Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre‐ and Post‐Natal Stress Programming: Developmental Exposure to Glucocorticoids Causes Long‐Term Brain‐Region Specific Changes to Transcriptome in the Precocial Japanese Quail

Exposure to stress during early development can permanently influence an individual's physiology and behaviour, and affect its subsequent health. The extent to which elevated glucocorticoids cause such long‐term ‘programming’ remains largely untested. In the present study, using the Japanese quail as our study species, we independently manipulated exposure to corticosterone during pre‐ and/or post‐natal development and investigated the subsequent effects on global gene expression profiles within the hippocampus and hypothalamus upon achieving adulthood. Our results showed that the changes in transcriptome profiles in response to corticosterone exposure clearly differed between the hippocampus and the hypothalamus. We also showed that these effects depended on the developmental timing of exposure and identified brain‐region specific gene expression patterns that were either: (i) similarly altered by corticosterone regardless of the developmental stage in which hormonal exposure occurred or (ii) specifically and uniquely altered by either pre‐natal or post‐natal exposure to corticosterone. Corticosterone‐treated birds showed alterations in networks of genes that included known markers of the programming actions of early‐life adversity (e.g. brain‐derived neurotrophic factor and mineralocorticoid receptor within the hippocampus; corticotrophin‐releasing hormone and serotonin receptors in the hypothalamus). Altogether, for the first time, these findings provide experimental support for the hypothesis that exposure to elevated glucocorticoids during development may be a key hormonal signalling pathway through which the long‐term phenotypic effects associated with early‐life adversity emerge and potentially persist throughout the lifespan. These data also highlight that stressors might have different long‐lasting impacts on the brain transcriptome depending on the developmental stage in which they are experienced; more work is now required to relate these mechanisms to organismal phenotypic differences.
Transcriptome-Wide Mapping of 5-methylcytidine RNA Modifications in Bacteria, Archaea, and Yeast Reveals m5C within Archaeal mRNAs

The presence of 5-methylcytidine (m5C) in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago. However, detection of this modification was limited to specific, abundant, RNA species, due to the usage of low-throughput methods. To obtain a high resolution, systematic, and comprehensive transcriptome-wide overview of m5C across the three domains of life, we used bisulfite treatment on total RNA from both gram positive (B. subtilis) and gram negative (E. coli) bacteria, an archaeon (S. solfataricus) and a eukaryote (S. cerevisiae), followed by massively parallel sequencing. We were able to recover most previously documented m5C sites on rRNA in the four organisms, and identified several novel sites in yeast and archaeal rRNAs. Our analyses also allowed quantification of methylated m5C positions in 64 tRNAs in yeast and archaea, revealing stoichiometric differences between the methylation patterns of these organisms. Molecules of tRNAs in which m5C was absent were also discovered. Intriguingly, we detected m5C sites within archaeal mRNAs, and identified a consensus motif of AUCGANGU that directs methylation in S. solfataricus. Our results, which were validated using m5C-specific RNA immunoprecipitation, provide the first evidence for mRNA modifications in archaea, suggesting that this mode of post-transcriptional regulation extends beyond the eukaryotic domain.
Stochastic Zeroth-order Optimization in High Dimensions

We consider the problem of optimizing a high-dimensional convex function using stochastic zeroth-order queries. Under sparsity assumptions on the gradients or function values, we present two algorithms: a successive component/feature selection algorithm and a noisy mirror descent algorithm using Lasso gradient estimates, and show that both algorithms have convergence rates that de- pend only logarithmically on the ambient dimension of the problem. Empirical results confirm our theoretical findings and show that the algorithms we design outperform classical zeroth-order optimization methods in the high-dimensional setting.
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus‐Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis

A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA).
Adaptive RBFNN control of robot manipulators with finite-time convergence

In this paper, the position tracking control with finite-time convergence has been studied for a class of nonlinear uncertain robot manipulators. Radial basis function neural network (RBFNN) based adaptive control is designed to compensate for the effect of the unknown dynamics. To achieve the finite-time convergence of both trajectory tracking error and RBFNN learning error, barrier Lyapunov functions (BLFs) and and filtering techniques are employed to design a performance function and a tracking error region to ensure position tracking error converge to a pair of specified bounds in a finite time. The effectiveness and efficiency of the proposed control method is tested and verified by simulation studies.
Metabolomic analysis of alterations in lipid oxidation, carbohydrate and amino acid metabolism in dairy goats caused by exposure to Aflotoxin B1

