Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular adenosine regulates epigenetic programming in endothelial cells to promote angiogenesis

The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine‐metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the levels of intracellular adenosine in human endothelial cells. Knockdown (KD) of ADK elevated intracellular adenosine, promoted proliferation, migration, and angiogenic sprouting in human endothelial cells. Additionally, mice deficient in endothelial ADK displayed increased angiogenesis as evidenced by the rapid development of the retinal and hindbrain vasculature, increased healing of skin wounds, and prompt recovery of arterial blood flow in the ischemic hindlimb. Mechanistically, hypomethylation of the promoters of a series of pro‐angiogenic genes, especially for VEGFR2 in ADK KD cells, was demonstrated by the Infinium methylation assay. Methylation‐specific PCR, bisulfite sequencing, and methylated DNA immunoprecipitation further confirmed hypomethylation in the promoter region of VEGFR2 in ADK‐deficient endothelial cells. Accordingly, loss or inactivation of ADK increased VEGFR2 expression and signaling in endothelial cells. Based on these findings, we propose that ADK downregulation‐induced elevation of intracellular adenosine levels in endothelial cells in the setting of hypoxia is one of the crucial intrinsic mechanisms that promote angiogenesis.
Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT)

Abstract Background Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Methods Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Results Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. Conclusion The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients.
Growth of children at high risk of obesity during the first 6 y of life: implications for prevention.

BACKGROUND The contribution of familial factors to adiposity in children is poorly understood. OBJECTIVE The objective was to assess differences in growth in the first 6 y of life in children born to either overweight or lean mothers. DESIGN The body size and composition of 33 children at high risk and 37 children at low risk of obesity on the basis of the mother's overweight [body mass index (BMI; in kg/m(2)) of 30.2 +/- 4.2 and 19.5 +/- 1.1, respectively] were measured repeatedly from 3 mo to 6 y of age at the Children's Hospital of Philadelphia. RESULTS At year 2, no significant differences in any measure were observed between the high- and low-risk groups. By year 4, weight, BMI, and lean body mass were greater in the high-risk than in the low-risk children. By year 6, weight was even greater in the high-risk than in the low-risk children (23.4 +/- 6.4 compared with 20.4 +/- 2.1 kg; P < 0.02), and, for the first time, fat mass was greater in the high-risk than in the low-risk children (6.7 +/- 5.7 compared with 3.8 +/- 1.2 kg; P < 0.02). Ten of 33 high-risk children exceeded the 85th percentile of BMI at year 6 compared with 1 of 37 low-risk children (odds ratio = 15.7). Accelerated weight gain was predicted by high-risk group status, greater weight at year 2, and lower family income. CONCLUSION Anthropometric measures were not significantly different between groups at year 2; weight and lean body mass were greater at years 4 and 6, and fat mass was greater at year 6 in high-risk children.
Combining field phenological observations with distribution data to model the potential distribution of the fruit fly Ceratitis rosa Karsch (Diptera: Tephritidae)

Abstract Despite the potential for phenological and abundance data to improve the reliability of species niche models, they are seldom used. The aim of this study was to combine information on the distribution, relative abundance and seasonal phenology of Natal fruit fly, Ceratitis rosa Karsch (Diptera: Tephritidae), in South Africa to model its potential global distribution. Bucket traps, baited with Biolure, were used to trap C. rosa in different climatic regions of South Africa over a two-year period. A CLIMEX niche model of the potential global distribution of C. rosa was fitted using the collected trapping data and other distribution records from South Africa. Independent distribution records for elsewhere in Africa were reserved for model validation. The CLIMEX model results conformed well to the South African trapping data, including information on relative abundance and seasonal phenology, as well as to the pattern of presence records of the species elsewhere in Africa. The model suggests that under recent historical conditions a large part of South America, Central America, Mexico and southern USA may be climatically suitable for establishment of C. rosa. In Europe, climatically suitable habitat is restricted to coastal regions of the Mediterranean, in Asia, mostly to the southern and south eastern countries, and in Australia mostly to the wetter south and east. The independent cross-validation provided by South African relative abundance and seasonal phenology data, central African distribution data and relevant species specific biological information provides greater confidence in the modelled potential distribution of C. rosa.
Dietary patterns associated with colon and rectal cancer: results from the Dietary Patterns and Cancer (DIETSCAN) Project.

