gebhart/patrepeval huggingface dataset:
IL-17A–Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis (2020)

Hypersensitivity pneumonitis (HP) typically presents with interstitial inflammation and granulomas induced by an aberrant immune response to inhaled Ags in sensitized individuals. Although IL-17A is involved in the development of HP, the cellular sources of IL-17A and the mechanisms by which IL-17A contributes to granuloma formation remain unclear. Recent studies report that γδ T cells produce IL-17A and exhibit memory properties in various diseases. Therefore, we focused on IL-17A-secreting memory γδ T cells in the sensitization phase and aimed to elucidate the mechanisms by which IL-17A contributes to granuloma formation in HP. We induced a mouse model of HP using pigeon dropping extract (PDE) in wild-type and IL-17A knockout (IL-17A<sup>-/-</sup>) mice. IL-17A<sup>-/-</sup> mice exhibited reduced granulomatous areas, attenuated aggregation of CD11b<sup>+</sup> alveolar macrophages, and reduced levels of CCL2, CCL4, and CCL5 in the bronchoalveolar lavage fluid. Among IL-17A<sup>+</sup> cells, more γδ T cells than CD4<sup>+</sup> cells were detected after intranasal PDE administration. Interestingly, the expansion of IL-17A-secreting Vγ4<sup>+</sup> or Vγ1<sup>-</sup>Vγ4<sup>-</sup> cells of convalescent mice was enhanced in response to the sensitizing Ag. Additionally, coculture of macrophages with PDE and Vγ4<sup>+</sup> cells purified from PDE-exposed convalescent mice produced significantly more IL-17A than coculture with Vγ4<sup>+</sup> cells from naive mice. Our findings demonstrate that in the sensitization phase of HP, IL-17A-secreting memory γδ T cells play a pivotal role. Furthermore, we characterized the IL-17A/CCL2, CCL4, CCL5/CD11b<sup>+</sup> alveolar macrophage axis, which underlies granuloma formation in HP. These findings may lead to new clinical examinations or therapeutic targets for HP.
Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size (2019)

Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.
High expression of glycosphingolipids involved in procoagulant activity of cancer cells. (1999)

To investigate the involvement of tumor-associated antigens such as sLe(a) and sLe(x), as well as Le(y) glycosphingolipid in the procoagulant activity of cancer cells, we examined the relationship between the inhibitory effect of anti-sLe(a) or anti-sLe(x) antibodies on the procoagulant activity of cancer cells, and cell surface expression of sLe(a) and sLe(x) antigens. We observed that the procoagulant activity of cancer cells which highly expressed sLe(a) or sLe(x) antigens (expression rate >70%) was significantly inhibited by the relevant antibodies. These data suggested that not only Le(y) but also sLe(a) and sLe(x) antigens play an important role in coagulation induced by various cancer cells.
Alteration of the fecal microbiota in Chinese patients with Schistosoma japonicum infection (2021)

Schistosoma japonicum infection causes pathological injury to the host. Multiple studies have shown that intestinal helminth infection causes dysbiosis for the gut microbial community and impacts host immunology. However, the effect of acute S. japonicum infection on the gut microbiome structure (abundance and diversity) is still unclear. We collected fecal samples from healthy and infected patients from a single hospital in Hunan Province, China. The bacterial community was analyzed using 16S ribosomal RNA gene sequencing of the V4 hypervariable region using the HiSeq platform. Compared with healthy subjects, infected patients exhibited an increase in relative abundance of the TM7 phylum. At the genus level, there were seven differentially abundant genera between groups. The most significant finding was a Bacteroides enterotype in patients with acute schistosomiasis. These results suggest that S. japonicum infection has a significant effect on microbiome composition characterized by a higher abundance of the TM7 phylum and development of a Bacteroides enterotype.
Systemic mastocytosis associated with acute myeloid leukaemia: report of two cases and detection of the c‐kit mutation Asp‐816 to Val (1998)

A subset of patients with systemic mastocytosis (SM) develop acute myeloid leukaemia (AML). However, little is known about the biology of such leukaemias and their relationship to the mast cell (MC) lineage. We report on two female patients who suffered from SM and AML. According to FAB criteria, the leukaemias were classified as AML-M4 (patient 1) and AML-MO (patient 2). The coexistence of the two distinct neoplasms (AML and SM) was demonstrable by immunostaining of serial bone marrow (BM) sections with monoclonal antibodies (mAb). In particular, the MC infiltrates were found to react with mAb against MC-tryptase and MC growth factor receptor c-kit (CD117), but not with mAb to CD15 or CD34. In contrast, the AML blasts were immunoreactive for CD15 (patient 1) or CD34 (patient 2), but did not express tryptase. The c-kit point mutation Asp-->Val at codon 816, considered to play a role in the transformation of MC progenitors, was detected in patient 1 in a BM cell fraction containing 4% MC. However, no c-kit mutation was found in pure AML blasts (<1% MC). These findings argue against an evolution of the AML clone from neoplastic MC or MC-committed progenitors.
Alternative Materials for Mask Construction by the Public (2020)

