gebhart/patrepeval huggingface dataset:
Molecular basis for heterogeneity of the human p53 protein. (1986)

The human p53 tumor antigen comprises several physically distinct proteins. Two p53 proteins, separable by polyacrylamide gel electrophoresis, are expressed by the human transformed cell line SV-80. The individual cDNAs which code for these proteins were isolated and constructed into the SP6 transcription vector. The proteins encoded by these clones were identified by in vitro transcription with the SP6 vector and translation in a cell-free system. p53-H-1 and p53-H-19 cDNA clones code for the faster- and slower-migrating p53 protein species, respectively, of SV-80. The in vitro-expressed proteins of p53-H-1 and p53-H-19 had the same antigenic determinants and were structurally indistinguishable from their in vivo counterparts. By expressing defined restricted cDNA fragments in vitro, the region of heterogeneity between the respective cDNAs was located at the 5' end of the cDNAs. Exchanging the 5' fragments of interest and expressing the chimeric clones in vitro confirmed that the DNA heterogeneity was responsible for the difference in the electrophoretic mobility of these proteins. The sequences of the two cDNAs revealed a single base pair difference (G versus C) in the coding region of the clones. This sequence difference resulted in an arginine being coded for in clone p53-H-1 and a proline being coded for at the equivalent position in clone p53-H-19. This variation accounted for the change in the electrophoretic mobility of the individual p53 protein species.
Suppression of Mevalonate Pathway Activities by Dietary Isoprenoids: Protective Roles in Cancer and Cardiovascular Disease (1995)

Diet-cancer and diet-cardiovascular disease interrelationships may be explained by the mevalonate-suppressive action of isoprenoid end products of plant secondary metabolism. Assorted monoterpenes, sesquiterpenes, carotenoids and tocotrienols posttranscriptionally down regulate 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, a key activity in the sterologenic pathway. The modest decrease in cholesterol synthesis is associated with a concomitant lowering of low-density lipoprotein cholesterol. The reductase activity in tumor tissues differs from that of liver in being resistant to sterol feedback regulation. Tumor reductase activity retains sensitivity to posttranscriptional regulation. As a consequence, the isoprenoid-mediated suppression of mevalonate synthesis depletes tumor tissues of two intermediate products, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are incorporated posttranslationally into growth control-associated proteins. At 10-fold higher concentrations, monoterpenes inhibit the protein isoprenyl transferases that catalyze this incorporation. At levels of intake likely provided by a diet based on Food Pyramid guidelines, assorted isoprenoids decrease cardiovascular disease risk and suppress the growth of initiated cells. At pharmacological levels of intake, isoprenoids block the initiation phase of chemical carcinogenesis. Isoprenoids targeted to the inhibition of the isoprenylation of oncogenic forms of ras proteins may offer a novel approach to chemotherapy. Adjunctive isoprenoids might decrease the level of competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase required to manage hypercholesterolemia.
Endogenous mono‐ADP‐ribosylation mediates smooth muscle cell proliferation and migration via protein kinase N‐dependent induction of c‐fos expression (2002)

ADP-ribosylation has been coupled to intracellular events associated with smooth muscle cell vasoreactivity, cytoskeletal integrity and free radical damage. Additionally, there is evidence that ADP-ribosylation is required for smooth muscle cell proliferation. Our investigation employed selective inhibitors to establish that mono-ADP-ribosylation and not poly(ADP-ribosyl)ation was necessary for the stimulation of DNA synthesis by mitogens. Mitogen treatment increased concomitantly the activity of both soluble and particulate mono-ADP-ribosyltransferase, as well as the number of modified proteins. Inclusion of meta-iodobenzylguanidine (MIBG), a selective decoy substrate of arginine-dependent mono-ADP-ribosylation, prevented the modification of these proteins. MIBG also blocked the stimulation of DNA and RNA synthesis, prevented smooth muscle cell migration and suppressed the induction of c-fos and c-myc gene expression. An examination of relevant signal transduction pathways showed that MIBG did not interfere with MAP kinase and phosphatidylinositol 3-kinase stimulation; however, it did inhibit phosphorylation of the Rho effector, PRK1/2. This novel observation suggests that mono-ADP-ribosylation participates in a Rho- dependent signalling pathway that is required for immediate early gene expression.
Antimitotic agents. Synthesis of imidazo[4,5-c]pyridin-6-ylcarbamates and imidazo[4,5-b]pyridin-5-ylcarbamates (1990)

