Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep

The search for the genetic determinism of prolificacy variability in sheep has evidenced several major mutations in genes playing a crucial role in the control of ovulation rate. In the Noire du Velay (NV) sheep population, a recent genetic study has evidenced the segregation of such a mutation named FecLL. However, based on litter size (LS) records of FecLL non-carrier ewes, the segregation of a second prolificacy major mutation was suspected in this population. In order to identify this mutation, we have combined case/control genome-wide association study with ovine 50k SNP chip genotyping, whole genome sequencing and functional analyses. A new single nucleotide polymorphism (OARX:50977717T>A, NC_019484) located on the X chromosome upstream of the BMP15 gene was evidenced highly associated with the prolificacy variability (P =1.93E-11). The variant allele was called FecXN and shown to segregate also in the Blanche du Massif Central (BMC) sheep population. In both NV and BMC, the FecXN allele frequency was estimated close to 0.10, and its effect on LS was estimated at +0.20 lamb per lambing at heterozygous state. Homozygous FecXN carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affecting BMP15. At the molecular level, FecXN was shown to decrease BMP15 promoter activity and to impact BMP15 expression in oocyte. This regulatory action was proposed as the causal mechanism for the FecXN mutation to control ovulation rate and prolificacy in sheep. Author Summary In the genetic etiology of women infertility syndromes, a focus was done on the oocyte-expressed BMP15 and GDF9 genes harboring several mutations associated with ovarian dysfunctions. In sheep also, mutations in these two genes are known to affect the ovarian function leading to sterility or, on the opposite, increasing ovulation rate and litter size constituting the prolificacy trait genetically selected in this species. Through a genome-wide association study with the prolificacy phenotype conducted in the French Noire du Velay sheep breed, we describe a novel mutation located in the regulatory region upstream of the BMP15 gene on the X chromosome. This mutation increases litter size by +0.2 lamb per lambing at the heterozygous state, possibly through an inhibition of BMP15 expression within the oocyte. Our findings suggest a novel kind of BMP15 variant responsible for high prolificacy, in contrast to all other BMP15 variants described so far in the coding sequence.
Clinical Pharmacokinetics of CAL-101, a p110δ Isoform-Selective PI3K Inhibitor, Following Single- and Multiple-Dose Administration In Healthy Volunteers and Patients with Hematological Malignancies

Abstract 1774 Phosphatidylinositol 3-kinases (PI3Ks) regulate several cellular functions including motility, proliferation, and survival. PI3K pathway signaling is mediated by the Class I PI3K isoforms, α, β, δ and γ. The PI3K p110δ isoform is preferentially expressed in cells of hematological origin and in a variety of malignant cells. CAL-101 is a potent p110δ inhibitor with an EC50 of 62 nM in a whole-blood p110δ assay and >200-fold selectivity for p110δ relative to other PI3K isoforms. Consistent with this target selectivity, nonclinical toxicology and safety pharmacology data supported initial clinical assessment of oral CAL-101 in single-dose, multiple-dose, and food-effect studies in healthy volunteers. Because CAL-101 is a CYP450 3A4 substrate, the effect of ketoconazole (a potent CYP450 3A4 inhibitor) on CAL-101 pharmacokinetics was also evaluated in healthy volunteers. Preliminary evaluation of disposition, metabolism and elimination in healthy volunteers was achieved by coadministering a trace amount of [14C]CAL-101 and unlabeled CAL-101 either orally or intravenously (IV) with samples evaluated by accelerator mass spectrometry. CAL-101 pharmacokinetics (PK) were subsequently evaluated in patients with lymphoid malignancies. In healthy volunteers, CAL-101 was well tolerated at 400 mg (the highest single dose tested) and at 200 mg BID through 7 days (the highest multiple dose tested). The drug has also been symptomatically well tolerated in patients with lymphoid malignancies receiving CAL-101 at dose levels through 350 mg/kg (the highest dose tested) over many months. Monitorable, reversible transaminase elevations have been observed in some patients, most commonly in patients with lymphoma. No maximum tolerated dose (MTD) has been apparent. Increases in Cmax and AUC are less than dose proportional, revealing minimal gains in plasma exposure at dose levels >150 mg BID. The mean volume of distribution was moderate at 57.7 L. The t1/2 was ∼8 hours across all dose levels and there was no plasma accumulation over 7 or 28 days. The collective data support BID dosing at ≥150 mg; dose levels in this range maintain steady-state trough plasma concentrations that are >10-fold above the EC50 for the in vitro whole-blood assay. [14C]CAL-101 was metabolized to only 1 metabolite in plasma and CAL-101-derived materials were primarily excreted in feces (>65% of total dose) with minimal elimination via urine ( Disclosures: Webb:Calistoga Pharmaceuticals: Employment. Chen:Calistoga Pharmaceuticals: Employment. Yu:Calistoga Pharmaceuticals: Employment. Peterman:Calistoga Pharmaceuticals: Employment. Holes:Calistoga Pharmaceuticals: Employment. Lannutti:Calistoga Pharmaceutical Inc.: Employment. Miller:Calistoga Pharmaceuticals: Employment. Ulrich:Calistoga Pharmaceuticals: Employment, Equity Ownership.
Different methods to achieve hybrid mode locking

