Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin and Incident Breast Cancer among Diabetic Women: A Population-Based Case–Control Study in Denmark

Background: Preliminary evidence suggests that metformin may decrease breast cancer risk by decreasing insulin levels and reducing cell proliferation. We evaluated the effect of metformin medication on the risk of incident breast cancer among peri- and postmenopausal women. Methods: We used Danish medical registries to conduct a nested case–control study among type 2 diabetic women 50 years or older who resided in northern Denmark from 1989 to 2008 (n = 4,323). We identified 393 diabetic cases and used risk-set sampling to select 10 diabetic controls per case (n = 3,930) matched on county of residence. Odds ratios (OR) and 95% CIs were estimated by conditional logistic regression associating metformin use with breast cancer occurrence. Results: Ninety-six cases (24%) and 1,154 controls (29%) used metformin for at least 1-year duration. Cases were slightly older on average than controls, but they were similar in distribution for parity, use of hormone replacement therapy, and history of diabetes complications. Metformin users were less likely with a diagnosis of breast cancer (OR = 0.77; 95% CI = 0.61–0.99) than nonmetformin users. Adjustment for diabetes complications, clinically diagnosed obesity, and important predictors of breast cancer did not substantially alter the association (OR = 0.81; 95% CI = 0.63–0.96). Conclusion: Our results suggest that metformin may protect against breast cancer in type 2 diabetic peri- or postmenopausal women. Impact: This study supports the growing evidence of a role for metformin in breast cancer chemoprevention. Cancer Epidemiol Biomarkers Prev; 20(1); 101–11. ©2011 AACR.
Manufacturing schedule of dual-armed cluster tools based on heuristic search

Cluster tools are fundamental equipments in over-8-inch wafer manufacturing. Due to the toolspsila unique physical structure and particular semiconductor manufacturing demands, the scheduling of cluster tools is more complex than normal Job-Shop problems. This paper proposes a scheduling algorithm for dual-armed cluster tools based on Heuristic Search. We mainly examine the scheduling technique under the most complex situation including residency constraints and multi-visit requirements. A periodic idea that every wafer enters into cluster tools in the same interval is proved still feasible under this situation. To find a conflict-free schedule under a fundamental period (FP) in short time, we define an evaluation function to select the most proper operation sequence from all the possibilities, and some feedback information from a conflict is used to prevent over pruning. Experiments under the most complex situations demonstrate the feasibility and effectiveness of this algorithm. Other experiments with looser constraints show its expansibility and adaptability.
Influence of exercise training on heart rate variability in post-menopausal women with elevated arterial blood pressure.

Low heart rate variability (HRV) has been reported to be an independent risk factor for the development of coronary heart disease in women and has recently been identified as a risk factor for cardiac sudden death and all-cause mortality. We have recently demonstrated that endurance-trained post-menopausal women demonstrate higher levels of HRV than sedentary control subjects. The purpose of the present study was to test the hypothesis that 12 weeks of regular aerobic exercise would increase HRV in sedentary post-menopausal women with elevated arterial blood pressure (BP) (i.e. either high normal BP or stage I hypertension). A secondary aim was to test the hypothesis that the increase in HRV with exercise training, if observed, would be associated with an increase in spontaneous cardiac baroreflex sensitivity (SBRS), an important physiological determinant of HRV. To accomplish these aims, we studied eight sedentary post-menopausal women (age = 54.5 +/- 1.3 years) before and after 12 weeks of aerobic exercise training (3.3 +/- 0.3 days per week at 70% +/- 2% of maximal heart rate for 43 +/- 3 min per day). Maximal oxygen uptake and body weight did not change (P > 0.05) with training, but percentage fat (35.5 +/- 2.6% vs. 34.5 +/- 2.3%, P < 0.05) decreased and treadmill time to exhaustion increased (9.8 +/- 0.5 vs. 11.3 +/- 0.5 min, P < 0.05). Supine resting levels of heart rate, RR interval and the standard deviation of the RR interval (time domain measure of HRV) were unchanged (all P > 0.05) from baseline levels after 12 weeks of aerobic training. Similarly, the high-frequency, low-frequency and total power of HRV (frequency domain measures) were also unchanged from baseline (all P > 0.05). SBRS was also not different before and after aerobic exercise training (10 +/- 2 vs. 13 +/- 3 ms mmHg-1 respectively, P > 0.05). In contrast, systolic and diastolic BP were reduced approximately 8 and approximately 5 mmHg with training (both P < 0.05) respectively. These results indicate that 12 weeks of moderate-intensity aerobic exercise training does not increase HRV or SBRS, despite producing a clinically significant reduction in BP at rest in post-menopausal women with elevated BP. Considered together with our previous findings in female master endurance athletes, these findings suggest that more intense and prolonged exercise training may be required to produce increases in HRV and SBRS in sedentary post-menopausal women.
Tactical Increases in Operating Room Block Time for Capacity Planning Should Not Be Based on Utilization