N95 respirators became scarce to the general public in mid-to-late March of 2020 due to the SARS-CoV-2 epidemic. By mid-April of 2020, most states in the United States were requiring face coverings to be worn while in public enclosed places and in busy outdoor areas where groups of people were in close proximity. Many resorted to cloth masks, homemade masks, procedure masks obtained through online purchases, and other ad-hoc means. Thus, there was and still is a need to determine the aerosol filtration efficacy of commonly available materials that can be used for homemade mask construction. This study focused on non- woven polymeric fabrics that are readily available for homemade mask construction. The conclusion of this study is that non-woven materials that carry a high electric charge or those that can easily acquire charge had the highest aerosol filtration efficiency per unit of pressure drop. Future work should examine a wider variety of these materials and determine the maximum pressure drop that a nominal homemade mask can withstand before a significant portion of airflow is diverted around the mask. More broadly, a better understanding of the charge state on non-woven materials and impact of that charge state on filtration efficiency is needed.
Exercise and thiazolidinedione therapy normalize insulin action in the obese Zucker fatty rat. (2000)

Thiazolidinediones and exercise are both known to improve insulin action independently. Therefore, we determined whether combined therapy could normalize insulin action in the Zucker fatty (ZF) rat. Rats were fed troglitazone as a 0.2% food admixture over a 3-week exercise training period (treadmill running 5 days/week, 20 m/min, 0% grade, 60 min/day). Subsequent to drug and/or exercise therapy, animals were chronically cannulated in the carotid artery (sampling) and jugular vein (infusion). After a 4-day recovery from surgery, animals were exposed to a hyperinsulinemic (40 mU x kg(-1) x min(-1)) euglycemic clamp (8.5 +/- 0.12 mmol/l; P = 0.45 between groups). Independently, exercise (n = 7) and troglitazone (n = 7) improved the glucose disposal rate 20% (P = 0.04) and 76% (P = 0.001), respectively, when compared with untreated ZF controls (n = 11). In combination, exercise and troglitazone therapy (n = 6) produced significant increments in the following: tracer-determined glucose disposal rate (combined therapy, 52.4 +/- 2.9 mg x kg(-1) x min(-1), vs. untreated ZF, 25.8 +/- 0.8 mg x kg(-1) x min(-1); P = 0.0001), total GLUT4 protein (twofold increase; P = 0.001), insulin receptor substrate (IRS)-1 protein (fourfold increase; P = 0.0001), and Akt phosphorylation (2.9-fold increase; P = 0.002). In conclusion, 1) exercise and troglitazone therapy each improved insulin action in the ZF rat, whereas the combination of the two led to complete normalization of insulin sensitivity, and 2) combination treatment also resulted in normalization of GLUT4 total protein, IRS-1 protein, and Akt phosphorylation compared with lean littermates.
Identification of Novel Tumor-Associated Cell Surface Sialoglycoproteins in Human Glioblastoma Tumors Using Quantitative Proteomics (2014)

Glioblastoma multiform (GBM) remains clinical indication with significant "unmet medical need". Innovative new therapy to eliminate residual tumor cells and prevent tumor recurrences is critically needed for this deadly disease. A major challenge of GBM research has been the identification of novel molecular therapeutic targets and accurate diagnostic/prognostic biomarkers. Many of the current clinical therapeutic targets of immunotoxins and ligand-directed toxins for high-grade glioma (HGG) cells are surface sialylated glycoproteins. Therefore, methods that systematically and quantitatively analyze cell surface sialoglycoproteins in human clinical tumor samples would be useful for the identification of potential diagnostic markers and therapeutic targets for malignant gliomas. In this study, we used the bioorthogonal chemical reporter strategy (BOCR) in combination with label-free quantitative mass spectrometry (LFQ-MS) to characterize and accurately quantify the individual cell surface sialoproteome in human GBM tissues, in fetal, adult human astrocytes, and in human neural progenitor cells (NPCs). We identified and quantified a total of 843 proteins, including 801 glycoproteins. Among the 843 proteins, 606 (72%) are known cell surface or secreted glycoproteins, including 156 CD-antigens, all major classes of cell surface receptor proteins, transporters, and adhesion proteins. Our findings identified several known as well as new cell surface antigens whose expression is predominantly restricted to human GBM tumors as confirmed by microarray transcription profiling, quantitative RT-PCR and immunohistochemical staining. This report presents the comprehensive identification of new biomarkers and therapeutic targets for the treatment of malignant gliomas using quantitative sialoglycoproteomics with clinically relevant, patient derived primary glioma cells.
Faecalibacterium: a bacterial genus with promising human health applications (2023)

