gebhart/patrepeval huggingface dataset:
Clusterin and IGFBPs as Antisense Targets in Prostate Cancer (2003)

The primary hurdle to improved survival of advanced prostate cancer is our failure to prevent or treat the tumor's progression to its lethal and untreatable stage of androgen independence. Novel treatment modalities designed to prevent androgen-independent progression including prostate cancer metastasis are required. Accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anticancer agents that specifically inhibit a progression-relevant target. Antisense oligonucleotides, short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene, promise to show enhanced specificity for malignant cells with a favorable side-effect profile due to well-defined and tailored modes of action. Although not all of the challenges have been met to date, emerging clinical evidence supports the premise that antisense oligonucleotides stand a realistic chance of emerging as major partners of rationally designed anticancer regimens. The rationale and status of antisense targeting of the treatment resistance factor clusterin and of insulin-like growth factor binding protein (IGFBP) 2 and 5 are discussed.
Technical Note: A Computerized System for Monitoring Feeding Behavior and Individual Feed Intake of Dairy Cattle (2004)

The objective of this study was to develop and validate a computerized system to monitor feeding behavior and feed intake of loose-housed dairy cattle. The system consisted of 28 scales located in front of each self-locking place of a regular feedbunk. All cows had access to all scales indifferently. Each visit to the feedbunk was monitored by a transponder in the ear of each cow that was detected by a proximity reader located at the top right corner of each headlock. The data from the scales and the proximity readers were continuously recorded by a computer with an average scanning time of 3.5 s. The monitoring system was validated using all 28 feeding places and 51 lactating cows in a series of 4-h observations during 5 different d. During the observation periods, for each feeder, 2 observers recorded the cow number and the exact time of the visit. The observed data were then compared with the computer records. To validate the ability of the system to monitor feed consumption, on separate days, the amount of feed consumed by a cow during a visit was also measured manually with an external scale, and the feed that disappeared from each scale in 2 different 24-h periods was compared with the sum of feed consumed in each scale during these 2 periods. The average time spent in a given scale by each cow determined by direct observations was similar to that determined by the computer. The system was accurate and showed a high specificity (98.8%) and sensitivity (99.6%) for cow detections. Feed weights determined by the computer system were similar to those measured manually with an external scale, implying that the system was also accurate in measuring individual intake weights. In conclusion, the system provided a reasonable estimate of the number of visits per animal, length of each visit, amount of feed consumed per visit and animal, the total amount of feed consumed daily by each animal, and the rate at which animals consume feed.
Potentiation of TRPV3 channel function by unsaturated fatty acids (2006)

Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31-39 degrees C. We have previously shown that TRPV3 is activated by 2-aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB-induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA-induced potentiation is observed in intracellular Ca2+ measurement, whole-cell and two-electrode voltage clamp studies, as well as single channel recordings of excised inside-out and outside-out patches. The fatty acid-induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non-metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel.
Review of Phase II Trial Designs Used in Studies of Molecular Targeted Agents: Outcomes and Predictors of Success in Phase III (2008)

In practice, phase II design for targeted agents is similar to that for cytotoxics. Objective response seems to be a useful end point for screening new targeted agents because, in our review, its observation predicted for eventual success. Improvements in design are recommended, as is more frequent inclusion of biological questions as part of phase II trials.
Steal syndrome strategies to preserve vascular access and extremity (2007)

causes a retrograde flow in the artery distal to the AV anastomosis and into the AV access. This ‘physiologic’ steal phenomenon can be observed in 73% of AV fistulae and in 91% of access grafts [2]. Approximately 75% of the blood flow through distal radio-cephalic fistulae is supplied by the proximal radial artery, but 25% comes from a patent ulnar artery via the distal radial artery and palmar arch [12]. In elbow fistulae, the periarticular arterial collaterals have the same impact. When an AV fistula is created using healthy vessels, dilatation of the proximal and distal arteries, as well as dilatation of the collaterals around the anastomosis, compensates for enhanced systolic AV flow and also for diastolic retrograde inflow into the fistula. Any vascular pathology affecting one or several of these adaptive mechanisms can causedistalischaemiabyastealmechanism.Arterialstenosisupstreamoftheanastomosispreventsthenecessaryflow increase in the feeding artery; severe peripheral arterial occlusive disease (PAOD) or vasculitis enhance the resistance of distal arteries and simultaneously impair the function of natural collaterals [13]. Under these conditions, during diastole virtually all blood coming from the collaterals is drained into the access [14]. Instead of a steal syndrome stage I (also named steal phenomenon), the further dreaded stages II to IV develop, with clinical signs of peripheral ischaemia. The likelihood that a steal syndrome develops depends more on the severity of arterial pathology and less on the volume of intra-access blood flow.
Propagation of Tau Misfolding from the Outside to the Inside of a Cell (2009)

