gebhart/patrepeval huggingface dataset:
Vanilloid Receptor Agonists Potentiate the In Vivo Local Anesthetic Activity of Percutaneously Injected Site 1 Sodium Channel Blockers (1999)

Site 1 sodium channel blockers and vanilloids have synergistic effects on nerve blockade in vivo. These interactions may be useful in developing prolonged local anesthetics and elucidating mechanisms of functionally selective nerve blockade.
A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations (2005)

Referral-based studies indicate that a mutation (G2019S) in exon 41 of the LRRK2 gene might be a common cause of Parkinson disease (PD). The authors sequenced leucine-rich repeat kinase 2 (LRRK2) exons 31, 35, and 41 in 371 consecutively recruited patients with PD and found mutations in six (1.6%) subjects, including two heterozygous for new putative pathogenic variants (R1441H, IVS31 + 3A-->G). These data confirm the important contribution of LRRK2 to PD susceptibility in a clinic-based population.
The Efficacy of Omega-3 Supplementation for Major Depression (2010)

controlled-trials.com Identifier: ISRCTN47431149.
[Pathogenicity factors of enteric Salmonellae]. (1994)

The number of cases of salmonellosis has steadily increased during the last decade. Until the end of the 70s, the serotype Salmonella typhimurium was most commonly isolated, but since 1986 the serotype S. enteritidis has become more common. Recent research has shown that the colon is more frequently infected than was earlier recognized, but most common is still an acute enterocolitis during an infection with salmonella. In severe cases, salmonella can spread from the gut, the site of infection, to cause a systemic disease. As in vitro studies have shown, gastroenteritic salmonellae seem to possess a number of so-called virulence factors that help them to evade the host's defenses against bacterial infection. Colonisation in the gut seems to be dependent on a 66 kD heat shock protein (HSP), which binds to a 15 kD glycoprotein present in gut mucus. For penetration into the mucosa, by invasion of the epithelial cells, bacterial invasions are newly synthesized. These proteins distort the epithelial membrane and induce a port of entrance. Macrophages will attack and engulf the bacteria, but salmonella can withstand these professional killers, and even grow intracellularly in them. In order to do so, not only LPS is required, but also specific outer membrane proteins (OMP), porins. Moreover, during their intracellular survival the bacteria need to adapt to the new microenvironment, and in reaction to stress, new HSPs are expressed. Finally, the O-specific sugar chains prevent the otherwise lytic action of complement in blood serum.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of cellular retinoic acid-binding protein (type II) in Escherichia coli. Characterization and comparison to cellular retinoic acid-binding protein (type I). (1993)

Cellular retinoic acid-binding protein type II, CRABP(II), has been expressed efficiently in Escherichia coli from the mouse cDNA and compared to E. coli-expressed cellular retinoic acid-binding protein type I, CRABP(I). CRABP(II) had a molecular weight approximately 15,700, a pI of 5.46, an Amax of 350 nm with A350/A280 of 1.8, a fluorescence excitation maximum at 347 nm, and a fluorescence emission maximum at 465 nm (holoprotein). All-trans-retinoic acid and 3,4-didehydro-, 4-hydroxy-, 4-oxo-, 16-hydroxy-4-oxo-, and 18-hydroxy-retinoic acids bind CRABP(II) and CRABP(I) stoichiometrically (Kd values no greater than approximately 10-20 nM). 9-cis-Retinoic acid exhibited saturation binding to both CRABP(II) and CRABP(I) with similar affinities, Kd = approximately 50-70, as did 13-cis-retinoic acid, Kd = approximately 160-240 nM, demonstrating that CRABP(II) and CRABP(I) have similar orders of selectivity for known retinoids. HoloCRABP(II) transferred approximately 70% of its all-trans-retinoic acid to CRABP(I), however, indicating that CRABP(II) has approximately a 3-fold lower affinity for stoichiometrically binding retinoids than CRABP(I). Stern-Volmer plots of both native and denatured CRABP(II) and CRABP(I) were consistent with comparable loci for the tryptophan residues and similar three-dimensional structures. These results suggest that CRABP(II) and CRABP(I), when expressed in vivo in excess of total retinoids, bind several ligands, and functional dissimilarities between the two proteins would not be related to unique preferences for known endogenous retinoids. Rather, CRABP(I) and CRABP(II) may modulate the steady-state concentrations of retinoids to different set points.
Simple, Rapid, Quantitative, Syncytium-Forming Microassay for the Detection of Human Immunodeficiency Virus Neutralizing Antibody (1987)