BACKGROUND An analysis of dietary patterns or combinations of foods may provide insight regarding the influence of diet on the risk of colon and rectal cancer. OBJECTIVE A primary aim of the Dietary Patterns and Cancer (DIETSCAN) Project was to develop and apply a common methodologic approach to study dietary patterns and cancer in 4 European cohorts: the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (Finland-ATBC), the Netherlands Cohort Study (NLCS) on Diet and Cancer, the Swedish Mammography Cohort (SMC), and the Ormoni e Dieta nella Eziologia dei Tumori (Italy-ORDET). Three cohorts (ATBC, NLCS, and SMC) provided data on colon and rectal cancer for the present study. DESIGN The cohorts were established between 1985 and 1992; follow-up data were obtained from national cancer registries. The participants completed validated semiquantitative food-frequency questionnaires at baseline. RESULTS Exploratory factor analysis, conducted within each cohort, identified 3-5 stable dietary patterns. Two dietary patterns-Vegetables and Pork, Processed Meats, Potatoes (PPP)-were common across all cohorts. After adjustment for potential confounders, PPP was associated with an increased risk of colon cancer in the SMC women (quintile 4(multivariate) relative risk: 1.62; 95% CI: 1.12, 2.34; P for trend = 0.01). PPP was also associated with an increased risk of rectal cancer in the ATBC men (quintile 4(multivariate) relative risk: 2.21; 95% CI: 1.07, 4.57; P for trend = 0.05). Neither pattern was associated with the risk of colon or rectal cancer in the NLCS women and men. CONCLUSION Although certain dietary patterns may be consistent across European countries, associations between these dietary patterns and the risk of colon and rectal cancer are not conclusive.
Using a Cultural Framework to Assess Motivation for Physical Activity Among Older Hispanic Women: Application of the PEN-3 Model

Culturally relevant strategies for intervention design and implementation, emphasizing strengths and resources, are essential to address cardiovascular health disparities among older Hispanic women. The purpose of this article is to present the process and results of focus group discussions conducted to understand the meaning of cultural, social, and contextual strengths to promote motivation for physical activity and cardiovascular health in this population. The PEN-3 model guided analysis of focus group data. Fifteen older Hispanic women (mean = 61, SD = 6) participated in 3 focus groups. Three interrelated domains were evaluated: (a) cultural identity, (b) relationships and expectations, and (c) cultural empowerment.
Properties of aluminium free-cutting alloys with tin. Part II

Standard aluminium free-cutting alloys contain lead and bismuth for improving their machinability. Tin as environment more friendly element can be used to replace lead and bismuth in these alloys. The paper deals with the properties ofAlCu5PbBi (standard 2011 alloy) and AlCuMgPb (standard 2030 alloy) in which lead and bismuth have been replaced with tin. The microstructure, composition of 'free machining inclusions, flow stresses during the working of these alloys, and the influence of tin on the mechanical properties and machinability of as-extruded alloys are described in comparison with the properties of standard leaded alloys. The breakage of these alloys at various experimental conditions, which simulated the cutting processes is discussed. Tin has reduced flow stresses during the working of AlCu5Sn and AlCuMgSn alloys in comparison with the standard alloys. Mechanical properties have decreased with an increasing tin content. The machinability of as-extruded alloys was satisfactory at a tin content higher than 1 mass percent.
Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats.

Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury. These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease.
Ketogenic dietary therapies in adults with epilepsy: a practical guide

Ketogenic dietary therapies are an effective treatment option for children with drug-resistant epilepsy. There is an increasing worldwide interest in using these diets to manage adult epilepsy; uncontrolled studies show similar response rates to those in children. Despite this, there are only a few centres with dedicated services for adults. We clearly need controlled studies of this treatment in adults. Here, we aim to familiarise adult neurologists with the evidence base for these diets and give practical advice on starting and maintaining them in adults.
Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems

The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosidase through MRs (mannose receptors). Three enzymes are commercially available for the treatment of GD by ERT. Taliglucerase alfa, imiglucerase and velaglucerase alfa are each produced in different cell systems and undergo various post-translational or post-production glycosylation modifications to expose their mannose residues. This is the first study in which the glycosylation profiles of the three enzymes are compared, using the same methodology and the effect on functionality and cellular uptake is evaluated. While the major differences in glycosylation profiles reside in the variation of terminal residues and mannose chain length, the enzymatic activity and stability are not affected by these differences. Furthermore, the cellular uptake and in-cell stability in rat and human macrophages are similar. Finally, in vivo studies to evaluate the uptake into target organs also show similar results for all three enzymes. These results indicate that the variations of glycosylation between the three regulatory-approved β-glucocerebrosidase enzymes have no effect on their function or distribution.
Estimation of service-life reduction of asphalt pavement due to short-term ageing measured by GPC from asphalt mixture

If the aggregate is heated higher than the specified level, the asphalt binder in the mixture will be aged at a much higher level during the short-term ageing (STA) period. The asphalt binder in that mixture will be oxidised (aged) more than expected during STA time due to the highly elevated temperature. If the binder in the mixture is severely oxidised, the asphalt pavement will have to lose its service life, or the expected service life will be reduced. Therefore, the objective of this study was to evaluate the ageing level of asphalt in the mixture at different STA temperatures and to estimate the service-life reduction (SLR) of asphalt mixture due to the STA. In this study, various temperatures were used for STA to evaluate ageing levels of the binder in the mixture before and after STA. A gel-permeation chromatography technique was used on the mixture particles without binder recovery to estimate the significance of ageing for each case of STA. Statistical analyses were carried out to examine the difference in ageing levels among STA temperatures. Statistical test results found that the ageing level of the binder after STA was significantly higher than that of binders before STA at α = 0.05 level. It was also found that the ageing level of binders in the warm-mix asphalt mixture was significantly lower than that of binders in hot-mix asphalt (HMA) after STA at the α = 0.05 level. It was also observed that if an HMA mixture was short-term aged at the higher temperature, a significant SLR could be induced due to the higher temperature during STA time.
Temperature-induced pseudopolymorphism of molecular salts from a pyridyl bis-urea macrocycle and naphthalene-1,5-disulfonic acid.

Molecular salts, often observed as cocrystals, play an important role in the fields of pharmaceutics and materials science, where salt formation is used to tune the properties of active pharmaceutical ingredients (APIs) and improve the stability of solid-state materials. Salt formation via a proton-transfer reaction typically alters hydrogen-bonding motifs and influences supramolecular assembly patterns. We report here the molecular salts formed by the pyridyl bis-urea macrocycle 3,5,13,15,21,22-hexaazatricyclo[15.3. 1.17,11]docosa-1(21),7(22),8,10,17,19-hexaene-4,14-dione, (1), and naphthalene-1,5-disulfonic acid (H2NDS) as two salt cocrystal solvates, namely 4,14-dioxo-3,5,13,15,21,22-hexaazatricyclo[15.3. 1.17,11]docosa-1(21),7(22),8,10,17,19-hexaene-21,22-diium naphthalene-1,5-disulfonate dimethyl sulfoxide disolvate, C16H20N6O22+·C10H6O6S22-·2C2H6OS, (2), and the corresponding monosolvate, C16H20N6O22+·C10H6O6S22-·C2H6OS, (3). This follows the ΔpKa rule such that there is a proton transfer from H2NDS to (1), forming the reported molecular salts through hydrogen bonding. Prior to salt formation, (1) is relatively planar and assembles into columnar structures. The salt cocrystal solvates were obtained upon slow cooling of dimethyl sulfoxide-acetonitrile solutions of the molecular components from two temperatures (363 and 393 K). The proton transfer to (1) significantly alters the conformation of the macrocycle, changing the formerly planar macrocycle into a step-shaped conformation with trans-cis urea groups in (2) or into a bowl-shape conformation with trans-trans urea groups in (3).
Efficiently packing unequal disks in a circle: a computational approach which exploits the continuous and combinatorial structure of the problem

Placing N non-overlapping circles in a smallest container is a well known, widely studied problem that can be easily formulated as a mathematical programming model. Solving this problem is notoriously extremely hard. Recently a public contest has been held for finding putative optimal solutions to a special case in circle packing. The contest saw the participation of 155 teams who submitted a total of 27490 tentative solutions. In this paper we will explain the strategy we used for attacking this problem. The main aim of the paper is to show how we could win the competition with relatively little computational power, by properly mixing local and global optimization strategies with random search and local moves. The main lesson learnt in participating to this context has been that although computational power surely helps, it is not strictly necessary, and clever utilization of relatively standard ideas from global optimization can beat special purpose methods.
DeepEM3D: approaching human‐level performance on 3D anisotropic EM image segmentation