Tauopathies are neurodegenerative diseases characterized by aggregation of the microtubule-associated protein Tau in neurons and glia. Although Tau is normally considered an intracellular protein, Tau aggregates are observed in the extracellular space, and Tau peptide is readily detected in the cerebrospinal fluid of patients. Tau aggregation occurs in many diseases, including Alzheimer disease and frontotemporal dementia. Tau pathology begins in discrete, disease-specific regions but eventually involves much larger areas of the brain. It is unknown how this propagation of Tau misfolding occurs. We hypothesize that extracellular Tau aggregates can transmit a misfolded state from the outside to the inside of a cell, similar to prions. Here we show that extracellular Tau aggregates, but not monomer, are taken up by cultured cells. Internalized Tau aggregates displace tubulin, co-localize with dextran, a marker of fluid-phase endocytosis, and induce fibrillization of intracellular full-length Tau. These intracellular fibrils are competent to seed fibril formation of recombinant Tau monomer in vitro. Finally, we observed that newly aggregated intracellular Tau transfers between co-cultured cells. Our data indicate that Tau aggregates can propagate a fibrillar, misfolded state from the outside to the inside of a cell. This may have important implications for understanding how protein misfolding spreads through the brains of tauopathy patients, and it is potentially relevant to myriad neurodegenerative diseases associated with protein misfolding.
Transfer of Learning After Updating Training Mediated by the Striatum (2008)

Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.
Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease (1991)

The brains of patients with Alzheimer9s disease (AD) invariably exhibit neuropathology in the hippocampus and entorhinal cortex when examined postmortem. Magnetic resonance imaging (MRI) offers a noninvasive, high-resolution method for quantifying volumetric changes in the AD brain antemortem. Eight patients diagnosed with probable AD and 7 age- matched controls had MRI scans and were tested on a battery of cognitive and olfactory tests. The hippocampus and entorhinal cortex (parahippocampal gyrus) showed significant atrophy, with over 40% reduction in size. Areas of the brain that are not highly involved in the degenerative state of AD, such as the striatum, did not show significant volumetric changes. Hippocampal and parahippocampal gyrus volumes had the highest correlation with scores on the Mini-Mental State Examination (<i>r</i> = 0.89), with lower correlations for a smell identification test (<i>r</i> = 0.65), odor match-to-sample test (<i>r</i> = 0.72), and a visual match-to- sample test (<i>r</i> = 0.26).
Palladium‐Catalyzed Cross‐Coupling of Organozinc Bromides with Aryl Iodides in Perfluorinated Solvents (1997)

A remarkable selectivity for iodide is characteristic of the Pd0 catalyst obtained from (F13C6C6H4)3P and [Pd(dba)2] in the cross-coupling of organozinc bromides with aryl iodides in a biphasic perfluorinated solvent [Eq. (a)]. In general, this method provides CC coupled products in high yields and requires only a small amount of catalyst (0.15 mol %), which can be separated by simple phase separation and reused several times; dba = dibenzylideneacetone, TIPS = iPr3Si.
The mass spectra of alkyl‐ and phenyl‐4‐imidazolin‐2‐ones (1979)

Abstract The mass spectra of a variety of alkyl‐ and aryl‐4‐imidazolin‐2‐ones have been determined and the fragmentation mechanisms have been analyzed by deuterium labelling, high resolution and metastable transitions allowing certain differentiations of positional isomers. In contrast to the benzoid systems the mass spectra of isomeric alkyl‐4‐imidazolin‐2‐ones are distinctive. The influence of the position of substituents is demonstrated by phenyl‐4‐imidazolin‐2‐ones establishing an exact prediction of fragmentation pathways. Fragment ions ( e.g . [M‐HNCO]. + ) which are the result of rearrangement processes were excluded for structure determinations. The ion structures involved were elucidated by collisional activation comparing model ions. Alkyl‐phenyl‐4‐imidazolin‐2‐ones give almost identical mass spectra, but the positional isomers can easily be distinguished by different fragmentation patterns in both metastable and collisional activation spectra of the molecular ions.
Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223) (2002)

Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand expressed on activated T and NK cells. A LAG-3Ig fusion protein has been used in mice as an adjuvant protein to induce antitumor responses and specific CD8 and CD4 Th1 responses to nominal Ags. In this work we report on the effect of LAG-3Ig on the maturation and activation of human monocyte-derived dendritic cells (DC). LAG-3Ig binds MHC class II molecules expressed in plasma membrane lipid rafts on immature human DC and induces rapid morphological changes, including the formation of dendritic projections. LAG-3Ig markedly up-regulates the expression of costimulatory molecules and the production of IL-12 and TNF-alpha. Consistent with this effect on DC maturation, LAG-3Ig disables DC in their capacity to capture soluble Ags. These events are associated with the acquisition of professional APC function, because LAG-3Ig increases the capacity of DC to stimulate the proliferation and IFN-gamma response by allogeneic T cells. These effects were not observed when using ligation of MHC class II by specific mAb. Class II-mediated signals induced by a natural ligand, LAG-3, lead to complete maturation of DC, which acquire the capacity to trigger naive T cells and drive polarized Th1 responses.
Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland (2012)

The luminal cell compartment in the mammary epithelium is more heterogeneous than initially perceived since progenitors of varying levels of luminal cell differentiation and proliferative capacities can be identified. An understanding of these cells will be essential for understanding the origins and the cellular context of human breast tumours.
Liver-specific Overexpression of Scavenger Receptor BI Decreases Levels of Very Low Density Lipoprotein ApoB, Low Density Lipoprotein ApoB, and High Density Lipoprotein in Transgenic Mice (1998)

Scavenger receptor BI (SR-BI) is known to mediate the selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) in liver and steroidogenic tissues. To evaluate the role of SR-BI in plasma lipoprotein metabolism, we have generated transgenic mice with liver-specific overexpression of murine SR-BI. On a chow diet SR-BI transgenic (SR-BI Tg) mice have decreased HDL-CE, apoA-I, and apoA-II levels; plasma triglycerides, low density lipoprotein (LDL) cholesterol, and very low density lipoprotein (VLDL) and LDL apoB were also decreased, compared with control mice. Turnover studies using non-degradable CE and protein labels showed markedly increased total and selective uptake of HDL-CE in the liver and increased HDL protein catabolism in both liver and kidney. To evaluate the changes in apoB further, mice were challenged with high fat, high cholesterol diets. In SR-BI Tg mice plasma apoB levels were only 3-15% of control levels, and the dietary increase in VLDL and LDL apoB was virtually abolished. These studies show that steady state overexpression of hepatic SR-BI reduces HDL levels and increases reverse cholesterol transport. They also indicate that SR-BI can play a role in the metabolism of apoB-containing lipoproteins. The dual effects of increased reverse cholesterol transport and lowering of apoB-containing lipoproteins that result from hepatic SR-BI overexpression could have anti-atherogenic consequences.
Cloning and sequencing of the genes of β-glucosyl-HMC-α-glucosyl-transferases of bacteriophages T2 and T6 (1993)

Journal Article Cloning and sequencing of the genes of β-glucosyl-HMC-α-glucosyl-transferases of bacteriophages T2 and T6 Get access Michael Winker, Michael Winker Arbeitsgruppe Molekulare Genetik, Lehrstuhl Biologie der Mikroorganismen, Ruhr-Universität BochumD-4630 Bochum 1, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Wolfgang Rüger Wolfgang Rüger * Arbeitsgruppe Molekulare Genetik, Lehrstuhl Biologie der Mikroorganismen, Ruhr-Universität BochumD-4630 Bochum 1, Germany * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 21, Issue 6, 25 March 1993, Page 1500, https://doi.org/10.1093/nar/21.6.1500 Published: 25 March 1993 Article history Revision received: 11 February 1992 Accepted: 11 February 1992 Received: 12 November 1992 Published: 25 March 1993
SHIP deficiency causes Crohn's disease-like ileitis (2010)

SHIP plays a pivotal role in immune function in the intestine; further scrutiny of this pathway in IBD patients is warranted. It is proposed that SHIP-deficient ileitis results from a local deficit in mucosal T cell immunity that promotes a damaging granulocyte-monocyte inflammation of the distal ileum.
Characterization of Alzheimer's β-Secretase Protein BACE (2000)