A simple, rapid, quantitative syncytium-forming microassay for the detection of human immunodeficiency virus (HIV-I) isolates is described. A virus-syncytial sensitive clone of CEM cells (CEM-SS) was identified and made adherent to flat bottom 96-well microtiter dishes. Following the addition of virus, these cells develop easily quantifiable, adherent syncytia on a background of confluent, normal CEM-SS monolayer in 4 to 6 days. One-hit kinetics for syncytia formation were obtained at various multiplicities of infection. Syncytia are associated with complete virion production and cytoplasmic localization of the p24 core protein (detected by immunofluorescence). Total infectious virus can be accurately determined in this assay; these results showed a close correlation with p24 and gp120 induction when microtiter well supernatants were passed to fresh cells and evaluated by competitive radioimmunoassay. Studies of p24 antigen induction at and beyond the end point of syncytia formation indicate that there are no detectable nonsyncytial variants in standard HIV-I stocks. Six divergent HIV-I isolates (HTLV-IIIB, -RFII, -MN, -RUTZ, -CC, and LAV-1), as well as HTLV-IIIB and LAV-1 reisolated from persistently infected chimpanzees, produce quantifiable syncytia which vary slightly in their developmental morphology. Accurate neutralization titers are readily obtained from easily constructed multiplicity curves derived from serial dilutions of test sera. Inherent within this system is a flexible method for studying various kinetics of antibody/virus interactions, as well as blocking and interference studies with any candidate antiviral compounds.
Reduced-order modeling and adaptive observer design for lithium-ion battery cells (2017)

Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.
A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness (2006)

Adalimumab, etanercept and infliximab are effective treatments compared with placebo for RA patients who are not well controlled by conventional DMARDs, improving control of symptoms, improving physical function, and slowing radiographic changes in joints. The combination of a TNF inhibitor with methotrexate was more effective than methotrexate alone in early RA, although the clinical relevance of this additional benefit is yet to be established, particularly in view of the well-established effectiveness of MTX alone. An increased risk of serious infection cannot be ruled out for the combination of methotrexate with adalimumab or infliximab. The results of the economic evaluation based on BRAM are consistent with the observations from the review of clinical effectiveness, including the ranking of treatments. TNF inhibitors are most cost-effective when used as last active therapy. In this analysis, other things being equal, etanercept may be the TNF inhibitor of choice, although this may also depend on patient preference as to route of administration. The next most cost-effective use of TNF inhibitors is third line, as recommended in the 2002 NICE guidance. Direct comparative RCTs of TNF inhibitors against each other and against other DMARDs, and sequential use in patients who have failed a previous TNF inhibitor, are needed. Longer term studies of the quality of life in patients with RA and the impact of DMARDs on this are needed, as are longer studies that directly assess effects on joint replacement, other morbidity and mortality.
Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis (2008)

