Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of Peptide Transporter 1 in the Intestinal Permeability of Valacyclovir in Wild-Type and PepT1 Knockout Mice

The purpose of this study was to quantitatively determine the contribution of PepT1 [peptide transporter 1 (SLC15A1)] to the intestinal permeability of valacyclovir, an ester prodrug of the antiviral drug acyclovir. In situ single-pass intestinal perfusions were employed (pH 6.5 3 90 minutes) to assess the effective permeability ( P eff ) of 100 m M [ 3 H]valacyclovir in wild-type and PepT1 knockout mice. Acyclovir pharmacokinetics was also evaluated after oral administration of 25 nmol/g valacyclovir. In wild-type mice, jejunal uptake of valacyclovir was best described by both saturable ( K m = 10.2 mM) and nonsaturable components where the saturable path-way accounted for 82% of total transport. Valacyclovir P eff was 2.4 3 10 2 4 cm/s in duodenum, 1.7 3 10 2 4 cm/s in jejunum, 2.1 3 10 2 4 cm/s in ileum, and 0.27 3 10 2 4 cm/s in colon. In Pept1 knockout mice, P eff values were about 10% of that in wild-type animals for these small intestinal segments. Valacyclovir P eff was similar in the colon of both genotypes. There were no differences in valacyclovir P eff between any of the intestinal segments of PepT1 knockout mice. Valacyclovir P eff was significantly reduced by the dipeptide glycylsarcosine and the aminocephalosporin cefadroxil, but not by the amino acids L -valine or L -histidine, the organic acid p -aminohippurate, or the organic base tetraethylammonium (all at 25 mM). PepT1 ablation resulted in 3- to 5-fold reductions in the in vivo rate and extent of valacyclovir absorption. Our findings conclusively demonstrate, using in situ and in vivo validations in genetically modified mice, that PepT1 has a major influence in improving the oral absorption of valacyclovir.
AHEART January 47/1

SAID H. AUDI,1,2 LARS E. OLSON,1,3 ROBERT D. BONGARD,3 DAVID L. ROERIG,4,5,6 MARIE L. SCHULTE,3 AND CHRISTOPHER A. DAWSON1,2,3,4,5,6 1Department of Biomedical Engineering, Marquette University, Milwaukee 53201-1881; Departments of 2Pulmonary and Critical Care Medicine, 3Physiology, 4Anesthesiology, and 5Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226; and 6Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295
Pathways Follow Different Rules Thymic and Extrathymic T Cell Development

Separation between primary and secondary lymphoid organs is a universal feature in jawed vertebrates. Strikingly, oncostatin M (OM)-transgenic mice present massive extrathymic T cell development, localized exclusively in the lymph nodes (LN). According to the prevailing paradigm, the thymus is the main source of T lymphocytes in gnathostomes mainly because thymic epithelial cells have a unique ability to support early steps in T cell development. It is therefore remarkable that productive T cell development occurs in the OM (cid:1) LN, despite the absence of epithelial cells. The present study shows that in the OM (cid:1) LN: 1) MHC class I expression strictly on hemopoietic cells is sufﬁcient to support the development of a diversiﬁed repertoire of CD8 T cells; 2) the efﬁciency of positive selection of speciﬁc TCR-transgenic T cells is not the same as in the thymus; 3) negative selection is very effective, despite the lack of an organized thymic-like medulla. Furthermore, our data suggest that extrathymic T lymphocytes developing in the OM (cid:1) LN undergo extensive postselection expansion because they live in the microenvironment in which they were positively selected. This work illustrates how the division of labor between primary and secondary lymphoid organs inﬂuences the repertoire and homeostasis of T lymphocytes. The Journal of Immunology, 2002, 169: 684–692. he central peripheral negative selection
Oxygen Generation Influx and Mitochondrial Reactive 2+of DRAK2 in Response to TCR-Induced Ca Protein Kinase D Orchestrates the Activation

