Miracle-dz/UniFAR-FTUs huggingface dataset:
Dominant‐negative mutants reveal a role for the Cdk7 kinase at the mid‐blastula transition in Drosophila embryos

The metazoan cyclin‐dependent kinase Cdk7 was purified originally as part of a biochemical activity called CAK (Cdk‐activating kinase) capable of phosphoryla‐ting and activating in vitro the Cdks that promote the different cell cycle transitions. Cdk7 is also found in the transcription factor complex TFIIH, suggesting that it participates in vivo in the control of RNA polymerase II. We have examined the physiological role of Cdk7 during the course of Drosophila development. By expressing dominant‐negative forms of the kinase, we were able to alter Cdk7 function at given developmental stages. Expression of Cdk7 mutants severely delayed the onset of zygotic transcription in the early embryo, but did not alter the timing of the first 13 embryonic nuclear cycles. These results implicate Cdk7 in the control of transcriptional machinery in vivo. While cell cycle regulation is not sensitive to our manipulations of Cdk7 activity, it suggests that a distinct pool of CAK activity that is unaffected by expression of the cdk7DN mutants is present in these embryos.
New anticoagulant treatments to protect against stroke in atrial fibrillation

Warfarin has long been the ‘gold standard’ of oral anticoagulation for stroke prevention in atrial fibrillation (AF). Recently, the oral direct thrombin inhibitors and direct factor Xa inhibitors have emerged as attractive alternatives to warfarin and have already changed the landscape of stroke prevention in AF. The new anticoagulants have important advantages over warfarin. Despite their impressive performance in clinical trials, their long-term efficacy and safety still require evaluation in ‘real-world’ clinical practice. In this review, the emerging role of the new oral anticoagulants for stroke prevention in patients with AF is discussed.
Photoactivated Ethidium Monoazide Directly Cleaves Bacterial DNA and Is Applied to PCR for Discrimination of Live and Dead Bacteria

Ethidium monoazide (EMA) is a DNA intercalating agent and a eukaryotic topoisomerase II poison. We found that EMA treatment and subsequent visible light irradiation (photoactivation or photolysis) shows a bactericidal effect, hence the mechanism was analyzed. When bacterial cells were treated with more than 10 μg/ml of EMA for 1 hr plus photoactivation for 20 min, cleavage of bacterial DNA was confirmed by agarose gel electrophoresis and electron microscopic studies. The cleavage of chromosomal DNA was seen when it was treated in vitro with EMA and photolysis, which showed that the cleavage directly took place without the assistance of DNA gyrase/topoisomerase IV and the DNA repair enzymes of bacteria. It was also verified, by using negatively supercoiled pBR322 DNA, that medium/high concentrations of EMA (1 to 100 μg/ml) led to breaks of double‐stranded DNA and that low concentrations of EMA (10 to 100 ng/ml) generated a single‐stranded break. EMA is known to easily penetrate dead but not live bacteria. After treatment of 10 μg/ml of EMA for 30 min and photoactivation for 5 min, EMA cleaved the DNA of dead but not live Klebsiella oxytoca. When the cleaved DNA was used for templates in PCR targeting 16S rDNA, PCR product from the dead bacteria was completely suppressed. We demonstrated that EMA and photolysis directly cleaved bacterial DNA and are effective tools for discriminating live from dead bacteria by PCR.
Evidence-based choice of dialysis technique in diabetics with end-stage kidney disease: half a loaf is better than no bread.

insight into the mechanism underlying renal damage in UAKD, suggesting a mild dysfunction of the TAL, compensated in basal conditions, and unmasked after frusemide infusion during the early stage of the disease. Later, the reduction of the renal function is coupled with a clear decline of NKCC2 staining in renal biopsy, and a more diffuse damage of renal parenchyma, predicting the evolution to the end stage renal disease.
Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis.