The purposes of this study were to investigate the systemic and characteristic metabolites in the serum of dairy goats induced by aflatoxin B1 (AFB1) exposure and to further understand the endogenous metabolic alterations induced by it. A nuclear magnetic resonance (NMR)-based metabonomic approach was used to analyse the metabolic alterations in dairy goats that were induced by low doses of AFB1 (50 µg/kg DM). We found that AFB1 exposure caused significant elevations of glucose, citrate, acetate, acetoacetate, betaine, and glycine yet caused reductions of lactate, ketone bodies (acetate, β-hydroxybutyrate), amino acids (citrulline, leucine/isoleucine, valine, creatine) and cell membrane structures (choline, lipoprotein, N-acetyl glycoproteins) in the serum. These data indicated that AFB1 caused endogenous metabolic changes in various metabolic pathways, including cell membrane-associated metabolism, the tricarboxylic acid cycle, glycolysis, lipids, and amino acid metabolism. These findings provide both a comprehensive insight into the metabolic aspects of AFB1-induced adverse effects on dairy goats and a method for monitoring dairy animals exposed to low doses of AFB1.
3D modeling of historic sites using range and image data

Preserving cultural heritage and historic sites is an important problem. These sites are subject to erosion, vandalism, and as long-lived artifacts, they have gone through many phases of construction, damage and repair. It is important to keep an accurate record of these sites using 3-D model building technology as they currently are, so preservationists can track changes, foresee structural problems, and allow a wider audience to "virtually" see and tour these sites. Due to the complexity of these sites, building 3-D models is time consuming and difficult, usually involving much manual effort. This paper discusses new methods that can reduce the time to build a model using automatic methods. Examples of these methods are shown in reconstructing a model of the Cathedral of Ste. Pierre in Beauvais, France.
Bearing fault detection of induction motor using SWPT and DAG support vector machines

Bearings are considered as a critical component in Induction Motors (IM). An approach based on Motor current Signature analysis (MCSA) is presented to detect bearing faults (BF). This study is subject for a novel pattern recognition approach for BF detection in IM combining Stationary Wavelet Packet Transform (SWPT) and DAG SVM. Four bearing conditions are tested. As results, it is shown that the proposed approach permits to distinguish with full accuracy different bearing conditions regardless the load level.
Designing Equitable Antiretroviral Allocation Strategies in Resource-Constrained Countries

Background Recently, a global commitment has been made to expand access to antiretrovirals (ARVs) in the developing world. However, in many resource-constrained countries the number of individuals infected with HIV in need of treatment will far exceed the supply of ARVs, and only a limited number of health-care facilities (HCFs) will be available for ARV distribution. Deciding how to allocate the limited supply of ARVs among HCFs will be extremely difficult. Resource allocation decisions can be made on the basis of many epidemiological, ethical, or preferential treatment priority criteria. Methods and Findings Here we use operations research techniques, and we show how to determine the optimal strategy for allocating ARVs among HCFs in order to satisfy the equitable criterion that each individual infected with HIV has an equal chance of receiving ARVs. We present a novel spatial mathematical model that includes heterogeneity in treatment accessibility. We show how to use our theoretical framework, in conjunction with an equity objective function, to determine an optimal equitable allocation strategy (OEAS) for ARVs in resource-constrained regions. Our equity objective function enables us to apply the egalitarian principle of equity with respect to access to health care. We use data from the detailed ARV rollout plan designed by the government of South Africa to determine an OEAS for the province of KwaZulu–Natal. We determine the OEAS for KwaZulu–Natal, and we then compare this OEAS with two other ARV allocation strategies: (i) allocating ARVs only to Durban (the largest urban city in KwaZulu–Natal province) and (ii) allocating ARVs equally to all available HCFs. In addition, we compare the OEAS to the current allocation plan of the South African government (which is based upon allocating ARVs to 17 HCFs). We show that our OEAS significantly improves equity in treatment accessibility in comparison with these three ARV allocation strategies. We also quantify how the size of the catchment region surrounding each HCF, and the number of HCFs utilized for ARV distribution, alters the OEAS and the probability of achieving equity in treatment accessibility. We calculate that in order to achieve the greatest degree of treatment equity for individuals with HIV in KwaZulu–Natal, the ARVs should be allocated to 54 HCFs and each HCF should serve a catchment region of 40 to 60 km. Conclusion Our OEAS would substantially improve equality in treatment accessibility in comparison with other allocation strategies. Furthermore, our OEAS is extremely different from the currently planned strategy. We suggest that our novel methodology be used to design optimal ARV allocation strategies for resource-constrained countries.
Within‐day energy deficiency and reproductive function in female endurance athletes

