gebhart/patrepeval huggingface dataset:
Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis (2016)

Targeted antifolates with heteroatom replacements of the carbon vicinal to the phenyl ring in 1 by N (4), O (8), or S (9), or with N-substituted formyl (5), acetyl (6), or trifluoroacetyl (7) moieties, were synthesized and tested for selective cellular uptake by folate receptor (FR) α and β or the proton-coupled folate transporter. Results show increased in vitro antiproliferative activity toward engineered Chinese hamster ovary cells expressing FRs by 4-9 over the CH2 analogue 1. Compounds 4-9 inhibited de novo purine biosynthesis and glycinamide ribonucleotide formyltransferase (GARFTase). X-ray crystal structures for 4 with FRα and GARFTase showed that the bound conformations of 4 required flexibility for attachment to both FRα and GARFTase. In mice bearing IGROV1 ovarian tumor xenografts, 4 was highly efficacious. Our results establish that heteroatom substitutions in the 3-atom bridge region of 6-substituted pyrrolo[2,3-d]pyrimidines related to 1 provide targeted antifolates that warrant further evaluation as anticancer agents.
Effect of enucleation procedures and maturation conditions on the development of nuclear-transferred rabbit oocytes receiving male fibroblast cells (2002)

Enucleated oocytes matured in vitro, from which chromosomes were removed by treatment with ionomycin and demecolcine, were used as recipient oocytes for nuclear transfer of fibroblast cells from a mature male rabbit. The enucleated oocytes with donor nuclei were electrically activated 2 h after fusion. The potential of nuclear-transferred oocytes matured in vitro and ovulated oocytes to develop into blastocysts was high (33-55%), except for oocytes cultured for 8.0 (19%) and 8.5 h (25%) in vitro. After transfer of nuclear-transferred oocytes to recipients, ten of 62 (16%) and one of eight (13%) recipients that received in vitro-matured and ovulated oocytes, respectively, had 19 (1%) and one (0.6%) implantation sites at the time of laparotomy on days 8-17 after transfer. Four fetuses, including two with beating hearts, were obtained on day 15 of gestation after transfer of nuclear-transferred oocytes matured in vitro. The reason for the low efficiency of fetus production was not clear. One possibility is chromosomal abnormalities of nuclear-transferred oocytes, as most (21 of 22) of the oocytes had chromosomes dispersed along the spindle fibre at the first cell cycle. This is the first report of successful production of fetuses after nuclear transfer of rabbit somatic cells.
Expression of the low-affinity nerve growth factor receptor enhances beta-amyloid peptide toxicity. (1994)

The low-affinity nerve growth factor receptor (NGFR) p75NGFR induces apoptosis in the absence of nerve growth factor (NGF) binding but enhances neural survival when bound by NGF. Basal forebrain cholinergic neurons express the highest levels of p75NGFR in the adult human brain and are preferentially involved in Alzheimer disease, raising the question of whether there may be a functional relationship between the expression of p75NGFR and basal forebrain cholinergic neuronal degeneration in Alzheimer disease. The expression of p75NGFR by wild-type and mutant PC12 cells potentiated cell death induced by beta-amyloid peptide. NGF binding to p75NGFR inhibited the toxicity of beta-amyloid peptide, whereas NGF binding to TrkA, the high-affinity NGFR, enhanced it. These results suggest a possible link between beta-amyloid peptide toxicity and preferential degeneration of cells expressing p75NGFR.
An evaluation of cardiac output by five arterial pulse contour techniques during cardiac surgery (2007)

