gebhart/patrepeval huggingface dataset:
Expression profiling of fecal colonocytes for RNA-based screening of colorectal cancer (2007)

The early detection of colorectal cancer originating from any part of the colorectum is desirable because this cancer can be cured surgically if diagnosed early. We searched for marker genes for a fecal RNA-based colorectal cancer screening method by comparison of genome-wide expression profiles among cancerous and non-cancerous tissues, and healthy volunteer- and cancer patient-derived colonocytes from the feces, and the peripheral blood. Of 14,564 genes, only 3 (PAP, REG1A, and DPEP1) were selectable as final candidates which were expressed frequently at any stage of this cancer and were suppressed in non-cancerous tissues and also in the peripheral blood and colonocytes of healthy volunteers. Next, we directly compared fecal RNA-expression profiles between colorectal cancer patients and healthy volunteers, and found that most of the genes (92%) expressed in the colonocytes of the cancer patients were not expressed in those of the healthy volunteers. Six genes (SEPP1, RPL27A, ATP1B1, EEF1A1, SFN, and RPS11) selected randomly from 85 cancer patient-derived colonocyte-specific genes were evaluated. In total, reverse transcription-polymerase chain reaction or focused microarray of all those 9 genes detected 18 (78%) of 23 curable colorectal cancers (Dukes stages A-C), 9 or 10 (64% or 71%) of 14 early cancers with no lymph node metastasis (Dukes stage A or B) and 4 (80%) of 5 right-sided cancers. Our extensive gene list provides other markers for fecal RNA-based colorectal cancer screening.
Systematic Structure Modifications of Multitarget Prostate Cancer Drug Candidate Galeterone To Produce Novel Androgen Receptor Down-Regulating Agents as an Approach to Treatment of Advanced Prostate Cancer (2013)

As part of our program to explore the influence of small structural modifications of our drug candidate 3β-(hydroxy)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (galeterone, 5) on the modulation of the androgen receptor (AR), we have prepared and evaluated a series of novel C-3, C-16, and C-17 analogues. Using structure activity analysis, we established that the benzimidazole moiety at C-17 is essential and optimal and also that hydrophilic and heteroaromatic groups at C-3 enhance both antiproliferative (AP) and AR degrading (ARD) activities. The most potent antiproliferative compounds were 3β-(1H-imidazole-1-carboxylate)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (47), 3-((EZ)-hydroximino)-17-(1H-benzimidazol-1-yl)androsta-4,16-diene (36), and 3β-(pyridine-4-carboxylate)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (43), with GI50 values of 0.87, 1.91, and 2.57 μM, respectively. Compared to 5, compound 47 was 4- and 8-fold more potent with respect to AP and ARD activities, respectively. Importantly, we also discovered that our compounds, including 5, 36, 43, and 47, could degrade both full-length and truncated ARs in CWR22rv1 human prostate cancer cells. With these activities, they have potential for development as new drugs for the treatment of all forms of prostate cancer.
Fibronectin-mediated binding and phagocytosis of polystyrene latex beads by baby hamster kidney cells. (1983)

The binding and phagocytosis of fibronectin (pFN)-coated latex beads by baby hamster kidney (BHK) cells was studied as a function of fibronectin concentration and bead diameter. Cells were incubated with radioactive pFN-coated beads, and total bead binding (cell surface or ingested) was measured as total radioactivity associated with the cells. Of the bound beads, those that also were phagocytosed were distinguished by their insensitivity to release from the cells by trypsin treatment. In continuous incubations, binding of pFN-coated beads to cells occurred at 4 degrees C or 37 degrees C, but phagocytosis was observed only at 37 degrees C. In addition, degradation of 3H-pFN from ingested beads occurred at 37 degrees C, as shown by the release of trichloroacetic acid-soluble radioactivity into the incubation medium. When the fibronectin density on the beads was varied, binding at 4 degrees C and ingestion at 37 degrees C were found to have the same dose-response dependencies, which indicated that pFN densities that permitted bead binding were sufficient for phagocytosis to occur. The fibronectin density for maximal binding of ingestion was approximately 250 ng pFN/cm2. When various sized beads (0.085-1.091 micron), coated with similar densities of pFN, were incubated with cells at 4 degrees C, no variation in binding as a function of bead size was observed. Under these conditions, the absolute amount of pFN ranged from less than 100 molecules on the 0.085-micron beads to greater than 15,000 molecules on the 1.091-micron beads. Based upon these results it can be concluded that the critical parameter controlling fibronectin-mediated binding of latex beads by BHK cells is the spacing of the pFN molecules on the beads. Correspondingly, it can be suggested that the spacing between pFN receptors on the cell surface that is optimal for multivalent interactions to occur is approximately 18 nM. When phagocytosis of various sized beads was compared, it was found that the largest beads were phagocytosed slightly better (two fold) than the smallest beads. This occurred both in continuous incubations of cells with beads and when the beads were prebound to the cells. Finally, the kinetic constants for the binding of 0.085 microM pFN-coated beads to the cells were analyzed. There appeared to be approximately 62,000 binding sites and the KD was 4.03 X 10(-9) M. Assuming a bivalent interaction, it was calculated that BHK cells have approximately 120,000 pFN receptors/cell and the binding affinity between pFN and its receptor is approximately 6 X 10(-5) M.
On the FER performance and decoding complexity of turbo codes (2003)