DRAK2 is a serine/threonine kinase highly enriched in lymphocytes that raises the threshold for T cell activation and maintains T cell survival following productive activation. T cells lacking DRAK2 are prone to activation under suboptimal conditions and exhibit enhanced calcium responses to AgR stimulation. Despite this, mice lacking DRAK2 are resistant to organ-speciﬁc autoimmune diseases due to defective autoreactive T cell survival. DRAK2 kinase activity is induced by AgR signaling, and in this study we show that the induction of DRAK2 activity requires Ca 2+ inﬂux through the Ca 2+ release-activated Ca 2+ channel formed from Orai1 subunits. Blockade of DRAK2 activity with the protein kinase D (PKD) inhibitor Go¨6976 or expression of a kinase-dead PKD mutant prevented activation of DRAK2, whereas a constitutively active PKD mutant promoted DRAK2 function. Knockdown of PKD in T cells strongly blocked endogenous DRAK2 activation following TCR ligation, implicating PKD as an essential intermediate in the activation of DRAK2 by Ca 2+ inﬂux. Furthermore, we identify DRAK2 as a novel substrate of PKD, and demonstrate that DRAK2 and PKD physically interact under conditions that activate PKD. Mitochondrial generation of reactive oxygen intermediates was necessary and sufﬁcient for DRAK2 activation in response to Ca 2+ inﬂux. Taken together, DRAK2 and PKD form a novel signaling module that controls calcium homeostasis following T cell activation. The Journal of Immunology , 2011, 186: 940–950. 12 on WT-DRAK2 in the presence of CA-PKD1. The 293T cells were transfected with pEGFP-DRAK2 or pEGFP-DRAK2-K62A in combination with pcDNA3.1 or pEGFP-PKD1-S738/742E (CA-PKD1). Thirty minutes before lysis, cells were left untreated or treated with 12 mM LNAC. E , LNAC blocks DRAK2 and PKD coimmunoprecipitation. Mitochondrial fractions were obtained from D10 T cells stimulated with 1 m M thapsigargin for 5 min, or with vehicle, in the presence or absence of 12 mM LNAC. Anti-PKD1 was used to immunoprecipitate DRAK2 and PKD from mitochondrial lysate. F , ROS generation through inhibition of mitochondrial complex I using CCCP is sufﬁcient to activate DRAK2. D10 T cells were stimulated with 200 ng/ml PMA, 1 m M thapsigargin or DMSO for 5 min, or CCCP at the indicated times and concentrations. Lysates were resolved by SDS-PAGE and probed with the indicated Abs. G , Model for PKD-dependent DRAK2 activation. TCR stimulation leads to activation of PLC g , which leads to production of IP 3 , and subsequent release of calcium from the ER through IP 3 receptors. ER calcium release allows Orai1 to form functional CRAC channels in the plasma membrane, resulting in a large inﬂux of extracellular calcium, which accelerates mitochondrial respiration and the production of ROS. ROS positively feed back on PLC g activation and, through Src and Abl, can activate PKD. PKD, following activation through potentially one of these pathways, is then able to activate DRAK2, which serves to limit calcium inﬂux.
Passive fuel cell heat recovery using heat pipes to enhance metal hydride canisters hydrogen discharge rate: an experimental simulation

This paper reports on an experimental investigation of a passive thermal coupling arrangement between a Proton Exchange Membrane (PEM) fuel cell and a Metal Hydride (MH) hydrogen storage canister using heat pipes for enhancing the release rate of hydrogen. The performance of this arrangement was measured by inserting the evaporator sections of the heat pipes into an aluminum plate mimicking one out of five cooling plates of a 500-W fuel cell (that is a 100 W section of the stack). Thermal pads were attached on both sides of the plate to represent the fuel cell heat to be supplied to a 660-sl MH canister. The results showed that the operating temperature of the fuel cell can be maintained in the desired range of 60–80 °C. A complementary experimental study was also conducted on an 800-sl MH canister supplying hydrogen to a 130-W fuel cell stack (a slightly scaled-up setup compared to the first experiment). The study confirmed the findings of an earlier theoretical study by the authors that by supplying about 20% of the total cooling load of the stack to a MH canister, its maximum sustainable hydrogen supply rate increased by 70%, allowing for continuous operation of the stack at its rated power.
University of Birmingham Investors' choices between cash and voting rights

This paper examines for the first time dual-class equity crowdfunding as a digital ownership model. Unique to this context, companies can set an investment threshold under which no voting rights are granted, making the issuance of Class A vs. Class B shares, depending on individual investors. Using a sample of 491 offerings on the UK platform Crowdcube from 2011 to 2015, we find that a higher separation between ownership and control rights lowers the probability of success of the offering, the likelihood of attracting professional investors, as well as the long-run prospects. Different from small investors, professional investors care about the implementation of a threshold for the attribution of voting rights and often bid the Class A threshold exactly. Family businesses, although less attractive to small investors, are relatively safer investments, because of their lower chances of failure.
Constraining magma storage conditions 2 at a restless volcano in the Main 3 Ethiopian Rift using phase equilibria 4 models 5

