a metastasis-promoting role of ERβ2 and ERβ5 in PCa, and show that the two isoforms, singularly and conjointly, have prognostic values for PCa progression. These findings may aid future clinical management of PCa.
Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies.

AIMS To explore the usefulness of data derived from observational studies on adverse drug reactions (ADRs) in defining and preventing the risk of pharmacological interventions in children in different health care settings. METHODS A systematic review of studies on ADRs in hospitalized children, in outpatient children, and on ADRs causing paediatric hospital admissions was performed. Studies were identified through a search of the MEDLINE and EMBASE databases. The inclusion criteria required that the population was not selected for particular conditions or drug exposure and prospective monitoring was used for identifying ADRs. Data were analysed by a random-effects model. RESULTS Seventeen prospective studies were included. In hospitalized children, the overall incidence of ADRs was 9.53% (95% confidence interval [CI], 6.81, 12.26); severe reactions accounted for 12.29% (95%CI, 8.43,16.17) of the total. The overall rate of paediatric hospital admissions due to ADRs was 2.09% (95%CI, 1.02, 3.77); 39.3% (95%CI, 30.7,47.9) of the ADRs causing hospital admissions were life threatening reactions. For outpatient children the overall incidence of ADRs was 1.46% (95%CI, 0.7, 3.03). CONCLUSIONS The results show that ADRs in children are a significant public health issue. The completeness and accuracy of prescription reporting as well as clinical information from studies was a rarity, making it difficult for health practitioners to implement evidence based preventive strategies. Further, methodologically sound drug surveillance studies are necessary for an effective promotion of a safer use of drugs in children.
The Rotterdam Radial Access Research: Ultrasound-Based Radial Artery Evaluation for Diagnostic and Therapeutic Coronary Procedures

Background—Radial artery wall might be damaged after cannulation for cardiac catheterization. We investigated structural changes of the radial artery wall after catheterization to understand whether these might predict radial pulsation loss or occlusion and local pain or functional impairment of the upper extremity. Methods and Results—Ninety patients underwent transradial coronary angiography or intervention and were scanned with a high-resolution 40-MHz ultrasound before cannulation and at 3 hours and 30 days after procedure. Acute injuries of the radial artery occurred in all patients: dissection and intramural hematoma were the most common. However, these phenomena did not predict loss of radial pulsation or occlusion, local pain, or functional impairment at 30 days. Overall, the radial artery lumen was significantly reduced distal to the puncture site. Radial artery intima and total wall thickness increased 3 hours after puncture and persisted at 30 days. Radial occlusion and pulsation loss were observed in 3.9% and 9.2% of patients, respectively, at 30 days. Smaller radial artery lumen at baseline increased the risk of radial pulsation loss at 30 days (odds ratio, 1.23; P=0.049). The number of radial puncture attempts predicted pulsation loss (odds ratio, 2.64; P=0.027), occlusion (odds ratio, 3.49; P=0.022), and symptoms (odds ratio, 2.24; P=0.05) at 30-day follow-up. Conclusions—After catheterization, radial artery puncture site is associated with increased intima and total wall thickness and with modest decrease of inner lumen diameter. Acute injuries of the vessel wall were ubiquitous, but contrary to repeated puncture attempts, did not seem to affect postprocedural radial occlusion or loss of pulsation.
Skeletal microstructural abnormalities in postmenopausal women with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and µCT and compared with age‐matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (±SD) cancellous bone volume (15.20 ± 5.91 versus 21.34 ± 5.53%, p = .01), trabecular number (1.31 ± 0.26 versus 1.77 ± 0.51/mm, p = .003), and trabecular thickness (141 ± 23 versus 174 ± 36 µm, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 ± 2.78 versus 7.94 ± 3.08/mm, p = .04), and correlated negatively with smoking (r = −0.67; p = .0005). Trabecular separation (785 ± 183 versus 614 ± 136 µm, p = .01) and cortical porosity (4.11 ± 1.02 versus 2.32 ± 0.94 voids/mm2; p < .0001) were higher in COPD while cortical width (458 ± 214 versus 762 ± 240 µm; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 ± 0.16 versus 0.66 ± 0.12 µm/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLD I and II (0.028 ± 0.009 versus 0.016 + 0.011 µm3/µm2/day; p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease. © 2010 American Society for Bone and Mineral Research
Pembrolizumab in Programmed Death Ligand 1-Positive Endometrial Cancer.

