gebhart/patrepeval huggingface dataset:
Can urinary exosomes act as treatment response markers in prostate cancer? (2009)

Abstract Background Recently, nanometer sized vesicles (termed exosomes) have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy. Methods Ten patients (with locally advanced PCa) provided spot urine specimens at three time points during standard therapy. Patients received 3–6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA) and tumour-associated marker 5T4 was examined. Results The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8) patient. Conclusion Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide clinically useful information.
Characterization of Binding Proteins from Ovarian Carcinoma and Kidney Tubule Cells that are Specific for Cisplatin Modified DNA (1991)

We have detected proteins in nuclear extracts from ovarian carcinoma cells and kidney tubule cells that bind specifically to platinated DNA. A 123-bp restriction fragment was platinated with cisplatin (DDP) to a formal molar platinum to nucleotide ratio of 0.05 and end-labeled with [32P]-dCTP. Incubation with nuclear extracts from 2008 human ovarian carcinoma cells caused shifts in the mobility of this probe in non-denaturing polyacrylamide gels. Proteinase K, but not ribonuclease A, destroyed the bands. Comparison of the shifted bands generated by DDP-resistant 2008 and A2780 human ovarian carcinoma cell nuclear extracts with bands from the corresponding sensitive cells showed no differences in protein levels. The affinity of the proteins for the probe was the same in sensitive and resistant 2008 nuclear extracts as determined by competition with platinated salmon sperm DNA. These proteins also bound to a probe damaged with 1,2-diaminocyclohexaneplatinum(II) dichloride but did not bind to a trans-DDP platinated probe. No differences were found in the levels of UV4 or UV5 Chinese hamster ovary cells, which were hypersensitive to DDP compared to wild-type AA8 cells. MDCK and LLC-PK1 kidney tubule cells, which were more resistant to DDP cytotoxicity than 2008 cells, exhibited decreased levels of these proteins. We conclude that, although these proteins that recognize DDP damage in DNA may be involved in excision repair, their levels did not correlate with DDP sensitivity in this panel of cell lines.
Myelin-associated glycoprotein, a member of the L2/HNK-1 family of neural cell adhesion molecules, is involved in neuron-oligodendrocyte and oligodendrocyte-oligodendrocyte interaction. (1987)

A monoclonal antibody to the myelin-associated glycoprotein (MAG) was prepared and characterized to probe for the involvement of MAG in cell surface interactions among neural cells in vitro. The antibody reacts specifically with oligodendrocyte cell surface and myelin-rich brain regions as expected from previous investigations. Not all O4 antigen-positive oligodendrocytes express MAG in vitro. Fab fragments of the antibody interfere with neuron to oligodendrocyte and oligodendrocyte to oligodendrocyte adhesion, but not with oligodendrocyte to astrocyte adhesion. MAG-containing liposomes bind to the cell surfaces of the appropriate target cells by a mechanism that is specifically inhibitable by Fab fragments of monoclonal MAG antibodies, demonstrating that MAG is a neural cell adhesion molecule.
A stable approach forQ-compensated viscoelastic reverse time migration using excitation amplitude imaging condition (2018)

The earth [Formula: see text] filtering causes poor illumination of the subsurface. Compensating for the attenuated amplitude and distorted phase is crucial during elastic reverse time migration (ERTM) to improve the imaging quality. Conventional [Formula: see text]-compensated ERTM ([Formula: see text]-ERTM) methods tend to boost the attenuated energy to inverse the [Formula: see text] effects. These methods usually suffer from severe numerical instability because of the unlimited amplification of the high-frequency noise. Low-pass filtering is generally used to stabilize the process, however, at the expense of precision. We have developed a stable compensation approach in this paper. Based on the decoupled fractional Laplacians viscoelastic wave equation, two compensation operators are obtained by extrapolating wavefield in the dispersion-only and viscoelastic media. Because no explicit amplification is included, these two operators are absolutely stable for implementation. To improve the division morbidity for calculating the compensation operators, we use the excitation amplitude criterion and embed the operators into a vector-based [Formula: see text]-compensated excitation amplitude imaging condition. With the derived imaging condition, we could compensate for the absorption accurately without needing to concern the stability issue. The [Formula: see text]-ERTM results for noise-free data are carried out over a simple layered model and a more realistic Marmousi model with an attenuating area to verify the feasibility of the proposed approach. The migration results for noisy data from the Marmousi model further prove that the proposed method performs better fidelity, adaptability, and antinoise performance compared with conventional compensation method with low-pass filtering.
Purified human MSH2 protein binds to DNA containing mismatched nucleotides. (1994)

