gebhart/patrepeval huggingface dataset:
Secure Computer System: Unified Exposition and Multics Interpretation (1976)

Abstract : A unified narrative exposition of the ESD/MITRE computer security model is presented. A suggestive interpretation of the model in the context of Multics and a discussion of several other important topics (such as communications paths, sabotage and integrity) conclude the report. A full, formal presentation of the model is included in the Appendix.
Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation. (1996)

One of the earliest events induced by interleukin 2 (IL-2) is tyrosine phosphorylation of cellular proteins, including the IL-2 receptor beta chain (IL-2Rbeta). Simultaneous mutation of three tyrosines (Y338, Y392, and Y510) in the IL-2Rbeta cytoplasmic domain abrogated IL-2-induced proliferation, whereas mutation of only Y338 or of Y392 and Y510 inhibited proliferation only partially. While Y392 and Y510 were critical for IL-2-induced activation of signal transducers and activators of transcription (STAT proteins), Y338 was required for Shc-IL-2Rbeta association and for IL-2-induced tyrosine phosphorylation of Shc. Thus, activation of both Jak-STAT and Shc-coupled signaling pathways requires specific IL-2Rbeta tyrosines that together act in concert to mediate maximal proliferation. In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway.
Paracrine Transactivation of the CB1 Cannabinoid Receptor by AT1 Angiotensin and Other Gq/11 Protein-coupled Receptors (2009)

Intracellular signaling systems of G protein-coupled receptors are well established, but their role in paracrine regulation of adjacent cells is generally considered as a tissue-specific mechanism. We have shown previously that AT(1) receptor (AT(1)R) stimulation leads to diacylglycerol lipase-mediated transactivation of co-expressed CB(1)Rs in Chinese hamster ovary cells. In the present study we detected a paracrine effect of the endocannabinoid release from Chinese hamster ovary, COS7, and HEK293 cells during the stimulation of AT(1) angiotensin receptors by determining CB(1) cannabinoid receptor activity with bioluminescence resonance energy transfer-based sensors of G protein activation expressed in separate cells. The angiotensin II-induced, paracrine activation of CB(1) receptors was visualized by detecting translocation of green fluorescent protein-tagged beta-arrestin2. Mass spectrometry analyses have demonstrated angiotensin II-induced stimulation of 2-arachidonoylglycerol production, whereas no increase of anandamide levels was observed. Stimulation of G(q/11)-coupled M(1), M(3), M(5) muscarinic, V(1) vasopressin, alpha(1a) adrenergic, B(2) bradykinin receptors, but not G(i/o)-coupled M(2) and M(4) muscarinic receptors, also led to paracrine transactivation of CB(1) receptors. These data suggest that, in addition to their retrograde neurotransmitter role, endocannabinoids have much broader paracrine mediator functions during activation of G(q/11)-coupled receptors.
Analysis and processing of shaft angular velocity signals in rotating machinery for diagnostic applications (2002)

The paper presents the application of some modern signal processing methods to the analysis of angular velocity signals in a rotating machine for diagnostic purposes. The signal processing techniques considered in this paper include: classical non-parametric spectral analysis; principal component analysis; joint time-frequency analysis; the discrete wavelet transform; and change detection algorithm based on residual generation. These algorithms are employed to process shaft angular velocity data measured from an internal combustion engine, with the intent of detecting engine misfire. The results of these analyses show that these algorithms have potential for on-board diagnostic application in passenger and commercial vehicles, and more generally for failure detection of other classes of rotating machines.
Development of Glomerular Endothelial Cells, Podocytes and Mesangial Cells in the Human Fetus and Infant (2007)