TO THE EDITOR: In the article by Ott et al, the aim of the study, KEYNOTE-028 (NCT02054806), was to evaluate the activity and safety profile of pembrolizumab in patients with heavily pretreated advanced endometrial cancer (EC), a subgroup with a poor prognosis. This article deserves some consideration to give the study proper meaning. Unfortunately, it is a small study, as are others that explore the activity of different agents in advanced and metastatic EC. Of the 75 patients evaluated for programmed death ligand 1 expression, 36 (48%) had positive tumors. According to eligibility criteria, up to 12 patients were excluded; moreover, another woman was excluded for lack of post-baseline assessment, and three received no assessment at the time of the data cutoff. The study design stated that sarcomas should be excluded; in our opinion, even a patient with a carcinosarcoma should have been excluded to have a more homogeneous group for this investigation. For the same reason, the two patients who received adjuvant radiotherapy should have been excluded. Therefore, only 17 patients were eligible by clinical assessment—certainly too few to answer to the question about clinical activity of pembrolizumab in patients with programmed death ligand 1–positive EC. In this article, the authors reported the promising role of bevacizumab in EC according to available scientific data. Other articles recently have highlighted the role of bevacizumab in this neoplasia as well as in other gynecologic malignancies. In the trial reported by Aghajanian et al, 56 patients were recruited to evaluate the activity of bevacizumab in recurrent or persistent EC. Of 55 patients, 52 were eligible and evaluable. In the study, one complete and six partial responses were observed (together, 13.5% response rate); the median response duration reported was 6 months. Moreover, 21 patients (40.4%) were progression free for at least 6 months. The median progression-free survival and overall survival (OS) times were 4.2 and 10.5 months, respectively. According to these data, bevacizumab use was proposed as singleagent therapy for patients with EC who experienced progression after standard chemotherapy. In the study by Ott et al, the 6and 12-month progression-free survival rates were 19.9% and 14.3%, respectively, similar to results observed by Aghajanian et al. The median OS was not reached, and the 6and 12-month OS rates were 67.0% and 51.0%, respectively. Unfortunately, the study was not powered to evaluate OS in this subset of patients. Because of the small number of patients evaluable for clinical assessment, it is difficult to correlate microsatellite instability status with clinical outcome after therapy with pembrolizumab in these patients. Given the results of these two studies, it seems premature to suggest treatment with pembrolizumab in patients with EC after disease failure with standard therapies. We await results from controlled clinical trials, and the results of the multicohort KEYNOTE-158 trial in particular.
The synaptic plasticity and memory hypothesis: encoding, storage and persistence

The synaptic plasticity and memory hypothesis asserts that activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the encoding and trace storage of the type of memory mediated by the brain area in which it is observed. Criteria for establishing the necessity and sufficiency of such plasticity in mediating trace storage have been identified and are here reviewed in relation to new work using some of the diverse techniques of contemporary neuroscience. Evidence derived using optical imaging, molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing the strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain.
Gravitational solution to the Pioneer 10/11 anomaly

A fully relativistic modified gravitational theory including a fifth force skew-symmetric field is fitted to the Pioneer 10/11 anomalous acceleration. The theory allows for a variation with distance scales of the gravitational constant G, the fifth force skew-symmetric field coupling strength ω and the mass of the skew-symmetric field μ = 1/λ. A fit to the available anomalous acceleration data for the Pioneer 10/11 spacecraft is obtained for a phenomenological representation of the ‘running’ constants and values of the associated parameters are shown to exist that are consistent with fifth force experimental bounds. The fit to the acceleration data is consistent with all current satellite, laser ranging and observations for the inner planets.
Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer.

BACKGROUND The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy. PATIENTS AND METHODS The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion at day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by 5-FU bolus 400 mg/m(2) and 22-h continuous infusion of 600 mg/m(2) at days 1-2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry. RESULTS The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037). CONCLUSION Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.