Miracle-dz/UniFAR-FTUs huggingface dataset:
Power transduction of actin filaments ratcheting in vitro against a load

Significance How the continuous polymerization of actin filaments pushes the cell membrane forward in migrating cells is an intriguing issue that has yet to be fully understood. Molecular mechanisms were proposed, but testing them experimentally is a challenge, due to hardly accessible length scales and to the influence of regulatory proteins constantly changing the mechanical properties of polymerizing filaments. We present an experimental setup designed to minimize the number of parameters influencing filament growth to focus on the mechanism of force generation. We demonstrate that it is consistent with the Brownian ratchet model. Furthermore, we define a criterion for cell migration efficiency and quantify the number of filaments that need to push the membrane to maximize this efficiency. The actin cytoskeleton has the unique capability of producing pushing forces at the leading edge of motile cells without the implication of molecular motors. This phenomenon has been extensively studied theoretically, and molecular models, including the widely known Brownian ratchet, have been proposed. However, supporting experimental work is lacking, due in part to hardly accessible molecular length scales. We designed an experiment to directly probe the mechanism of force generation in a setup where a population of actin filaments grows against a load applied by magnetic microparticles. The filaments, arranged in stiff bundles by fascin, are constrained to point toward the applied load. In this protrusion-like geometry, we are able to directly measure the velocity of filament elongation and its dependence on force. Using numerical simulations, we provide evidence that our experimental data are consistent with a Brownian ratchet-based model. We further demonstrate the existence of a force regime far below stalling where the mechanical power transduced by the ratcheting filaments to the load is maximal. The actin machinery in migrating cells may tune the number of filaments at the leading edge to work in this force regime.
Long-term follow-up of co-administration of diltiazem and cyclosporine in Chinese kidney transplant recipients

Background: Co-administration of diltiazem and cyclosporine A (CsA) in kidney transplant recipients shows improvement of renal transplantation outcomes. Methods: We respectively analyzed 1531 kidney transplant recipients treated by different immunosuppressive therapy schemes from 1986 to 2003. They were divided into three groups depending on their immunosuppressive therapy schemes: control group with a standard triple therapy without use of diltiazem; study group I with the combination of diltiazem and the standard triple therapy but slightly low CsA; study group II with combination of diltiazem and a modified standard triple therapy but lower CsA. The CsA blood concentrations, posttransplant complications, and long-term survival in the three groups were compared. Results: The results showed that the patient and allograft survival in the study group II was 69.9 and 65.1%, respectively, significantly higher than that in the control group (50.7 and 47.6%). Occurrence of hepatotoxicity and nephrotoxicity episodes was higher in the control group than those in the study group I and the study group II. The incidence of acute rejection in the control group was 30.3% (23/76), similar to 28.0% (184/657) in study group I, but statistically significantly higher than 7.6% (61/798) in the study group II. Conclusion: Combination of diltiazem and CsA in the kidney allograft recipients tends to reduce the CsA oral dosage, improve patient survival, and decrease the occurrence of hepatotoxicity and nephrotoxicity.
Local Knowledge and Professional Background Have a Minimal Impact on Volunteer Citizen Science Performance in a Land-Cover Classification Task

The idea that closer things are more related than distant things, known as ‘Tobler’s first law of geography’, is fundamental to understanding many spatial processes. If this concept applies to volunteered geographic information (VGI), it could help to efficiently allocate tasks in citizen science campaigns and help to improve the overall quality of collected data. In this paper, we use classifications of satellite imagery by volunteers from around the world to test whether local familiarity with landscapes helps their performance. Our results show that volunteers identify cropland slightly better within their home country, and do slightly worse as a function of linear distance between their home and the location represented in an image. Volunteers with a professional background in remote sensing or land cover did no better than the general population at this task, but they did not show the decline with distance that was seen among other participants. Even in a landscape where pasture is easily confused for cropland, regional residents demonstrated no advantage. Where we did find evidence for local knowledge aiding classification performance, the realized impact of this effect was tiny. Rather, the inherent difficulty of a task is a much more important predictor of volunteer performance. These findings suggest that, at least for simple tasks, the geographical origin of VGI volunteers has little impact on their ability to complete image classifications.
l-Malyl-Coenzyme A Lyase/β-Methylmalyl-Coenzyme A Lyase from Chloroflexus aurantiacus, a Bifunctional Enzyme Involved in Autotrophic CO2 Fixation