Cyclization of ethyl 5,6-diamino-4-hydrazinopyridin-2-ylcarbamate (10) with a mixture of CS2 and Et3N in dimethylacetamide gave mainly ethyl 1,4-diamino-2(3H)-thioxoimidazo[4,5-c]pyridin-6-ylcarbamate (15), whereas, in the absence of dimethylacetamide, a double cyclization gave mainly ethyl 5-amino-2(1H)-4-dithioxodiimidazo-[4,5-b:5,4-c]pyridin-7-ylcarb amate (16). Cyclization of the benzylidenehydrazino derivative (6) of 10 with either CS2-Et3N or (EtO)3CH-HCl gave 1-(benzylideneamino)imidazo[4,5-c]pyridines 11 and 7 as major products and 7-(benzylidenehydrazino)imidazo[4,5-b]pyridines 12 and 8 as minor products. Dethiolation of 11 to give 7 and of 12 to give 8 was effected with excess Raney nickel in refluxing ethanol. The benzylidene group of 11 was removed with hydrazine in ethanolic HCl to give 15. This key compound was condensed with benzaldehydes to give 1-benzylideneamino derivatives (20, 21) and alkylated with benzyl halides to give 2-benzylthio derivatives (24-26). In addition, cyclization of ethyl 5,6-diamino-4-(benzylidene-1-methylhydrazino)pyridin-2-ylcarbam ate (30) with (EtO)3CH provided a method for the synthesis of an imidazo[4,5-c]- and -[4,5-b]pyridines gave compounds that inhibited proliferation of growth and caused mitotic arrest against lymphoid leukemia L1210 at micromolar concentrations. However, the more active in vitro compounds (7, 8, 24-26) gave only borderline activity in mice against lymphocytic leukemia P388.
Molecular Single-Cell PCR Analysis of Rearranged Immunoglobulin Genes As a Tool to Determine the Clonal Composition of Normal and Malignant Human B Cells (2004)

Owing to the nearly limitless diversity of immunoglobulin (Ig) variable-region gene rearrangements, such rearrangements represent ideal clonal markers for B-lineage cells. This chapter describes an approach to isolate single cells from frozen tissue sections by microdissection using a hydraulic micromanipulator and the subsequent amplification of rearranged IgH and Igκ genes from the cells in a seminested polymerase chain reaction (PCR) approach. The amplification of a priori unknown V-gene rearrangements is made possible by the usage of a collection of V-gene family-specific primers recognizing nearly all V-gene segments together with primer mixes for the J-gene segments. By sequence comparison of V-gene amplificates from distinct cells, the clonal relationship of the B-lineage cells can unequivocally be determined. As a large part of the V-gene rearrangements is amplified, the approach is also useful to address additional issues, such as V-, D-, and J-gene usage and the presence and pattern of somatic mutations.
Characterization of a Mycobacterium leprae antigen related to the secreted Mycobacterium tuberculosis protein MPT32 (1994)