When a decision has been made to expand operating room (OR) capacity, the choice of surgical subspecialties to receive additional block time and fill the additional OR capacity is a tactical decision. Such decisions are made approximately once a year. Afterwards, typically a few months before the day of surgery, a second stage occurs in which operational decisions allocate OR time and determine the hours of staffing for each specialty based on its expected workload. In practice, cases are not scheduled into block time that has been planned tactically, but instead are scheduled during the second stage into the staffed time that is allocated operationally. This article reviews the literature on tactical decision-making for expansion of OR capacity. When additional OR capacity is available, it should be planned for those subspecialties that have the greatest contribution margin per OR hour, that have the potential for growth, and that have minimal need for limited resources such as intensive care unit beds. Numerous reasons are presented to explain why tactical planning of additional block time should not be based on current or past utilization of block time.
Changes in phenolics and antioxidant activity at each step of processing from pomegranate into nectar

Abstract Effect of all processing steps on polyphenols and antioxidant activity was investigated during an industrial scale pasteurized pomegranate nectar production, from which sampling was done at 12 steps of the process. Total phenolic (TPC), flavonoid (TFC), anthocyanin (TAC), tannin contents (TTC), antioxidant activity (TAA) (2,2′-azinobis-3-ethylbenzo-thiazoline-6-sulphonic acid diammonium salt (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of plasma (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays), phenolic and anthocyanin profiles were analyzed in those samples. TPC, TFC, TTC and TAA were highest in whole pomegranate. For all analyses, peeling and processing into nectar resulted in significant losses, except for TAC data obtained for peeling. Losses at mashing (for TFC 24%), pressing (for TAC 13%, TTC 48%, TAA 21–63%), pasteurization (for TFC 76%, TAA 42–77%) and ultrafiltration (for TPC 18%, TFC 28%, AA 17–19%) were also significant. Pomegranate nectar, when compared with fresh edible fruit, retained 19% of TPC and 14% of TAC at the end of processing, however, as initial values were very high for pomegranate, pasteurized nectar is still a promising source of polyphenols.
Development of a microfluidic platform for high‐throughput screening of non‐viral gene delivery vectors

The grail of gene delivery is the development of delivery vectors as effective and non‐cytotoxic as possible. In this regard, there is an urgent need of new tools for the straightforward and quantitative assessment of transfection efficiency and cytotoxicity simultaneously. We herein reported the development and validation of an easy‐to‐use lab‐on‐chip platform to perform cell transfection assays for unbiased, high‐throughput selection of more and more effective gene delivery vectors by using two commercially sourced lipids, Lipofectamine 2000® and FuGene® 6. A single PDMS‐layer platform was endowed with: i) a chaotic serial dilution generator, designed for the automatic generation of a linear lipoplex dilution (from 100% to 0% with 25% steps) independently delivered to; and ii) the downstream culture and transfection module consisting in five units, each composed of 33 serially connected and fluidically connected culture chambers for trapping small populations of ≈10 cells/chamber. In the absence of any transfectant, cells spread and duplicated up to 2 days. Besides, cells were transfected with EGFP‐encoding reporter gene. The very facile visual inspection of the microdevice by means of a microscope and a semi‐automated analytical method allowed pinpointing the best transfection conditions in terms of efficiency, cytotoxicity, cell doubling rates, and morphological changes at once.
[Inhibitory effect of 4-chlorobenzoyl berbamine on imatinib-resistant K562 cells in vitro and in vivo].