Abstract Mode locked pulse generation has been reported using both active and passive mode locking schemes. Active mode locking technique has been proven to be an effective way to generate high-repetition-rate pulses by incorporating a modulator inside the laser cavity. Compared to actively mode locked lasers, passively mode locked lasers can generate pulse train at ultrashort pulse width but with relatively lower repetition rate. Thus, it is a brilliant idea to build a hybrid mode locked system combining both active and passive mode lockers. In this review, several hybrid mode locked fiber ring laser systems are discussed and summarized. Hybrid mode locking is a promising method to generate high-speed ultrashort optical pulses for fiber-optic telecommunication system.
Prevalence of MTX Intolerance in Rheumatoid Arthritis- A 3 Year Prospective Hospital Based Study

Background: Rheumatoid arthritis is most common inflammatory arthritis. Methotrexate is backbone of treatment regimens. Objective: To determine the prevalence of Methotrexate intolerance in rheumatoid arthritis. Material and Methods: 150 patients of RA including 120 females and 30 males attending rheumatology services of hospital from December 2012 to December 2015 were prescribed MTX as per approved protocol and were followed for Methotrexate Intolerance Severity Score (MISS). Results: Out of 150 patients of RA on methotrexate (MTX), 21 (14%) were found to have MISS ≥ 6. Conclusion: MISS is an important tool for application in RA to know Methotrexate intolerance and timely intervention to mitigate the same in order to prevent the incompliance of an otherwise very effective DMARD for RA.
Salivary gland function after radiotherapy for head and neck cancer.

In the treatment of head and neck cancer by radiotherapy the major salivary glands are often inevitably included in the treatment volume. The impairment of salivary gland function that can result is an important cause of late morbidity following treatm ent. Clinical experience has suggested that impaired salivary gland function after radiotherapy is less following treatm ent using the CHART regime as compared with conventionally fractionated treatment. The salivary gland function of 73 patients treated by radiotherapy (CHART or conventionally fractionated treatment) for head and neck tumours has been studied. 26 were tested nine months to nine years after treatment and 47 were studied serially before, during and for up to 2 years after treatment. In 41 patients serum amylase was monitored before and during radiotherapy. Pronounced falls in salivary flow and pH are seen once radiotherapy has commenced when significant amounts of salivary tissue are included in the treatment volume. Marked rises in the serum amylase accompany these very early changes. The parotid glands show the greatest sensitivity to radiotherapy compared to the other salivary glands. The early changes are as marked for patients receiving either CHART or conventionally fractionated treatment but a greater recovery of function after CHART results in the improved function seen in patients nine months or more following treatment with CHART. The reduction in the late impairment of salivary gland function following radiotherapy with CHART is the result of the low dose per fraction employed combined with the reduced total dose. Patient comfort is greater and quality of life improved. Salivary gland function has proved measurable and is a valuable system for the study of human radiobiology. The evidence from this study gives support for the concept of reduced late change resulting from a reduction in dose per fraction, an area of importance to the development of improved radiotherapy treatment schedules.
Apoptosis in chronic lymphocytic leukaemia