OBJECTIVE To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). METHODS Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs. RESULTS A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. CONCLUSION Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial.
Estrus detection tools and their applicability in cattle: recent and perspectival situation

Good reproduction is key for successful dairy farming. Detection of estrus is the first step in getting a cow pregnant. Visual detection of estrus is a challenging job, to aid the farmer, estrus detection tools (EDT), such as pedometers, neck mounted collars to measure activity and pressure sensing devices to measure standing estrus, have been developed. EDT have proven useful in practical dairy farming, however, studies from the last five years reveal a great variation in sensitivity, specificity and positive predictive values. In research, the standard that is used to define a true estrus period can affect the performance of the EDT under investigation. Cow factors that can affect performance of EDT are number of ovulation after calving, milk production, lactation number, body condition score and lameness. The second step in getting a cow pregnant is insemination at the correct time. With EDT it is easier to determine optimal insemination time, which is 12 to 24 h before ovulation. The optimal time interval in which to inseminate seems to be about 5 to 17 h after an increase in activity as measured by pedometers or neck mounted collars. Novel measurements, such as rumination time, eating time, lying behavior, ultra-wide band technology to measure mounting and standing-tobe-mounted behavior and infrared thermography to measure temperature are being studied to further aid estrus detection.
Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen

Mature peripheral double negative T (DNT) cells expressing αβ TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated CD4 and CD8 genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors. Because HLA class II molecules present superantigens more efficiently than murine MHC class II molecules, CD4 CD8 double knockout (DKO) mice transgenically expressing HLA-DR3 or HLA-DQ8 molecules were generated. Although thymic cellularity was comparable between wild type (WT) and DKO mice, CD3+ αβ TCR+ thymocytes were significantly reduced in DKO mice, implying defects in thymic-positive selection. Splenic CD3+ αβ TCR+ cells and Foxp3+ T regulatory cells were present in DKO mice but significantly reduced. However, the in vivo inflammatory responses and immunopathology elicited by acute challenge with the staphylococcal superantigen enterotoxin B were comparable between WT and DKO mice. Choric exposure to staphylococcal enterotoxin B precipitated a lupus-like inflammatory disease with characteristic lympho-monocytic infiltration in lungs, livers, and kidneys, along with production of anti-nuclear Abs in DKO mice as in WT mice. Overall, our results suggest that DNT cells can develop efficiently in vivo and chronic exposure to bacterial superantigens may precipitate a lupus-like autoimmune disease through activation of DNT cells.
Stabilization of feedback linearizable systems using a radial basis function network

The main obstacle in the practical use of the feedback linearization is the difficulty in obtaining a linearizing feedback and a coordinate transformation map. Finding a desired transformation map and feedback turns out to be finding an integrating factor for an annihilating one-form. In this work, we develop numerical algorithms for an integrating factor and the corresponding zero-form. Employing a radial basis function (RBF) neural network as an interpolation method for the data resulted from the numerical algorithms, the authors obtained an approximate integrating factor and zero-form in closed forms. Finally, they construct a stabilizing controller based on a linearized system with the use of the approximate integrating factor and zero-form.
DECREASE IN DYNAMIC VISCOSITY AND AVERAGE MOLECULAR WEIGHT OF ALGINATE FROM LAMINARIA DIGITATA DURING ALKALINE EXTRACTION 1

Alginates are natural polysaccharides that are extracted from brown seaweeds and widely used for their rheological properties. The central step in the extraction protocol used in the alginate industry is the alkaline extraction, which requires several hours. In this study, a significant decrease in alginate dynamic viscosity was observed after 2 h of alkaline treatment. Intrinsic viscosity and average molecular weight of alginates from alkaline extractions 1–4 h in duration were determined, indicating depolymerization of alginates: average molecular weight decreased significantly during the extraction, falling by a factor of 5 between 1 and 4 h of extraction. These results suggested that reducing extraction time could enable preserving the rheological properties of the extracted alginates.
Automated traffic measurement system based on FCD and image processing

The core feature of any intelligent transportation system (ITS) is the vehicle measurement technique incorporated to measure road traffic volumes. Sensors or detectors placed along roads are used to acquire traffic flow data for further processing either manually or through fully automated intelligent systems. Although several different technologies exist, no single vehicle count method is absolutely ideal. This limitation accounts to environmental factors and system limitations of modern vehicle measurement techniques. This paper proposes a composite detection system to measure vehicle volumes on roads. The underlying approach discussed here integrates both floating car data (FCD) and image processing with the aim to diminish the drawbacks of contemporary detector technologies. A small scale system was developed under the scope of this research and a certain degree of field testing was carried out to conclude upon the viability of the endeavor. The results of the field tests indicate that an amalgamation of two vehicle detection technologies indeed reduces the shortcomings of single modal traffic measurement techniques and also advocates a practical implementation of such system.
Efficient Channel Contracting for Vertically Differentiated Products

