gebhart/patrepeval huggingface dataset:
Kinetic Analysis of Human T-cell Leukemia Virus Type I Tax-Mediated Activation of NF-κB (1994)

The human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of cellular genes, at least in part, by activating the endogenous NF-kappa B transcription factors. Induced expression of cellular genes is thought to be important for transformation of T cells to continued growth, a prelude to the establishment of adult T-cell leukemia. However, neither underlying mechanisms nor kinetics of the Tax-mediated activation of NF-kappa B are understood. We have analyzed a permanently transfected Jurkat T-cell line in which the expression of Tax is entirely dependent on addition of heavy metals. The initial NF-kappa B binding activity seen after induction of Tax is due almost exclusively to p50/p65 heterodimers. At later times, NF-kappa B complexes containing c-Rel and/or p52 accumulate. The early activation of p50/p65 complexes is a posttranslational event, since neither mRNA nor protein levels of NF-kappa B subunits had increased at that time. We demonstrate for the first time a Tax-induced proteolytic degradation of the NF-kappa B inhibitor, I kappa B-alpha, which may trigger the initial nuclear translocation of NF-kappa B. As nuclear NF-kappa B rapidly and potently stimulates resynthesis of I kappa B-alpha, the steady-state level of I kappa B-alpha does not significantly change. Thus, the dramatic Tax-induced increase in the I kappa B-alpha turnover may continually weaken inhibition and activate NF-kappa B. Additional, distinct actions of Tax may contribute further to the high levels of NF-kappa B activity seen.
Biomarkers for evaluation of mast cell and basophil activation (2018)

Mast cells and basophils play a pathogenetic role in allergic, inflammatory, and autoimmune disorders. These cells have different development, anatomical location and life span but share many similarities in mechanisms of activation and type of mediators. Mediators secreted by mast cells and basophils correlate with clinical severity in asthma, chronic urticaria, anaphylaxis, and other diseases. Therefore, effective biomarkers to measure mast cell and basophil activation in vivo could potentially have high diagnostic and prognostic values. An ideal biomarker should be specific for mast cells or basophils, easily and reproducibly detectable in blood or biological fluids and should be metabolically stable. Markers of mast cell and basophil include molecules secreted by stimulated cells and surface molecules expressed upon activation. Some markers, such as histamine and lipid mediators are common to mast cells and basophils whereas others, such as tryptase and other proteases, are relatively specific for mast cells. The best surface markers of activation expressed on mast cells and basophils are CD63 and CD203. While these mediators and surface molecules have been associated to a variety of diseases, none of them fulfills requirements for an optimal biomarker and search for better indicators of mast cell/basophil activation in vivo is ongoing.
The DSS development system (1983)

As decision support systems become more commonplace, the demand for automatic and semiautomatic DSS development systems increases proportionately. Such systems provide a set of tools that guide the construction of models in response to a user's query. This paper describes a set of such tools that provide capabilities for analysis, design, module management, and report and graphics generation.
Inhibition of the hydrosmotic response to antidiuretic hormone by 3,3′‐diallyldiethylstilbestrol (DADES) (1989)

3,3'-diallyldiethylstilbestrol (DADES), a blocker of the facilitated diffusion of glucose, was found to interfere markedly with the hydrosmotic response to antidiuretic hormone and its related agonists. Frog urinary bladders were isolated and monitored for transmural net water flow. DADES was added either to the serosal or to the apical medium at concentrations ranging from 10(-4) M to 10(-6) M. Pretreatment for 30 min with apical 10(-4) M DADES drastically reduced the subsequent hydrosmotic response: (a) to oxytocin (4.4 x 10(-8) M) by 91.7 +/- 17.6% versus 6.2 +/- 7.8 in control; (b) to 8-bromo 3',5'-cyclic AMP by 93.5 +/- 19.4% versus 19.4 +/- 11.4%; (c) to serosal hyperosmolarity (mannitol 220 mOsm) by 99.3 +/- 0.5% versus 12.3 +/- 18.2%. This effect was dose-dependent. Inhibitory action of DADES was more effective on the apical side than on the serosal side (97.0 +/- 1.5 versus 45.8 +/- 10.8). Freeze-fracture studies revealed a modified distribution of the particles and unusual endocytotic pits and vesicles in the apical membrane of both granular and mitochondria-rich epithelial cells. These observations point to multiple and complex effects of the drug. Thus, it seems that DADES has numerous effects on urinary epithelium, which makes it a nonspecific inhibitor of water permeation. Conclusions on its use should therefore be drawn with suitable caution.
Expanding the donor pool: use of marginal donors for solid organ transplantation (1996)