ABSTRACT The 3-hydroxypropionate cycle is a bicyclic autotrophic CO2 fixation pathway in the phototrophic Chloroflexus aurantiacus (Bacteria), and a similar pathway is operating in autotrophic members of the Sulfolobaceae (Archaea). The proposed pathway involves in a first cycle the conversion of acetyl-coenzyme A (acetyl-CoA) and two bicarbonates to l-malyl-CoA via 3-hydroxypropionate and propionyl-CoA; l-malyl-CoA is cleaved by l-malyl-CoA lyase into acetyl-CoA and glyoxylate. In a second cycle, glyoxylate and another molecule of propionyl-CoA (derived from acetyl-CoA and bicarbonate) are condensed by a putative β-methylmalyl-CoA lyase to β-methylmalyl-CoA, which is converted to acetyl-CoA and pyruvate. The putative l-malyl-CoA lyase gene of C. aurantiacus was cloned and expressed in Escherichia coli, and the recombinant enzyme was purified and studied. β-Methylmalyl-CoA lyase was purified from cell extracts of C. aurantiacus and characterized. We show that these two enzymes are identical and that both enzymatic reactions are catalyzed by one single bifunctional enzyme, l-malyl-CoA lyase/β-methylmalyl-CoA lyase. Interestingly, this enzyme works with two different substrates in two different directions: in the first cycle of CO2 fixation, it cleaves l-malyl-CoA into acetyl-CoA and glyoxylate (lyase reaction), and in the second cycle it condenses glyoxylate with propionyl-CoA to β-methylmalyl-CoA (condensation reaction). The combination of forward and reverse directions of a reversible enzymatic reaction, using two different substrates, is rather uncommon and reduces the number of enzymes required in the pathway. In summary, l-malyl-CoA lyase/β-methylmalyl-CoA lyase catalyzes the interconversion of l-malyl-CoA plus propionyl-CoA to β-methylmalyl-CoA plus acetyl-CoA.
Reciprocal gene expression of osteoclastogenesis inhibitory factor and osteoclast differentiation factor regulates osteoclast formation.

Osteoblasts/stromal cells support the formation of osteoclast-like cells (OCL) from osteoclast progenitor cells via expressing a membrane-associated protein, osteoclast differentiation factor (ODF), in the presence of osteotropic factors, whereas the cells secrete a substantial amount of osteoclastogenesis inhibitory factor (OCIF) in the unstimulated state. There are both OCL formation-supporting and the nonsupporting cell lines in osteoblasts/stromal cell lineages. The mechanism that divides osteoblasts/stromal cell lines into the two types is not known. The present study reports that OCL formation-supporting cell line ST2 showed a greatly increased level of ODF mRNA, whereas their OCIF mRNA was drastically diminished in the presence of 1alpha, 25(OH)2-dihydroxyvitamin D3 or prostaglandin E2. In contrast, MC3T3-E1 cells lacking OCL formation-supporting ability did not show a decrease in OCIF mRNA in response to the factors, despite a similar increase in ODF mRNA as ST2 cells. However, inactivated MC3T3-E1 cells secreting nothing supported OCL formation in coculture with human promyelocytic cells, HL60. On the contrary, ST2 cells did not support OCL formation from HL60 cells when cocultured in medium conditioned by 1alpha, 25(OH)2 vitamin D3-treated MC3T3-E1. These findings indicate that reciprocal gene expression of ODF and OCIF in osteoblasts/stromal cells is essential for supporting OCL formation.
More is not always better: balancing sense distributions for all-words Word Sense Disambiguation

