Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylated DNA and Total DNA in Serum Detected by One-Step Methylation-Specific PCR Is Predictive of Poor Prognosis for Breast Cancer Patients

Purpose: We recently developed the one-step methylation-specific PCR (OS-MSP) assay which can detect methylated DNA (met-DNA) in serum with high sensitivity. To examine its prognostic value, we applied this new assay to the detection of met-DNA in serum of breast cancer patients. Methods: Serum samples taken before surgery from 336 primary invasive breast cancer patients were subjected to the OS-MSP assay for the promoter regions of GSTP1, RASSF1A, and RARβ2. The assay outcome was considered positive when methylation was detected in at least one of these three genes. Total DNA content in serum was also determined. Results: Of the 336 stage I/II patients, 33 (10%) were positive for met-DNA in serum and showed a significantly worse overall survival (OS) rate at 100 months (78 vs. 95%; p = 0.002) than those with negative findings (n = 303). Patients with high total DNA in serum (n = 112) also showed a significantly worse OS rate at 100 months (86 vs. 97%; p = 0.001) than those with low total DNA in serum (n = 224). Moreover, patients both positive for met-DNA and with high total DNA in serum (n = 18) showed a much worse OS rate at 100 months (65 vs. 94%; p < 0.001) than the others (n = 318). Conclusions: Met-DNA in serum detected with the OS-MSP assay constitutes a significant and independent prognostic factor, and its combination with total DNA in serum seems to be even more effective for prediction of prognosis for breast cancer patients.
Petrogenesis of the Back-arc East Scotia Ridge, South Atlantic Ocean

The East Scotia Ridge is an active back-arc spreading centre located to the west of the South Sandwich island arc in the South Atlantic Ocean, consisting of nine main segments, E1 (north) to E9 (south). Major and trace element and Sr–Nd–Pb isotope compositions are presented, together with water contents, for lavas sampled along the active ridge axis. Magmatism along the East Scotia Ridge is chemically heterogeneous, but there is a common mid-ocean ridge basalt (MORB)-type source component for all the magmas. An almost unmodified MORB-source mantle appears to underlie the central part of the back-arc. Subduction components are found at the northern and southern ends of the ridge, and there is a marked sediment melt input of up to 2% in segment E4. Enriched (plume) mantle is present beneath segment E2 at the northern end of the ridge, suggesting that plume mantle is flowing westward around the edges of the subducting slab. The southern part of segment E8 is unique in that its magma source is similar to sub-arc depleted mantle.
Fast Source Location Method Using Anti-reverberant Searching Space Pre-estimation

Source location attracts more attentions in speech communication systems. Multiple signal classification (MUSIC) and time difference of arrival (TDOA) based location methods are two kinds of source localization techniques. However, MUSIC requires a search of whole region of interest (ROI), which is supposed to be computationally expensive. For another, the location accuracy of second group is restricted by the sampling rate of microphones. This paper proposes a new location method which greatly reduce the calculation of steering vector of MUSIC using efficient TDOA preestimate, while still remain super resolution feature of spectral estimation method. Our simulation manifest that such algorithm is efficient both in anechoic chamber and in meeting room. Additionally, the reliable area derived by robust TDOA estimation method will partially improve the location performance of MUSIC algorithm under reverberant and noisy environment
Sleep Monitoring Through a Textile Recording System

In this paper, we present a home device for the continuous monitoring of sleep and investigate its reliability regarding sleep evaluation. The system has been particularly designed for healthy people and for preventive purposes. It is not obtrusive and therefore can be used every night without impeding sleep in itself and without interfering with the normal way of life. The signal used for sleep evaluation is the HRV derived from the ECG recorded by means of a sheet and a pillow. Patients in a sleep lab and healthy subjects at home were monitored during sleep with the textile system, while also standard ECG and respiration were recorded. For the textile ECG sensor, coverage of the signal on a beat-to-beat basis ranged from 47,9 - 95,8% of the overall night for the healthy subjects, with a mean coverage of 81,8%. In the group of sleep laboratory patients, the mean coverage was lower - 64,4% - although even in this group the coverage of a single night ranged up to 98.4%. After frequency analysis, the spectral parameters used for sleep staging and derived at the same time from standard and textile ECG signals were compared. The trends along the night are very similar, indicating the possibility of using textile HRV for sleep evaluation.
31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients

Background: Differences in brain energy metabolism have been found between migraine patients and controls in previous phosphorus magnetic resonance spectroscopy (31P-MRS) studies, most of them emphasizing migraine with aura (MwA). The aim of this study was to verify potential changes in resting-state brain energy metabolism in patients with migraine without aura (MwoA) compared to control subjects by 31P-MRS at 3 tesla. Methods: Quantification was performed using the phantom replacement technique. MRS measurements were performed interictally and in the medial occipital lobe of 19 MwoA patients and 26 age-matched controls. Results: A significantly decreased phosphocreatine concentration ([PCr]) was found as in previous studies. While adenosine triphosphate concentration ([ATP]) was considered to be constant in previously published work, this study found a significant decrease in the measured [ATP] in MwoA patients. The inorganic phosphate ([Pi]) and magnesium ([Mg2+]) concentrations were not significantly different between MwoA patients and controls. Conclusions: The altered metabolic concentrations indicate that the energy metabolism in MwoA patients is impaired, certainly in a subgroup of patients. The actual decrease in [ATP] adds further strength to the theory of the presence of a mitochondrial component in the pathophysiology of migraine.
Association analysis of brain‐derived neurotrophic factor gene polymorphisms in asthmatic children

Brain‐derived neurotrophic factor (BDNF) has been described to modulate airway hyper‐responsiveness and inflammation and was involved in late allergic reaction in asthma and higher levels of circulating BDNF were present in allergic asthmatics. In BDNF gene, Val66Met and C‐270T polymorphisms were described. There were, however, very few studies analyzing BDNF gene polymorphisms in asthma. The aim of this study was to analyze the possible relationship between these two polymorphisms in the BDNF gene and asthma. Fifty‐six pediatric asthmatic patients were analyzed, aged from 6 to 18. The diagnosis of atopic asthma was based on clinical manifestation, lung function test and increased immunoglobulin E level, and/or positive skin prick tests. The control group consisted of 109 healthy subjects. The polymorphisms were genotyped with the use of polymerase chain reaction–restriction fragment length polymorphism method. We did not observe an association of Val/Met polymorphism and the presence of asthma. However, we observed that Val allele is much more frequent in the male group of asthmatic patients (p = 0.06). For −270C/T polymorphism, we found significant differences between asthmatic patients and the control group (p = 0.041 for genotypes and p = 0.005 for alleles). The results may suggest a relationship between the BDNF gene and asthma and male gender of asthmatic children.
In Vitro Age-Dependent Enzymatic Metabolism of Chlorpyrifos and Chlorpyrifos-Oxon in Human Hepatic Microsomes and Chlorpyrifos-Oxon in Plasma

Age-dependent chlorpyrifos (CPF) metabolism was quantified by in vitro product formation in human hepatic microsomes (ages 13 days to 75 years) and plasma (ages 3 days to 43 years) with gas chromatography-mass spectrometry. Hepatic CPF cytochrome P450 desulfuration [CPF to chlorpyrifos-oxon (CPF-oxon)] and dearylation (CPF to 3,5,6-trichloro-2-pyridinol) Vmax values were 0.35 ± 0.21 and 0.73 ± 0.38 nmol · min−1 · mg microsomal protein −1 (mean ± S.D.), respectively. The mean (±S.D.) hepatic CPF-oxon hydrolysis (chlorpyrifos-oxonase [CPFOase]) Vmax was 78 ± 44 nmol · min−1 · mg microsomal protein −1. None of these hepatic measures demonstrated age-dependent relationships on a per microsomal protein basis using linear regression models. Ratios of CPF bioactivation to detoxification (CPF desulfuration to dearylation) Vmax values were consistent across ages. CPFOase in plasma demonstrated age-dependent increases on a volume of plasma basis, as did total plasma protein levels. Mean (±S.D.) CPF-oxon hydrolysis Vmax values for children <6 months of age and adults (≥16 years) were 1900 ± 660 and 6800 ± 1600 nmol · min−1 · ml−1, respectively, and at environmental exposure levels, this high- capacity enzyme is likely to be sufficient even in infants. Plasma samples were phenotyped for paraoxonase status, and frequencies were 0.5, 0.4, and 0.1 for QQ, QR, and RR phenotypes, respectively. These results will be integrated into a physiologically based pharmacokinetic and pharmacodynamic model for CPF and, once integrated, will be useful for assessing biological response to CPF exposures across life stages.
Improved protein refolding using hollow-fibre membrane dialysis.