The bias, precision and tracking ability of five different pulse contour methods were evaluated by simultaneous comparison of cardiac output values from the conventional thermodilution technique (COtd). The five different pulse contour methods included in this study were: Wesseling's method (cZ); the Modelflow method; the LiDCO system; the PiCCO system and a recently developed Hemac method. We studied 24 cardiac surgery patients undergoing uncomplicated coronary artery bypass grafting. In each patient, the first series of COtd was used to calibrate the five pulse contour methods. In all, 199 series of measurements were accepted by all methods and included in the study. COtd ranged from 2.14 to 7.55 l.min(-1), with a mean of 4.81 l.min(-1). Bland-Altman analysis showed the following bias and limits of agreement: cZ, 0.23 and - 0.80 to 1.26 l.min(-1); Modelflow, 0.00 and - 0.74 to 0.74 l.min(-1); LiDCO, - 0.17 and - 1.55 to 1.20 l.min(-1); PiCCO, 0.14 and - 1.60 to 1.89 l.min(-1); and Hemac, 0.06 and - 0.81 to 0.93 l.min(-1). Changes in cardiac output larger than 0.5 l.min(-1) (10%) were correctly followed by the Modelflow and the Hemac method in 96% of cases. In this group of subjects, without congestive heart failure, with normal heart rhythm and reasonable peripheral circulation, the best results in absolute values as well as in tracking changes in cardiac output were measured using the Modelflow and Hemac pulse contour methods, based on non-linear three-element Windkessel models.
Clonal diseases of large granular lymphocytes [see comments] (1993)

Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL typically associated with chronic neutropenia and autoimmune features. NK-LGL leukemia is characterized by clonal CD3- LGL proliferation with an acute clinical presentation marked by massive hepatosplenomegaly and systemic illness. However, most patients with increased numbers of CD3- LGL do not have clinical features of NK-LGL leukemia and have a chronic clinical course. X-linked gene analyses have supported a polyclonal LGL lymphocytosis in this syndrome. Further studies are needed to determine whether clonal progression can occur in these patients.
Theoretical studies on the gravity drainage of heavy oil during in‐situ steam heating (1981)

Abstract One concept for the in‐situ production of oil from the tar sands involves the continuous injection of steam into a growing steam‐saturated volume or steam chamber. Steam flow to the boundary of the chamber, condenses and gives up its heat to the surrounding oil sands. The condensate and heated oil flow by gravity to a production well located at the bottom of a chamber and are removed continuously. The well may consist of a horizontal slotted pipe. This paper describes the theory of operation of such a process and an equation is derived which predicts the rate of drainage.
<title>Bayesian methods for the use of implicit polynomials and algebraic invariants in practical computer vision</title> (1992)

Implicit higher degree polynomials in x, y, z (or in x, y for curves in images) have considerable global and semiglobal representation power for objects in 3D space. (Spheres, cylinders, cones and planes are special cases of such polynomials restricted to second degree). Hence, they have great potential for object recognition and position estimation and for object geometric-property measurement. In this paper we deal with four problems pertinent to using these polynomials in real world robust systems: (1) Characterization and fitting algorithms for the subset of these algebraic curves and surfaces that is bounded and exists largely in the vicinity of the data; (2) The aposteriori distribution for the possible polynomial coefficients given a data set. This measures the extent to which a data set constrains the coefficients of the best fitting polynomial; (3) Geometric Invariants for determining whether one implicit polynomial curve or surface is a rotation and translation of another, or whether one implicit polynomial curve is an affine transformation of another; (4) A Mahalanobis distance for comparing the coefficients or the invariants of two polynomials to determine whether the curves or surfaces that they represent are close over a specified region. In addition to handling objects with easily detectable features such as vertices, high curvature points, and straight lines, the polynomials and tools discussed in this paper are ideally suited to smooth curves and smooth curved surfaces which do no have detectable features.
The how and why of electronic noses (1998)

Witnessing the swift advances in the electronic means of seeing and hearing, scientists and engineers scent a market for systems mimicking the human nose. Already commercial systems from several companies are targeting applications, present and potential, that range from quality assurance of food and drugs to medical diagnosis, environmental monitoring, safety and security and military use. Here, the authors outline the major transducer technologies-in one sense, the key component of an electronic nose.
Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts. (1994)