Organ transplantation has become a viable treatment for an increasing number of patients suffering from irreversible organ failure. In response to the steeply rising demand for transplantation, both the number of transplant centers and the number of patients on waiting lists have grown rapidly. Because organ donation has not kept pace with demand, each year a greater number of patients die while awaiting donor organs. (About 9% of all patients on the list in 1993 but not transplanted died. Death rates were highest, 19% and 16% respectively, for patients awaiting hearts and livers.) Among the factors contributing to the organ shortage are cultural and psychological barriers to donation and missed opportunities to request donation. An accompanying diminution in traumatic deaths of potential young donors has made older and other marginal, or higher-risk, donors the focus of studies on expansion of the donor pool. The studies reviewed herein evaluated donor risk factors such as age, disease (including infection), obesity, cold ischemia time, suboptimal organ function, and nontraumatic causes of death. Overall, broadened criteria for acceptable donor kidneys, hearts, and livers appear to lessen graft survival rates somewhat compared with rates for ideal donor organs. Nonetheless, use of higher-risk organs allows lifesaving transplants that could not otherwise be performed and results in acceptable prognoses for survival. Further research is needed to identify better tests for evaluating donor organs, provide longer-term follow-up of recipients of higher-risk organs, and develop alternative means to fill the donor-organ shortfall.
Antibiotic-resistant ST38, ST131 and ST405 strains are the leading uropathogenicEscherichia coliclones in Riyadh, Saudi Arabia (2015)

Our findings highlight the presence of MDR, CTX-M-positive ST38, ST131 and ST405 UPEC in Saudi Arabia. The high proportion of isolates with CTX-M is a particular concern. We suggest that ST38 UPEC warrant further study.
Abstract CT079: Neoadjuvant PD-1 blockade in resectable lung cancer (2018)

Abstract Background: Programmed death-1 (PD-1) blocking antibodies improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, where little progress has been made over the last decade. Methods: Adults with untreated surgically resectable stage I-IIIA NSCLC received two doses of nivolumab (anti-PD-1) preoperatively. The primary endpoints of the study were safety and feasibility. Tumor pathologic response, PD-L1 expression, mutation burden and mutation-associated neoantigen-specific T-cell responses were evaluated. Results: Neoadjuvant nivolumab was had an acceptable side effect profile without surgical delays, and 20 of 21 tumors were completely resected. Major pathologic response occurred in 45% (9/20) of resected tumors. Responses occurred in both PD-L1 positive and negative tumors. Pathologic response significantly correlated with pre-treatment tumor somatic mutation burden. T-cell clones shared between the tumor and peripheral blood increased systemically upon anti-PD-1 treatment in 8 of 9 patients analyzed. Mutation-associated neoantigen-specific T-cell clones, from a primary tumor that underwent pathologic complete response, rapidly expanded in peripheral blood at 2-4 weeks post-treatment, some of these clones were not detected before anti-PD-1. Conclusions: Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced major pathologic responses in 45% of resected tumors. Tumor mutation burden is predictive of pathologic response to anti-PD-1. Anti-PD-1 can induce expansion of mutation-associated neoantigen-specific T-cell clones in peripheral blood. [P.M.F., J.E.C., and K.N.S. contributed equally to this work.] Citation Format: Patrick M. Forde, Jamie E. Chaft, Kellie N. Smith, Valsamo Anagnostou, Tricia R. Cottrell, Matthew D. Hellmann, Marianna Zahurak, Stephen C. Yang, David R. Jones, Stephen Broderick, Richard J. Battafarano, Moises J. Velez, Natasha Rekhtman, Zachary Olah, Jarushka Naidoo, Kristen A. Marrone, Franco Verde, Haidan Guo, Jiajia Zhang, Justina X. Caushi, Hok Yee Chan, John-William Sidhom, Robert B. Scharpf, James White, Edward Gabrielson, Hao Wang, Gary L. Rosner, Valerie Rusch, Jedd D. Wolchok, Taha Merghoub, Janis M. Taube, Victor E. Velculescu, Suzanne L. Topalian, Julie R. Brahmer, Drew M. Pardoll. Neoadjuvant PD-1 blockade in resectable lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT079.
Label-Free Quantitative Proteomic Analysis Reveals Inflammatory Pattern Associated with Obesity and Periodontitis in Pregnant Women (2022)