We have used a cellulose acetate, hollow-fibre (HF) ultrafiltration membrane to refold bovine carbonic anhydrase, loaded into the lumen space, by removing the denaturant through controlled dialysis via the shell side space. When challenged with GdnHCl-denatured carbonic anhydrase, 70% of the loaded protein reptated through the membrane into the circulating dialysis buffer. Reptation occurred because the protein, in its fully unfolded configuration, was able to pass through the pores. The loss of carbonic anhydrase through the membrane was controlled by the dialysis conditions. Dialysis against 0.05 M Tris-HCl for 30 min reduced the denaturant around the protein to a concentration that allowed the return of secondary structure, increasing the hydrodynamic radius, thus preventing protein transmission. Under these conditions a maximum of 42% of carbonic anhydrase was recovered (from a starting concentration of 5 mg/mL) with 94% activity. This is an improvement over refolding carbonic anhydrase by simple batch dilution, which gave a maximum reactivation of 85% with 35% soluble protein yield. The batch refolding of carbonic anhydrase is very sensitive to temperature; however, during HF refolding between 0 and 25 degrees C the temperature sensitivity was considerably reduced. In order to reduce the convection forces that give rise to aggregation and promote refolding the dialyzate was slowly heated from 4 to 25 degrees C. This slow, temperature-controlled refolding gave an improved soluble protein recovery of 55% with a reactivation yield of 90%. The effect of a number of additives on the refolding system performance were tested: the presence of PEG improved both the protein recovery and the recovered activity from the membrane, while the detergents Tween 20 and IGEPAL CA-630 increased only the refolding yield.
Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex

Significance Despite the high antigenic diversity of the HIV envelope trimer (Env), broadly neutralizing antibodies (bnAbs) have identified conserved regions that serve as targets for vaccine design. One of these regions is located at the apex of Env and is expressed fully only in the context of the correctly folded trimer. This work describes the isolation of bnAbs that target this region using a recombinant native-like Env trimer as an affinity reagent to sort specific antibody-producing cells. Characterization of these antibodies reveals a highly diverse antibody response against the trimer apex and provides molecular information that will be useful in the design of immunogens to elicit bnAbs to this region of Env. Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named “PGDM1400–1412,” show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 µg/mL. Overall, our results highlight the utility of BG505 SOSIP.664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.
Effects of gamma irradiation on resistivity and absorption currents in nanocomposites based on thermoplastic polymers

The functional characteristics depend strongly on the chemical structure of polymer and on the formulation of material, as well. In the present work, the effects of gamma irradiation at different doses on the resistivity and on the absorption currents in nanocomposites of thermoplastic polymers, such as low density polyethylene (LDPE), polypropylene (PP) and ethylene-propylene-diene monomer rubber (EPDM) are analysed. The influences of the polymer structure as host matrix (LDPE, PP, EPDM) and nano SiO2 concentration (between 2 and 5 wt.%) on electrical features are discussed. A correlation between electrical and thermal properties is illustrated for all formulations.
Supplementation with vitamins C and E inhibits the release of interleukin‐6 from contracting human skeletal muscle