The process of glomerular development consists of four developmental stages: vesicle (V) stage, S-shaped body (S) stage, capillary loop (C) stage and maturation (M) stage. However, the development of glomerular endothelial, mesangial and epithelial cells in fetal and infant kidneys remains unclear. In order to determine the characteristics of human glomerular development, we investigated the process of glomerular development by staining fetal and infant kidneys for CD31, CD34 and FB21, markers for endothelial cells, alpha-smooth muscle actin (alpha-SMA), a marker for mesangial cells, and nephrin, a marker for podocytes. These series of studies were carried out on kidneys obtained at autopsy from 27 fetuses and 5 infants. The fetuses were divided into the following 5 groups according to gestational age; 13-19, 20-24, 25-29, 30-34 and 35-39 weeks. In each group, glomerular development was classified according to the developmental stage and the staining patterns for CD31, CD34, FB21, alpha-SMA and nephrin. The proportion of V-stage development in 100 glomeruli examined was highest at 13-19 weeks. After 20 weeks, the V-stage proportion decreased gradually, and the proportion of S stage became highest at 20-24 weeks. The C-stage proportion was highest at 25-29 weeks, while the M-stage proportion was highest in infants aged 1-6 months. The staining patterns for CD31, CD34 and FB21 were similar in endothelial cells after 25 weeks of gestation. Staining of alpha-SMA and nephrin was first observed in the S stage. In conclusion, maturation of endothelial cells starts at 25 weeks and is completed by 35 weeks of gestation. Epithelial cells and mesangial cells first appear during the S stage.
Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors (2004)

Calcitonin (CT) is a hormone that received its name because of its secretion in response to induced hypercalcemia and its hypocalcemic effect (1). It was shown to originate from the thyroid gland (2). More specifically, the hormone was revealed to be located within the thyroidal parafollicular cells, interspersed within and about the follicular epithelium (3–5). Subsequently termed C cells, they occur primarily in the central region of each lobe of the human thyroid gland (6, 7). These cells, which have CT-containing secretion granules, are neuroendocrine. Embryologically, they originate from the neural crest and migrate to the ultimobranchial glands (8). In mammals, the ultimobranchial glands fuse with the thyroid gland. It was the demonstration that medullary thyroid cancer (MTC) was a malignancy of the C cells (5, 9) that eventually led to the isolation of human CT from this tumor and the determination of its structure (10, 11). Simultaneously, the amino acid sequence of porcine CT was determined (12). Later, the development of immunoassays of serum CT in humans led to the observation that the level of this hormone was increased in the serum of patients with MTC (13–15) and to the demonstration that these levels were further augmented after iv calcium and/or pentagastrin administration (13, 16, 17). These findings had a great impact on the clinical diagnosis, the evaluation of efficacy of surgical extirpation, and the follow-up monitoring of MTC. Although RET germline mutation testing has replaced CT for the purpose of determining the presence of carriers of this tumor associated with multiple endocrine neoplasia type 2 (18, 19), the measurement of serum CT has become and has remained the classical clinical marker for MTC. Immature and mature CT
Estimator and controller design for LaneTrak, a vision-based automatic vehicle steering system (2002)

This work focuses on the underlying theory used in the design of a lane estimator and a lane controller to achieve automatic roadway tracking by a vehicle. In concert with a lane sensing algorithm, a comprehensive simulation assesses the roadway tracking performance of a Pontiac 6000 STE. The roadway curvature and the relative positioning of the vehicle within its lane are estimated using Kalman filtering. Inputs to the estimator are vehicle kinematical variables provided by a vehicle directional control (DIRCON) model, and lane boundary information provided by a video camera model. The design of the steering autopilot is formulated as a preview, path tracking and regulation problem. The steering autopilot uses the estimator outputs and the vehicle DIRCON model. The estimator and controller designs were tested, improved, and validated using a comprehensive simulation program which included models for the lane sensing system and the steering actuator. The credibility of the simulation has been further established through successful lane control of a Pontiac 6000 STE car on an unopened section of a limited-access freeway at highway speeds.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nordihydroguaiaretic Acid Analogues: Their Chemical Synthesis and Biological Activities (2009)

Nordihydroguaiaretic acid is a natural occurring lignan mainly isolated and commercially produced from desert plant, creosote bush (Larrea divaricata Cav. Or Corillea tridentate), which can be widely found in the border zone of southern of USA and northern of Mexico. During past 100 years, extensive research has demonstrated that nordihydroguaiaretic acid and its synthetic analogues are potentially useful in treating diseases related to cancers, diabetes, viral, bacterial infections, and inflammation. Remarkably, terameprocol, a tetra-O-methyl derivative of nordihydroguaiaretic acid, is currently in Phase I/II clinical trials as an anticancer agent. This review deals with the chemical synthesis and bioactivities of nordihydroguaiaretic acid and its structurally-related derivatives, which possess anticancer, antioxidant, antimicrobial, anti-inflammatory and immunosuppressive activities. The review consists of the data reported in over 100 publications.
Ubiquitin/26S proteasome-mediated degradation of topoisomerase I as a resistance mechanism to camptothecin in tumor cells. (2001)

Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. Studies using a panel of breast and colorectal cancer cell lines as well as primary nontransformed and oncogene-transformed cells have demonstrated that CPT-induced down-regulation exhibits a high degree of heterogeneity. In general, nontransformed cells are much more proficient in CPT-induced TOP1 down-regulation than their transformed counterparts. Among the breast and colorectal cancer cell lines, there was a general correlation between the extent of CPT-induced TOP1 down-regulation and CPT resistance. The breast cancer cell line ZR-75-1, the most sensitive to CPT, was completely defective in CPT-induced TOP1 down-regulation, whereas the breast cancer cell line BT474, the least sensitive to CPT, exhibited effective CPT-induced TOP1 down-regulation. The 26S proteasome inhibitor MG132 was shown to inhibit CPT-induced down-regulation of TOP1 in BT474 cells and selectively sensitized BT474 but not ZR-75-1 cells to CPT-induced cytotoxicity and apoptosis. In the aggregate, these results suggest that CPT-induced down-regulation of TOP1 could be an important parameter for determining CPT sensitivity/resistance in tumor cells. Analysis of the levels of TOP1 cleavable complexes, SUMO-1-TOP1 conjugates, and ubiquitin-TOP1 conjugates in ZR-75-1 and BT474 cells has suggested that the heterogeneity of CPT-induced down-regulation of TOP1 in tumor cells is at least in part attributable to altered regulation of a process(es) downstream from the TOP1 cleavable complex.
Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients (2004)

Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used to search for genomic alterations in liver metastases that were clinically resistant to 5-fluorouracil (5-FU). In two of four patients, we identified amplification of an approximately 100-kb region on 18p11.32 that was of particular interest because it contained the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU. Analysis of TYMS by fluorescence in situ hybridization identified TYMS gene amplification in 23% of 31 5-FU-treated cancers, whereas no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplification had a substantially shorter median survival (329 days) than those without amplification (1,021 days, P <0.01). These data suggest that genetic amplification of TYMS is a major mechanism of 5-FU resistance in vivo and have important implications for the management of colorectal cancer patients with recurrent disease.
Low-Impedance VHF and UHF Capacitive Silicon Bulk Acoustic-Wave Resonators—Part II: Measurement and Characterization (2007)

In this part of the paper, extensive measurement results on the resonance, frequency tuning, and temperature characteristics of the silicon bulk acoustic-wave resonators (SiBARs) that were described in Part I will be presented and justified. Bulk acoustic wave resonators, high-aspect- ratio polysilicon and single-crystal silicon (HARPSS), MEMS, micromachining, micromechanical resonators, silicon resonators.
Urine Fingerprinting: Detection of Sample Tampering in an Opiate Dependency Program (1999)

Methadone treatment programs commonly monitor patient compliance by screening urine samples for drugs of abuse. Our experience suggests that re-submission of urine samples (for example, providing a urine sample that is either not that of the patient or was previously submitted) is often used as a method of sample tampering. We have developed an algorithm that combines urine sodium, chloride, creatinine and pH values with urine drug screening results to effectively detect resubmitted samples. Given the widespread use of urine drug screening in drug and alcohol rehabilitation programs, we believe this technique has significant practical benefits. This technique may also have an application in forensic identification of duplicate samples.
A compound chimeric antigen receptor strategy for targeting multiple myeloma (2017)

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.
Derivation of pluripotent stem cells from cultured human primordial germ cells (1998)