OBJECTIVE To observe the inhibitory effect of 4-chlorobenzoyl berbamine (BBD9) on imatinib-resistant cell line K562 (K562/IR) in vitro and in vivo and explore the mechanisms. METHODS The IC50 of BBD9 and berbamine (BBM) was determined by MTT assay. The expressions of p210(Bcr-Abl), IKKa, cytoplasmic and nuclear NF-κBp65 were determined using Western blotting in K562/IR cells following a 48-h exposure to 0.5 µg/ml BBD9 or 8 µg/ml BBM. Flow cytometry was used to analyze the cell viability, apoptosis and necrosis; Western blotting was employed to determine the expressions of PARP, caspase-3, caspase-9 and LC3II in K562/IR cells exposed to different concentrations of BBD9 for 48 h. In nude mouse models bearing K562/IR cell xenograft, the tumor weight, tumor regression, and body weight changes of the mice were measured after treatments with 15 mg/kg and 30 mg/kg BBD9 and 100 mg/kg imatinib. RESULTS The IC50 of BBD9 and BBM was 0.73 µg/ml and 5.43 µg/ml, respectively. In K562/IR cell cultures, the expressions of p210(Bcr-Abl), IKKa and nuclear NF-κB p65 were all decreased following BBD9 and BBM treatments, but BBD9 produced more potent effect; cytoplasmic NF-κB p65 showed no obvious changes after the treatments. The cell apoptosis and necrosis increased with the concentrations of BBD9, which also dose-dependently increased the levels of cleaved caspase-3, csapase-9, PARP, and LC3II expression. In the tumor-bearing mouse model, BBD9 showed stronger effects than imatinib in reducing the tumor weight, promoting tumor regression, and increasing the body weight. CONCLUSION BBD9 can effectively inhibit the growth of K562/IR cells in vitro and in vivo by activating cell apoptosis, necrosis and autophage pathways, down-regulating expressions of p210(Bcr-Abl) and IKKa and suppressing the cytoplasm-to- nucleus translocation of NF-κBp65.
Caffeine Metabolism in Premature Infants

Caffeine has been used frequently in the treatment and prevention of apnea of prematurity. The metabolism of caffeine depends on the activities of the hepatic enzymes that vary from one infant to another. The objective of this study was to determine the influence of postnatal age (PNA), birth weight (BW), study weight (SW), gestational age (GA), postconceptual age (PCA), and gender on the maturation of caffeine metabolism in premature infants. The caffeine base was administered orally as a loading dose of 10 mg/kg, followed by a maintenance dose of 2 mg/kg every 24 hours. The steady‐ state concentration of caffeine and metabolites was measured in plasma taken on the 5th‐day postloading dose. The molar concentration ratios for the N3 (N3‐), N7 (N7‐), N1 (N1‐), and all methyl (N‐) demethylation processes; clear‐ance (CL); and the percentage of molar concentration of caffeine found in plasma to that of the total caffeine and metabolites (%CAF) were calculated from samples collected from 80 neonatal infants. The 48 male and 32 female premature infants had median (range) BW (g), GA (weeks), SW (g), PCA (weeks), and PNA (days) of 1300 (650–2260), 30 (24–34), 1630 (980–2670), 34 (29–40), and 28 (5–60), respectively. The median (range) of the ratios for the %CAF, CL, and the N3‐, N7‐, N1‐, and Nall‐ were 86.9 (52.9–99.0), 0.127 (0.046‐0.503) ml·kg−1 ·min−1, 0.032 (0‐0.438), 0.070 (0.007‐0.471), 0.026 (0‐0.283), and 0.0463 (0.003‐0.303), respectively. When the patients were stratified into four PNA age groups, each older group showed a consistently higher level of caffeine metabolic activity for the N3‐, N7‐, and Nall‐‐ pathways with a corresponding decrease in the %CAF, whereas no significant differences were seen for the N1‐pathway or for CL. No pattern of significant differences between the demethylation process ratios, %CAF, or CL was seen between groups of infants when they were stratified according to BW, SW, PCA, or GA. The female infants were found to have significantly higher rates of caffeine metabolism as shown by %CAF, N1‐, N3‐, and Nall‐ processes but not the N7‐. Multivariate linear regression analysis by two methods demonstrated that PNA is significantly related to %CAF and Nall‐, whereas the female patients had higher levels of metabolic activity for the %CAF and N1‐ process. The authors conclude that the N7‐demethy‐ lation process is the predominate caffeine metabolic process in premature infants. Furthermore, the maturation of the caffeine metabolism in premature infants with a PNA of less than 60 days increases with postnatal age, regardless of birth weight, gestational age, postconceptual age, and study weight. The female neonatal patients demonstrated a higher rate of caffeine metabolism than the males.
Domain Wall Processes, Rotations, and High-Frequency Losses in Thin Laminations