Contracting human skeletal muscle is a major contributor to the exercise‐induced increase of plasma interleukin‐6 (IL‐6). Although antioxidants have been shown to attenuate the exercise‐induced increase of plasma IL‐6, it is unknown whether antioxidants inhibit transcription, translation or translocation of IL‐6 within contracting human skeletal muscle. Using a single‐blind placebo‐controlled design with randomization, young healthy men received an oral supplementation with either a combination of ascorbic acid (500 mg day−1) and RRR‐α‐tocopherol (400 i.u. day−1) (Treatment, n= 7), or placebo (Control, n= 7). After 28 days of supplementation, the subjects performed 3 h of dynamic two‐legged knee‐extensor exercise at 50% of their individual maximal power output. Muscle biopsies from vastus lateralis were obtained at rest (0 h), immediately post exercise (3 h) and after 3 h of recovery (6 h). Leg blood flow was measured using Doppler ultrasonography. Plasma IL‐6 concentration was measured in blood sampled from the femoral artery and vein. The net release of IL‐6 was calculated using Fick's principle. Plasma vitamin C and E concentrations were elevated in Treatment compared to Control. Plasma 8‐iso‐prostaglandin F2α, a marker of lipid peroxidation, increased in response to exercise in Control, but not in Treatment. In both Control and Treatment, skeletal muscle IL‐6 mRNA and protein levels increased between 0 and 3 h. In contrast, the net release of IL‐6 from the leg, which increased during exercise with a peak at 3.5 h in Control, was completely blunted during exercise in Treatment. The arterial plasma IL‐6 concentration from 3 to 4 h, when the arterial IL‐6 levels peaked in both groups, was ∼50% lower in the Treatment group compared to Control (Treatment versus Control: 7.9 pg ml−1, 95% confidence interval (CI) 6.0–10.7 pg ml−1, versus 19.7 pg ml−1, CI 13.8–29.4 pg ml−1, at 3.5 h, P < 0.05 between groups). Moreover, plasma interleukin‐1 receptor antagonist (IL‐1ra), C‐reactive protein and cortisol levels all increased after the exercise in Control, but not in Treatment. In conclusion, our results show that supplementation with vitamins C and E attenuated the systemic IL‐6 response to exercise primarily via inhibition of the IL‐6 protein release from the contracting skeletal muscle per se.
Nanotube-Mode-Locked Fiber Laser Delivering Dispersion-Managed or Dissipative Solitons

We have proposed a bidirectional erbium-doped fiber laser delivering dispersion-managed soliton (DMS) or dissipative soliton (DS) based on a single-wall carbon nanotube mode-locker. In the proposed scheme, the net cavity dispersion approaches to zero in the counter-clockwise (CCW) direction while is normal in the clockwise (CW) direction. By properly adjusting the intracavity attenuators, DMS in the CCW direction and DS in the CW direction can be obtained, respectively. However, attributing to the cavity asymmetry between CCW and CW directions, simultaneous generation of DMS and DS is not achieved. Although the output DMS and DS almost have the same central wavelength, they exhibit distinct optical spectra, pulse durations, and repetition rates. The switchable all-fiber laser delivers two different types of ultra-short pulses, which significantly facilitates the practical applications.
Masc2, a gene from Ascobolus encoding a protein with a DNA‐methyltransferase activity in vitro, is dispensable for in vivo methylation

We have shown previously that masc1, a gene encoding a putative C5‐DNA‐methyltransferase (MTase), was necessary for the de novo‘Methylation Induced Premeiotically’ (MIP) process and sexual reproduction in Ascobolus, whereas it was dispensable for maintenance methylation. A second MTase gene from Ascobolus, masc2, encodes a protein, Masc2, which possesses the large amino‐terminal part characteristic of eukaryotic maintenance MTases. In vitro assays have shown that Masc2 displays a methylation activity, suggesting that it might be the MTase responsible for maintenance methylation. To check its function in vivo, we engineered a disruption of the masc2 gene. The resulting mutant strains did not exhibit any particular phenotype during either vegetative growth or sexual reproduction. Neither the masc2 mutation nor the double masc1 masc2 mutation had any detectable effect upon the maintenance of the pre‐existing methylation of single gene copies previously subjected to MIP, natural retroelement‐like repeats and tandemly repeated rDNA. The masc2 mutation did not alter either MIP or the other de novo methylation process that operates in vegetative cells. Nor did it impair the meiotic process of methylation transfer. These results suggest that at least a third MTase gene responsible for maintenance and vegetative de novo methylation is present in Ascobolus.
Product market integration in the Euro area