We describe research on a supply chain contracting problem that was sponsored by a major semi-conductor manufacturer. The manufacturer sells products (semiconductor parts) with varying quality levels through a network of distributors to end consumers (independent computer shops, system configurators, hobbyists, etc.) who have heterogeneous valuations for quality. Since production costs for semi-conductors are essentially independent of quality levels (within a part family), the manufacturer earns much more selling higher quality parts. However, the firm’s distributors traditionally care more about total unit volume since their margins are similar on all products. As a result, the economics of the two parties have historically not been well aligned. The manufacturer wanted to better understand this incentive problem and develop new strategies to improve its own and distributors profits. The analysis presented here supported this effort. To analyze this problem, we consider the simple case in which the product family consists of two parts with high and low quality. We first identify the distortions inherent in the firm’s status quo wholesale pricing contracts. We then investigate alternative mechanisms that may better coordinate their channel. We start our analysis with the single-distributor case and show that revenue sharing coordinates the channel and can be designed to arbitrarily allocate profits. We study potential asymmetric contracts which create different incentives for different parts within a given product line and show which ones can potentially improve channel performance. Taking into account the fact that in many regions the manufacturer has a network of distributors, we then extend our results to the case of Cournot competition. We first characterize the distributor’s strategic interaction and then analyze a similar set of coordinating mechanisms. We show that the efficiency of the wholesale pricing contract improves as the number of competitors increases. Lastly, we discuss some of the challenges and roadblocks encountered as we tried to implement a revenue sharing program at our sponsor and why other contracts were not good candidates for implementation. The experience sheds some light on the challenges transforming supply chain contracting concepts into workable real-world programs.
Afa/Dr-Expressing, Diffusely Adhering Escherichia coli Strain C1845 Triggers F1845 Fimbria-Dependent Phosphatidylserine Externalization on Neutrophil-Like Differentiated PLB-985 Cells through an Apoptosis-Independent Mechanism

ABSTRACT The enterovirulent Escherichia coli strains potentially involved in inflammatory bowel diseases include diffusely adherent strains expressing Afa/Dr fimbriae (Afa/Dr DAEC). We have previously observed type 1 pilus-mediated interleukin-8 (IL-8) hyperproduction in infected neutrophils. As pathogen induction of host cell death programs and clearance of apoptotic infected cells are crucial for innate immune system homeostasis and host integrity, we examined modulation of neutrophil cell death by Afa/Dr DAEC. Using the human PLB-985 cell line differentiated into fully mature neutrophils, we found that the wild-type enterovirulent E. coli strain C1845 and the recombinant strain DH5α/pF1845 (expressing the fimbrial adhesin F1845) similarly induced time-dependent phosphatidylserine (PS) externalization, suggesting a major specific role of this virulence factor. Using small interfering RNA (siRNA) decay-accelerating factor (DAF)-transfected PLB-985 cells, we then showed that this PS externalization was triggered in part by glycosylphosphatidylinositol (GPI)-anchored DAF receptor engagement (leading to tyrosine kinase and protein kinase C activation) and that it required cytoskeleton and lipid raft architectural integrity. PS externalization under these conditions was not dependent on caspases, mitochondria, lysosomes, or reactive oxygen or nitrogen species. F1845-mediated PS externalization was sufficient to enable macrophage engulfment of infected differentiated PLB-985 cells. These findings provide new insights into the neutrophil response to Afa/Dr DAEC infection and highlight a new role for F1845 fimbriae. Interestingly, although apoptosis pathways were not engaged, C1845-infected PLB-985 cells displayed enhanced removal by macrophages, a process that may participate in the resolution of Afa/Dr DAEC infection and related inflammation.
Leader-Member Exchange, Transformational Leadership, and Value System

This study looked at the relationship between leader-member exchange (LMX), transformational leadership, and terminal and instrumental value system congruence between leader and follower, and their relative impact on four outcomes, using a sample of 100 pairs of managers and subordinates from a non-profit organization in the United States. The four outcomes studied are perceived effectiveness of leader and work unit, follower satisfaction with leader, follower’s motivation to put in extra effort, and follower’s intention to quit the organization. Results of correlation analyses indicate that LMX is positively related to transformational leadership, which in turn is positively related to terminal value system congruence. Results of regression analyses using the forward option show that transformational leadership is a stronger predictor of effectiveness, satisfaction, and extra effort than LMX and terminal value system congruence. LMX explains significant additional variance in satisfaction and extra effort than what is already explained by transformational leadership. LMX is a stronger predictor of follower’s intention to quit than transformational leadership and terminal value system congruence. LMX also mediates the relationship between transformational leadership and intention to quit. Instrumental value system congruence between leader and follower is not significantly related to any of the variables.
The role of eukaryotic subtilisin-like endoproteases for the activation of human immunodeficiency virus glycoproteins in natural host cells