We have investigated and modeled the magnetization process in thin amorphous and nanocrystalline ribbons from DC to 1 GHz. These transverse anisotropy laminations, their thickness ranging between 6 and 20 μm, display excellent broadband magnetic behavior, ensuing from the dominant role of magnetization rotations. Combination of fluxmetric, aftereffect, and high-speed magneto-optical experiments put in evidence that the domain wall processes, the obvious source of losses at low and medium frequencies in spite of negligible contribution to the magnetization reversal, fully damp on attaining the MHz range. Here the energy dissipation chiefly descends from the rotations and conforms to the so-called classical regime. To describe the high-frequency spin dynamics, the coupled Maxwell and Landau-Lifshitz-Gilbert equations are therefore considered. We have worked out a numerical solution of such equations by a finite element approach, based on a very fine time discretization and a computing scheme preserving the magnetization modulus. From the calculation of hysteresis loop and eddy current density at each mesh point, the separate contributions to the rotational losses by the eddy currents and the spin damping mechanism are obtained. The overall energy loss behavior versus frequency is thus eventually predicted in terms of separate contributions by the domain wall processes and the rotations.
Dynamic multi-time regression analysis of gross domestic product in Shanghai

As an important part of the Yangtze River Delta Economic Circle (YRDEC), Shanghai is impacting other members of YRDEC in political, economic and other aspects greatly. This article used multi-regression model to research the gross domestic product (GDP) in ShangHai, and aimed for making a deep understanding about the YRDEC. Using technical included: factors comparison and selection, the variables identified, the evaluation of calculated values, multi-layer dynamic regression analysis, and ultimately determined the related variable of GDP in Shanghai, and calculated the corresponding coefficient. This study would provide insights into the economic development and economic structure of the YRDCE, and directly promote the follow-up research on the bubble early warning management system for the YRDCE.
Trafficking and Gating of Hyperpolarization-activated Cyclic Nucleotide-gated Channels Are Regulated by Interaction with Tetratricopeptide Repeat-containing Rab8b-interacting Protein (TRIP8b) and Cyclic AMP at Distinct Sites*

Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly with two distinct sites of HCN channel pore-forming subunits to control channel trafficking and gating. Here we use mutagenesis combined with electrophysiological studies to define and distinguish the functional importance of the HCN/TRIP8b interaction sites. Interaction with the last three amino acids of the HCN1 C terminus governed the effect of TRIP8b on channel trafficking, whereas TRIP8b interaction with the HCN1 cyclic nucleotide binding domain (CNBD) affected trafficking and gating. Biochemical studies revealed that direct interaction between TRIP8b and the HCN1 CNBD was disrupted by cAMP and that TRIP8b binding to the CNBD required an arginine residue also necessary for cAMP binding. In accord, increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. These data illustrate the distinct roles of the two TRIP8b-HCN interaction domains and suggest that TRIP8b and cAMP may directly compete for binding the HCN CNBD to control HCN channel gating, kinetics, and trafficking.
β‐Actin is confined to structures having high capacity of remodelling in developing and adult rat cerebellum