Secreted proteins may serve as major targets in the immune response to mycobacteria. To identify potentially secreted Mycobacterium leprae antigens, antisera specific for culture filtrate proteins of Mycobacterium tuberculosis were used to screen a panel of recombinant antigens selected previously by leprosy patient sera. Four potentially secreted antigens were identified by this approach, and one was recognized by antibodies specific for MPT32, a secreted M. tuberculosis protein. The DNA coding for the M. leprae antigen, which we have designated 43L, was isolated and characterized and found to encode a 25.5-kDa protein that is preceded by a consensus signal peptide of 39 amino acids. The N-terminal amino acid sequence of 43L shows 50% homology with the 20 known N-terminal amino acids of MPT32, and 47% homology was found with the N terminus of a 45/47-kDa antigen complex identified in Mycobacterium bovis BCG. These findings indicate that 43L represents an antigen related to MPT32 and the M. bovis BCG 45/47-kDa complex and that 43L is likely to be a protein secreted by M. leprae. Purified recombinant 43L protein is recognized by antibodies and T cells from healthy contacts and leprosy patients, illustrating that secreted proteins are of importance in the immune response to M. leprae.
Bacterial Arthritis (1985)

BACTERIAL arthritis is a common and serious problem at major urban medical centers. We review the pathophysiology of bacterial arthritis, clinical and microbiologic characteristics of its common forms, and current approaches to diagnosis and treatment of this condition.PathophysiologyBacterial arthritis is usually hematogenously acquired. In 1939 Shaffer and Bennett demonstrated that pneumococcal bacteremia in rabbits often caused pneumococcal arthritis,1 and other laboratory models of bacterial arthritis were subsequently described.2 , 3 The synovium is extremely vascular and contains no limiting basement membrane, thus promoting easy access of blood contents to the synovial space. Certain bacteria, such as Neisseria gonorrhoeae, are . . .
Specific inhibition of plasma kallikrein modulates chronic granulomatous intestinal and systemic inflammation in genetically susceptible rats (1998)

The kallikrein-kinin (K-K) (contact) system is activated during acute and chronic relapsing phases of enterocolitis induced in genetically susceptible Lewis rats by intramural injection of peptidoglycan-polysaccharide (PG-APS). Using the selective plasma kallikrein inhibitor P8720, we investigate whether activation of the K-K system plays a primary role in chronic granulomatous intestinal and systemic inflammation in this model. Group I (negative control) received human serum albumin intramurally. Group II (treatment) received PG-APS intramurally and P8720 orally. Group III (positive control) received PG-APS intramurally and albumin orally. P8720 attenuated the consumption of the contact proteins, high molecular weight kininogen (P<0.03), and factor XI (P<0.04) in group II vs. group III. P8720 decreased chronic intestinal inflammation measured by blinded gross (P<0.01) and histologic (P<0.0005) scores as well as systemic complications (arthritis, splenomegaly, hepatomegaly, leukocytosis, and acute-phase reaction) (P<0.01) in group II as compared with group III. We conclude that relapsing chronic enterocolitis and systemic complications are in part due to plasma K-K system activation, and that inhibition of this pathway is a potential therapeutic approach to human inflammatory bowel disease and associated extraintestinal manifestations.
VP16 Targets an Amino-Terminal Domain of HCF Involved in Cell Cycle Progression (1997)

The herpes simplex virus (HSV) regulatory protein VP16 activates HSV immediate-early gene transcription through formation of a multiprotein-DNA complex on viral promoters that includes the preexisting nuclear proteins HCF and Oct-1. The HCF protein is a complex of amino- and carboxy-terminal polypeptides derived from a large (approximately 2,000-amino-acid) precursor by proteolytic processing. Here we show that a 361-residue amino-terminal region of HCF is sufficient to bind VP16, stabilize VP16-induced complex assembly with Oct-1 and DNA, and activate transcription in vivo. This VP16 interaction region contains six kelch-like repeats, a degenerate repeat motif that is likely to fold as a distinctive beta-propeller structure. The third HCF kelch repeat includes a proline residue (P134) that is mutated to serine in hamster tsBN67 cells, resulting in a temperature-sensitive defect in cell proliferation. This missense mutation also prevents direct association between HCF and VP16, suggesting that VP16 mimics a cellular factor required for cell proliferation. Rescue of the tsBN67 cell proliferation defect by HCF, however, requires both the VP16 interaction domain and an adjacent basic region, indicating that HCF utilizes multiple regions to promote cell cycle progression.
Sodium cromoglycate attenuates pulmonary inflammation without influencing bronchial responsiveness in healthy subjects exposed to organic dust (2001)

Sodium cromoglycate alters the airway inflammatory response to inhaled organic dust without influencing the dust-induced increase in bronchial responsiveness to methacholine.
Interactive data exploration with a supercomputer (1991)

Scientific data of high-dimensionality is particularly difficult to understand if there are complex (and perhaps unknown) interactions among parameters. In such situations, the scientist can turn to a process Tukey has called exploratory data visualization. In exploratory data visualisation, we typically do not know exactly what we are looking for; instead, we explore the data with a variety of visualization techniques that can help us understand the nature of the data by demonstrating patterns in it. Given the complexity of the data and the large number of ways to map the data to a display, exploratory visualization can be truly effective only if it can also be interactive. In this paper we describe an experiment in exploratory data visualization using a massively parallel processor. With this approach we were able to find new features in some of our oldest datasets and to create more vivid presentations of familiar features in these datasets. Our experience has also led us to a better understanding of the nature of exploratory visualization and has resulted in some formal representations of the interaction process in this environment.
State-of-the-art harmonic-balance simulation of forced nonlinear microwave circuits by the piecewise technique (1992)

The theoretical foundations and the numerical performance of an advanced nonlinear circuit simulator based on the piecewise harmonic-balance (HB) technique are discussed. The exact computation of the Jacobian matrix for Newton-iteration based HB simulation and the related conversion-matrix technique for fast mixer analysis are formulated in a general form. Convergence problems at high drive levels are solved by a parametric formulation of the device models coupled with an advanced norm-reducing iteration. A physics-based approximation is shown to allow the HB equations to be effectively decoupled in many practical cases, bringing large-sized jobs, such as pulsed-RF analysis, within the reach of ordinary workstations. The exact Jacobian is used in conjunction with an exact formula for the gradient of the objective function, to implement an efficient broadband nonlinear circuit optimization capability. Examples are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Using artificial intelligence planning to automate science image data analysis (1999)

In recent times, improvements in imaging technology have made available an incredible array of information in image format. While powerful and sophisticated image processing software tools are available to prepare and analyze the data, these tools are complex and cumbersome, requiring significant expertise to properly operate. Thus, in order to extract (e.g., mine or analyze) useful information from the data, a user (in our case a scientist) often must possess both significant science and image processing expertise. This article describes the use of artificial intelligence (AI) planning techniques to represent scientific, image processing and software tool knowledge to automate knowledge discovery and data mining (e.g., science data analysis) of large image databases. In particular, we describe two fielded systems. The Multimission VICAR Planner (MVP) which has been deployed for since 1995 and is currently supporting science product generation for the Galileo mission. MVP has reduced time to fill certain classes of requests from 4 h to 15 min. The Automated SAR Image Processing system (ASIP) was deployed at the Department of Geology at Arizona State University in 1997 to support aeolian science analysis of synthetic aperture radar images. ASIP reduces the number of manual inputs in science product generation by ten-fold.
Flow cytometric quantification of cyclin E in human cell lines and hematopoietic malignancies (1998)

Cyclins are important in the regulatory system controlling cell cycle progression and overexpression or aberrant expression of G1 cyclins, as cyclin E, may result in an inadequate G1-S transition. In this study, the expression of cyclin E was analyzed in 12 human cell lines and 18 hematological malignancies by flow cytometry, and protein levels were quantified using calibrating microbeads. The majority of the tested cell lines demonstrated a cell cycle-specific expression of cyclin E, even though some cell lines expressed lower and more constant cyclin E levels throughout the cell cycle. No correlation between the fraction of cyclin E-positive cells and cyclin E content could be observed in the cell lines. Similar cyclin E levels were observed in the tumor samples as for the cell lines, although the fractions of positive cells were low. The flow cytometric quantification of cyclin E was compared with densitometric quantification of cyclin E Western blots, and a significant correlation between the two methods was observed (rs = 0.56, P = 0.03). The variation of cyclin E levels between cell lines was significantly higher than the variation for repetitive analyses of the same cell line, suggesting that the expression of cyclin E could reliably be quantified using flow cytometry. Because of the potential to analyze specific subgroups such as cyclin E-positive cells, this method may facilitate the detection of cyclin E-overexpressing tumor cells.
Translocon‐associated protein α transcripts are induced by granulocyte‐macrophage colony‐stimulating factor and exhibit complex alternative polyadenylation (1999)