Three complete cDNA clones encoding Id-related helix-loop-helix (HLH) proteins lacking a basic region were isolated from a pcD2 cDNA expression library prepared from TIG-3 human diploid fibroblasts (HDF). Of these cDNAs (Id-1H, Id-1H', and Id-2H), two (Id-1H and Id-1H') appeared to be derived by alternative RNA splicing. Id-1H and Id-2H seem to be human homologues of mouse Id-1 and Id-2, respectively, and have potential to encode 154 and 135 amino acid proteins. The Id-1H and Id-2H mRNAs were barely detectable in quiescent early passage HDF; serum coordinately induced both mRNAs, with two peaks of expression, in early and late in G1. Antisense oligomers complementary to Id-1H and Id-2H mRNA prevented early passage HDF from entering the S phase of the cell cycle. The treatment of serum-stimulated early passage cells with the antisense Id-1H oligomer completely abolished Id-1H. In senescent cells, serum barely induced the Id-1H and Id-2H mRNAs, although the levels of c-myc expression induced were similar in early passage and senescent cells. The expression levels of these Id genes vary among immortal human cell lines. Both genes were overexpressed in VA4 SV40-transformed lung fibroblasts and EJ-1 bladder carcinoma cells, while these genes were expressed at a very low level in SVts8 cells derived from SV40 tsA-transformed TIG-3 cells. SVts8 cells may acquire some function redundant to Id proteins. HT1080 fibrosarcoma cells expressed the Id-1H gene but not the Id-2H gene, suggesting these Id genes may subserve redundant functions.
Conjugates of folate and anti-T-cell-receptor antibodies specifically target folate-receptor-positive tumor cells for lysis. (1995)

High-affinity folate receptors (FRs) are expressed at elevated levels on many human tumors. Bispecific antibodies that bind the FR and the T-cell receptor (TCR) mediate lysis of these tumor cells by cytotoxic T lymphocytes. In this report, conjugates that consist of folate covalently linked to anti-TCR antibodies are shown to be potent in mediating lysis of tumor cells that express either the alpha or beta isoform of the FR. Intact antibodies with an average of five folate per molecule exhibited high affinity for FR+ tumor cells but did not bind to FR- tumor cells. Lysis of FR+ cell lines could be detected at concentrations as low as 1 pM (approximately 0.1 ng/ml), which was 1/1000th the concentration required to detect binding to the FR+ cells. Various FR+ mouse tumor cell lines could be targeted with each of three different anti-TCR antibodies that were tested as conjugates. The antibodies included 1B2, a clonotypic antibody specific for the cytotoxic T cell clone 2C; KJ16, an anti-V beta 8 antibody; and 2C11, an anti-CD3 antibody. These antibodies differ in affinities by up to 100-fold, yet the cytolytic capabilities of the folate/antibody conjugates differed by no more than 10-fold. The reduced size (in comparison with bispecific antibodies) and high affinity of folate conjugates suggest that they may be useful as immunotherapeutic agents in targeting tumors that express folate receptors.
Great amount of C.pneumoniae in ruptured plaque vessel segments at autopsy. A comparative study with stable plaques (2000)

A possible relationship between C.pneumoniae (CP) infection, atherosclerosis and acute myocardial infarction is a debated matter. Now we performed the search of CP in histological segments of fatal ruptured plaques and of stable plaques by histochemistry (Macchiavello stain), immunohistochemistry and in situ hybridization techniques. Electron microscopy and confocal laser microscopy techniques were used in two additional cases. The semi-quantification of CP + cells (0-4+) and quantification of lymphocytes demonstrated greater amount of CP + cells and more inflammation in the adventitia of vulnerable plaque vessel segments than of stable ones, larger amount of CP + cells in adventitia than in the plaque and high frequency of CP + cells in all groups studied. This preliminary study strongly suggests a direct pathogenetic involvement of adventitial CP in the rupture of the atheromatous plaque, development of acute myocardial infarction and also in the development of atherosclerosis.
Catalytically active nickel {110} surfaces in growth of carbon tubular structures (2000)

Recent interest in the growth of aligned carbon nanotube films using transition metal catalysts has led to questions concerning the growth mechanism involved. In our experiment carbon tubules grown using Ni catalysts exhibit a preferred orientation relative to the catalytically active surfaces of Ni. The axial directions of the tubular structure are mainly parallel to the 〈110〉 and 〈042〉 directions of Ni. The faceted shape of the Ni particles determines the intrinsic structure of the tubules. A mechanism involving spiral growth is proposed to explain the nucleation and growth of such tubules.
A sensitive microwave interferometer for plasma diagnostics (1969)