Current Word Sense Disambiguation systems show an extremely poor performance on low frequent senses, which is mainly caused by the difference in sense distributions between training and test data. The main focus in tackling this problem has been on acquiring more data or selecting a single predominant sense and not necessarily on the meta properties of the data itself. We demonstrate that these properties, such as the volume, provenance, and balancing, play an important role with respect to system performance. In this paper, we describe a set of experiments to analyze these meta properties in the framework of a state-of-the-art WSD system when evaluated on the SemEval-2013 English all-words dataset. We show that volume and provenance are indeed important, but that approximating the perfect balancing of the selected training data leads to an improvement of 21 points and exceeds state-of-the-art systems by 14 points while using only simple features. We therefore conclude that unsupervised acquisition of training data should be guided by strategies aimed at matching meta properties.
High-performance liquid chromatography method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug.

A high-performance liquid chromatography method was developed for determination of flunixin in bovine plasma. The extraction procedure was easily performed and made it possible to detect low concentrations of flunixin with high accuracy. The limit of quantitation was 7 ng/ml (relative standard deviation = 18% n = 10). The analytic method permits processing of 60 samples/d. Flunixin, as well as the internal standard (diclofenac sodium), belong to the group of nonsteroidal anti-inflammatory drugs, which are known to have a high degree of binding to plasma proteins. Therefore, an evaluation of several buffer systems was undertaken to optimize analytic conditions. Cattle were given 2.2 mg of flunixin melgumine/kg of body weight. In experiment 1, single injections were administered IV to 1 cow and IV and IM to 1 heifer (7 days apart), and pharmacokinetic variables were calculated. The IV data were best described by a two-compartment model. The half-life after single IV or IM administration was around 4.0 hours. In experiment 2, the decreasing flunixin concentration was determined after the last of either 4 IM injections daily (n = 3 cows) or 2 IM injections daily (n = 3 cows) administered during a 14-day postpartum period. The half-life, determined between 48 and 96 hours after the last dose, was approximately 26 hours in both groups, and flunixin could be detected in plasma up to 8 days, on average. The protein binding of flunixin was studied, using the method of equilibrium dialysis. (ABSTRACT TRUNCATED AT 250 WORDS)
Common‐ and multi‐offset ground‐penetrating radar study of a Roman villa, Tourega, Portugal

A ground‐penetrating radar (GPR) survey was conducted at the site of the first to fourth century AD Roman villa of Tourega, near Évora, Alentejo region, Portugal. This site has been partially excavated, revealing a bathhouse complex consisting of a tank reservoir, multiple bathing rooms and a major corridor. The excavated portion of Tourega provides direct archaeological feedback as to the size, shape, depth and orientation of structures revealed by GPR surveys. A 4500 m2 area surrounding the known site was surveyed using common‐offset 500 MHz and 200 MHz pseudo‐three‐dimensional acquisition. Amplitude time‐slice analysis reveals a large number of well‐defined additional structures confirming a much broader extension of the site. For shallow buried rectilinear structural targets, the high frequency 500 MHz common‐offset data provide excellent imaging. However, limited depth penetration at 500 MHz necessitated a lower frequency of investigation; therefore 200 MHz common‐ offset and multi‐offset data were also acquired. Two 200 MHz multi‐offset GPR profiles were obtained over the large double‐walled structure identified on the time‐slices, acquired using a newly proposed multi‐offset acquisition technique – rapid multi‐offset acquisition. This acquisition technique uses the existing single‐channel GPR system, is extremely cost‐effective, and easily acquires a high fold. Rapid multi‐offset acquisition provides an average time saving up to five times that of stationary multi‐offset profiling. The 200 MHz multi‐offset profiles provide a greater depth penetration and enhanced structural detail (i.e. improved imaging of dipping structures) than comparable 200 MHz common‐offset profiles. Post‐stack, inverse‐Q filtering increases vertical resolution and interpretability of the multi‐offset sections via removal of wavelet dispersion. Although multi‐offset data are less feasible for characterizing this site in three dimensions because of the large time commitment in data collection, two multi‐offset profiles over key structures of interest improved the final site interpretation, with enhanced image quality and higher resolution than comparable common‐offset profiles. The combined results of the multi‐offset survey with a common‐offset grid should encourage a more frequent use of multi‐offset data at archaeological sites when the depth extent of the archaeological site is uncertain. Copyright © 2007 John Wiley & Sons, Ltd.
Sex hormones, inflammation and the metabolic syndrome: a population-based study.