In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases in the abundance of specific bacterial groups. One example is the genus Faecalibacterium. Numerous studies have underscored that low levels of Faecalibacterium are correlated with inflammatory conditions, with inflammatory bowel disease (IBD) in the forefront. Its representation is also diminished in the case of several diseases, including colorectal cancer (CRC), dermatitis, and depression. Additionally, the relative presence of this genus is considered to reflect, at least in part, intestinal health status because Faecalibacterium is frequently present at reduced levels in individuals with gastrointestinal diseases or disorders. In this review, we first thoroughly describe updates to the taxonomy of Faecalibacterium, which has transformed a single-species taxon to a multispecies taxon over the last decade. We then explore the links discovered between Faecalibacterium abundance and various diseases since the first IBD-focused studies were published. Next, we examine current available strategies for modulating Faecalibacterium levels in the gut. Finally, we summarize the mechanisms underlying the beneficial effects that have been attributed to this genus. Together, epidemiological and experimental data strongly support the use of Faecalibacterium as a next-generation probiotic (NGP) or live biotherapeutic product (LBP).
Evaluation of clinical outcomes by analysis of mutations in tumor tissue and circulating plasma DNA using next-generation sequencing (NGS) from STEAM, a prospective, randomized, multicenter study in metastatic colorectal cancer (mCRC). (2017)

11510 Background: STEAM (NCT01765582) assessed the efficacy and safety of concurrent (c) and sequential (s) FOLFOXIRI-bevacizumab (BEV) vs FOLFOX-BEV for first-line treatment of mCRC. Methods: The AVENIO ctDNA Expanded Kit (Research Use Only) was used to assess somatic mutations in 77 cancer-related genes by NGS in tissue, and both pre- and post-induction plasma samples (n = 182, 150 and 118 respectively) from STEAM. Four mutation classes including single-nucleotide variants (SNVs), indels, copy number amplifications (CNAs) and fusions were identified. SNVs and indels were called in tissue and plasma at allele frequencies of 5% and 0.25% respectively. Results: Overall concordance of mutations in pre-induction plasma with tissue was 83%. Concordance for the seven most mutated genes ranged from 91.5%-100%. In pts with matched samples (n = 118), RAS WT pts showed significantly longer progression-free survival (PFS) in both cFOLFOXIRI-BEV (A) and sFOLFOXIRI-BEV (B) arms versus FOLFOX-BEV (C), using genotyping of either tissue or plasma. This was not seen in RAS MUT pts. In contrast, TP53 WT showed no significant treatment differences while TP53 MUT showed longer PFS for cFOLFOXIRI-BEV versus FOLFOX-BEV. A list of mutation frequencies for all samples, as well as hierarchical clustering analysis of tissue mutations will be presented. Conclusions: The AVENIO ctDNA Expanded Kit identified mutations in 77 cancer-related genes, in both plasma and tissue, with high overall concordance. Compared to FOLFOX-BEV, longer PFS was observed for c- or s- FOLFOXIRI-BEV in RAS WT pts and for cFOLFOXIRI-BEV in TP53 MUT pts, irrespective of sample type. These results are hypothesis generating and require further clinical validation. Clinical trial information: NCT01765582. [Table: see text]
Expanded Performance Characterization of the NASA HERMeS Hall Thruster (2022)

View Video Presentation: https://doi.org/10.2514/6.2022-1353.vid This work presents a summary of a detailed performance assessment of the Hall Effect Rocket with Magnetic Shielding (HERMeS) Technology Demonstration Unit 3 (TDU-3) thruster at an expanded set of throttle conditions. First, an assessment was performed of TDU3 performance and stability at the previously-tested throttle points of 300 V/6.25 kW, 400 V/8.33 kW, 500 V/10.42 kW, and 600 V/12.5 kW that confirmed TDU-3 was operating nominally and consistent with historical baselines. TDU-3 performance and stability were then assessed throughout the throttle range of 2.6-12 kW and shown to mirror the characteristics observed at the previously tested conditions. Finally, a statistical estimate for the thrust specification at the expanded set of throttle conditions was computed and found to yield similar tolerance ranges to those calculated for the heritage conditions. Taken together, these results provide strong evidence that the demonstrated performance characteristics of the HERMeS design are preserved at the expanded set of throttle conditions.
Contact with stimulated T cells up-regulates expression of peptidylarginine deiminase 2 and 4 by human monocytes (2012)

Contact between stimulated T cells and monocyte-macrophages or cytokine-activated monocyte-macrophages constitutes a highly likely source of PAD2 and PAD4, which are observed in inflamed synovial tissues. In contrast, it is most unlikely that fibroblastic synoviocytes contribute to PAD expression in rheumatoid synovial membranes.
Conformational change of band 3 protein induced by diethyl pyrocarbonate modification in human erythrocyte ghosts (1989)