B cell chronic lymphocytic leukaemia (B-CLL) is the most common adult leukaemia in the western world. The disease is characterised by the accumulation of a CD5+ B cell clone. Drug resistance is a major problem in B-CLL and complete remissions are uncommon. The lymphoaccumulative nature of B-CLL implies that dysregulation of the apoptotic process may be responsible for the development and progression of the disease. B-CLL cells were freshly isolated from patients, and an in vitro apoptosis sensitivity assay was developed using flow cytometric techniques. Initial studies confirmed the existence of ‘spontaneous apoptosis’ when B-CLL cells were cultured in vitro, and demonstrated a strong correlation between sensitivity to spontaneous apoptosis and sensitivity to apoptosis induced by the chemotherapeutic drug chlorambucil in vitro. Immunoblotting of chlorambucil and prednisolone treated B-CLL cells demonstrated the expression and activation of caspases -3, -7 and -8 in all samples analysed, whilst activation of caspase-2 was seen in cells from only one patient. Activation of caspases -3 and -7 was accompanied by the proteolysis of the DNA repair enzyme, poly (ADP-ribose) polymerase (PARP). Induction of apoptosis and activation of all the caspases was inhibited by the cell permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.fmk). These results demonstrated a key role for the activation and processing of caspases in the execution phase of apoptosis in B-CLL cells. The B cell growth factors interleukin-4 and CD40 were demonstrated to strongly influence survival of B-CLL cells in in vitro culture, and also to modulate the response of the cells to chemotherapeutic drugs. Investigations into Fas induced apoptosis in B-CLL cells demonstrated the expression of the adapter protein, FADD, but no overexpression of the caspase-8 inhibitory protein, c-FLIP. Additionally, B-CLL cells did not show rapid assembly of the death inducing signalling complex (DISC) in response to stimulation of Fas receptor, implying that these cells may preferentially utilise the Bcl-2inhibitable Type II (mitochondrial) pathway of apoptosis induction, underlining the important role that Bcl-2 plays in determining the apoptotic sensitivity of B-CLL cells.
Eurycoma longifolia Root Aqueous Extract Augments the Testosterone Level and Spermatogenesis in Adult Male Rats

Introduction The Eurycoma longifolia (EL) root aqueous extract has long been used as an enhancer of male sexual performance. However, data from previous studies in both human males and experimental male animals on the testosterone level in those given the EL extract orally were at best insufficiently conclusive. Materials and Method Sixty-four healthy adult male Sprague Dawley rats were acclimatized, and randomized into six test groups and one control group. All rats where given either the aqueous EL extract or distilled water via metal gavage needle. The first three test groups received the low (50mg/kg bw), medium (100mg/ kg bw) and high (200mg/kg bw) doses respectively of the EL daily for 15 days only. The second three test groups continued receiving the same daily treatment doses for 30 days. The controls were given distilled water only. At the end of each of the study period, blood samples were collected via cardiac puncture and the rats were euthanized. The testicles were obtained, weighed, and processed for histological examination. Results The sera testosterone levels were higher in animals which received the medium and high doses for both treatment duration. Rats which received medium and high oral doses of EL showed an increase of spermatogenesis and mature spermatozoa. Conclusion The optimal enhancing effect on sera testosterone levels and testicular spermatogenesis of EL treatment in adult male rats was observed with the medium dose of 100mg/kg bw given once daily for both 15 and 30 days.
Prevalence of hypertension in school going children in tea garden community in Dibrugarh town, Assam, India