The human hMSH2 protein is a member of a highly conserved family of postreplication mismatch repair components found from bacteria to humans. Alterations of the gene coding for this protein cosegregate with, and are the likely cause of, chromosome 2-linked hereditary nonpolyposis colon cancer. Postreplication mismatch repair has been found to faithfully replace misincorporated nucleotides, thereby increasing the overall fidelity of DNA replication. Loss of postreplication mismatch repair function leads to a mutator phenotype, which is proposed to account for the multiple mutations required for multistep carcinogenesis. Although the functions of hMSH2 can be anticipated based on its similarity to well-characterized bacterial and yeast proteins, proof of its functions has not been established. Here we demonstrate that purified hMSH2 binds specifically to mismatched nucleotides, providing a target for the excision repair processes characteristic of postreplication mismatch repair.
Kinetics and reaction mechanism of potassium-activated aldehyde dehydrogenase from Saccharomyces cerevisiae (1978)

Data from steady-state kinetic analysis of yeast K+-activated aldehyde dehydrogenase are consistent with a ternary complex mechanism. Evidence from alternative substrate analysis and product-inhibition studies supports an ordered sequence of substrate binding in which NAD+ is the leading substrate. A preincubation requirement for NAD+ for maximum activity is also consistent with the importance of a binary enzyme-NAD+ complex. Dissociation constant for enzyme-NAD+ complex determined kinetically is in reasonable agreement with that determined by direct binding. The order of substrate addition proposed here differs from that proposed for a yeast aldehyde dehydrogenase previously reported. Different methods of purification produced an enzyme that showed similar kinetic characteristics to those reported here.
Electronic Differences between Coordinating Functionalities of Chiral Phosphine−Phosphites and Effects in Catalytic Enantioselective Hydrogenation (2002)

A convenient synthesis of new chiral phosphine−phosphites (P−OP) has been described. The versatility of the synthetic protocol developed has allowed the preparation of ligands with different phosphine fragments and the choice of the stereogenic element location. Analyses of the values of 1JPSe of the corresponding diselenides are in accord with the expected lower σ-donor ability of the phosphite fragment, with respect to the phosphine group, and with an increase of phosphine basicity after substitution of phenyl substituents by methyl groups. Inspection of υ(CO) values on a series of complexes RhCl(CO)(P−OP) demonstrated a variable π-aceptor ability of the phosphite group, compensating for the change of basicity of the phosphine functionality, as well as having a rather reduced electron density at the metal center compared with diphosphine analogues. The distinct nature of the phosphorus functionalities has also been evidenced in rhodium-catalyzed enantioselective hydrogenation of methyl Z-α-acetamido-cinnamate (MAC). Thus, the coordination mode of the substrate is governed by the chiral ligand, directing the olefinic bond to a cis position with respect to the phosphite group, as demonstrated by NMR studies performed with [Rh(P−OP)(MAC)]+ complexes. In consequence, the phosphite group has a greater impact on the enantioselectivity of the product. However, the optical purity of the process also depends on the nature of the phosphine group, and hence, an appropriate election of both phosphorus functionalities is required for the attainment of excellent enantioselectivities (99% ee).
Perceptuallly based scheduling algorithms for real-time synthesis of complex sonic environments (1997)

Presented at the 4th International Conference on Auditory Display (ICAD), Palo Alto, California, November 2-5, 1997.
Spontaneous Deletion Mutants of Bacteriophage Pf3: Mapping of Signals Involved in Replication and Assembly (1987)

Defective deletion mutants (miniphages) arise spontaneously during serial propagation of the filamentous bacteriophage Pf3. They contain a circular single-stranded (ss) DNA molecule which is up to 80% smaller than the wild-type single-stranded genome. Analysis of the genomic structure of three of these miniphages revealed that they consist of sequences that in the wild-type genome are flanked by direct repeats 5-8 nucleotides long; only one copy of these repeats was found again in the miniphage genome. One miniphage genome contained a tandemly duplicated sequence, and from its structure we concluded that the duplication had occurred after a primary deletion event. Also, short direct repeats must have been involved in the duplication process. We conclude that the deletion and duplication events have occurred by an identical recombination process, probably the "slipped mispairing" mechanism. In the presence of helper functions, the three miniphage genomes are replicated and assembled into ssDNA containing virus-like particles. Hence, the assembly signal and the replication origins for viral and complementary strand synthesis are located within the region shared by all three miniphage genomes, i.e., nucleotides 4092-4678 of the wild-type genome (Luiten et al., 1985).
Identification of the streptococcal competence‐pheromone receptor (1996)