Obesity and pregnancy may have synergistic effects on periodontal condition, and proteomics could be an ideal approach to highlight the pathophysiological mechanisms associated with these outcomes. This study analyzed the salivary proteomics related to obesity and periodontitis in women during pregnancy (T1) and after delivery (T2). Initially, 126 women were recruited and forty were allocated into groups: with obesity and periodontitis (OP); with obesity, but without periodontitis (OWP); with normal BMI, but with periodontitis (NP); with normal BMI and without periodontitis (NWP). Whole-mouth saliva was collected in T1 and T2, and proteins were extracted and individually processed by label-free proteomics (<i>nLC-ESI-MS/MS</i>). The up-regulations of <i>Heat shock 70 kDa protein 1A</i>, <i>1B</i>, and <i>1-like</i> were related to both obesity and periodontitis, separately. <i>Albumin</i> and <i>Thioredoxin</i> were up-regulated in periodontitis cases, while <i>Cystatins</i> (mainly <i>S</i>, <i>SA</i>, <i>SN</i>) and <i>Lactotransferrin</i> were down-regulated. The high abundances of <i>Submaxillary gland androgen-regulated protein 3B</i>, <i>Protein S100-A8</i>, <i>Matrix metalloproteinase-9</i>, <i>Heat shock 70 kDa protein 2</i> and <i>6</i>, <i>Putative Heat shock 70 kDa protein 7</i>, <i>Heat shock 71 kDa protein</i>, <i>Haptoglobin</i> and <i>Plastin-1</i> were significant in the combination of obesity and periodontitis. Obesity and periodontitis remarkably altered the proteome of the saliva during pregnancy with substantial alterations after delivery.
The SMAC mimetic, LCL-161, reduces survival in aggressive MYC-driven lymphoma while promoting susceptibility to endotoxic shock (2016)

Inhibitor of apoptosis proteins (IAPs) antagonize caspase activation and regulate death receptor signaling cascades. LCL-161 is a small molecule second mitochondrial activator of caspase (SMAC) mimetic, which both disengages IAPs from caspases and induces proteasomal degradation of cIAP-1 and -2, resulting in altered signaling through the NFκB pathway, enhanced TNF production and sensitization to apoptosis mediated by the extrinsic pathway. SMAC mimetics are undergoing clinical evaluation in a range of hematological malignancies. Burkitt-like lymphomas are hallmarked by a low apoptotic threshold, conveying sensitivity to a range of apoptosis-inducing stimuli. While evaluating LCL-161 in the Eμ-Myc model of aggressive Burkitt-like lymphoma, we noted unexpected resistance to apoptosis induction despite 'on-target' IAP degradation and NFκB activation. Moreover, LCL-161 treatment of lymphoma-bearing mice resulted in apparent disease acceleration concurrent to augmented inflammatory cytokine-release in the same animals. Indiscriminate exposure of lymphoma patients to SMAC mimetics may therefore be detrimental due to both unanticipated prolymphoma effects and increased susceptibility to endotoxic shock.
Structure and function of nicotinic receptors (1994)

