gebhart/patrepeval huggingface dataset:
Triggering of T Cell-Mediated Immune Responses by Allogenic Tumor Cell Vaccine in Patients with Oral Cancer (2006)

We investigated the immunomodulatory activity of allogenic whole tumor cell vaccine in oral cancer patients in vitro by two-color flow cytometry. Vaccine treatment significantly increased the expression of CD69 and HLA-DR in CD3+ T-cell subsets. The frequency of Interferon-gamma and Interleukin (IL)-2 expressing CD4+/CD8+ T-cell subsets was significantly higher with a concomitant reduction in IL-4 and IL-10 expressing T-cells in the vaccine treated group as compared with the untreated controls. Vaccine treatment significantly increased T-cell receptor (TCR), Vbeta3, Vbeta5 and Vbeta8 usage. The results indicate that the allogenic whole tumor cell vaccine is able to trigger T-cell mediated immunity in patients with intraoral squamous cell carcinoma.
RETRACTED: Cancer-Associated PP2A Aα Subunits Induce Functional Haploinsufficiency and Tumorigenicity (2005)

The introduction of SV40 small t antigen or the suppression of PP2A B56gamma subunit expression contributes to the experimental transformation of human cells. To investigate the role of cancer-associated PP2A Aalpha subunit mutants in transformation, we introduced several PP2A Aalpha mutants into immortalized but nontumorigenic human cells. These PP2A Aalpha mutants exhibited defects in binding to other PP2A subunits and impaired phosphatase activity. Although overexpression of these mutants failed to render immortalized cells tumorigenic, partial suppression of endogenous PP2A Aalpha expression activated the AKT pathway and permitted cells to form tumors in immunodeficient mice. These findings suggest that cancer-associated Aalpha mutations contribute to cancer development by inducing functional haploinsufficiency, disturbing PP2A holoenzyme composition, and altering the enzymatic activity of PP2A.
Serum Levels of Glycosyltransferases and Related Glycoproteins as Indicators of Cancer: Biological and Clinical Implications (1981)

Many studies have suggested that malignant transformation is associated with fundamental changes in the cell surface; similar changes have been described for normal stem cells and cells of embryonic or fetal origin. There is now evidence that the tumor cell secretes or sheds glycoproteins and glycosyltransferases into the surrounding medium and into serum. There are claims that some of these serum glycoproteins and glycosyltransferases are associated with, or specifically related to, the extent of tumor growth and may serve as a cancer marker. A cancer-associated galactosyltransferase isoenzyme (GT-II) has been described and purified. Different isoelectric forms of fucosyltransferase have also been described as indicative of malignancy. The articles to be published in CRC Critical Reviews in Clinical Laboratory Sciences will analyze the evidence for the association of these membrane factors with tumor growth. In order to better understand the possible significance of altered glycoproteins and of increased or different forms of glycosyltransferases during tumor growth, recent data on glycoprotein synthesis will be discussed including the new concepts on the control of glycoprotein synthesis through lipid intermediates. The possible mechanisms whereby malignant transformation could alter glycoprotein synthesis will be discussed with particular emphasis on the significance of these alterations to the biology of the malignant cell. Changes in surface membrane glycoproteins have long been implicated in the ability of a cell to metastasize. Secretion and/or shedding of the cell surface may also be important in the process of metastasis and in altering the host immune response. Detection and the study of these "shed" materials in patients appear to be indicating a new approach to cancer biology detection and therapy.
Characterization and Mutational Analysis of a Cluster of Three Genes Expressed Preferentially during Sporulation of Saccharomyces cerevisiae (1986)

A differential hybridization screen of a genomic yeast DNA library previously identified 14 genes of Saccharomyces cerevisiae that are expressed preferentially during sporulation. Three of these sporulation-specific genes, SPS1, SPS2, and SPS3, have been shown to be closely linked. A mutational analysis has demonstrated that expression of the SPS1 gene, but not the SPS2 gene, is essential for the completion of sporulation. A diploid MATa/MAT alpha strain homozygous for a disruption of the SPS1 gene failed to form asci when subjected to sporulation conditions. The 3' end of the transcript encoded by the SPS1 gene was found to map only 185 base pairs from the 5' end of the SPS2 gene. The SPS1-SPS2 intergenic region was shown to contain all of the regulatory sequences necessary for the sporulation-specific activation of the SPS2 gene as assessed by expression of a translational SPS2-lacZ fusion gene present on a replicating, centromere-containing plasmid. The fusion gene was found to be expressed at the same time during sporulation as the chromosomal wild-type SPS2 gene.
Identification of a novel virulence gene, virA, on the large plasmid of Shigella, involved in invasion and intercellular spreading (1995)