Competence for genetic transformation in certain species of streptococci has been known for many years to be induced by a secreted protease-sensitive pheromone, referred to as the competence factor or activator, which acts as a quorum-sensing signal to co-ordinate expression of late competence genes. We recently reported identification of the pheromone of Streptococcus pneumoniae strain Rx as a small unmodified peptide, which was termed competence-stimulating peptide (CSP). By identifying the gene (comC) encoding the Rx CSP we were able to show that it is synthesized as a precursor peptide containing an N-terminal double-glycine type leader. In the present work, we describe two alleles of the corresponding gene from Streptococcus gordonii strains Challis and NCTC 7865, which are strains with distinct competence pheromones and corresponding specific pheromone reactivities. In addition, the nucleic acid sequences of two genes located downstream of comC were determined; interestingly, these genes encode a two-component signal transduction system. We therefore speculated that their products, a histidine kinase (ComD) and its cognate response regulator (ComE), act downstream of the CSP in competence regulation. By tracing the CSP specificity of the competence response in these strains to strain-specific alleles of comD, we obtained evidence demonstrating that the histidine kinase ComD is the competence-pheromone receptor.
Fat depot origin affects adipogenesis in primary cultured and cloned human preadipocytes (2002)

Fat distribution varies among individuals with similar body fat content. Innate differences in adipose cell characteristics may contribute because lipid accumulation and lipogenic enzyme activities vary among preadipocytes cultured from different fat depots. We determined expression of the adipogenic transcription factors peroxisome proliferator activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein-alpha (C/EBP-alpha) and their targets in abdominal subcutaneous, mesenteric, and omental preadipocytes cultured in parallel from obese subjects. Subcutaneous preadipocytes, which had the highest lipid accumulation, glycerol-3-phosphate dehydrogenase (G3PD) activity, and adipocyte fatty acid binding protein (aP2) abundance, had highest PPAR-gamma and C/EBP-alpha expression. Levels were intermediate in mesenteric and lowest in omental preadipocytes. Overexpression of C/EBP-alpha in transfected omental preadipocytes enhanced differentiation. The proportion of differentiated cells in colonies derived from single subcutaneous preadipocytes was higher than in mesenteric or omental clones. Only cells that acquired lipid inclusions exhibited C/EBP-alpha upregulation, irrespective of depot origin. Thus regional variation in adipogenesis depends on differences at the level of transcription factor expression and is a trait conferred on daughter cells.
A histone deacetylase corepressor complex regulates the Notch signal transduction pathway (1998)

The Delta-Notch signal transduction pathway has widespread roles in animal development in which it appears to control cell fate. CBF1/RBP-Jkappa, the mammalian homolog of Drosophila Suppressor of Hairless [Su(H)], switches from a transcriptional repressor to an activator upon Notch activation. The mechanism whereby Notch regulates this switch is not clear. In this report we show that prior to induction CBF1/RBP-Jkappa interacts with a corepressor complex containing SMRT (silencing mediator of retinoid and thyroid hormone receptors) and the histone deacetylase HDAC-1. This complex binds via the CBF1 repression domain, and mutants defective in repression fail to interact with the complex. Activation by Notch disrupts the formation of the repressor complex, thus establishing a molecular basis for the Notch switch. Finally, ESR-1, a Xenopus gene activated by Notch and X-Su(H), is induced in animal caps treated with TSA, an inhibitor of HDAC-1. The functional role for the SMRT/HDAC-1 complex in CBF1/RBP-Jkappa regulation reveals a novel genetic switch in which extracellular ligands control the status of critical nuclear cofactor complexes.
Enrichment for CFU-C from murine and human bone marrow using soybean agglutinin (1982)

Mouse bone marrow and spleen cells agglutinated by soybean agglutinin (SBA) or peanut agglutinin (PNA) were previously shown to be enriched for spleen colony-forming cells (CFU-S) and sufficiently depleted of graft-versus-host reaction producing cells to allow hematologic reconstitution of lethally irradiated allogeneic recipient mice. A similar enrichment for cells capable of forming colonies in soft agar culture (CFU-C) has now been found in the SBA-agglutinated fraction of mouse bone marrow cells, in contrast to the finding that in human bone marrow the majority of the CFU-C are in the fraction not agglutinated by SBA. Cytofluorometric studies with fluorescein-labeled SBA (FITC- SBA) revealed that the majority of both mouse and human bone marrow cells bind the lectin. Experiments mixing the human marrow fractions separated by SBA reveal that true enrichment for CFU-C is achieved in the unagglutinated fraction, as opposed to a possible depletion of a suppressor cell population. Granulocytic, monocytic, and mixed cell colonies were all enriched in the SBA-unagglutinated cell fraction from human bone marrow.
Nanoscale Conducting Oxide PlasMOStor (2014)