The neuronal nicotinic acetylcholine receptor gene family encodes proteins that form either homo­oligomeric or hetero-oligomeric ligand gated ion channels. Although the total number of combinations of possible receptors is large, only a few have been demonstrated to function in the oocyte expression system. However, those that have been expressed differ from each other in several important ways. Receptors expressed in oocytes differ with respect to the ligands that activate them, their single channel properties, their permselectivity, and their modulation by external calcium. Furthermore, some cells express several of the genes that encode these receptor subunits and assemble receptors that contain a subset of the expressed genes. There are, therefore, probably mechanisms responsible for the assembly and targeting of receptors containing specific combinations of subunits. We investigated this possibility initially focussing on the homo-oligomeric alpha7 receptor and identified a requirement for the activity of a peptidyl prolyl isomerase in the assembly of this receptor. This requirement is shared by the serotonin-gated ion channel. We have created a number of mutations in the alpha 7 protein to try to identify relevant proline residues and have examined the expression of these mutant receptors in the Xenopus oocyte expression system.
Mechanisms of Alloimmunization and Subsequent Bone Marrow Transplantation Rejection Induced by Platelet Transfusion in a Murine Model (2012)

For many nonmalignant hematological disorders, HLA-matched bone marrow transplantation (BMT) is curative. However, due to lack of neoplasia, the toxicity of stringent conditioning regimens is difficult to justify, and reduced intensity conditioning is used. Unfortunately, current reduced intensity regimens have high rates of BMT rejection. We have recently reported in a murine model that mHAs on transfused platelet products induce subsequent BMT rejection. Most nonmalignant hematological disorders require transfusion support prior to BMT and the rate of BMT rejection in humans correlates with the number of transfusions given. Herein, we perform a mechanistic analysis of platelet transfusion-induced BMT rejection and report that unlike exposure to alloantigens during transplantation, platelet transfusion primes alloimmunity but does not stimulate full effector function. Subsequent BMT is itself an additional and distinct immunizing event, which does not induce rejection without antecedent priming from transfusion. Both CD4(+) and CD8(+) T cells are required for priming during platelet transfusion, but only CD8(+) T cells are required for BMT rejection. In neither case are antibodies required for rejection to occur.
Modeling Mercury Removal by Sorbent Injection (1999)

Sorbents for removing mercury from flue gases of coal-fired power plants are presently being evaluated due to potential regulation of mercury emissions under Title III of the 1990 Clean Air Act Amendments. Laboratory tests have been conducted to evaluate the adsorption characteristics of potential sorbents and the effects of flue gas constituents on these characteristics. This paper presents a theoretical model that combines the adsorption characteristics measured in the lab with mass transfer considerations to predict mercury removal by the duct injection process in actual flue gas streams. The model was used to determine the effect of various sorbent properties on mercury removal when injecting a powdered sorbent upstream of either an electrostatic precipitator (ESP) or fabric filter. Mercury removal is expected to differ between these configurations since the mass transfer conditions are different in an ESP and fabric filter. The model was used to determine when mercury removal is limited by mass transfer and when it is limited by sorbent capacity. This information defines conditions when removal can be improved by reducing particle size or increasing sorbent capacity. In both cases, removal can be increased by injecting more sorbent.
On spatial beam self-cleaning from the perspective of optical wave thermalization in multimode graded-index fibers (2023)

The input power-induced transformation of the transverse intensity profile at the output of graded-index multimode optical fibers from speckles into a bell-shaped beam sitting on a low intensity background is known as spatial beam self-cleaning. Its remarkable properties are the output beam brightness improvement and robustness to fiber bending and squeezing. These properties permit to overcome the limitations of multimode fibers in terms of low output beam quality, which is very promising for a host of technological applications. In this review, we outline recent progress in the understanding of spatial beam self-cleaning, which can be seen as a state of thermal equilibrium in the complex process of modal four-wave mixing. In other words, the associated nonlinear redistribution of the mode powers which ultimately favors the fundamental mode of the fiber can be described in the framework of statistical mechanics applied to the gas of photons populating the fiber modes. On the one hand, this description has been corroborated by a series of experiments by different groups. On the other hand, some open issues still remain, and we offer a perspective for future studies in this emerging and controversial field of research.
Phospholipase Dα1-derived phosphatidic acid interacts with ABI1 phosphatase 2C and regulates abscisic acid signaling (2004)