Background: The disease burden of hypertension among workers in tea gardens is large, despite the community not being obese. Consumption of high quantity of common salt (NaCl) is considered to be the main factor. Therefore it is expected that prevalence of hypertension and level of blood pressure would be higher among these group of children. Hence the present study was taken to determine the prevalence of hypertension in apparently healthy, asymptomatic school children of tea garden workers in the age group of 6-12 years. Methods: Blood pressure was recorded in the right arm in the sitting position by using a standard Hg sphygmomanometer using appropriate cuff sizes. Three readings were taken at an interval of at least 5 minutes and the average of these three readings was considered as the blood pressure of the individual. Average SBP or DBP levels that are greater than or equal to the 95th percentile for sex, age, and height was taken as hypertension. Results: The prevalence of systolic, diastolic and both systolic and diastolic hypertension are 3.86%, 1.71% and 4.29% and 2.62%, 0.37% and 5.24% in boys and girls respectively and the overall prevalence of hypertension was found to be 9.0% (systolic 3.2%, diastolic 1.0% and systolic and diastolic 4.8%). Conclusions: The high risk children need to be considered for close follow ups for modification of risk factors by advising lifestyle changes like reduction in intake of salt.
Analytical models for comparing Demand Responsive Transport with bus services in low demand interurban areas

ABSTRACT As new shared mobility services emerge there is an increasing need for better understanding of the role and potential markets of these services which would result in viable business models. The current research aims at exploring Demand Responsive Transport (DRT) services, as a case of efficient mobility service provision for low demand interurban areas. Analytical models are developed and applied in a real case identifying critical demand thresholds for the alternative modes. Finally, the analysis points out the trade-offs between costs and level of service a transport operator or mobility provider needs to consider to implement a successful service.
Water productivity analysis in irrigated central rice production area of SolokRegency, Indonesia

To feed the increasing world population, the demand for food and consequently irrigation water is predicted to increase in the future. However, the amount of water available for agriculture is increasingly becoming uncertain in the face of global climate change. Therefore, improvement in water productivity is necessary for sustainable production of crops such as rice. Water productivity varies across regions and across fields within a region, and is dependent on several factors such as crop patterns, climate patterns, irrigation technology and field water management, land and infrastructure, and other inputs, including labor, fertilizer, and machinery. The objective of this study was to estimate water supply and demand in Sumani watershed, a primary rice-producing region, to analyze water productivity for sustainable rice production. Approximately 30% of the area in Sumaniis paddy fields, which depend on the availability of water resources. In this area. Approximately 67% of the rice fields are cultivated three times a year. In general, the planting schedule of rice is divided into three periods: main planting season (wet season), Gadu planting season (planting in the end of wet season and harvesting in the dry season), and dry planting season. Although the planting schedules are not uniform, we assumed these as uniform, to simplify the analysis, by using majority cropping schedule in the study site. To ensure water availability in the dry season, four types of irrigation systems were used: technical irrigation (TI), semi-technical irrigation (STI), simple irrigation (SI), and non-government irrigation (NGI). The results showed thatdepending on the planting season and irrigation system, water productivity varied from 0.33 kg/m3 in the Gadu season in areas irrigated by the SI and NGI systems to 0.73 kg/m3 in the wet season in area irrigated by the TI system. The average water productivity in the study area was 0.53kg/m3. Water productivity in this study area was lower than the average water productivity in other rice production areas in Java and Bali.
Radio Galaxies at TeV Energies: Preface

The majority of the known extragalactic sky from TeV gamma-ray energies consists of blazars having plasma jets pointing in the direction of the line-of-sight, which results in a large Doppler boosting of their emission. Up to now, only six galaxies with a larger viewing angle have been detected in the TeV range. These objects also show fascinating properties, such as fast variability or spectral features and are called “radio galaxies”. The TeV radio galaxies provide a unique laboratory for studying key aspects of active galactic nuclei. This Special Issue of Galaxies targets these exciting objects.
PET en el diagnóstico de la patología de tiroides

La PET/TC es una tecnica cuyas indicaciones en Oncologia se encuentran en expansion y el cancer de tiroides es una de ellas. En el presente articulo se revisan las indicaciones establecidas hasta la fecha, asi como aquellos campos en los que son necesarias investigaciones adicionales que permitan establecer la utilidad de esta tecnica en los distintos tipos de patologia maligna tiroidea.
A Hybrid Meta-heuristic Approach to Cope with State Space Explosion in Model Checking Technique for Deadlock Freeness