More accurate methods of measuring microwave attenuation and phase are constantly being sought, particularly for such applications as plasma diagnostics. The microwave bridge technique described here was developed for the study of a quiescent plasma having an electron density of 10 15 to 10 18 m −3 corresponding to a plasma frequency of 3 × 10 8 to 10 10 Hz, and an electron collision frequency of 10 10 to 10 11 s −1 . The plasma had a broad dimension of 0·3 m. For such a plasma a probing frequency of 10 GHz was considered to be the most suitable; at this frequency the attenuation α and phase shift δβ expected were 0·1 &lt; α&lt; 50 dB and 1° &lt; δβ &lt; 1000° respectively.
Enhanced bactericidal action of lysozyme to Escherichia coli by inserting a hydrophobic pentapeptide into its C terminus. (1994)

The mechanism of the enhanced bactericidal action to Escherichia coli of the lysozyme having a hydrophobic pentapeptide (Phe-Phe-Val-Ala-Pro) at its C terminus was investigated. The modified lysozyme, hydrophobic pentapeptide-fused lysozyme (HLz), was secreted in the culture medium from yeast harboring the expression plasmid, in which a synthetic DNA fragment encoding a hydrophobic pentapeptide was introduced to the 3'-end of the coding region of the lysozyme cDNA. Although CD analysis showed that HLZ was considerably different from wild-type lysozyme (WLz) in the secondary and tertiary structures, it retained 76% of the lytic activity of WLz. When E. coli cells were exposed to the WLz or HLz, the survival cells were significantly reduced only in the case of HLz. Periplasmic proteins from the HLz-treated cells were released to an extent similar to that from the WLz-treated cells, indicating that HLz has nearly the same action as WLz with respect to the disruption of the outer membrane and peptidoglycan. Experiments with E. coli phospholipid liposomes revealed that HLz dissipated the valinomycin-induced transmembrane electrochemical potential, but WLz did not. These results suggest that the enhanced bactericidal action of HLz to E. coli is due to disruption of the electrochemical potential of the inner membrane in cooperation with the inherent function of the lysozyme to the outer membrane and peptidoglycan.
THREE-DIMENSIONAL PROBE AND SURFACE RECONSTRUCTION FOR ATOMIC FORCE MICROSCOPY USING A DECONVOLUTION ALGORITHM (1998)

Atomic force microscope (AFM) images often contain distortions caused by the convolution of the tip and sample surface. The offered numerical deconvolution, with the use of an inverted tip located at a constant height from the surface, noticeably differs from methods previously published and is essentially simple for a concrete practical realization. Nanometer-sized spheres were successfully used to extract the shape of the AFM square pyramidal tip by means of this algorithm. Once a deconvolution procedure was used with the reconstructed AFM tip shape, truer structures of the spherical 90 nm sized particles were obtained.
Image-based procedural modeling of facades (2007)

This paper describes algorithms to automatically derive 3D models of high visual quality from single facade images of arbitrary resolutions. We combine the procedural modeling pipeline of shape grammars with image analysis to derive a meaningful hierarchical facade subdivision. Our system gives rise to three exciting applications: urban reconstruction based on low resolution oblique aerial imagery, reconstruction of facades based on higher resolution ground-based imagery, and the automatic derivation of shape grammar rules from facade images to build a rule base for procedural modeling technology.
Sequence and molecular characterization of a multicopy invasion plasmid antigen gene, ipaH, of Shigella flexneri (1990)