Proteolytic activation of the precursor envelope glycoproteins gp160 of human immunodeficiency virus type 1 (HIV-1) and gp140 of HIV-2, a prerequisite for viral infection, results in the formation of gp120/gp41 and gp125/gp36, respectively. Cleavage is mediated by cellular proteases. Furin, a member of the eukaryotic subtilisin family, has been shown to be an activating protease for HIV. Here, we compared the presence of furin and other mammalian subtilisins in lymphatic cells and tissues. Northern blot analyses revealed that furin and the recently discovered protease LPC/PC7 were the only subtilisin-like enzymes transcribed in such cells. Furin was identified as an enzymatically active endoprotease present in different lymphocytic, as well as monocytic, cell lines. When expressed from vaccinia virus vectors, the proprotein convertases were correctly processed, transported, and secreted into the media and enzymatically active. Coexpression of different subtilisins with the HIV envelope precursors revealed that furin and LPC/PC7 are able to cleave HIV-1 gp160. Moreover, both enzymes proteolytically processed the envelope precursor of HIV-2. gp140 was also cleaved to some extent by PC1, which is not, however, present in lymphatic cells. Furin- and LPC/PC7-catalyzed cleavage of HIV-1 gp160 resulted in biologically active envelope protein. In conclusion, among the known members of the subtilisin family, only furin and LPC/PC7 fulfill the requirements of a protease responsible for in vivo activation of HIV envelope glycoproteins.
Treatment of Crohn’s disease with certolizumab pegol

Biologic therapies have revolutionized the treatment of Crohn’s disease (CD). Targeting TNF-α with monoclonal antibodies has changed the therapeutic landscape for tackling refractory and complicated CD. Intravenous use of infliximab, a chimeric monoclonal antibody to TNF-α is, however, limited by the occurrence of adverse events, infusion reactions, infectious complications, aggravation of heart failure, the occurrence of neurological demyelinating conditions and induction of rare malignancies. The incremental development of next-generation TNF-α antibodies and binding proteins through antibody-engineering techniques has followed, with the aim of producing efficacious drugs that are less expensive to produce, have a convenient route of administration and have fewer side effects. Certolizumab pegol (CDP870, Cimzia®) is an engineered humanized anti-TNF-α antibody Fab´ fragment that minimizes the protein component and is conjugated to polyethylene glycol. Clinical studies have demonstrated efficacy in the treatment of moderate-to-severe active CD. Reported adverse events in the clinical trial program have been largely of mild-to-moderate severity, and occurred at similar frequencies in the active-treatment and placebo groups. Certolizumab pegol will be a useful addition to the armamentarium of biologic agents that can be used for the long-term treatment of CD.
Instructions for use Title Effect of oral administration of sodium bicarbonate on surface EMG activity during repeated cyclingsprints

The purpose of this study was to determine the effect of oral administration of sodium bicarbonate (NaHCO3) on surface electromyogram (SEMG) activity from the vastus lateralis (VL) during repeated cycling sprints (RCS). Subjects performed two RCS tests (ten 10-s sprints) interspersed with both 30-s and 360-s recovery periods 1 h after oral administration of either NaHCO3 (RCSAlk) or CaCO3 (RCSPla) in a random counterbalanced order. Recovery periods of 360 s were set before the 5th and 9th sprints. The rate of decrease in plasma HCO3 concentration during RCS was significantly greater in RCSAlk than in RCSPla, but the rates of decline in blood pH during the two RCS tests were similar. There was no difference between change in plasma lactate concentration in RCSAlk and that in RCSPla. Performance during RCSAlk was similar to that during RCSPla. There were no differences in oxygen uptake immediately before each cycling sprint (preV . O2) and in SEMG activity between RCSAlk and RCSPla. In conclusion, oral administration of NaHCO3 did not affect SEMG activity from the VL. This suggests that the muscle recruitment strategy during RCS is not determined by only intramuscular pH.