Turbo codes have drawn much attention due to its remarkable error correcting capability in digital communication systems. However, its high decoding complexity and potential poor frame error rate (FER) are major problems in practical implementation. We present two algorithms for reducing the decoding complexity and the FER of turbo codes. Specifically, an adaptive iteration decoding algorithm is proposed by making use of cyclic redundancy check (CRC) bits for reducing the decoding complexity of turbo codes. In addition, a serial concatenated coding system is used to lower the FER of turbo codes. The simulation results demonstrate that a lower decoding complexity and a lower FER can be obtained by using the two proposed methods.
Thin Film Transistors Fabricated in Printed Silicon (1999)

We report the fabrication of thin film transistors (TFTs) from printed silicon. The printing is performed by irradiating a hydrogenated amorphous silicon-coated quartz wafer facing a glass substrate with a high-energy laser pulse. The ensuing explosive effusion of hydrogen from the layer results in transfer of the silicon onto the glass substrate. Adhesion and smoothing of the transferred film is ensured by high-energy laser annealing. Top-gate TFTs were fabricated in this material using standard photolithographic processing and ion implantation. These transistors, which have reasonable electrical characteristics, are the first step towards the fabrication of directly printed electronic devices.
Neutrophils and acute lung injury (2003)

The accumulation of activated neutrophils in the lungs is an early step in the pulmonary inflammatory process that leads to ALI. Although experimental models indicate that the activation of p38, Akt, and nuclear factor-kappaB in neutrophils contributes to ALI, the relative importance of these pathways in critically ill patients remains to be determined. Nevertheless, modulation of the activation of p38, Akt, and nuclear factor-kappaB in neutrophils appears to be an appropriate therapeutic target in severely ill patients with ALI.
Design and Synthesis of Dual Inhibitors of Acetylcholinesterase and Serotonin Transporter Targeting Potential Agents for Alzheimer's Disease (2002)

Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT. [structure: see text]
Quantitative evaluation of protein-protein and ligand-protein equilibria of a large allosteric enzyme by electrospray ionization time-of-flight mass spectrometry (1998)

A mass spectrometer coupling electrospray ionization with time-of-flight mass spectrometry (ESI-TOFMS) has been used to investigate the oligomeric species of Escherichia coli citrate synthase, and to determine the effect of nicotinamide adenine dinucleotide (NADH), an allosteric inhibitor of this enzyme, on the equilibrium between the oligomeric forms. An equilibrium mixture of dimers (M = 95,770 Da) and hexamers (M = 287,310 Da) was found under the conditions used (KA = 6.9 x 10(10) M-2), and NADH was observed to bind selectively to the hexamer (KD = 1.1 microM), shifting the equilibrium to the latter form. The power of ESI-TOFMS to measure ions of very large mass-to-charge ratio (up to m/z approximately 10,000 in this case) is shown to be a valuable tool for obtaining accurate information about compositions of noncovalent complexes and equilibrium constants. The measured constants agree with those determined by conventional means.
Adaptive dereverberation of speech signals with speaker-position change detection (2009)

This paper proposes a method for adaptive speech dereverberation and speaker-position change detection, which have not previously been addressed. Signal transmission channels in rooms are modeled as auto-regressive systems in individual frequency bands. The proposed method adaptively estimates the regression coefficients of this model, which are called room regression coefficients (RRCs). The proposed method has two distinguishing features: (1) The method is based on the weighted recursive least squares algorithm, which enables an efficient RRC-estimate update as well as a fast convergence rate; (2) The method detects changes in speaker position and so can quickly catch up with the sudden channel changes that such position changes cause. Detection is realized by finding time frames where the power of dereverberated speech is anomalously amplified. Experimental results showed that the proposed method attained convergence in 5 seconds and successfully detected changes in speaker position.
Role of the Vitreous in Posterior Segment Neovascularization in Central Retinal Vein Occlusion (1991)