A novel virulence gene (virA) was identified upstream of the virG gene on the large plasmid of Shigella flexneri 2a YSH6000. Characterization of virA mutants infecting MK2 epithelial cell monolayers revealed that their invasive capacity was decreased to less than one fifth of the wild-type level. Nevertheless, the bacteria were capable of expressing and secreting IpaB, IpaC and IpaD proteins. The virA mutants were also impaired in their ability to spread intercellularly, since the bacteria gave rise to a small number of foci in a focus-plaque-forming test with MK2 cells. Although virG expression was slightly decreased in the virA mutants, introduction of a cloned virG gene into a virA mutant, N1945, failed to restore spreading ability. Although, introduction of a cloned virA gene into N1945 restored invasiveness and spreading ability, the reduced virG transcription level was not affected, indicating that the reduced virG expression in virA mutants does not play a major role in defective intercellular spreading. The nucleotide sequence of the virA region revealed that the virA gene was located 528 bp upstream of the virG gene, in the opposite orientation. The deduced amino acid sequence of the VirA protein indicated a 44.7 kDa protein with no homology to known proteins. The VirA protein was secreted into the culture supernatant, a process that required the Mxi and Spa loci. The expression of virA was under the control of the virB gene, the positive regulator of the ipa, mxi and spa operons. These results indicate that virA is a new member of the invasion regulon directed by virB and that the VirA function is involved in invasion and intercellular spreading.
Next Generation Sequencing of Ancient DNA: Requirements, Strategies and Perspectives (2010)

The invention of next-generation-sequencing has revolutionized almost all fields of genetics, but few have profited from it as much as the field of ancient DNA research. From its beginnings as an interesting but rather marginal discipline, ancient DNA research is now on its way into the centre of evolutionary biology. In less than a year from its invention next-generation-sequencing had increased the amount of DNA sequence data available from extinct organisms by several orders of magnitude. Ancient DNA research is now not only adding a temporal aspect to evolutionary studies and allowing for the observation of evolution in real time, it also provides important data to help understand the origins of our own species. Here we review progress that has been made in next-generation-sequencing of ancient DNA over the past five years and evaluate sequencing strategies and future directions.
Disparities in the Use of Sacral Neuromodulation among Medicare Beneficiaries (2015)

Sacral neuromodulation use significantly increased among Medicare beneficiaries in a 10-year period. Patients were more likely to be treated with sacral neuromodulation if they were female, white, younger (younger than 65 years) and living outside the western United States.
Effects of the Infusion of Insulin-like Growth Factor I in a Child with Growth Hormone Insensitivity Syndrome (Laron Dwarfism) (1991)

THE clinical manifestations of the growth hormone insensitivity syndrome (Laron dwarfism) result from the inability of growth hormone to exert its biologic actions.1 , 2 Affected children have the ...
Semiconductor Electrodes: XIV . Electrochemistry and Electroluminescence at n‐Type in Aqueous Solutions (1978)

The electrochemical behavior of single crystal was investigated in aqueous solutions. Charge transfer at the semiconductor/electrolyte interface was probed with several redox couples with standard redox potentials spanning a wide range. Most reductions occurred at potentials close to , the flatband potential and the current‐voltage behavior suggested involvement of surface states in the charge transfer process. Evidence for the adsorption of phosphate ion and its effect on the reduction of is also presented. Electroluminescence was observed during reduction of at wavelengths longer than 700 nm, suggesting the existence of intermediate levels.
Hepatic effects assessed by review of safety data in enzalutamide castration-resistant prostate cancer (CRPC) trials. (2018)

199 Background: Androgen receptor inhibitor enzalutamide (ENZA) improves survival in patients with metastatic CRPC. As the liver is the main route of ENZA elimination, this post hoc analysis evaluated the hepatic effects of ENZA versus comparators in controlled CRPC trials. Methods: Safety data from two large Phase 3, placebo (PBO)- (PREVAIL, NCT0121299; AFFIRM, NCT00974311) and two smaller Phase 2, bicalutamide (BIC)-controlled (STRIVE, NCT01664923; TERRAIN, NCT01288911) ENZA trials in men with CRPC were assessed for hepatic impairment-related adverse events (AEs) using the following standardized narrow MedDRA queries V19.1: hepatic failure, fibrosis and cirrhosis, and other liver damage-related conditions; hepatitis, non-infectious; and liver-related investigation, signs, and symptoms. Liver-related laboratory test results were also evaluated. Data were summarized as follows: patients receiving ENZA in Phase 3 trials (n = 1671); patients receiving ENZA in Phase 2 trials (n = 380); patients receiving PBO (n = 1243); patients receiving BIC (n = 387); and combined ENZA-treated patients (n = 2051). Results: Percentages of hepatic impairment-related AEs ranged between 2.9% and 4.5% with ENZA, and were 2.7% with PBO and 5.4% with BIC (Table). The most common hepatic impairment-related AEs were increased aspartate (AST) and alanine aminotransferase (ALT; Table). Within each trial, the incidences of grade ≥3 AEs were similar, and dose reductions or discontinuations due to hepatic impairment-related AEs were low (Table). When adjusted for treatment exposure, AEs per 100 patient-years were lower with ENZA versus either PBO or BIC (Table). Conclusions: This combined analysis of CRPC trials demonstrates no hepatic safety signal with ENZA and thus routine liver tests are not required. Clinical trial information: NCT0121299; NCT00974311; NCT01664923; NCT01288911. [Table: see text]
Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity (2019)