We aimed to estimate and compare within‐day energy balance (WDEB) in athletes with eumenorrhea and menstrual dysfunction (MD) with similar 24‐hour energy availability/energy balance (EA/EB). Furthermore, to investigate whether within‐day energy deficiency is associated with resting metabolic rate (RMR), body composition, S‐cortisol, estradiol, T3, and fasting blood glucose. We reanalyzed 7‐day dietary intake and energy expenditure data in 25 elite endurance athletes with eumenorrhea (n = 10) and MD (n = 15) from a group of 45 subjects where those with disordered eating behaviors (n = 11), MD not related to low EA (n = 5), and low dietary record validity (n = 4) had been excluded. Besides gynecological examination and disordered eating evaluation, the protocol included RMR measurement; assessment of body composition by dual‐energy X‐ray absorptiometry, blood plasma analysis, and calculation of WDEB in 1‐hour intervals. Subjects with MD spent more hours in a catabolic state compared to eumenorrheic athletes; WDEB < 0 kcal: 23.0 hour (20.8‐23.4) vs 21.1 hour (4.7‐22.3), P = . 048; WDEB < −300 kcal: 21.8 hour (17.8‐22.4) vs 17.6 hour (3.9‐20.9), P = . 043, although similar 24‐hour EA: 35.6 (11.6) vs 41.3 (12.7) kcal/kg FFM/d, (P = .269), and EB: −659 (551) vs −313 (596) kcal/d, (P = .160). Hours with WDEB <0 kcal and <−300 kcal were inversely associated with RMRratio (r = −.487, P = .013, r = −.472, P = .018), and estradiol (r = −.433, P = .034, r = −.516, P = .009), and positively associated with cortisol (r = .442, P = .027, r = .463, P = .019). In conclusion, although similar 24‐hour EA/EB, the reanalysis revealed that MD athletes spent more time in a catabolic state compared to eumenorrheic athletes. Within‐day energy deficiency was associated with clinical markers of metabolic disturbances.
Targeting FGFR1 to suppress leukemogenesis in syndromic and de novo AML in murine models

Although over expression of chimeric FGFR1 kinase consistently leads to the development of AML in the rare Stem Cell Leukemia and Lymphoma syndrome, we now show that overexpression of FGFR1 is also seen in up to 20% of non-syndromic, de novo AML. To determine whether targeting FGFR1 in both of these AML subtypes can suppress leukemogenesis, we evaluated the effects of different FGFR1 inhibitors in a side-by-side comparison for their ability to affect in vitro proliferation in FGFR1 overexpressing murine and human cells lines. Three newly developed pan-FGFR inhibitors, AZD4547, BGJ398 and JNJ42756493, show a significantly improved efficacy over the more established FGFR inhibitors, PD173074 and TKI258. To examine whether targeting FGFR1 suppresses leukemogenesis in de novo AML in vivo, we created xenografts in immunocompromized mice from primary, de novo AML that showed > 3-fold increased expression of FGFR1. Using BGJ398, the most potent inhibitor identified in the in vitro studies, AML progression in these mice was significantly suppressed compared with vehicle treated animals and overall survival improved. Importantly, no difference in disease course or survival was seen in AML xenografts that did not show overexpression of FGFR1. These observations support the idea that FGFR1 is a driver oncogene in de novo, FGFR1-overexpressing AML and that molecularly targeted therapies using FGFR1 inhibitors may provide a valuable therapeutic regimen for all FGFR1-overexpressing AML.
Mitigating fisheries-induced evolution in lacustrine brook charr (Salvelinus fontinalis) in southern Quebec, Canada

Size‐selective mortality caused by fishing can impose strong selection on harvested fish populations, causing evolution in important life‐history traits. Understanding and predicting harvest‐induced evolutionary change can help maintain sustainable fisheries. We investigate the evolutionary sustainability of alternative management regimes for lacustrine brook charr (Salvelinus fontinalis) fisheries in southern Canada and aim to optimize these regimes with respect to the competing objectives of maximizing mean annual yield and minimizing evolutionary change in maturation schedules. Using a stochastic simulation model of brook charr populations consuming a dynamic resource, we investigate how harvesting affects brook charr maturation schedules. We show that when approximately 5% to 15% of the brook charr biomass is harvested, yields are high, and harvest‐induced evolutionary changes remain small. Intensive harvesting (at approximately >15% of brook charr biomass) results in high average yields and little evolutionary change only when harvesting is restricted to brook charr larger than the size at 50% maturation probability at the age of 2 years. Otherwise, intensive harvesting lowers average yield and causes evolutionary change in the maturation schedule of brook charr. Our results indicate that intermediate harvesting efforts offer an acceptable compromise between avoiding harvest‐induced evolutionary change and securing high average yields.
Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation.
Single Wall Carbon Nanotubes Based Cryogenic Temperature Sensor Platforms