A lambda gt11 expression library of Tn5-tagged invasion plasmid pWR110 (from Shigella flexneri serotype 5, strain M90T-W) contained a set of recombinants encoding a 60-kilodalton protein (designated IpaH) recognized by rabbit antisera raised against S. flexneri invasion plasmid antigens (J. M. Buysse, C. K. Stover, E. V. Oaks, M. M. Venkatesan, and D. J. Kopecko, J. Bacteriol. 169:2561-2569, 1987). Southern blot analysis of wild-type S. flexneri serotype 5 invasion plasmid DNA (pWR100) digested with various combinations of five restriction enzymes and hybridized with defined ipaH probes showed complex hybridization patterns resulting from multiple copies of the ipaH gene on pWR100. DNA sequence analysis of a 2.9-kilobase (kb) EcoRI fragment directing IpaH antigen synthesis in plasmid recombinant pWR390 revealed an open reading frame coding for a 532-amino-acid protein (60.8 kilodaltons); this size matched well with the estimated size of IpaH determined by Western blot analysis of M90T-W cells and maxicell analysis of Escherichia coli HB101(pWR390) transformants. Examination of the amino acid sequence of IpaH revealed a hydrophilic protein with six evenly spaced 14-residue (L-X2-L-P-X-L-P-X2-L-X2-L) repeat motifs in the amino-terminal end of the molecule. Southern blot analysis of HindIII-digested pWR100 DNA probed with defined segments of the pWR390 2.9-kb insert demonstrated that the multiple band hybridization pattern resulted from repeats of a significant portion of the ipaH structural gene in five distinct HindIII fragments (9.8, 7.8, 4.5, 2.5, and 1.4 kb). Affinity-purified IpaH antibody, used to monitor the expression of the antigen in M90T-W cells grown at 30 and 37 degrees C, showed that IpaH synthesis was not regulated by growth temperature.
Bacteriological evaluation of midecamycin acetate and its metabolites. (1982)

In vitro midecamycin acetate was shown to have broad spectrum of antibacterial activities similar to those of other macrolides (midecamycin, josamycin, 9-propionyl josamycin and 2'-ethylsuccinyl erythromycin), which include Gram-positive organisms, a part of Gram-negative organisms and anaerobes. Metabolites of midecamycin acetate also showed certain degree of antibacterial activities although they gave higher MIC values than midecamycin acetate. The antibacterial activities of midecamycin acetate were potentiated in the medium with pH 7 or pH 8 and little affected by inoculum size or addition of human serum into the medium. Both midecamycin acetate and its metabolites were found to have relatively high protein binding rates. In vivo therapeutic experiments in experimental infections in mice, midecamycin acetate was shown to be much superior to other drugs tested in the therapeutic efficacy against intraperitoneal infections caused by Staph. aureus, Strept. pyogenes, Strept. pneumoniae and Cl. perfringens. In infections transnasally induced by Strept. pneumoniae, midecamycin acetate showed therapeutic efficacy 2 or 5 times greater than that of josamycin or midecamycin, despite that MICs of midecamycin acetate were equal to josamycin or midecamycin. Moreover, midecamycin acetate showed high therapeutic efficacy for subcutaneous infections due to Staph. aureus, suggesting that it exerts pronounced antibacterial activities against not only systemic infections but also local infections.
UAF1 Is a Subunit of Multiple Deubiquitinating Enzyme Complexes (2008)

A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific deubiquitinating enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 deubiquitinating enzyme, which regulates the Fanconi anemia pathway by deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both enzyme complexes, suggesting that this activator protein may regulate a subclass of human deubiquitinating enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human deubiquitinating enzymes and thereby regulate their activity and substrate specificity.
Expanding the Psoriasis Disease Profile: Interrogation of the Skin and Serum of Patients with Moderate-to-Severe Psoriasis (2012)

Psoriasis is a complex disease with an expanding definition of its pathological features. We sought to expand/refine the psoriasis transcriptome using 85 paired lesional and non-lesional samples from a cohort of patients with moderate-to-severe psoriasis vulgaris who were not receiving active psoriasis therapy. This new analysis identified 4,175 probe sets (representing 2,725 unique known genes) as being differentially expressed in psoriasis lesions compared with matched biopsies of non-lesional skin when the following criteria were applied: >2-fold change and false discovery rate <0.05. These probe sets represent the largest and most comprehensive set of genes defining psoriasis at the molecular level and within the previously unidentified genes, a link to functional pathways associated with metabolic diseases/diabetes and to cardiovascular risk pathways is identified. In addition, we profiled the serum of moderate-to-severe psoriatics compared with healthy controls to assess the overlap of overexpressed lesional genes with overexpressed systemic proteins. We identified linkage of functional pathways in lesional skin associated with metabolic diseases/diabetes and cardiovascular risk with those pathways overexpressed in the serum, suggesting a potential linkage between altered gene transcription in the skin and comorbidities commonly seen in patients with moderate-to-severe psoriasis.