The cloning of full length cDNA for the translocon-associated protein alpha subunit, previously called signal sequence receptor alpha, is reported as a result of differential display experiments in search of genes induced by granulocyte-macrophage colony-stimulating factor. Its messenger RNA was more abundant in growing cells than in either factor-deprived cells or quiescent cells and comprised four species, each having microheterogeneity, as a result of complex alternative polyadenylation apparently dependent on arrays of non-canonical polyadenylation signals. Radiation hybrid mapping of the gene showed that the gene is on the short arm of chromosome 6.
A role for Y‐box proteins in cell proliferation (1995)

Members of the Y-box (YB) family of transcription factors are expressed in a wide range of cell types and are implicated in the regulation of a rapidly increasing number of genes. Although the biological activities of YB proteins appear to be varied, distinct patterns, relating to the timing of their expression and the identity of their target genes, are beginning to emerge. A recent report by Ito et al. focusses attention on cell proliferation and adds support to earlier suggestions that a primary function of YB proteins is to help activate growth-associated genes.
Contribution of regulatory T cells to cancer: A review (2018)

Abstract Regulatory T cells (Tregs) represent a low number of T‐cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross‐talks with other immunosuppressive cells including cancer‐associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid‐derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor‐β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor‐bearing receptors in Tregs, including FOXP3, programmed death‐1, T‐cell immunoglobulin mucin‐3, and CTL‐associated antigen‐4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.
Rapid Generation of Human-Like Neutralizing Monoclonal Antibodies in Urgent Preparedness for Influenza Pandemics and Virulent Infectious Diseases (2013)

The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs).
Atherosclerosis and Vascular Disease: Effects of Peptide Mimetics of Apolipoproteins (2006)

Levels of high density lipoprotein (HDL) and its major protein component, apolipoprotein (apo) A-I, are strongly inversely correlated to risk of atherosclerosis and other vascular diseases. A number of properties of apo A-I may contribute to this protection, including removal of cholesterol from peripheral tissues to the liver (reverse cholesterol transport), anti-inflammatory and anti-oxidative activities, and modulation of vascular function. Apo A-I has lipid-associating domains that form class A amphipathic helices. Peptide analogs that have no sequence homology to the domains in apo A-I but possess the class A motif have been shown to not only associate with phospholipid but also mimic several of the functional properties of apo A-I. Peptide 4F, with four phenylalanines on the non-polar face, was found to be maximally effective in mimicking the positive qualities of apo A-I; this peptide inhibited atherosclerosis, reduced inflammation and oxidation, and improved vascular function in a number of animal models, and when synthesized with D-amino acids is orally bioavailable. Several other classes of peptide mimetics are now being studied, and may contribute to our understanding of the functions of apo E and apo J. The use of peptide mimetics to study apolipoprotein function has proved to be a powerful tool, and may lead to novel therapeutic agents in the prevention of atherosclerosis and other vascular diseases.
Nonadiabatic Kohn Anomaly in a Doped Graphene Monolayer (2006)

We compute, from first principles, the frequency of the E(2g), Gamma phonon (Raman G band) of graphene, as a function of the charge doping. Calculations are done using (i) the adiabatic Born-Oppenheimer approximation and (ii) time-dependent perturbation theory to explore dynamic effects beyond this approximation. The two approaches provide very different results. While the adiabatic phonon frequency weakly depends on the doping, the dynamic one rapidly varies because of a Kohn anomaly. The adiabatic approximation is considered valid in most materials. Here, we show that doped graphene is a spectacular example where this approximation miserably fails.