The inflammatory bowel disease ulcerative colitis (UC) frequently progresses to colon cancer. To understand the mechanisms by which UC patients develop colon carcinomas, we used a mouse model of the disease whereby administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion causes severe colonic inflammation and the subsequent development of multiple tumors. We found that treating WT mice with AOM and DSS increased TNF-alpha expression and the number of infiltrating leukocytes expressing its major receptor, p55 (TNF-Rp55), in the lamina propria and submucosal regions of the colon. This was followed by the development of multiple colonic tumors. Mice lacking TNF-Rp55 and treated with AOM and DSS showed reduced mucosal damage, reduced infiltration of macrophages and neutrophils, and attenuated subsequent tumor formation. WT mice transplanted with TNF-Rp55-deficient bone marrow also developed significantly fewer tumors after AOM and DSS treatment than either WT mice or TNF-Rp55-deficient mice transplanted with WT bone marrow. Furthermore, administration of etanercept, a specific antagonist of TNF-alpha, to WT mice after treatment with AOM and DSS markedly reduced the number and size of tumors and reduced colonic infiltration by neutrophils and macrophages. These observations identify TNF-alpha as a crucial mediator of the initiation and progression of colitis-associated colon carcinogenesis and suggest that targeting TNF-alpha may be useful in treating colon cancer in individuals with UC.
Parkinson's disease transgenic mitochondrial cybrids generate Lewy inclusion bodies (2004)

Many models of Parkinson's disease (PD) have succeeded in replicating dopaminergic neuron loss or alpha-synuclein aggregation but not the formation of classical Lewy bodies, the pathological hallmark of PD. Our cybrid model of sporadic PD was created by introducing the mitochondrial genes from PD patients into neuroblastoma cells that lack mitochondrial DNA. Previous studies using cybrids have shown that information encoded by mitochondrial DNA in patients contributes to many pathogenic features of sporadic PD. In this paper, we report the generation of fibrillar and vesicular inclusions in a long-term cybrid cell culture model that replicates the essential antigenic and structural features of Lewy bodies in PD brain without the need for exogenous protein expression or inhibition of mitochondrial or proteasomal function. The inclusions generated by PD cybrid cells stained with eosin, thioflavin S, and antibodies to alpha-synuclein, ubiquitin, parkin, synphilin-1, neurofilament, beta-tubulin, the proteasome, nitrotyrosine, and cytochrome c. Future studies of these cybrids will enable us to better understand how Lewy bodies form and what role they play in the pathogenesis of PD.
Targeting ROR1 identifies new treatment strategies in hematological cancers (2017)

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy. Current understanding attributes a survival role for ROR1 in cancer cells; however, its oncogenic function is cancer-type-specific and involves various signaling pathways. High interest in ROR1-targeted therapies resulted in the development of ROR1 monoclonal antibodies such as cirmtuzumab, currently in a phase I clinical trial for chronic lymphocytic leukemia. Despite these advances in translational studies, the molecular mechanism employed by ROR1 in different cancers is not yet fully understood; therefore, more insights into the oncogenic role of ROR1 signaling are crucial in order to optimize the use of targeted drugs. Recent studies provided evidence that targeting ROR1 simultaneously with inhibition of B-cell receptor (BCR) signaling is more effective in killing ROR1-positive leukemia cells, suggesting a synergistic correlation between co-targeting ROR1 and BCR pathways. Although this synergy has been previously reported for B-cell acute lymphoblastic leukemia, the molecular mechanism appears rather different. These results provide more insights into ROR1-BCR combinatorial treatment strategies in hematological malignancies, which could benefit in tailoring more effective targeted therapies in other ROR1-positive cancers.
Blood plasma not so simple after all (2013)

The thinning and breaking of blood-plasma filaments reveals the fluid’s viscoelasticity. The thinning and breaking of blood-plasma filaments reveals the fluid’s viscoelasticity.
Protein targeting by tyrosine- and di-leucine-based signals: evidence for distinct saturable components. (1996)