Human pluripotent stem cells would be invaluable for in vitro studies of aspects of human embryogenesis. With the goal of establishing pluripotent stem cell lines, gonadal ridges and mesenteries containing primordial germ cells (PGCs, 5-9 weeks postfertilization) were cultured on mouse STO fibroblast feeder layers in the presence of human recombinant leukemia inhibitory factor, human recombinant basic fibroblast growth factor, and forskolin. Initially, single PGCs in culture were visualized by alkaline phosphatase activity staining. Over a period of 7-21 days, PGCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells termed embryonic stem and embryonic germ (EG) cells. Throughout the culture period most cells within the colonies continued to be alkaline phosphatase-positive and tested positive against a panel of five immunological markers (SSEA-1, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) that have been used routinely to characterize embryonic stem and EG cells. The cultured cells have been continuously passaged and found to be karyotypically normal and stable. Both XX and XY cell cultures have been obtained. Immunohistochemical analysis of embryoid bodies collected from these cultures revealed a wide variety of differentiated cell types, including derivatives of all three embryonic germ layers. Based on their origin and demonstrated properties, these human PGC-derived cultures meet the criteria for pluripotent stem cells and most closely resemble EG cells.
Copy number alteration burden predicts prostate cancer relapse (2014)

Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input whole-genome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts.
Antisense oligonucleotide derivatives as gene-targeted drugs. (1990)

The strategies and problems involved in designing oligonucleotide derivatives as gene-targeted drugs are discussed. Experiments with isolated and cellular nucleic acids, studies with infected cell cultures, and preliminary animal tests all demonstrate that various derivatives of complementary oligonucleotides (antisense oligonucleotide derivatives) can act as extremely specific and potent inhibitors of gene expression. The design and synthesis of more stable oligonucleotide analogues that can enter mammalian cells and efficiently affect preselected nucleic acids will result in the development of a new generation of drugs, including those with antiviral and anticancer properties.
Mini-review: In vitro Metabolic Engineering for Biomanufacturing of High-value Products (2017)

With the breakthroughs in biomolecular engineering and synthetic biology, many valuable biologically active compound and commodity chemicals have been successfully manufactured using cell-based approaches in the past decade. However, because of the high complexity of cell metabolism, the identification and optimization of rate-limiting metabolic pathways for improving the product yield is often difficult, which represents a significant and unavoidable barrier of traditional <i>in vivo</i> metabolic engineering. Recently, some <i>in vitro</i> engineering approaches were proposed as alternative strategies to solve this problem. In brief, by reconstituting a biosynthetic pathway in a cell-free environment with the supplement of cofactors and substrates, the performance of each biosynthetic pathway could be evaluated and optimized systematically. Several value-added products, including chemicals, nutraceuticals, and drug precursors, have been biosynthesized as proof-of-concept demonstrations of <i>in vitro</i> metabolic engineering. This mini-review summarizes the recent progresses on the emerging topic of <i>in vitro</i> metabolic engineering and comments on the potential application of cell-free technology to speed up the "design-build-test" cycles of biomanufacturing.
Full-length dominant-negative survivin for cancer immunotherapy. (2003)

DCs transduced with dominant-negative survivin induce potent survivin-specific CTL responses able to recognize and kill tumor cells. This response does not significantly affect HPCs. Thus, this study may provide rationale for immunotherapeutic clinical trials using a DC vaccine transduced with the dominant-negative survivin.
Practical Stereoselective Synthesis of an α-Trifluoromethyl-α-alkyl Epoxide via a Diastereoselective Trifluoromethylation Reaction (2006)

A practical stereoselective synthesis is reported for an alpha-trifluoromethyl-alpha-alkyl epoxide (1), which is an important pharmaceutical intermediate. The key step involves a chiral auxiliary-controlled asymmetric trifluoromethylation reaction for the introduction of the unique trifluoromethyl-substituted tertiary alcohol stereogenic center in the target molecule. The fluoride-initiated CF3 addition to chiral keto ester 6a proceeded with a diastereoselectivity up to 86:14. The major diastereomer was readily obtained with a >99.5:0.5 dr through a simple crystallization of the crude product mixture.
Construction of Immunoglobulin Fusion Proteins (2002)

Recombinant DNA technology has allowed the preparation of chimeric genes encoding proteins with novel properties. This unit describes the construction and subsequent testing of genes encoding immunoglobulin chimeras. The first protocol details fusion of a protein (or protein fragment) of interest onto an immunoglobulin constant region using a modified version of the expression vector pCDM8. The resulting fusion protein generally retains the functional properties of both the protein of interest and the immunoglobulin constant region; this can be demonstrated as described here.
Ensembl 2002: accommodating comparative genomics (2003)

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.