Diethyl pyrocarbonate inhibited the phosphate exchange across the human erythrocyte membrane. The exchange rate was inhibited only when the membranes were modified with the reagent from the cytosolic surface of resealed ghosts. The intracellular modification by diethyl pyrocarbonate inhibited the extracellular binding of [3H]dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid to band 3 protein. Furthermore, the extracellular 4,4'-dinitrostilbene-2,2'-disulfonic acid protected the membranes from the intracellular modification by diethyl pyrocarbonate. These results suggest that the extracellular binding of 4,4'-dinitrostilbene-2,2'-disulfonic acid to band 3 protein induces the conformational change of the intracellular counterpart of band 3 protein and the diethyl pyrocarbonate susceptible residue(s) is (are) hidden from the cytosolic surface of the cell membrane in connection with the conformational change. Conversely, under the conditions where the diethyl pyrocarbonate modification is confined to the intracellular side of the membrane, the extracellular binding site of [3H]dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid is hidden from the cell surface.
Subunit Analyses of a Novel Thermostable Glucose Dehydrogenase Showing Different Temperature Properties According to Its Quaternary Structure (1999)

We previously reported a novel glucose dehydrogenase (GDH) showing two peaks in the optimum temperature for the reaction at around 45°C and at around 75°C. Each peak derived from hetero-oligomeric enzyme, constructed from two distinct peptides with an α-subunit (MWs 67,000) and β-subunit (MWs 43,000), and a single peptide enzyme containing an α-subunit alone. The function of the two subunits in the thermostable co-factor binding GDH was investigated. The results of spectroscopic analyses indicated that the α-subunit contained an unknown co-factor showing specific fluorescence spectra like pyrroloquinoline quinone (PQQ), and the β-subunit was cytochrome c. Moreover, the results of a urea denaturation and reconstitution experiment suggested that the dissociation of the hetero-oligomeric complex to a single peptide was reversible. The kinetic parameter analyses for glucose and the electron mediator also suggested that the β-subunit was responsible for electron transfer from the catalytic center of the α-subunit to the electron mediator.
Parameterized congruences in ACL2 (2006)

Support for congruence-based rewriting is built into ACL2. This capability allows ACL2 to treat certain predicate relations "just like equality" under appropriate conditions and allows specific theorems involving those equivalence relations to be used as rewrite rules to guide the simplification process. Although this has proven to be an extremely powerful capability, it comes with limitations. One significant limitation is that equivalence relations cannot be parameterized. This precludes one very natural application of congruences: their use in reasoning about arbitrary modulus arithmetic. We have developed a technique for emulating parameterized congruence-based rewriting on a stock ACL2 system using binding hypotheses and bind-free. We have also developed a library (nary) that provides a means of expressing and utilizing such congruences with a high degree of automation. We demonstrate the application of this library to problems in modular arithmetic and other similar domains.
SILP at SIPS: Combining Pharmaceuticals with Ionic Liquids on Silica-Supports (2018)

Ionic Liquids (ILs, salts that melt below 100 °C) loaded on silica have been studied for gas phase reactions, but they have not been used in solution due to the leaching properties of the ILs and the deactivation of the catalyst. One area where the Supported Ionic Liquid Phase (SILP) strategy would be a tremendous advantage would be in the loading of ILs that are intended and necessarily leached in order to carry out their functions, as is the case of ILs of Active Pharmaceutical Ingredients (APIs). We have found that IL-APIs are readily loaded and leached from silica, giving to the material a few advantages, including the ability to deliver these liquid salt drugs in solid form as free flowing powders. This presentation will discuss the loading, leaching, and favorable physical and chemical properties exhibited by these IL-APIs in solid form.
Overcoats for the improved performance of PdCr high temperature thin film strain gages (1998)

Overcoat protection schemes for thin film devices have typically focused on inhibiting the growth of native oxides formed on the sensor surface, rather than on improving the passivating nature of these native oxides. Here, thin sputtered Cr overcoats and heat treatments in varying oxygen partial pressures enhanced the passivating nature of native Cr203 films formed on PdCr thin film strain gages. Results of strain tests using sensors protected using this approach are presented and the implications are discussed. PdCr gages with sputtered Cr overcoats withstood 12,000 dynamic strain cycles of 1100 micro-epsilon during 100 hours of testing at a temperature of 1000 C in air. Gage factors of 1.3 with drift rates as low as 0.1 Omega/hr were achieved for devices having a nominal resistance of approximately 100 Omega's. TCR's ranging from +550 ppm/C to +798 ppm/C were realized depending on the overcoat and thermal history. Possible mechanisms for an anomaly in the electrical characteristics of these films at 800 C and improvements in stability due to the use of overcoats are presented.