OBJECTIVE Mild hypoandrogenism in men is associated with features of the metabolic syndrome, but the association with the metabolic syndrome itself using an accepted definition has not been described. DESIGN Men with the metabolic syndrome were identified and testosterone and sex hormone-binding globulin (SHBG) levels were determined in a population-based cohort of 1896 non-diabetic middle-aged Finnish men. RESULTS Calculated free testosterone and SHBG were 11% and 18% lower (P<0.001) in men with the metabolic syndrome (n=345, World Health Organisation definition). After categorisation by tertiles and adjusting for age and body mass index, total and free testosterone and SHBG were inversely associated with concentrations of insulin, glucose, triglycerides, C-reactive protein (CRP) and CRP-adjusted ferritin and positively associated with high-density lipoprotein cholesterol. Men with free testosterone levels in the lowest third were 2.7 (95% confidence interval (CI) 2.0-3.7) times more likely to have the metabolic syndrome in age-adjusted analyses, and 1.7 (95% CI 1.2-2.4) times more likely even after further adjusting for body mass index. Exclusion of men with cardiovascular disease did not alter the association. The inverse association of SHBG with the metabolic syndrome was somewhat stronger. CONCLUSIONS Low testosterone and SHBG levels were strongly associated not only with components of the metabolic syndrome, but also with the metabolic syndrome itself, independently of body mass index. Furthermore, sex hormones were associated with inflammation and body iron stores. Even in the absence of late-stage consequences such as diabetes and cardiovascular disease, subtle derangements in sex hormones are present in the metabolic syndrome, and may contribute to its pathogenesis.
Effect of flow and stretch on the [Ca2+]i response of principal and intercalated cells in cortical collecting duct.

An acute increase in tubular fluid flow rate in the microperfused cortical collecting duct (CCD), associated with a approximately 20% increase in tubular diameter, leads to an increase in intracellular Ca2+ concentration ([Ca2+]i)in both principal and intercalated cells (Woda CB, Leite M Jr, Rohatgi R, and Satlin LM. Am J Physiol Renal Physiol 283: F437-F446, 2002). The apical cilium present in principal but not intercalated cells has been proposed to be a flow sensor. To determine whether flow across the cilium and/or epithelial stretch mediates the [Ca2+]i response, CCDs from New Zealand White rabbits were microperfused in vitro, split-open (to isolate the effect of flow across cilia), or occluded (to examine the effect of stretch and duration/magnitude of the flow impulse), and [Ca2+]i was measured using fura 2. In perfused and occluded CCDs, a rapid (<1 s) but not slow (>3 min) increase in luminal flow rate and/or circumferential stretch led to an approximately threefold increase in [Ca2+]i in both principal and intercalated cells within approximately 10 s. This response was mediated by external Ca2+ entry and inositol 1,4,5-trisphosphate-mediated release of cell Ca2+ stores. In split-open CCDs, an increase in superfusate flow led to an approximately twofold increase in [Ca2+]i in both cell types within approximately 30 s. These experimental findings are interpreted using mathematical models to predict the fluid stress on the apical membranes of the CCD and the forces and torques on and deformation of the cilia. We conclude that rapid increases in luminal flow rate and circumferential stretch, leading to shear or hydrodynamic impulses at the cilium or apical membrane, lead to increases in [Ca2+]i in both principal and intercalated cells.
High levels of parasite-specific IgG1 correlate with the amicrofilaremic state in Loa loa infection.