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40-OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8<sup>+</sup> T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40-OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40-OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40-OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies.
Autocrine and Paracrine Regulation of Kidney Epithelial Cell Growth (1989)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Asymmetric Hydrogenation of Ketones Catalyzed by RuII–bicp Complexes (2004)

Variations on a theme: A RuII–bicp complex used in combination with an achiral 2-(alkylthio)amine ligand (or achiral 1,2-diamine ligand) is an efficient catalyst for the highly enantioselective hydrogenation of a variety of ketones (see scheme). In some cases simply changing the amine ligand and/or the solvent leads to opposite enantioselectivity. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z53441_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
TPM Meets DRE: Reducing the Trust Base for Electronic Voting Using Trusted Platform Modules (2009)

We reduce the required trusted computing base for direct recording electronic (DRE) voting machines with a design based on trusted platform modules (TPMs). Our approach ensures election data integrity by binding the voter's choices with the presented ballot using a platform vote ballot (PVB) signature key managed by the TPM. The TPM can use the PVB key only when static measurements of the software reflect an uncompromised state and when a precinct judge enters a special password revealed on election day. Using the PVB with the TPM can expose authorized software, ballot modifications, vote tampering, and creation of fake election records early in the election process. Our protocol places trust in tamper resistant hardware, not in mutable system software. Although we are not the first to suggest using TPMs in voting, we are the first to provide a detailed engineering protocol that binds the voter choices with the presented ballot and uses the TPM to enforce election policy. We present the protocol, architecture, assumptions, and security arguments in enough detail to support further analysis or implementation.
First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers (2017)

YS110 is well tolerated up to 6 mg kg<sup>-1</sup> Q1W, which has been defined as the RP2D, with encouraging prolonged disease stabilisations observed in a number of patients with advanced/refractory mesothelioma.
A Cost-Effective, High Bandwidth Server I/O network Architecture for Cluster Systems (2007)

In this paper we present a cost-effective, high bandwidth server I/O network architecture, named PaScal (Parallel and Scalable). We use the PaScal server I/O network to support data-intensive scientific applications running on very large-scale Linux clusters. PaScal server I/O network architecture provides (1) bi-level data transfer network by combining high speed interconnects for computing inter-process communication (IPC) requirements and low-cost gigabit Ethernet interconnect for global IP based storage/file access, (2) bandwidth on demand I/O network architecture without re-wiring and reconfiguring the system, (3) multi-path routing scheme, (4) reliability improvement through reducing large number of network components in server I/O network, and (5) global storage/file systems support in heterogeneous multi-cluster and grids environments. We have compared the PaScal server I/O network architecture with the federated server I/O network architecture (FESIO). Concurrent MPI-I/O performance testing results and deployment cost comparison demonstrate that the PaScal server I/O network architecture can outperform the FESIO network architecture in many categories: cost-effectiveness, scalability, and manageability and ease of large-scale I/O network.
The Molecular Mechanism of Substrate Engagement and Immunosuppressant Inhibition of Calcineurin (2013)

Ser/thr phosphatases dephosphorylate their targets with high specificity, yet the structural and sequence determinants of phosphosite recognition are poorly understood. Calcineurin (CN) is a conserved Ca(2+)/calmodulin-dependent ser/thr phosphatase and the target of immunosuppressants, FK506 and cyclosporin A (CSA). To investigate CN substrate recognition we used X-ray crystallography, biochemistry, modeling, and in vivo experiments to study A238L, a viral protein inhibitor of CN. We show that A238L competitively inhibits CN by occupying a critical substrate recognition site, while leaving the catalytic center fully accessible. Critically, the 1.7 Å structure of the A238L-CN complex reveals how CN recognizes residues in A238L that are analogous to a substrate motif, "LxVP." The structure enabled modeling of a peptide substrate bound to CN, which predicts substrate interactions beyond the catalytic center. Finally, this study establishes that "LxVP" sequences and immunosuppressants bind to the identical site on CN. Thus, FK506, CSA, and A238L all prevent "LxVP"-mediated substrate recognition by CN, highlighting the importance of this interaction for substrate dephosphorylation. Collectively, this work presents the first integrated structural model for substrate selection and dephosphorylation by CN and lays the groundwork for structure-based development of new CN inhibitors.
Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. (1995)