Model checking is an automatic technique for software verification through which all reachable states are generated from an initial state to finding errors and desirable patterns. In the model checking approach, the behavior and structure of system should be modeled. Graph transformation system is a graphical formal modeling language to specify and model the system. However, modeling of large systems with the graph transformation system suffers from the state space explosion problem which usually requires huge amounts of computational resources. In this paper, we propose a hybrid meta-heuristic approach to deal with this searching problem in the graph transformation system because meta-heuristic algorithms are efficient solutions to traverse the graph of large systems. Our approach, using Artificial Bee Colony and Simulated Annealing, replaces a full state space generation, only by producing part of it checking the safety, and finding errors (e.g., deadlock). The experimental results show that our proposed approach is more efficient and accurate compared to other approaches.
Engineering of Klebsiella oxytoca for production of 2,3‐butanediol using mixed sugars derived from lignocellulosic hydrolysates

2,3‐Butanediol (2,3‐BDO) is a promising bulk chemical owing to its high potential in industrial applications. Here, we engineered Klebsiella oxytoca for the economic production of 2,3‐BDO using mixed sugars from renewable biomass. First, to improve xylose consumption, the xylose transporter gene (xylE) was integrated into the methylglyoxal synthase A (mgsA)‐coding gene loci, and the engineered CHA004 strain showed much faster consumption of xylose than wild‐type (WT) strain with 1.4‐fold increase of overall sugar consumption rate. To further improve sugar utilization, we performed adaptive laboratory evolution for 90 days. The evolved strain (CHA006) was evaluated by cultivating it in the media containing single‐ or mixed‐sugars, and it was clearly observed that CHA006 has improved sugar consumption and 2,3‐BDO production than those of the parental strain. Finally, we demonstrated the superiority of CHA006 by culturing in two lignocellulosic hydrolysates derived from sunflower or pine tree. Particularly, in the pine tree hydrolysate containing xylose, glucose, galactose, and mannose, the CHA006 strain showed much improved consumption rates for all sugars, and 2,3‐BDO productivity (0.73 g L−1 hr−1) increased by 3.2‐fold compared to WT strain. We believe that the engineered CHA006 strain can be a potential host in the development of economic bioprocess for 2,3‐BDO through efficient utilization of mixed sugars derived from lignocellulosic biomass.
Effects of Fish Meat-derived Peptide and Dipeptides on Dexamethasone-induced Fatigue in Mice

In patients with inflammatory diseases, exogenous glucocorticoids have become the most common cause of drug-induced muscle wasting. In this study, we showed that isoleucine-arginine (IR) and arginine-isoleucine (RI) are the main dipeptides with antioxidant activity in fish meat-derived peptide extract (FMDP). To investigate the anti-fatigue effect of FMDP and the two dipeptides (IR or RI), dexamethasone (DEX)-treated mice performed a weighted forced swimming test. Despite no change in body weight, the shortened swim time after DEX administration returned to baseline levels following the administration of FMDP, IR, and RI. However, the swim time of naive mice cannot be extended with the administration of FMDP, IR, or RI. Our data suggest that FMDP, IR, and RI may have beneficial effects on DEX-induced fatigue in mice. Nevertheless, further research is required to determine the mechanism through which FMDP reduces fatigue.
How Did Women Workers Get Benefit From Revolution 4.0?

—The development of information and communication technology (ICT) not only raises optimism for economic progress, but also concerns for the increasing level of economic inequality due to the technological nature of capital and skill-biased. There is also fear that the digital revolution will harm women workers. This paper aims to analyze how did women can get benefits from the ICT development in Indonesia’s labor market. Using data obtained from the National Bureau of Statistics, we analyze distribution of women in labor forces, based on the type of jobs and employment sectors, to understand whether they are benefited or not from the ICT development. We found that distribution of women workers in the four type of jobs (namely (1) Professionals, Technicians and similar workers, (2) Leadership and Management Personnel, (3) Administrative and similar workers, and (4) Sales Workers) and the three sector of employment (namely (1) Finance, Insurance, Building or Land Rental Business, and Company Services, (2) Large Trade, Retail, Restaurants and Hotels, and (3) Buildings), is higher than men. These are the type of jobs and employment sectors that benefited from ICT development. So, although the level of use of technology (internet and mobile phones) among women is still low, Indonesian women in workforces are more benefited from the ICT development, than men.