We experimentally demonstrate an ultracompact PlasMOStor, a plasmon slot waveguide field-effect modulator based on a transparent conducting oxide active region. By electrically modulating the conducting oxide material deposited into the gaps of highly confined plasmonic slot waveguides, we demonstrate field-effect dynamics giving rise to modulation with high dynamic range (2.71 dB/μm) and low waveguide loss (∼0.45 dB/μm). The large modulation strength is due to the large change in complex dielectric function when the signal wavelength approaches the surface plasmon resonance in the voltage-tuned conducting oxide accumulation layer. The results provide insight about the design of ultracompact, nanoscale modulators for future integrated nanophotonic circuits.
HUMAN MILK GLYCANS PROTECT INFANTS AGAINST ENTERIC PATHOGENS (2005)

▪ Abstract Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides are the third largest component of human milk. They were initially considered to be functionless by-products of glycoprotein and glycolipid synthesis during milk production. However, in the past few decades it has become apparent that the human milk oligosaccharides are composed of thousands of components, at least some of which protect against pathogens. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. Most human milk oligosaccharides are fucosylated, and their production depends on enzymes encoded by the genes associated with expression of the Lewis blood group system. The expression of specific fucosylated oligosaccharides in milk thus varies in relation to maternal Lewis blood group type, and is significantly associated with the risk of infectious disease in breastfed infants. Specific fucosylated moieties of oligosaccharides and related glycoconjugates (glycans) are able to inhibit binding and disease by specific pathogens. This review presents the argument that specific glycans, especially the oligosaccharides, are the major constituent of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. The large input of energy expended by the mother in the synthesis of milk oligosaccharides is consistent with the human reproductive strategy of large parental input into rearing relatively few offspring through a prolonged period of maturation. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit diseases caused by mucosal pathogens.
Soluble Neuregulin-1 Has Bifunctional, Concentration-Dependent Effects on Schwann Cell Myelination (2010)

Members of the neuregulin-1 (Nrg1) growth factor family play important roles during Schwann cell development. Recently, it has been shown that the membrane-bound type III isoform is required for Schwann cell myelination. Interestingly, however, Nrg1 type II, a soluble isoform, inhibits the process. The mechanisms underlying these isoform-specific effects are unknown. It is possible that myelination requires juxtacrine Nrg1 signaling provided by the membrane-bound isoform, whereas paracrine stimulation by soluble Nrg1 inhibits the process. To investigate this, we asked whether Nrg1 type III provided in a paracrine manner would promote or inhibit myelination. We found that soluble Nrg1 type III enhanced myelination in Schwann cell-neuron cocultures. It improved myelination of Nrg1 type III(+/-) neurons and induced myelination on normally nonmyelinated sympathetic neurons. However, soluble Nrg1 type III failed to induce myelination on Nrg1 type III(-/-) neurons. To our surprise, low concentrations of Nrg1 type II also elicited a similar promyelinating effect. At high doses, however, both type II and III isoforms inhibited myelination and increased c-Jun expression in a manner dependent on Mek/Erk (mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) activation. These results indicate that paracrine Nrg1 signaling provides concentration-dependent bifunctional effects on Schwann cell myelination. Furthermore, our studies suggest that there may be two distinct steps in Schwann cell myelination: an initial phase dependent on juxtacrine Nrg1 signaling and a later phase that can be promoted by paracrine stimulation.
Uplink power control for TDMA portable radio channels (2002)

A closed-loop power control algorithm for the portable transmitter is introduced for TDMA (time division multiple access) portable radio systems. This method enables the portable radio handset to output no more power than is required at its access port receiver for the desired performance. This avoids causing excessive interference to cochannel ports. The fading of a radio channel due to shadowing effects and moderate-rate multipath propagation can be tracked and mitigated simultaneously. By simulating a prototype hardware implementation of the receiver baseband processing, the authors study the link performance as a function of signal to impairment ratio under different channel conditions. It is found that radio link performance can be significantly improved with little additional complexity and little signaling overhead. An improvement of as much as 9 dB was found for slow fading channels impaired by noise, and as much as 7 dB was found for slow fading channels impaired by synchronous interference.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>