Abdominal aortic aneurysms (AAA) are characterized by disruption and degradation of the elastic media, yet the elastolytic proteinases involved and their cellular sources are undefined. We examined if 92-kD gelatinase, an elastolytic matrix metalloproteinase, participates in the pathobiology of AAA. Gelatin zymography of conditioned medium from normal, atheroocclusive disease (AOD), or AAA tissues in organ culture showed that all tissues produced 72-kD gelatinase. AOD and AAA cultures also secreted 92-kD gelatinase, but significantly more enzyme was released from AAA tissues. ELISA confirmed that AAA tissues released approximately 2-fold more 92-kD gelatinase than AOD tissue and approximately 10-fold more than normal aorta. Phorbol ester induced a 5.3-fold increase in 92-kD gelatinase secretion by normal aorta and AOD and an 11.5-fold increase by AAA. By immunohistochemistry, 92-kD gelatinase was not detected in normal aorta and was only occasionally seen within the neointimal lesions of AOD tissue. In all AAA specimens, however, 92-kD gelatinase was readily localized to numerous macrophages in the media and at the adventitial-medial junction. The expression of 92-kD gelatinase mRNA by aneurysm-infiltrating macrophages was confirmed by in situ hybridization. These results demonstrate that diseased aortic tissues secrete greater amounts of gelatinolytic activity than normal aorta primarily due to increased production of 92-kD gelatinase. In addition, the localization of 92-kD gelatinase to macrophages in the damaged wall of aneurysmal aortas suggests that chronic release of this elastolytic metalloproteinase contributes to extracellular matrix degradation in AAA.
Most Comprehension Tests Do Measure Reading Comprehension: A Response to McLean and Goldstein (2022)

Abstract There is nothing wrong with the NAEP reading exercises, the sampling design, or the NAEP Reading Proficiency Scale, these authors maintain. But adding a rich criterion-based frame of reference to the scale should yield an even more useful tool for shaping U.S. educational policy.
Characterization of the Antiapoptotic Bcl-2 Family Member Myeloid Cell Leukemia-1 (Mcl-1) and the Stimulation of Its Message by Gonadotropins in the Rat Ovary (1999)

The majority of ovarian follicles undergo atresia mediated by apoptosis. Bcl-2-related proteins act as regulators of apoptosis via the formation of dimers with proteins inside and outside the Bcl-2 family. Previous studies have identified BAD as a proapoptotic Bcl-2 family member expressed in the ovary. It is known that BAD phosphorylation induced by survival factors leads to its preferential binding to 14–3-3 and suppression of the death-inducing function of BAD. To identify ovarian binding partners for hypophosphorylated BAD, we performed a yeast two-hybrid screening of a rat ovary complementary DNA library using as bait a mutant BAD incapable of binding to 14–3-3. Screening of yeast transformants yielded positive clones encoding the rat ortholog of Mcl-1 (myeloid cell leukemia-1), an antiapoptotic Bcl-2 protein. Amino acid sequence analysis revealed that rat and human Mcl-1 showed a complete conservation of the Bcl-2 homology domains BH1, BH2, and BH3. In the yeast two-hybrid system, Mcl-1 binds to the hypophosphorylated mutant of BAD and interacts preferentially with different proapoptotic (Bax, Bak, Bok, Bik, and BOD) compared with antiapoptotic Bcl-2 family members (Bcl-2, Bcl-xL, Bcl-w, Bfl-1, CED-9, and BHRF-1). Northern blot hybridization demonstrated expression of Mcl-1 transcripts of 2.3 and 3.7 kb in the ovary and diverse other rat tissues. In immature rats, PMSG treatment led to a transient increase in the 2.3-kb Mcl-1 transcript, peaking at 6 h after injection and returning to baseline levels after 24 h. Moreover, the same transcript was induced in the PMSG-primed preovulatory rat ovary 6 h after the administration of ovulatory doses of either hCG or FSH. In situ hybridization studies revealed that the gonadotropin stimulation of ovarian Mcl-1 message occurs in both granulosa and thecal cells. In conclusion, rat Mcl-1 was identified as an ovarian BAD-interacting protein and the message for the antiapoptotic Mcl-1 protein was induced after treatment with gonadotropins in granulosa and thecal cells of growing follicles.
Compartmental analysis of the complete dynamic scan data for scintigraphic determination of effective renal plasma flow. (1997)

A scintigraphic estimation of ERPF without blood samples using time-activity data from the heart, kidneys and bladder acquired over the entire renogram is feasible and correlates well with more invasive techniques requiring blood samples.