The cerebral deposition of amyloid beta-peptide is an early and critical feature of Alzheimer's disease. Amyloid beta-peptide is released from the amyloid precursor protein by the sequential action of two proteases, beta-secretase and gamma-secretase, and these proteases are prime targets for therapeutic intervention. We have recently cloned a novel aspartic protease, BACE, with all the known properties of beta-secretase. Here we demonstrate that BACE is an N-glycosylated integral membrane protein that undergoes constitutive N-terminal processing in the Golgi apparatus. We have used a secreted Fc fusion-form of BACE (BACE-IgG) that contains the entire ectodomain for a detailed analysis of posttranslational modifications. This molecule starts at Glu(46) and contains four N-glycosylation sites (Asn(153), Asn(172), Asn(223), and Asn(354)). The six Cys residues in the ectodomain form three intramolecular disulfide linkages (Cys(216)-Cys(420), Cys(278)-Cys(443), and Cys(330)-Cys(380)). Despite the conservation of the active site residues and the 30-37% amino acid homology with known aspartic proteases, the disulfide motif is fundamentally different from that of other aspartic proteases. This difference may affect the substrate specificity of the enzyme. Taken together, both the presence of a transmembrane domain and the unusual disulfide bond structure lead us to conclude that BACE is an atypical pepsin family member.
Randomised, double‐blind, placebo‐controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia (2002)

Cannabis may have medicinal uses in a variety of diseases. The neural mechanisms underlying dystonia involve abnormalities within the basal ganglia-in particular, overactivity of the lateral globus pallidus (GPl). Cannabinoid receptors are located presynaptically on GABA terminals within the GPi, where their activation reduces GABA reuptake. Cannabinoid receptor stimulation may thus reduce overactivity of the GPl and thereby reduce dystonia. A double-blind, randomised, placebo-controlled, crossover study using the synthetic cannabinoid receptor agonist nabilone in patients with generalised and segmental primary dystonia showed no significant reduction in dystonia following treatment with nabilone.
Bidirectional Regulation of Smooth Muscle Cell Proliferation by IFN-^|^gamma; (1994)

We studied the effects of interferon gamma (IFN-gamma), a T-cell lymphokine, on the proliferation and chemotaxis of vascular smooth muscle cells (SMC). Recombinant human IFN-gamma dose-dependently inhibited the proliferation of SMC cultured in the presence of 20% fetal calf-serum. It also inhibited PDGF-induced chemotaxis of SMC. Similar concentrations of IFN-gamma induced DNA-synthesis of SMC cultured in mitogen-depleted medium for 5 days. The inhibition and the stimulation of SMC proliferation were accompanied by concomitant decrease and increase in the number of PDGF receptors. Our study indicated that IFN-gamma is a bidirectional regulator of SMC proliferation.
EphB2 and EphB4 receptors forward signaling promotes SDF-1–induced endothelial cell chemotaxis and branching remodeling (2006)

The complex molecular mechanisms that drive endothelial cell movement and the formation of new vessels are poorly understood and require further investigation. Eph receptor tyrosine kinases and their membrane-anchored ephrin ligands regulate cell movements mostly by cell-cell contact, whereas the G-protein-coupled receptor CXCR4 and its unique SDF-1 chemokine ligand regulate cell movement mostly through soluble gradients. By using biochemical and functional approaches, we investigated how ephrinB and SDF-1 orchestrate endothelial cell movement and morphogenesis into capillary-like structures. We describe how endogenous EphB2 and EphB4 signaling are required for the formation of extracellular matrix-dependent capillary-like structures in primary human endothelial cells. We further demonstrate that EphB2 and EphB4 activation enhance SDF-1-induced signaling and chemotaxis that are also required for extracellular matrix-dependent endothelial cell clustering. These results support a model in which SDF-1 gradients first promote endothelial cell clustering and then EphB2 and EphB4 critically contribute to subsequent cell movement and alignment into cord-like structures. This study reveals a requirement for endogenous Eph signaling in endothelial cell morphogenic processes, uncovers a novel link between EphB forward signaling and SDF-1-induced signaling, and demonstrates a mechanism for cooperative regulation of endothelial cell movement.
A Macrophage-Derived Factor Required by Plasmacytomas for Survival and Proliferation in Vitro (1986)

Plasmacytoma (PCT) cell lines dependent for proliferation and survival on a factor elaborated by the murine macrophage cell line, P388D1, were established in vitro. Adherent peritoneal cells induced by pristane produced 50-fold greater amounts of this activity in vitro than did resident cells. The molecules responsible for plasmacytoma growth were distinct from a number of characterized factors including interleukin-1, -2, and -3, macrophage colony-stimulating factor, B-cell stimulatory factor-1, B-cell growth factor II, epidermal growth factor, transforming growth factor-beta, and gamma- and beta-interferon, none of which were able to support the growth of the factor-dependent PCT cell lines. These results suggest that PCT growth factor may be a novel factor that has not been previously characterized and, further, that its production is associated with the pristane-induced, chronic peritoneal inflammatory response that precedes plasmacytoma formation.