Corresponding Author Email: mlmg3@cam.ac. uk 1 Constraining magma storage conditions 2 at a restless volcano in the Main 3 Ethiopian Rift using phase equilibria 4 models 5 Matthew L. M. Gleeson1,2*, Michael J. Stock1,2, David M. Pyle1, Tamsin A. Mather1, William 6 Hutchison1,3, Gezahegn Yirgu4 and Jon Wade1 7 1Department of Earth Sciences, University of Oxford, South Parks Road, Oxford OX1 3AN, UK. 8 2Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ, UK. 9 3Department of Earth Sciences and Environmental Sciences, University of St Andrews, North Street, 10 St Andrews, KY16 9AL, UK 11 4 School of Earth Sciences, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia 12 ABSTRACT 13 The Main Ethiopian Rift hosts a number of peralkaline volcanic centres, several of which show signs of 14 recent unrest. Due to the low number of historical eruptions recorded in the region and lack of 15 volcanic monitoring, conditions of magma storage in the Main Ethiopian Rift remain poorly 16 constrained. Aluto is one of these restless volcanic centres and identifying magma storage conditions 17 is vital for evaluating the significance of recent periods of unrest. Using Aluto as a case study, we 18 explore magma storage conditions using Rhyolite-MELTS thermodynamic modelling software. We 19 performed ~150 fractional crystallisation models using a primitive basalt as the starting composition, 20 and for a range of pressures (50 – 300 MPa), initial H2O contents (0.5 – 3 wt%) and oxygen fugacities 21 (QFM-2 – QFM+1). Predicted liquid lines of descent from these models are compared with published 22 whole-rock data and, together with new observations of natural phase assemblages and erupted 23 mineral compositions, provide constraints on magma storage conditions.
Criteria and Characteristics of Elevator Noise in Apartments

Elevator noise in apartments can make annoying sounds depending on locations of elevators and the sensitivity of the residents. Some nations have their own criteria regarding noise from elevators, however, South Korea has no such criteria, which makes it difficult to handle the damage due to noise from elevators. Thus, the present study investigated noise criteria in elevators in other nations and identified the noise characteristics during elevator operation to provide foundational data at the time of setup on noise criteria forelevators. The noise criteria in other nations recommend the maximum noise level to be below NC-20–30 and 25–30 dB(A). The noise measurement in elevators showed that the maximum noise level at the adjacent room was NC-29, 31.4 dB(A) in A Apartment, and NC-26~29, 30.8–32.7 dB(A) in B Apartment.
Role of NKT Cells in the Digestive System. II. NKT cells and diabetes

killer T (NKT) cells are a subset of regulatory T lymphocytes that recognize glycolipid antigens presented by the major histocompatibility complex class I-related glycoprotein CD1d. NKT cells have been implicated in regulating the progression of Type 1 diabetes (T1D) in human patients and in an animal model for T1D. In addition, glycolipid agonists of NKT cells have been successful in preventing diabetes in mice, raising enthusiasm for the development of NKT cell-based therapies for T1D.
Queixa subjetiva de comprometimento da memória em idosos saudáveis: influência de sintomas depressivos, percepção de estresse e autoestima

O presente estudo analisou a relacao entre percepcao de estresse, sintomas depressivos e autoestima em idosos com e sem queixa subjetiva de comprometimento de memoria. Foram incluidos 204 idosos (104 sem e 100 com queixa de memoria) avaliados a partir do instrumento Memory Assessment Complain Questionnaire (MAC-Q). O protocolo de estudo incluiu a Escala de Estresse Percebido (EEP), a Escala de Depressao Geriatrica (GDS) e a Escala de Autoestima de Rosenberg (EAE). Os idosos com queixa de comprometimento apresentaram escores significativamente maiores na EEP e GDS e menores na EAE (p < 0.001). Foi observada correlacao negativa entre o escore do MAC-Q e EPP (p < 0.001) e EAE (p = 0.01). A analise de regressao multivariada identificou somente o estresse como fator preditor da queixa subjetiva de memoria. Esses dados sugerem que a percepcao de estresse e os sintomas depressivos estao associados com a queixa de memoria em idosos.
The Utility of PET/CT in External Radiation Therapy Planning of Prostate Cancer

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising PSA after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of Positron Emission Tomography (PET) into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-fluorodeoxyglucose (FDG) PET/CT is now routinely used in radiation planning for several cancer types. However, FDG-PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride (Na-F), 11 C-acetate, 11 C- or 18 F-choline, 18 F-FACBC (fluciclovine, [Axumin™]), and 68 Ga- or 18 F- labeled ligands that bind prostate specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific, but have not yet Food and Drug Administration (FDA) New Drug Application (NDA) approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of fluciclovine-PET/CT for planning of salvage radiotherapy with clinical endpoints are underway. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. homogenous patient
INHERITANCE STUDY OF MATURITY RELATED PLANT TRAITS IN TWO DIVERSE POPCORN GROUPS

