gebhart/patrepeval huggingface dataset:
The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases (2015)

The end of twentieth century has introduced some changes into T helper (Th) cells division. The identification of the new subpopulation of T helper cells producing IL-17 modified model of Th1-Th2 paradigm and it was named Th17. High abilities to stimulate acute and chronic inflammation made these cells ideal candidate for crucial player in development of autoimmune disorders. Numerous publications based on animal and human models confirmed their pivotal role in pathogenesis of human systemic and organ-specific autoimmune diseases. These findings made Th17 cells and pathways regulating their development and function a good target for therapy. Therapies based on inhibition of Th17-dependent pathways are associated with clinical benefits, but on the other hand are frequently inducing adverse effects. In this review, we attempt to summarize researches focused on the importance of Th17 cells in development of human autoimmune diseases as well as effectiveness of targeting IL-17 and its pathways in pre-clinical and clinical studies.
Synchronization-predictive coding for video compression: the SP frames design for JVT/H.26L (2003)

This paper discusses the new frame types considered for the video coding standard JVT/H26L developed jointly by ITU-T VCEG and ISO-IEC MPEG. The new frame types are called SP and SI-frames and provide functionalities in bitstream switching, splicing, random access, fast forward, fast backward and error resilience/recovery. Specific applications are illustrated as examples on how the properties of SP and SI-frames can be exploited. Later, detailed descriptions of SP and SI-frame decoder and encoder are provided.
Combination drug therapy of seropositive rheumatoid arthritis. (1995)

Combination therapy with multiple antirheumatic agents successfully controlled joint inflammation in 167 of 169 patients with seropositive RA; complete remission was achieved in 43% of patients. Survival of this patient cohort did not differ from that of the general population.
Identification of Mitogen-activated Protein (MAP) Kinase-activated Protein Kinase-3, a Novel Substrate of CSBP p38 MAP Kinase (1996)

CSBP p38 is a mitogen-activated protein kinase that is activated in response to stress, endotoxin, interleukin 1, and tumor necrosis factor. Using a catalytically inactive mutant (D168A) of human CSBP2 as the bait in a yeast two-hybrid screen, we have identified and cloned a novel kinase which shares approximately 70% amino acid identity to mitogen-activated protein kinase-activated protein kinase (MAPKAP kinase)-2, and thus was designated MAPKAP kinase-3. The binding of CSBP to MAPKAP kinase-3 was confirmed in vitro by the precipitation of epitope-tagged CSBP1, CSBP2, and CSBP2(D168A) and endogenous CSBP from mammalian cells by a bacterially expressed GST-MAPKAP kinase-3 fusion protein and in vivo by co-precipitation of the epitope-tagged proteins co-expressed in HeLa cells. MAPKAP kinase-3 was phosphorylated by both CSBP1 and CSBP2 and was then able to phosphorylate HSP27 in vitro. Treatment of HeLa cells with sorbitol or TNF resulted in activation of CSBP and MAPKAP kinase-3 and activation of MAPKAP kinase-3 could be blocked by preincubation of cells with SB203580, a specific inhibitor of CSBP kinase activity. These data suggest that MAPKAP kinase-3 is activated by stress and cytokines and is a novel substrate of CSBP both in vitro and in vivo.
Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. (1993)

Murine prostaglandin endoperoxide (PGH) synthase-1 and PGH synthase-2 expressed in cos-1 cells were found to be differentially sensitive to inhibition by common nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin completely inhibited bis-oxygenation of arachidonate by PGH synthase-1; in contrast, aspirin-treated PGH synthase-2 metabolized arachidonate primarily to 15-hydroxyeicosatetraenoic acid (15-HETE) instead of PGH2. ID50 values were determined for a panel of common NSAIDs by measuring instantaneous inhibition of cyclooxygenase activity using an oxygen electrode. Among common NSAIDs tested, indomethacin, sulindac sulfide, and piroxicam preferentially inhibited PGH synthase-1; ibuprofen, flurbiprofen, and meclofenamate inhibited both enzymes with comparable potencies; and 6-methoxy-2-naphthylacetic acid preferentially inhibited PGH synthase-2. These results demonstrate that the two PGH synthases are pharmacologically distinct and indicate that it may be possible to develop isozyme-specific cyclooxygenase inhibitors useful both for anti-inflammatory therapy and for delineating between the biological roles of the PGH synthase isozymes.
Genetic cholestasis, causes and consequences for hepatobiliary transport (2003)