We retrospectively studied the relationship between the vitreous condition and the development of retinal or optic disc neovascularization in 60 eyes with central retinal vein occlusion associated with extensive retinal ischemia. At initial examination, 24 of 60 eyes (40%) with central retinal vein occlusion had complete posterior vitreous detachment, a prevalence significantly higher than in the fellow eyes. During a mean follow-up period of 43 months, 13 of 34 eyes (38%) without posterior vitreous detachment developed retinal or disc neovascularization, or both, but none of the 24 eyes with complete posterior vitreous detachment developed neovascularization (P less than .001). Our results suggest that central retinal vein occlusion may induce the development of posterior vitreous detachment, and that posterior vitreous detachment may play a role in protecting eyes with central retinal vein occlusion from posterior segment neovascularization.
Volumetric B1+ Mapping of the Brain at 7T using DREAM (2013)

DREAM enables safe, very fast, and robust volumetric B1 (+) mapping of the brain at ultrahigh fields.
Effective Modular Iminooxazoline (IMOX) Ligands for Asymmetric Catalysis: [Zn(IMOX)]‐Promoted Enantioselective Reduction of Ketones by Catecholborane (2003)

Closing the door to nucleophilic attack on one face of the substrate by using a bulky substituent (see schematic formula) was the key to obtaining high enantiomeric excesses in the reduction of methyl ketones by catecholborane with promotion by zinc complexes of new chiral iminooxazoline (IMOX) ligands. The modular nature, simple design, and possibility to produce tailored IMOX ligands could be advantages in designing the next generation of these chiral ligands.
Relative rates of transport of peptidyl drugs by Candida albicans (1985)

A variety of peptide drugs are known to be active against Candida albicans; however, little is known about the transport of such agents into the target organism. To provide further information concerning transport of this type, we studied the uptake of two classes of small linear peptides: polyoxins which act intact within the cell and the m-fluorophenylalanyl (m-F-Phe) peptides which require peptidase cleavage to release m-F-Phe. Competition studies with a specific dipeptide detector (alanyl-alpha-thiophenylglycine) enabled us to determine Ki values of 2.6 microM for nikkomycin Z and 350 microM for polyoxin D. Rates of uptake of the peptidyl-nucleosides are approximately 30 times lower than those of the m-F-Phe peptides (apparent maximal velocities: nikkomycin Z, 62 pmol min-1 mg (dry weight) of cells-1; M-F-Phe alanine 1.3 nmol min-1 mg (dry weight) of cells-1). For both the m-F-Phe peptides and the peptidyl-nucleosides, the affinity of the drug for the transport system is an important determinant of its whole-cell activity.
High frequency of large spontaneous deletions of DNA in tumor-derived CHEF cells. (1989)

Spontaneous mutations arising at the HPRT locus were examined in 126 mutants recovered from a series of six CHEF-derived cell lines. Altered restriction fragment patterns were characterized by Southern blot hybridization, and gene expression by RNA blot hybridization. Point mutants and gene-expression mutants predominated in the control (nontumorigenic) 18-1D-3 cell line and in two tumor-derived lines, one of which (16-2 Tuk 4) displayed a mutator phenotype. In the other three lines, the majority of mutants had large partial or whole gene deletions. These results suggest that mutant enzymes in DNA replication or repair play an important role in neoplastic progression by causing extensive deletions in DNA, including excision of genes that encode tumor-suppressor functions, and deletion of regulatory sequences in protooncogenes.
LAMININ FUNCTIONS IN TISSUE MORPHOGENESIS (2004)

▪ Abstract Significant advances have been made in the application of genetics to probe the functions of basement membrane laminins. These studies have shown that different laminin subunits profoundly affect tissue morphogenesis, starting around the time of embryonic implantation and extending through organogenesis and into the postnatal period. Collectively they have revealed common functions that include the induction and maintenance of cell polarity, the establishment of barriers between tissue compartments, the organization of cells into tissues, and the protection of adherent cells from detachment-induced cell death, anoikis. Interpreted in light of what is known about laminin structure and self-assembly and binding activities, these advances have begun to provide insights into mechanisms of action. In this review we focus on the contributions of the laminins in invertebrate and vertebrate tissue morphogenesis.
Long-Term Converting Enzyme Inhibition Normalizes Urinary Kallikrein Activity in Young Spontaneously Hypertensive Rats (1986)

s: Groupe Hypertension de la Société Français de Cardiologie, Journées de L'Hypertension Artérielle: Oral Papers: PDF Only
Telomere Length and Mortality: A Study of Leukocytes in Elderly Danish Twins (2008)

Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality analysis in 548 same-sex Danish twins (274 pairs) aged 73-94 years, of whom 204 pairs experienced the death of one or both co-twins during 9-10 years of follow-up (1997-2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values of the shorter 50% (mTRFL(50)) and shortest 25% (mTRFL(25)) of TRFLs in the distribution and computed the mode of TRFL (MTRFL). They analyzed the proportions of twin pairs in which the co-twin with the shorter telomeres died first. The proportions derived from the intrapair comparisons indicated that the shorter telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL(50): 0.59, 95% CI: 0.52, 0.66; mTRFL(25): 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than in the rest of the follow-up period, and it grew stronger with increasing intrapair difference in all telomere parameters. Leukocyte telomere dynamics might help explain the boundaries of the human life span.
Borrelia burgdorferi membranes are the primary targets of reactive oxygen species (2008)

Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H(2)O(2) had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H(2)O(2) show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle.
A new abietane diterpenoid from Orthosiphon wulfenioides (2002)

A new abietane diterpenoid, orthosiphonol (11-methoxy-12, 14-dihydroxy-8, 11, 13-abieta trien-7-one) (1) together with known 11-hydroxysugiol (2) were isolated from Orthosiphon wulfenioides. Their structures were determined on the basis of spectroscopic evidence.
Role of the membrane surface in the activation of human coagulation factor X. (1992)

Coagulation factor X is activated by the extrinsic Xase complex composed of factor VIIa associated with the integral membrane protein tissue factor. The kinetics of human factor X activation was studied following reconstitution of this reaction system using purified human proteins and synthetic phospholipid vesicles composed of phosphatidylcholine and phosphatidylserine (PCPS) or phosphatidylcholine alone (PC). Factor X activation was evaluated by discontinuous measurements of the amidolytic activity of the product, factor Xa, or continuously monitored using the fluorescent serine protease inhibitor 4-aminobenzamidine. The results of both techniques were verified by direct physical measurements of zymogen activation using SDS-polyacrylamide gel electrophoresis. The rate of factor X activation with PC vesicles was less than 5% of that observed with PCPS vesicles. Since factor X does not bind to vesicles containing only PC, these data suggested an important role for the substrate-membrane interaction in the catalytic cycle. The importance of the substrate-membrane interaction in the activation process was investigated by using membrane-binding proteins to compete with the substrate for combining sites on PCPS vesicles. Prothrombin fragment 1 was an inhibitor of factor X activation. The dependence of inhibition by fragment 1 on PCPS and factor X was consistent with a significant reduction in initial velocity due to the displacement of factor X from the membrane surface. The inhibition data also suggested that the membrane-bound pool of factor X was the preferred substrate for the human extrinsic Xase complex. The influence of PCPS concentrations on the rate of factor X activation was systematically investigated. Increasing concentrations of PCPS resulted in a modest change in the Km,app and a dramatic change in the Vmax,app for the reaction. The initial velocity data could be globally analyzed according to the preferential utilization of membrane-bound factor X with the intrinsic kinetic constants: Km approximately equal to 1 microM and kcat = 37 s-1 at saturating PCPS. In addition, the equilibrium parameters for the factor X-membrane interaction inferred from these studies were in excellent agreement with the directly determined values. Collectively, the data suggest that the substrate-membrane interaction must precede catalysis for the efficient activation of human factor X by the extrinsic Xase complex.
Transcription inhibits the replication of autonomously replicating plasmids in human cells. (1994)

This study addresses the effect of transcription on replication, using a system based on autonomously replicating plasmids in human cells. We added transcriptional elements from the human cytomegalovirus promoter/enhancer and the human beta-actin promoter to autonomously replicating plasmids based on human sequences and found that the transcriptional elements inhibited plasmid replication. Furthermore, conditional inhibition of plasmid replication was demonstrated by using a tetracycline-responsive promoter. We found that replication activity of plasmids carrying this promoter was inversely correlated with promoter activity. Replication activity was partially restored on plasmids when a transcriptional termination sequence was placed directly downstream of the promoter element. Transcriptional activity of the promoters and the efficacy of the terminator sequence were confirmed by using steady-state RNA analysis. These experiments suggest that transcription inhibits DNA replication on these plasmids and that the degree of inhibition is dependent on transcription strength. The possible significance of these results for chromosomal DNA replication are discussed.
Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy againstStaphylococcus aureus (2017)

<i>Staphylococcus aureus</i>, especially methicillin-resistant <i>S. aureus</i> (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of <i>S. aureus</i>, staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of <i>S. aureus</i> pigment production that reduces the survival of <i>S. aureus</i> under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and <i>crtN</i> mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN). <i>S. aureus</i> treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in <i>S. aureus</i> and presents a potent and effective lead compound for the development of virulence factor-based therapy against <i>S. aureus</i><b>IMPORTANCE</b><i>S. aureus</i> staphyloxanthin contributes substantially to pathogenesis by interfering with host immune clearance mechanisms, but it has little impact on <i>ex vivo</i> survival of the bacterium. Agents blocking staphyloxanthin production may discourage the establishment and maintenance of bacterial infection without exerting selective pressure for antimicrobial resistance. Our newly discovered CrtN inhibitor, NP16, may offer an effective strategy for combating <i>S. aureus</i> infections.