Neurons undergo complex morphological changes during differentiation and in cases of plasticity. A major determinant of cell morphology is the actin cytoskeleton, which in neurons is comprised of two actin isoforms, non‐muscle γ‐ and β‐actin. To better understand their respective roles during differentiation and plasticity, their cellular and subcellular localization was examined in developing and adult cerebellar cortex. It was observed that γ‐actin is expressed at a constant level throughout development, while the level of β‐actin expression rapidly decreases with age. At the light microscopic level, γ‐actin staining is ubiquitous and the only developmental change observed is a relative reduction of its concentration in cell bodies and white matter. In contrast, β‐actin staining almost completely disappears from the cytoplasm of cell bodies, primary dendrites and axons. In young cerebellar cultures, γ‐actin is found in the cell body, neurites and growth cones, while β‐actin is mainly found in growth cones, as previously reported in other primary neuronal culture systems [Kaech et al. (1997), J. Neuroscience, 17, 9565–9572; Bassell et al. (1998), J. Neuroscience, 18, 251–265]. Electron microscopy of post‐embedding immunogold‐labelled tissue confirms the widespread distribution of γ‐actin, and also reveals an increased concentration of γ‐actin in dendritic spines in the adult. During development, β‐actin accumulation is observed in actively growing structures, e.g. growth cones, filopodia, cell bodies and axonal tracts. In the adult cerebellar cortex, β‐actin is preferentially found in dendritic spines, structures which are known to retain their capacity for morphological modifications in the adult brain. This differential subcellular localization and developmental regulation of the two actin isoforms point to their different roles in neurons.
Pulmonary and systemic response to atmospheric pollution

The inhalation of toxic particles and gases reduces the innate defences of the lung by increasing epithelial permeability, decreasing mucociliary clearance and depressing macrophage function. There is also substantial experimental evidence that lung epithelial cells and alveolar macrophages generate a rich milieu of inflammatory mediators when exposed to atmospheric particles that can be measured in induced sputum, BAL fluid and blood. Here we review evidence that these mediators produce an integrated local lung and systemic inflammatory immune response. That results in an increase in the release of leucocytes and platelets from the bone marrow, an increased production of acute phase proteins from the liver and activation of the vascular endothelium to favour the formation of new and destabilization and rupture of existing atherosclerotic plaques. We postulate that when this response is generated in elderly persons whose lungs are compromised by COPD, it may account for the acute exacerbations of COPD that destroy the quality of life and increase the need for medical attention and hospital admissions. Moreover, the accelerated spread of the atherosclerotic process, and destabilization of existing atherosclerotic plaques in experimental animals that develop atherosclerosis naturally when exposed to atmospheric particles, may account for the acute coronary syndromes, myocardial infarction, transient cerebral ischaemia and stroke that have been documented in humans exposed to episodes of air pollution.
Effectiveness of a lifestyle modification programme in weight maintenance in obese subjects after cessation of treatment with Orlistat.

OBJECTIVE To examine the efficacy of a lifestyle modification programme in weight maintenance for obese subjects after cessation of treatment with Orlistat. METHODS Fifty-five subjects with and without diabetes mellitus were randomized to a lifestyle modification programme or to usual care at the end of 6 months' treatment with Orlistat. The intervention programme was nutritionist led, consisting of components of dietary management, physical activity, peer group support and discussion using techniques of self-monitoring, stimulus control and cognitive restructuring. Anthropometric indices, body composition, basal metabolic rate, blood pressure, fasting glucose, glycosylated haemoglobin, lipid profile, 24-hour urinary albumin excretion, dietary intake, physical activity level, and quality of life were assessed before and after the intervention period. Results Subjects in the intervention group maintained their weight loss and favourable anthropometric, metabolic, dietary intake, physical activity and quality of life profiles, while most parameters deteriorated in the usual care group, being more marked in subjects with diabetes. The magnitude of weight gain was comparable to that lost during Orlistat treatment. CONCLUSION A specially designed nutritionist-led lifestyle modification programme for obese subjects is effective in weight maintenance after treatment with Orlistat, in the absence of which the benefits of drug treatment were lost. The magnitude of the effect of lifestyle modification is comparable to that observed with Orlistat.
Decade-bandwidth low cross-polarization UWB array

The proposed Sliced Notch Antenna (SNA) array fixes the longstanding problem of high cross-polarization radiation in Vivaldi arrays while maintaining their excellent wideband wide-scan impedance performance with a simple reconfiguration of the Vivaldi fins. The enabling technical innovation is the introduction of discontinuities at the upper region of the flared fins that control the ratio of vertical-to-horizontal current density, without introducing sizable reflections. Measurements and simulations suggest a 10:1 (1.2-12 GHz) SNA array operation with good scanning VSWR out to 45°, and about 15 dB polarization purity improvement over a well-designed Vivaldi counterpart.