The goal of this paper is to determine if the euro area (EA) accession and membership had a significant impact on the product market integration in the EA countries. The paper employs LM and RALS-LM unit root tests with two breaks on the seasonally adjusted monthly Harmonized Index of Consumer Prices (HICP), from 1996:01 to 2017:05. We find EA-accession related breaks in most of the EA11 countries, but, apart from Malta, no such breaks for the later-EA-joiners. However, EA formation had a significant impact on both EA and non-EA countries at that time. We also find greater product market integration and less adverse effects after negative shocks in the EA member countries. However, based on unit root analysis, we find that EA membership in not a sufficient condition for product market integration and integration is not necessarily related to being an EA member.
A Case-Control Study of Colorectal Adenomatous Polyps and Consumption of Foods Containing Partially Hydrogenated Oils 1

The trans fatty acids produced by partially hydrogenating vegetable oils may cause colorectal neoplasia by interfering with cell membrane function or eicosanoid synthesis. This possibility provides a rationale for looking at the relation between colorectal adenomatous polyps and consumption of foods containing partially hydrogenated vegetable oils (PHVOs). A total of 516 cases and 551 controls who underwent screening sigmoidoscopy from 1991–1993 were recruited from a prepaid Los Angeles health plan. Subjects were interviewed and given a self-administered food frequency questionnaire. Food items containing PHVOs were divided into four groups characterized by principal ingredients and preparation methods: sweetened baked goods, candy bars, oils and condiments, and french fries and chips. After adjusting for age, sex, physical activity, body mass index, smoking, total energy, and red meat and vegetable intake, there was a positive association between polyps and sweetened baked goods [350 1 versus <50 kcal/day (odds ratio, 2.1; 95% confidence interval, 1.3–3.5)]. No association was found with the other food groups after adjustment for dietary and nondietary covariates. Neither was total dietarytrans fatty acid associated with adenomas after adjustment for sweetened baked goods and other covariates. These results do not support the hypothesis that eating foods containing PHVOs increases the risk of colorectal adenomas, but they are consistent with the hypothesis that foods high in fat and sugar and low in fiber and correlated micronutrients increase the risk of adenomas.
Proarrhythmic Effects of Aldosterone During Myocardial Ischemia–Reperfusion: Implication of the Sarcolemmal-KATP Channels

Objective: To assess the electrophysiological impact of aldosterone during myocardial ischemia–reperfusion. Methods: We used an in vitro model of “border zone” using rabbit right ventricle and standard microelectrodes. Results: Aldosterone (10 and 100 nmol/L) shortened ischemic action potential [action potential duration at 90% of repolarization (APD90), from 55 ± 3 to 39 ± 1 ms and 36 ± 3 ms, respectively, P < 0.05] and induced resting membrane potential (RMP) hyperpolarization in the nonischemic zone (from −83 ± 1 to −93 ± 7 mV and −94 ± 3 mV, respectively, P < 0.05) and in the ischemic zone during reperfusion (from −81 ± 2 to −88 ± 2 mV and −91 ± 2 mV, respectively, P < 0.05). Bimakalim, an ATP-sensitive potassium (KATP) channel opener, also induced RMP hyperpolarization and APD90 shortening. Aldosterone (10 and 100 nmol/L) increased APD90 dispersion between ischemic and nonischemic zones (from 96 ± 3 to 117 ± 5 ms and 131 ± 6 ms, respectively, P < 0.05) and reperfusion-induced severe premature ventricular contraction occurrence (from 18% to 67% and 75%, respectively, P < 0.05). Adding glibenclamide, a nonspecific KATP antagonist, to aldosterone superfusion abolished these effects different to sodium 5-hydroxydecanoate, a mitochondrial-KATP antagonist. Conclusions: In this in vitro rabbit model of border zone, aldosterone induced RMP hyperpolarization and decreased ischemic APD90 evoking the modulation of K+ currents. Glibenclamide prevented these effects different to 5-hydroxydecanoate, suggesting that sarcolemmal-KATP channels may be involved in this context.