Motivation: Progress in 3D electron microscopy (EM) imaging has greatly facilitated neuroscience research in high‐throughput data acquisition. Correspondingly, high‐throughput automated image analysis methods are necessary to work on par with the speed of data being produced. One such example is the need for automated EM image segmentation for neurite reconstruction. However, the efficiency and reliability of current methods are still lagging far behind human performance. Results: Here, we propose DeepEM3D, a deep learning method for segmenting 3D anisotropic brain electron microscopy images. In this method, the deep learning model can efficiently build feature representation and incorporate sufficient multi‐scale contextual information. We propose employing a combination of novel boundary map generation methods with optimized model ensembles to address the inherent challenges of segmenting anisotropic images. We evaluated our method by participating in the 3D segmentation of neurites in EM images (SNEMI3D) challenge. Our submission is ranked #1 on the current leaderboard as of Oct 15, 2016. More importantly, our result was very close to human‐level performance in terms of the challenge evaluation metric: namely, a Rand error of 0.06015 versus the human value of 0.05998. Availability and Implementation: The code is available at https://github.com/divelab/deepem3d/ Contact: sji@eecs.wsu. edu Supplementary information: Supplementary data are available at Bioinformatics online.
Relationships between excretion of steroid hormones and tryptophan metabolites in patients with breast cancer.

The growth and maintenance of the mammary gland requires both steroid and polypeptide hormones. Malignant growth in this tissue may also be hormonally dependent. As a consequence, the ablation of hormoneproducing organs, such as the pituitary and adrenal glands, may benefit about half the patients with advanced breast cancer after mastectomy. Not all patients respond to endocrine ablation, however, and methods are required for selecting the patients who are most likely to benefit. Since hormonal imbalance is an etiological feature of breast cancer, the selection of patients for adrenalectomy could be based on either measurement of hormone levels themselves or other biochemical parameters that reflect this change in hormonal status. Of the methods based on levels of endogenous hormones, the discriminant method (1) is the most widely used. The results obtained in a large prospective trial in Guernsey (Channel Islands) (2) indicate the discriminant is of prognostic value even before the disease is manifest. In the discriminant method, the hormonal imbalance is reflected in changes in urinary levels of 1 7-hydroxycorticosteroids and etiocholanolone. An alternate method uses the ratio of urinary 1 1-deoxy-1 7-oxosteroids (3). As sensitive metabolic changes may be apparent before significant alterations in hormonal levels can be measured, an attempt has been made to correlate the discriminant with possible biochemical indicators of hormonal imbalance. The choice of tryptophan metabolites for this purpose was prompted by the work of Rose (4, 5), who attributed the elevation of the excretion of tryptophan metabolites in breast cancer patients to a stimulation of hepatic catabolism by estrogens. In the work to be described, the discriminant, urinary steroid ratio, and the excretory pattern of tryptophan metabolites were measured concurrently in a large group of breast cancer patients and in normal women.
Evaluation of neon focused ion beam milling for TEM sample preparation

Gallium‐based focused ion beams generated from liquid–metal sources are widely used in micromachining and sample preparation for transmission electron microscopy, with well‐known drawbacks such as sample damage and contamination. In this work, an alternative (neon) focused ion beam generated by a gas field‐ionization source is evaluated for the preparation of electron‐transparent specimens. To do so, electron‐transparent sections of Si and an Al alloy are prepared with both Ga and Ne ion beams for direct comparison. Diffraction‐contrast imaging and energy dispersive x‐ray spectroscopy are used to evaluate the relative damage induced by the two beams, and cross‐sections of milled trenches are examined to compare the implantation depth with theoretical predictions from Monte Carlo simulations. Our results show that for the beam voltages and materials systems investigated, Ne ion beam milling does not significantly reduce the focused ion beam induced artefacts. However, the Ne ion beam does enable more precise milling and may be of interest in cases where Ga contamination cannot be tolerated.