We present an investigation consisting of single walled carbon nanotubes (SWCNTs) based cryogenic temperature sensors, capable of measuring temperatures in the range of 2–77 K. Carbon nanotubes (CNTs) due to their extremely small size, superior thermal and electrical properties have suggested that it is possible to create devices that will meet necessary requirements for miniaturization and better performance, by comparison to temperature sensors currently available on the market. Starting from SWCNTs, as starting material, a resistive structure was designed. Employing dropcast method, the carbon nanotubes were deposited over pairs of gold electrodes and in between the structure electrodes from a solution. The procedure was followed by an alignment process between the electrodes using a dielectrophoretic method. Two sensor structures were tested in cryogenic field down to 2 K, and the resistance was measured using a standard four-point method. The measurement results suggest that, at temperatures below 20 K, the temperature coefficient of resistance average for sensor 1 is 1.473%/K and for sensor 2 is 0.365%/K. From the experimental data, it can be concluded that the dependence of electrical resistance versus temperature can be approximated by an exponential equation and, correspondingly, a set of coefficients are calculated. It is further concluded that the proposed approach described here offers several advantages, which can be employed in the fabrication of a microsensors for cryogenic applications.
Economic burden of multiple myeloma among patients in successive lines of therapy in the United States

Abstract This study characterized the costs of multiple myeloma (MM) during first-line (1L), second-line (2L) and third-line (3L) treatment from the US payer perspective. Patients with ≥2 outpatient or ≥1 inpatient claims with a primary MM diagnosis and 12 months continuous enrollment post index were identified in a retrospective claims database between 1 July 2006 and 30 June 2013. A cost per-patient per-month (PPPM) metric was used to calculate total all-cause and anti-MM pharmacy costs in 1L, 2L, and 3L treatment. Of 5704 patients included, 3626 initiated 1L treatment, 1797 initiated 2L and 817 initiated 3L. Average total all-cause PPPM costs were $22,527 in 1L, $35,266 in 2L and $47,417 in 3L. Anti-MM pharmacy costs represented 22%, 29% and 29% of total all-cause costs PPPM in 1L, 2L and 3L, respectively. Study results suggest that delaying 2L and/or 3L treatment initiation may result in lower treatment costs for patients with MM.
An Adaptive Orientation Estimation Method for Magnetic and Inertial Sensors in the Presence of Magnetic Disturbances

Magnetic and inertial sensors have been widely used to estimate the orientation of human segments due to their low cost, compact size and light weight. However, the accuracy of the estimated orientation is easily affected by external factors, especially when the sensor is used in an environment with magnetic disturbances. In this paper, we propose an adaptive method to improve the accuracy of orientation estimations in the presence of magnetic disturbances. The method is based on existing gradient descent algorithms, and it is performed prior to sensor fusion algorithms. The proposed method includes stationary state detection and magnetic disturbance severity determination. The stationary state detection makes this method immune to magnetic disturbances in stationary state, while the magnetic disturbance severity determination helps to determine the credibility of magnetometer data under dynamic conditions, so as to mitigate the negative effect of the magnetic disturbances. The proposed method was validated through experiments performed on a customized three-axis instrumented gimbal with known orientations. The error of the proposed method and the original gradient descent algorithms were calculated and compared. Experimental results demonstrate that in stationary state, the proposed method is completely immune to magnetic disturbances, and in dynamic conditions, the error caused by magnetic disturbance is reduced by 51.2% compared with original MIMU gradient descent algorithm.
Numerical simulation of copper recovery from converter slags by the utilisation of spent potlining (SPL) from aluminium electrolytic cells

An innovative method was devised to improve copper recovery and operational efficiency of the Cu converter slag-cleaning furnace, by utilising both carbon and fluoride values of an otherwise environmental hazardous material (i.e. spent potlining (SPL)) produced from the aluminium industry. Results based on numerical modelling show that 90% Cu recovery could be achieved by adding as little as 3–4 wt-% of SPL to the molten converter slag. The fluorides and sodium-containing compounds in the SPL reduced the slag viscosity, resulting in a much faster settling rate of matte droplets. In this process, the SPL could be detoxified by destroying the cyanides to form harmless N2 gas, and inertising the fluorides in a much diluted form in the ferro-silicate slag, ensuring a safe disposal to the environment.