Phospholipase D (PLD) and protein phosphatase 2C (PP2C) both play a role in mediating plant responses to abscisic acid (ABA). In this article, we show that PLD alpha 1 and its product, phosphatidic acid (PA), regulate a PP2C, ABI1, which is a negative regulator of ABA responses in Arabidopsis. Leaves from a T-DNA insertional mutant of PLD alpha 1 and PLD alpha 1-antisense plants lose more water than do wild-type plants. The stomatal closure of PLD alpha 1-null leaves is insensitive to ABA but is promoted by PA. ABA treatment promotes an increase in PA from phosphatidylcholine in wild type but not in PLD alpha 1-null cells. PLD alpha 1-derived PA binds to ABI1; the PA-ABI1 binding is demonstrated by coprecipitating PA with ABI1 from plant cells, measuring binding of PA from vesicles to ABI1, and assaying ABI1 bound to PA immobilized on a filter. Deletion and site-specific mutational analyses show that arginine 73 in ABI1 is essential for PA-ABI1 binding. PA binding decreases the phosphatase activity of ABI1. The lack of ABA-induced production of PA in PLD alpha 1-null cells results in a decrease in the association of ABI1 with the plasma membrane in response to ABA. These results indicate that PA produced by PLD alpha 1 inhibits the function of the negative regulator ABI1, thus promoting ABA signaling. The identification of ABI1 as a direct target of the lipid messenger PA provides a functional link between the two families of important signaling enzymes, PLD and PP2C.
The Correct Use of Platinum in the XRF Laboratory (1997)

The use of crucibles and dishes made of platinum and its alloys in the preparation of samples has become an essential feature of XRF analysis. The broad application of platinum results from its near-perfect oxidation resistance and its excellent resistance to corrosive attack by metal oxide melts such as XRF fluxing agents. However, a few basic rules must be adhered to if platinum ware is to give satisfactory service. A number of ‘platinum poisons,’ which are commonly encountered in samples, can cause destruction within a few sample preparation cycles. These ‘poisons,’ the reasons for their corrosive effects and techniques for minimizing or eliminating their influence are outlined. © 1997 by John Wiley & Sons, Ltd.
Utilizing Consumer Perception of Edamame to Guide New Variety Development (2021)

Consumption of edamame (vegetable soybeans) has increased significantly in the U.S. over the last 20 years. Although market demand has been increasing, most edamame is still imported from Asian countries. A team of multistate plant-breeding programs in the mid-Atlantic and Southeast U.S. has focused on developing new breeding lines that grow well in the U.S. and deliver what domestic growers, processors and consumers need and expect from their edamame. In our study, sensory evaluation was used to identify edamame genotypes and sensory attributes preferred by consumers to support breeding selection criteria. In the first year (reported as our “screening study”), 20 edamame genotypes were grown in three locations: Newport, AR, and Blacksburg and Painter, VA. In the second year (reported as our “validation study”), 10 edamame genotypes selected after our screening study were grown in Blacksburg and Painter, VA, Portageville, MO, and Stoneville, MS. In both years of research, untrained participants (adults; vegetable consumers not allergic to soy; N ≥ 50) used a traditional 9-point acceptability (hedonic) scale (1 = “dislike extremely”; 9 = “like extremely”) to evaluate overall-liking, aroma, appearance, taste, and texture, and a 5-point scale (1 = “not sweet,” 5 = “extremely sweet”) to evaluate sweetness intensity. Next, participants used a check-all-that-apply (CATA) list of selected sensory terms to describe the sensory characteristics of each edamame sample. Overall acceptability of edamame genotypes was significantly different among all genotypes ( p &amp;lt; 0.05). Samples described as “bitter,” “sour” (flavor) or “starchy” (texture) were associated with lower acceptability scores while “salty” and “sweet” (flavor) were correlated with higher acceptability. Sensory data from the screening study were used to select the best genotypes by use of a defined decision process based on the consumer data. The validation study tested the selection decisions and further supported the genotype choices. Sensory evaluation is a powerful tool to direct breeders to improve market acceptability and develop new edamame genotypes. Both screening and validation studies illustrate the significant role of consumer sensory data in support of genotypes targeted for domestic (U.S.) production.
Enhanced Energy Localization in Hyperthermia Treatment Based on Hybrid Electromagnetic and Ultrasonic System: Proof of Concept with Numerical Simulations (2017)

This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors.