gebhart/patrepeval huggingface dataset:
Cloning, expression, and characterization of chicken tissue inhibitor of metalloproteinase‐2 (TIMP‐2) in normal and transformed chicken embryo fibroblasts (1998)

Rous sarcoma virus-transformed chicken embryo fibroblasts (RSVCEF), when compared to normal CEF, produce elevated levels of matrix metalloproteinase-2 (MMP-2) that exists in a form free of complexed tissue inhibitor of metalloproteinase-2 (TIMP-2). In order to ascertain whether the increased levels of TIMP-free MMP-2 in RSVCEF cultures are due to diminished expression of TIMP-2 or alterations in TIMP-2 that diminish its MMP-2 binding ability, it was necessary to clone, characterize, and express chicken TIMP-2 cDNA. The TIMP-2 cDNA was cloned from a chick embryo λgt11 library by RT-PCR using primers based on amino-acid sequences determined from isolated TIMP-2. The deduced amino acid sequence for chicken TIMP-2 is 81% identical to human TIMP-2; most of the sequence differences lie in the carboxyl terminal portion of chicken TIMP-2. Northern analysis of mRNA levels in CEF and RSVCEF demonstrates that TIMP-2 mRNA levels are increased in RSVCEF. However, TIMP-2 protein levels, relative to proMMP-2 levels, appear to decrease upon transformation and suggest additional control of TIMP-2 at the post-transcriptional level. Addition of recombinantly expressed TIMP-2 to RSVCEF cultures causes a disappearance of TIMP-free (TF) proMMP-2 with a corresponding increase in the TIMP-complexed (TC) proMMP-2 levels, demonstrating that TF proMMP-2 is capable of converting to TC pro-MMP-2 when free TIMP-2 is available. Surprisingly, RSVCEF cultures manifest a TIMP-2 population that is not complexed to MMP-2, despite the coexistence of TIMP-free proMMP-2. Gel-filtration analysis indicates that this uncomplexed TIMP-2 exhibits an apparent molecular weight of 50 kDa, indicating it is not free TIMP-2 and that it exists in transformed cultures in a noncovalent complex with an undefined molecule. Thus transformed cells can alter the TIMP-2/MMP-2 balance by transcriptional and post-translational modifications, yielding a population of inhibitor-free, proteolytically active MMP2. J. Cell. Physiol. 174:342–352, 1998. © 1998 Wiley-Liss, Inc.
H-related defect complexes in HfO2: A model for positive fixed charge defects (2004)

Based on first-principles theoretical calculations, we investigate the hydrogenation effect on the defect properties of oxygen vacancies (VO) in HfO2. A defect complex of VO and H behaves as a shallow donor for a wide range of Fermi levels, with a positive charge state, and this complex is energetically stable against its dissociation into VO and H. We suggest that the VO–H complex is responsible for the formation of positive fixed charges, which neutralize negative fixed charges during the postannealing process of SiOx/HfO2 stack.
Visualization of differential gene expression using a novel method of RNA fingerprinting based on AFLP: Analysis of gene expression during potato tuber development (1996)

Using a highly synchronous in vitro tuberization system, in combination with an amplified restriction fragment polymorphism (AFLP)-derived technique for RNA fingerprinting (cDNA-AFLP), transcriptional changes at and around the time point of potato tuberization have been analyzed. The targeted expression analysis of a specific transcript coding for the major potato storage protein, patatin and a second transcript, coding for ADP-glucose pyrophosphorylase, a key gene in the starch biosynthetic pathway is described. This paper confirms that kinetics of expression revealed by cDNA-AFLP analysis are comparable to those found in Northern analysis. Furthermore, this paper reports the isolation and analysis of two tuber-specific transcript-derived fragments (TDFs) coding for the lipoxygenase enzyme, which are differentially induced around the time point of tuber formation. Analysis of the two lox TDFs demonstrates that it is possible to dissect the expression modalities of individual transcripts, not independently detectable by Northern analysis. Finally, it is shown that using cDNA-AFLP, rapid and simple verification of band identity may be achieved. The results indicate that cDNA-AFLP is a broadly applicable technology for identifying developmentally regulated genes.
Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation, Structure, and Partial Synthesis of an Active Constituent of HashishY. Gaoni and R. MechoulamCite this: J. Am. Chem. Soc. 1964, 86, 8, 1646–1647Publication Date (Print):April 1, 1964Publication History Published online1 May 2002Published inissue 1 April 1964https://pubs.acs.org/doi/10.1021/ja01062a046https://doi.org/10.1021/ja01062a046research-articleACS PublicationsRequest reuse permissionsArticle Views6938Altmetric-Citations1741LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Statistics for Critical Clinical Decision Making Based on Readings of Pairs of Implanted Sensors (1996)

Low error rates are essential if lives of patients are to depend on readings of implanted sensors, such as glucose sensors in insulin-dependent diabetic patients. To verify the operation and to calibrate on demand an implanted sensor, it is necessary that calibration through a single, independent measurement involving withdrawal of only one sample of blood and its independent analysis be feasible. Such a one-point calibration must be accurate. Borrowing from nuclear reactor safety assurance, where a likelihood ratio test is applied to readings of pairs of pressure sensors for shutdown/no shutdown decisions, we apply a similar test to sensor pairs implanted in rats. We show, for five sets of glucose sensor pairs, calibrated in vivo by withdrawal of a single sample of blood, that application of the likelihood ratio test increases the fraction of the clinically correct readings from 92.4% for their averaged readings to 98.8%.
A Four-Color Colloidal Multiplexing Nanoparticle System (2008)

Any labeling with multicolor markers can be affected by the autofluorescence of biological tissue due to the UV or blue light excitation sources, or the results are affected by fluorescence resonance energy transfer. In this work, we present novel IR-to-vis upconverting nanoparticles of different rare earth metal dopants. With a single excitation source of 980 nm, four different colors of nanocrystals can be spectrally separated under multiplexing conditions. The particles were phase transferred into polar solvents by means of silica encapsulation and were characterized by transmission electron microscopy, X-ray diffraction, and photoluminescence spectroscopy.
Inhibitory effects of a phosphate diester of alpha-tocopherol and ascorbic acid (EPC-K1) on myocardial infarction in rats. (1996)

The inhibitory effect of a phosphate diester of alpha-tocopherol and ascorbic acid (EPC-K1) was examined in myocardial infarction induced in rats, in comparison with a selective 5-lipoxygenase inhibitor, AA-861. EPC-K1 significantly reduced the infarct size at 24 and 48 h after ligation, whereas AA-861 reduced it only at 48 h after ligation. In in-vitro experiments, EPC-K1 inhibited not only superoxide anion generation (IC50 = 4.2 x 10(-5) M), but also acid phosphatase activity (IC50 = 2.4 x 10(-5) M) in rat polymorphonuclear leukocytes in a concentration-dependent manner, while AA-861 showed marginal effects on both actions. These results indicated that EPC-K1 induced cardioprotective effects by affecting neutrophil functions by inhibition of generation of superoxide-anion generation and acid-phosphatase activity. The mechanism of the reduction of the infarct size by EPC-K1 differed from that of AA-861, which latter inhibited 5-lipoxygenase and the formation of leukotriene B4.
Sketching Clothoid Splines Using Shortest Paths (2010)

Abstract Clothoid splines are gaining popularity as a curve representation due to their intrinsically pleasing curvature, which varies piecewise linearly over arc length. However, constructing them from hand‐drawn strokes remains difficult. Building on recent results, we describe a novel algorithm for approximating a sketched stroke with a fair (i.e., visually pleasing) clothoid spline. Fairness depends on proper segmentation of the stroke into curve primitives — lines, arcs, and clothoids. Our main idea is to cast the segmentation as a shortest path problem on a carefully constructed weighted graph. The nodes in our graph correspond to a vastly overcomplete set of curve primitives that are fit to every subsegment of the sketch, and edges correspond to transitions of a specified degree of continuity between curve primitives. The shortest path in the graph corresponds to a desirable segmentation of the input curve. Once the segmentation is found, the primitives are fit to the curve using non‐linear constrained optimization. We demonstrate that the curves produced by our method have good curvature profiles, while staying close to the user sketch.
Elevated endogenous serum macrophage colony-stimulating factor in the early stage of fungemia following bone marrow transplantation. (1994)

Murine studies have reported elevated serum macrophage colony-stimulating factor (M-CSF) concentrations in animals inoculated with fungus; however, the human cytokine response to fungemia has not been described. Endogenous M-CSF serum concentrations were measured in 18 autologous bone marrow transplant patients with positive blood fungal cultures. Seventeen of the 18 patients received the same high-dose chemotherapy regimen with autologous hematopoietic support. M-CSF concentrations were determined in serum samples obtained 1 week before and within 2 days of the first positive blood culture. Serum M-CSF rose more than three-fold in a majority of patients at the time of positive culture in contrast to concentrations obtained in the previous week (medians 11.1 and 2.8 ng/mL, respectively; p = 0.001). Median values at the time of positive blood culture were also significantly higher than those obtained in a matched control group of patients without positive blood cultures (n = 18; median 2.60 ng/mL; p = 0.001). These data demonstrate that endogenous serum M-CSF is elevated in the early stages of human systemic fungal infection and thus may have important diagnostic and therapeutic implications.
Anxiety symptom relief in depression treatment outcomes. (1995)

Depressive and anxiety disorders have a high lifetime prevalence--8% and 15%, respectively. Unipolar depression has a 5% lifetime prevalence, whereas the prevalence rate for all depressive disorders is between 6% to 8% at a minimum. Each disorder has also been found to have a high rate of chronicity and recurrence. It has become increasingly apparent over the past decade that within episodes of depression, anxiety symptoms often exist. Whether this phenomenon indicates two separate but comorbid illnesses or that the presence of anxiety symptoms is part of the course of depression is of particular significance for diagnosis and treatment. The author focuses on the issues of differential diagnosis, including physical and emotional manifestations of the illness. The consequences of comorbid anxiety and depression can be serious, ranging from social and physical disability to suicidal ideation and behavior. Anxiety has been found to be a predictor of suicide in depressed patients, and since anxiety symptoms respond to intervention, they can also serve as an indication of type of treatment. Antidepressants should be used in treating anxiety or panic symptoms when depression is also present. In studies comparing benzodiazepines, monoamine oxidase inhibitors (MAOIs), serotonin selective reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs) in the treatment of concurrent anxiety and depression, all have some measure of success depending on the degree of depression and the type of anxiety disorder. SSRIs may have the least amount of side effects, but more long-term studies are needed to determine the long-term efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of neovascularization by human rheumatoid synovial tissue macrophages (1986)

Synovial tissue from patients with rheumatoid arthritis was enzymatically dissociated, and single cell suspensions were fractionated into subpopulations by centrifugation on continuous Percoll gradients. Five fractions (F1-F5) with densities of 0.991-0.998 gm/ml, 0.998-1.042 gm/ml, 1.042-1.062 gm/ml, 1.062-1.082 gm/ml, and 1.082-1.180 gm/ml, respectively, were prepared. F3 consistently contained the highest number of macrophages, while F2 and F4 contained substantially fewer macrophages. Macrophages present in F2, F3, and F4 were enriched by differential adherence to fibronectin-coated collagen gels. These macrophage-enriched cell preparations were found to be Fc and C3 positive, esterase positive, and peroxidase negative, to stain positively with anti-HLA-DR, anti-Leu-M3, OKM1, and OKM5 monoclonal antibodies, and to show characteristic features of macrophages by electron microscopy. Macrophages from F3 consistently induced neovascularization in rat corneas, while equal numbers of macrophages from F2 and F4 did not. Fibroblastic synovial cells and cells that did not adhere to fibronectin-coated collagen gels did not induce neovascularization. Within the rheumatoid synovium, there appears to be a major subpopulation of macrophages capable of inducing neovascularization, a process vital to the development of the rheumatoid synovial pannus.
Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma (2015)

Early-stage cutaneous T-cell lymphoma (CTCL) is a skin-limited lymphoma with no cure aside from stem cell transplantation. Twelve patients with stage IA-IIA CTCL were treated in a phase 1 trial of 0.03% and 0.06% topical resiquimod gel, a Toll-like receptor 7/8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. Ninety-two percent of patients had more than a 50% improvement in body surface area involvement by the modified Severity-Weighted Assessment Tool analysis and 2 patients experienced complete clearing of disease. Four of 5 patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. T-cell receptor sequencing and flow cytometry studies of T cells from treated lesions demonstrated decreased clonal malignant T cells in 90% of patients and complete eradication of malignant T cells in 30%. High responses were associated with recruitment and expansion of benign T-cell clones in treated skin, increased skin T-cell effector functions, and a trend toward increased natural killer cell functions. In patients with complete or near eradication of malignant T cells, residual clinical inflammation was associated with cytokine production by benign T cells. Fifty percent of patients had increased activation of circulating dendritic cells, consistent with a systemic response to therapy. In summary, topical resiquimod is safe and effective in early-stage CTCL and the first topical therapy to our knowledge that can induce clearance of untreated lesions and complete remissions in some patients. This trial was registered at www.clinicaltrials.gov as #NCT813320.
Correction: Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth (2008)

It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR) fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC) gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than L of the probe signal was localized in CD11b + Gr1 + myeloid derived suppressor cells (MDSC) and CD11b + F4/80 + macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFa in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy.
Proteomic and immunologic analyses of brain tumor exosomes (2008)

Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles released from many cell types into the extracellular milieu; surprisingly, exosomes are virtually unstudied in neuro-oncology. These microvesicles were used as vaccines in other tumor settings, but their immunological significance is unevaluated in brain tumors. Our purpose here is to report the initial biochemical, proteomic, and immunological studies on murine brain tumor exosomes, following known procedures to isolate exosomes. Our findings show that these vesicles have biophysical characteristics and proteomic profiles similar to exosomes from other cell types but that brain tumor exosomes have unique features (e.g., very basic isoelectric points, expressing the mutated tumor antigen EGFRvIII and the putatively immunosuppressive cytokine TGF-beta). Administration of such exosomes into syngeneic animals produced both humoral and cellular immune responses in immunized hosts capable of rejecting subsequent tumor challenges but failed to prolong survival in established orthotopic models. Control animals received saline or cell lysate vaccines and showed no antitumor responses. Exosomes and microvesicles isolated from sera of patients with brain tumors also possess EGFR, EGFRvIII, and TGF-beta. We conclude that exosomes released from brain tumor cells are biochemically/biophysically like other exosomes and have immune-modulating properties. They can escape the blood-brain barrier, with potential systemic and distal signaling and immune consequences.
fleN , a Gene That Regulates Flagellar Number in Pseudomonas aeruginosa (2000)