To investigate the mechanisms of protective immunity operating in Loa loa infection, 56 persons from a L. ioa-endemic village in southeast Gabon were examined over a 7-year period. The level of L. loa-specific IgG subclasses in defined parasitologic groups was compared by use of ELISA with either adult, microfilarial, or third-stage larval (L3) antigens of L. loa. With all antigen preparations, IgG1 levels were significantly higher in amicrofilaremic persons than in persons with high or low levels of microfilariae. Moreover, there was a significant negative correlation between IgG1 levels to L3 antigen and the density of microfilariae (Spearman's r(s) = -. 701; P < . 01). There was no correlation between density of microfilariae and levels of other IgG subclasses or of IgE. These data indicate that IgG1 may play a role in the effector mechanism(s) involved in resistance against L. loa and suggest that L3 antigens may be important in eliciting protective responses.
Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a population-based study of Canadian patients.

UNLABELLED Breast cancer is heterogenous, with variable expression of the estrogen receptor (er), progesterone receptor (pr), and human epidermal growth factor receptor 2 (her2). Overexpression of her2 is generally considered a negative prognostic feature, but whether outcomes for her2-positive early breast cancer remain different from those for other subtypes in the era of trastuzumab-based adjuvant therapy is unknown. METHODS Using a retrospective chart review, we compared overall survival (os) and relapse-free survival (rfs) in 3 groups of patients with early-stage breast cancer: er-positive or pr-positive (or both) and her2-negative ["hormone receptor-positive" (hr+)]; her2-positive (her2+); and er-negative, pr-negative, and her2-negative ["triple-negative" (tn)]. RESULTS In the 503 charts analyzed (332 hr+, 94 her2+, 77 tn), the 5-year os and rfs were, respectively, 94.2% and 87.2% for hr+ patients, 88.6% and 74.9% for her2+ patients, and 85.4% and 76.2% for tn patients. On multivariate analysis, the os for the her2+ subtype was similar to that for the hr+ subtype (hazard ratio:1.07; 95% confidence interval: 0.31 to 3.67 with hr+ as reference), but os was significantly worse for tn patients than for hr+ patients (hazard ratio: 4.37; 95% confidence interval: 1.56 to 12.24). In her2+ patients, the 5-year os and rfs trended better for patients with er+ or pr+ disease than for patients with er-negative and pr-negative disease (5-year os: 92.1% vs. 86.9%; 5-year rfs: 79.8% vs. 71.4%). Of her2+ patients, just 80.9% received trastuzumab, including 33.3% of her2+ patients with sub-centimetre tumours. CONCLUSIONS In the trastuzumab era, patients with her2+ and hr+ early breast cancer have similar outcomes, while tn patients experience a significantly worse os than either of the foregoing groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab was underutilized in this cohort.
The 2dF-SDSS LRG and QSO Survey: evolution of the clustering of luminous red galaxies since z= 0.6

We present an analysis of the small-to-intermediate scale clustering of samples of luminous red galaxies (LRGs) from the Sloan Digital Sky Survey (SDSS) and the 2dF-SDSS LRG and QSO Survey (2SLAQ) survey carefully matched to have the same rest-frame colours and luminosity. We study the spatial two-point autocorrelation function in both redshift space [xi(s)] and real space [xi(r)] of a combined sample of over 10 000 LRGs, which represent the most massive galaxies in the universe with stellar masses > 10(11) h(-1) M-circle dot and space densities similar or equal to 10(-4) h(3) Mpc(-3). We find no significant evolution in the amplitude (r(0)) of the correlation function with redshift, but do see a slight decrease in the slope (gamma) with increasing redshift over 0.19 99.9 per cent significance) with a passive model whereby the LRGs do not merge with one another; a model with a merger rate of 7.5 +/- 2.3 per cent from z = 0.55 to 0.19 (i.e. an average rate of 2.4 per cent Gyr(-1)) provides a better fit to our observations. Our clustering and number density measurements are consistent with the hypothesis that the merged LRGs were originally central galaxies in different haloes which, following the merger of these haloes, merged to create a single brightest cluster galaxy. In addition, we show that the small-scale clustering signal constrains the scatter in halo merger histories. When combined with measurements of the luminosity function, our results suggest that this scatter is sub-Poisson. While this is a generic prediction of hierarchical models, it has not been tested before.