Just like both grain and fodder yield maturity traits are also important characters in maize breeding programs. In an experiment four each of parents, F 1 s, F 2 s, BC 1 s and BC 2 s were evaluated at Cereal Crops Research Institute (CCRI), Pirsabak, Nowshehra and The Agriculture University Peshawar. At both locations the experimental material was replicated thrice in randomized complete block design. Data obtained on maturity and plant parameters were subjected to combined analysis of variance. After observing significant generation effects gene actions were calculated using generation mean analysis. In all four crosses dominance gene action was found to be important in the inheritance of both days to anthesis and silking. In all crosses additive gene effect was found negative and significant except in cross PS-Pop-29-2-1 × BD- Pop-2-1-2 for anthesis. The digenic non-allelic epistasis of additive × dominance and dominance × dominance were considered the major contributors in the inheritance of days to anthesis in crosses PS- Pop-1-1-4 × BD-Pop-2-1-2 and PS- Pop-29-2-1 × BD- Pop-2-1-2. Duplicate type of epistasis was observed in cross, PS- Pop-1-1-4 × BD-Pop-1-2-3-3 for days to anthesis and silking, while complementary epistasis was observed in cross PS-Pop-1-2-3-3 × BD- Pop-2-1-2. Similarly, for both plant and ear height, dominant gene action was positive and significant in all crosses except, Pop-29-2-1 × BD- Pop-1-2-3-3 for plant height. Duplicate type of epistasis was observed for ear height in both crosses PS-Pop-1-2-3-3 × BD- Pop-1-2-3-3 and PS-Pop-1-2-3-3 × BD- Pop-2-1-2, while in crossesPS-Pop-29-2-1 × BD-Pop-1-2-3-3 and PS-Pop-29-2-1 × BD-Pop-2-1-2,complementary epistasis was found. It is concluded that crosses in which additive gene effects are high, could be improved effectively for studied characters in coming generations.
Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING Academic and private hospitals. PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION The study was terminated early. CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE Gilead Sciences.
IMMUNOLOGY, HEALTH, AND DISEASE Deletion of the BAC sequences from recombinant meq-null Marek’s disease (MD) virus increases immunosuppression while maintaining protective efﬁcacy against MD protective efficacy

Marek’s disease virus (MDV) GX0101 is a field strain of MDV with a naturally occurring insertion of the reticuloendotheliosis virus (REV) long terminal repeat (LTR) fragment. Both copies of the meq gene were knocked out in the GX0101 bacterial artificial chromosome (BAC) clone to construct the recombinant virus SC9-1, resulting in a complete lack of pathogenicity and providing better protection against MD than CVI988/Rispens. In the present study, the BAC sequences in SC9-1 were removed using a cre-loxP system, and the virus termed SC9-2. SC9-2 showed a significant increase in replication in vitro and in vivo. There was a significant decrease in chicken weight, immune organ index, and antibody levels compared with those of SC9-1-inoculated chickens. The immune protection index of SC9-2 was similar to that of SC9-1, and the difference was not significant. The results of our studies demonstrate that the SC9-2 virus provides protection in specific pathogen free (SPF) chickens when challenged with a very virulent MDV rMd5, but it induces immunosuppressive effects in SPF chickens.
Political Disorders and Economic Growth Nexus during 1960-2020: An Empirical Analysis of South-Asian Countries

Background: The election is a process of transferring power and authorities to lead the public position in democratic practice. This process not only hands over the power for the decision making but also introduces changes in the governing system that influence either way to the individual, firms, community, society, and the entire nation through various governing tools. An election affects the economic system from within and outside in south-Asian countries. Therefore, the south-Asian economy keeps tracking the different types of elections to adjust their economic system accordingly grounded on the level of its harm and benefits. Academic research can provide a directional understanding of how the election can influence the economy. Objective: The major objective of this study is to examine the impact of the national election on the economy in South Asian countries. Methods: This study has employed the panel data of five major south-Asian countries: Bangladesh, India, Nepal, Pakistan, and Sri Lanka, from 1960 to 2020. We collected the series of data from the World Bank database and the official websites of respective countries. The data were empirically analyzed using the difference-in-difference (DID) method and descriptive statistics. Results: An empirical analysis result shows a positive role of the national election in South Asia except for Pakistan. Further, this study also indicates that the coefficient of different-in-difference is positive, indicating a positive impact of the first Constituent Assembly Election-2008 on economic growth in Nepal. However, this analysis also shows that the national election before the Constituent Assembly (CA) Election-2008 had a more significant positive impact on economic growth than the post-CA elections in Nepal. Conclusions: Overall, this study concludes that the national election has a positive impact on economic growth in South Asia except for Pakistan, but the degree of influence depends on the socio-political and economic structure of the respective country in the region. Implications: The findings of this paper would be useful for scholars interested in a sociopolitical economy in the south Asian region and equally valuable for the policy stakeholders.