The single polar flagellum of Pseudomonas aeruginosa plays an important role in the pathogenesis of infection by this organism. However, regulation of the assembly of this organelle has not been delineated. In analyzing the sequence available at the Pseudomonas genome database, an open reading frame (ORF), flanked by flagellar genes flhF and fliA, that coded for a protein (280 amino acids) with an ATP-binding motif at its N terminus was found. The ORF was inactivated by inserting a gentamicin cassette in P. aeruginosa PAK and PAO1. The resulting mutants were nonmotile on motility agar plates, but under a light microscope they exhibited random movement and tumbling behavior. Electron microscopic studies of the wild-type and mutant strains revealed that the mutants were multiflagellate, with three to six polar flagella per bacterium as rather than one as in the wild type, indicating that this ORF was involved in regulating the number of flagella and chemotactic motility in P. aeruginosa. The ORF was named fleN. An intact copy of fleN on a plasmid complemented the mutant by restoring motility and monoflagellate status. The beta-galactosidase activities of eight flagellar operon or gene promoters in the wild-type and fleN mutant strains revealed a direct correlation between six promoters that were upregulated in the fleN mutant (fliLMNOPQ, flgBCDE, fliEFG, fliDS orf126, fleSR, and fliC) and positive regulation by FleQ, an NtrC-like transcriptional regulator for flagellar genes. Based on these results, we propose a model where FleN influences FleQ activity (directly or indirectly) in regulating flagellar number in P. aeruginosa.
Allelotype of neuroblastoma. (1995)

Although relatively high incidence of loss of heterozygosity (LOH) on chromosomes 1p, 11q, and 14q have been reported in neuroblastoma, it is still unclear whether or not LOH occurs specifically on these chromosome arms in neuroblastoma since only a few chromosomal arms have been examined for LOH in previous studies. Therefore, we screened 81 cases of tumors for LOH on all 22 autosomes and chromosome X using 35 restriction fragment length polymorphism markers and eight microsatellite markers. High incidence of LOH (> 20%) was observed on six chromosome arms; 1p (26%), 2q (30%), 9p (36%), 11q (24%), 14q (22%), and 18q (31%). Frequencies of LOH on other chromosome arms were less than 13%. Patients with 9p LOH in the tumors showed statistically significant association with advanced stage of the disease and poor prognosis (P = 0.037 and P = 0.003, respectively) independently from N-myc amplification, while LOH on other chromosomes did not show association with stage, prognosis, and N-myc amplification. Thus, besides LOH on chromosomes 1p, 11q, and 14q, LOH on chromosomes 2q, 9p, and 18q also occurs relatively frequently in neuroblastoma, indicating the involvement of multiple tumor suppressor genes in the development of neuroblastoma. It is possible that there is a novel tumor suppressor gene on chromosome 9p which is involved in the progression of neuroblastoma.
Transcription factor B cell lineage-specific activator protein regulates the gene for human X-box binding protein 1. (1996)

The transcription factor human X-box binding protein 1 (hXBP-1) is a basic region-leucine zipper protein implicated in the regulation of major histocompatibility complex class II gene expression as well as in exocrine gland and skeletal development. Multiple regulatory elements in the hXBP-1 promoter lie 3' to the transcription start site, including the hX2 site, whose core sequence is an AP-1-like element identical to the hXBP-1 target sequence in the HLA-DRA promoter. One complex identified by electrophoretic mobility shift assay (EMSA), complex 3, was previously shown to protect the hX2 site and more 3' bases. Sequence analysis now shows that this region contains a consensus binding site for transcription factor BSAP (B cell lineage-specific activator protein). Complex 3 and BSAP have identical cell-type specificities, as they are found only in pre-B and mature B cell lines. In EMSAs, BSAP antibody specifically recognized complex 3, and in vitro translated BSAP could bind to an hXBP promoter fragment. Cotransfections using an hXBP-1 reporter construct indicated that BSAP downregulates the hXBP-1 promoter. The highest levels of hXBP-1 mRNA were found when BSAP was not expressed, in pre-Pro-B cells and in plasma cell lines. In addition, hXBP-1 and BSAP levels were inversely correlated along the early stages of B cell development. In the regulation of the hXBP-1 promoter, a strong positive transcriptional influence at the hX2 site is opposed by the downregulatory actions of BSAP.