Targeting of transmembrane proteins to lysosomes, endosomal compartments, or the trans-Golgi network is largely dependent upon cytoplasmically exposed sorting signals. Among the most widely used signals are those that conform to the tyrosine-based motif, YXXO (where Y is tyrosine, X is any amino acid, and O is an amino acid with a bulky hydrophobic group), and to the di-leucine (or LL) motif. Signals conforming to both motifs have been implicated in protein localization to similar post-Golgi compartments. We have exploited the saturability of sorting to ask whether different YXXO or LL signals use shared components of the targeting machinery. Chimeric proteins containing various cytoplasmic domains and/or targeting signals were overexpressed in HeLa cells by transient transfection. Endogenous transferrin receptor and lysosomal proteins accumulated at the cell surface upon overexpression of chimeric proteins containing functional YXXO targeting signals, regardless of the compartmental destination imparted by the signal. Furthermore, overexpression of these chimeric proteins compromised YXXO-mediated endocytosis and lysosomal delivery. These activities were ablated by mutating the signals or by appending sequences that conformed to the YXXO motif but lacked targeting activity. Interestingly, overexpression of chimeric proteins containing cytoplasmic LL signals failed to induce surface displacement of endogenous YXXO-containing proteins, but did displace other proteins containing LL motifs. Our data demonstrate that: (a) Protein targeting and internalization mediated by either YXXO or LL motifs are saturable processes; (b) common saturable components are used in YXXO-mediated protein internalization and targeting to different post-Golgi compartments; and (c) YXXO- and LL-mediated targeting mechanisms use distinct saturable components.
Outputs of paired Gabor filters summed across the background frame of reference predict the direction of movement (vision) (1989)

A cortical neural network that computes the visibility of shifts in the direction of movement is proposed that computes: 1) the magnitude of the position difference between the test and background patterns, 2) localized contrast differences at different spatial scales analyzed by computing temporal gradients of the difference and sum of the outputs of paired even- and odd-symmetric bandpass filters convolved with the input pattern, and 3) using global processes that pool the output from paired even- and odd-symmetric simple and complex cells across the spatial extent of the background frame of reference to determine the direction a test pattern moved relative to a textured background. Evidence is presented that magnocellular pathways are used to discriminate the direction of movement. Since magnocellular pathways are used to discriminate the direction of movement, this task is not affected by small pattern changes such as jitter, short presentations, blurring, and different background contrasts that result when the veiling illumination in a scene changes.
Characterization of a 41-Residue Ovine Hypothalamic Peptide That Stimulates Secretion of Corticotropin and β-Endorphin (1981)

A peptide with high potency and intrinsic activity for stimulating the secretion of corticotropin-like and β-endorphin-like immunoactivities by cultured anterior pituitary cells has been purified from ovine hypothalamic extracts. The primary structure of this 41-residue corticotropin- and β-endorphin-releasing factor has been determined to be: H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Leu-Asp-Ile-Ala-NH 2 . The synthetic peptide is active in vitro and in vivo.
A detailed study of the substrate specificity of a chimeric restriction enzyme (1999)

Recently, the crystal structure of the designed zinc finger protein, DeltaQNK, bound to a preferred DNA sequence was reported. We have converted DeltaQNK into a novel site-specific endonuclease by linking it to the Fok I cleavage domain (FN). The substrate specificity and DNA cleavage properties of the resulting chimeric restriction enzyme (DeltaQNK-FN) were investigated, and the binding affinities of DeltaQNK and DeltaQNK-FN for various DNA substrates were determined. Substrates that are bound by DeltaQNK with high affinity are the same as those that are cleaved efficiently by DeltaQNK-FN. Substrates bound by DeltaQNK with lower affinity are cleaved with very low efficiency or not at all by DeltaQNK-FN. The binding of DeltaQNK-FN to each substrate was approximately 2-fold weaker than that for DeltaQNK. Thus, the fusion of the Fok I cleavage domain to the zinc finger motif does not change the DNA sequence specificity of the zinc finger protein and does not change its binding affinity significantly.
Mode conversion losses in silicon-on-insulator photonic wire based racetrack resonators (2006)

Two complimentary types of SOI photonic wire based devices, the add/drop (A/D) filter using a racetrack resonator and the Mach-Zehnder interferometer with one arm consisting of an identical resonator in all-pass filter (APF) configuration, were fabricated and characterized in order to extract the optical properties of the resonators and predict the performance of the optical delay lines based on such resonators. We found that instead of well-known waveguide bending and propagation losses, mode conversion loss in the coupling region of such resonators dominates when the air gap between the racetrack resonator and access waveguide is smaller than 120nm. We also show that this additional loss significantly degrades the performance of the optical delay line containing cascaded resonators in APF configuration.
Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats (2011)

The findings suggest that complement activation, and particularly C5a generation, may play a significant role in the development and progression of periodontitis. Blockade of the major C5a receptor, CD88, with specific inhibitors such as PMX205, may offer novel treatment options for periodontitis.
Detection of fluorescent-labeled probes at sub-picomolar concentrations by magnetic modulation (2008)

A sensitive and rapid method for detecting fluorescent dyes at low concentrations in homogenous solution is experimentally demonstrated. Fluorescent-labeled DNA probes are detected by attaching magnetic beads and applying alternating magnetic field gradient. This condenses the fluorescent probes into a small detection volume and eliminates the scattering noise from solution by synchronous detection. For DNA probes concentration of 1 x 10(-13) M the detection signal was 3.3 times higher than the noise, thereby implying detection sensitivity of 3 x 10(-14) M.
Electrophoretic Separations of Large DNA Molecules by Periodic Inversion of the Electric Field (1986)

In gel electrophoresis, nucleic acids and protein-detergent complexes larger than a threshold size all migrate at the same rate. For DNA molecules, this effect can be overcome by the simple procedure of periodically inverting the electric field. Tuning the frequency of the field inversions from 10 to 0.01 hertz, makes it possible to resolve selectively DNA's in the size range 15 to greater than 700 kilobase pairs.
Probing chelation motifs in HIV integrase inhibitors (2012)

A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance.
One-Pot Synthesis of 3(5)-Ethoxycarbonylpyrazoles (1995)

A one-pot synthesis of ethoxycarbonylpyrazoles 2a-e, by the cyclocondensation of β-alkoxyvinyl trichloromethyl ketones 1a-e with hydrazine hydrochloride under mild conditions, is reported. A study using compounds 1a-e with different substituents proved that these are versatile building blocks for the synthesis of pyrazole derivatives, having a 3(5)-ethoxycarbonyl substituent, in good yields (70-91%).
Differential increase of Fas ligand expression on metastatic and thin or thick primary melanoma cells compared with interleukin-10 (1999)

Fas ligand (FasL), a cell surface molecule belonging to the tumour necrosis factor family, binds to its receptor Fas and thus induces apoptosis of Fas-bearing cells such as activated lymphocytes. In this paper, we report the expression of FasL on melanoma cell lines and patient tumour specimens, and compare it with the expression of interleukin-10 (IL-10), a putative immunosuppressive factor. Apoptosis of Fas-bearing Jurkat cells was increased after interferon-alpha treatment of the FasL-positive melanoma cell line A375, suggesting a regulation of FasL function. We also tested whether FasL and IL-10 were ever co-expressed. Immunohistochemistry studies showed that IL-10 expression was highly positive in the same tumour samples which expressed FasL. In the melanoma patients with thin primaries, 10 of the 12 primaries and six of the seven metastatic lesions were positive for IL-10. In the melanoma patients with thick primaries (> 0.75 mm), four of the five primary lesions and nine of the 10 metastatic lesions were positive for IL-10. In contrast, FasL was generally negative in primary tumours and positive in metastatic tumours. In the thin primary melanoma patients, two of the 12 primaries and five of the seven metastatic tumours were positive for FasL. From the thick melanomas, one of the five primaries and five of the 10 metastatic lesions were positive for FasL. The function of melanoma-derived FasL was confirmed by four different cytotoxicity assays.