Bile salts take part in an efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum. In the liver, the sodium-dependent taurocholate transporter at the basolateral (sinusoidal) membrane and the bile salt export pump at the canalicular membrane mediate hepatic uptake and hepatobiliary secretion of bile salts. Canalicular secretion is the driving force for the enterohepatic cycling of bile salts and most genetic diseases are caused by defects of canalicular secretion. Impairment of bile flow leads to adaptive changes in the expression of transporter proteins and enzymes of the cytochrome P-450 system involved in the metabolism of cholesterol and bile acids. Bile salts act as ligands for transcription factors. As such, they stimulate or inhibit the transcription of genes encoding transporters and enzymes involved in their own metabolism. Together these changes appear to serve mainly a hepatoprotective function. Progressive familial intrahepatic cholestasis (PFIC) results from mutations in various genes encoding hepatobiliary transport proteins. Mutations in the FIC1 gene cause relapsing or permanent cholestasis. The relapsing type of cholestasis is called benign recurrent intrahepatic cholestasis, the permanent type of cholestasis PFIC type 1. PFIC type 2 results from mutations in the bile salt export pump (BSEP) gene. This is associated with permanent cholestasis since birth. Serum gamma-glutamyltransferase (gamma-GT) activity is low to normal in PFIC types 1 and 2. Bile diversion procedures, causing a decreased bile salt pool, have a beneficial effect in a number of patients with these diseases. However, liver transplantation is often necessary. PFIC type 3 is caused by mutations in the MDR3 gene. MDR3 is a phospholipid translocator in the canalicular membrane. Because of the inability to secrete phospholipids, patients with PFIC type 3 produce bile acid-rich toxic bile that damages the intrahepatic bile ducts. Serum gamma-GT activity is elevated in these patients. Ursodeoxycholic acid therapy is useful for patients with a partial defect. Liver transplantation is a more definitive therapy for these patients.
Searching geometric libraries using generalized ε-congruence (1993)

In computer vision, one of the major problems is how to identify an observed object in an image by comparing it to a set of models in a library. The comparison is made using a shape metric which measures the similarity between different shapes. The observed object is classified as the library object with which it minimizes the shape metric. This paper looks at algorithms for efficiently searching a geometric library to identify an observed object in the image. All objects are modeled as points and (epsilon) -congruence is used as the shape metric. Algorithms are presented for searching two classes of geometric libraries, ordered linear libraries and convex linear libraries. The complexity of the algorithms is expressed in terms of the number of objects in the library, the size of the objects, the error in the optimal match, and the geometric structure.
Chemotherapy for advanced hepatocellular carcinoma Adriamycin versus quadruple chemotherapy (1984)

In a prospective clinical trial, 39 patients with advanced hepatocellular carcinoma were randomized to receive either Adriamycin (20 patients) or a combination of 5-fluorouracil, methotrexate, cyclophosphamide, and vincristine (19 patients). Five patients receiving Adriamycin and none receiving quadruple chemotherapy responded (P less than 0.05 in favor of Adriamycin). A further 25 patients were treated with Adriamycin, making a total of 45. The overall objective response rate was 24% (11 patients), with 3 complete remissions and 8 partial remissions. The median survival for Adriamycin-treated patients (13.0 weeks for the first 20 patients and 14.4 weeks for all patients) was longer than those treated by quadruple chemotherapy (6.5 weeks). The difference, however, was not significant by the Wilcoxan test as modified by Gehan. Patients with positive HbsAg had a significantly higher chance of having a response, while serum alpha-fetoprotein levels did not correlate with response.
Recombinant soluble CR1 suppressed complement activation, inflammation, and necrosis associated with reperfusion of ischemic myocardium. (1990)

In summary, conversion of wild-type CR1 to a soluble form (sCR1) creates a potent inhibitor of complement activation by both the classical and alternative pathways by inhibiting the C3/C5 convertases. In the rat reperfusion infarct model, sCR1 significantly suppresses complement activation at the endothelial surface of capillaries and venules. This suppression of complement activation is accompanied by reduced accumulation of leukocytes within the infarct zone, perhaps because of reduction of the generation of C5a, which promotes expression of leukocyte adhesion receptors and leukocyte chemotaxis. In addition, formation of the C5b-9 attack complex, which may contribute to direct endothelial injury, was suppressed by sCR1. The inhibition of complement activation and leukocyte infiltration by sCR1 explains the observed significant reduction in myocardial necrosis after ischemia and reperfusion. These studies have identified sCR1 as a potential agent for therapeutic intervention in diseases associated with complement-dependent tissue injury.
Advocating the Use of Imprecisely Observed Data in Genetic Fuzzy Systems (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> In our opinion, and in accordance with current literature, the precise contribution of genetic fuzzy systems to the corpus of the machine learning theory has not been clearly stated yet. In particular, we question the existence of a set of problems for which the use of fuzzy rules, in combination with genetic algorithms, produces more robust models, or classifiers that are inherently better than those arising from the Bayesian point of view. </para>
Beware mixing mail and telephone administration of surveys (2003)

The Australian Longitudinal Study on Women's Health (ALSWH) provided an opportunity to describe differences in mail and telephone responses to questions about self-rated health for the same individuals who responded on two occasions two years apart. Whilst telephone reminders may be a useful method to improve response rates to mailed surveys, responses to telephone surveys are likely to differ from those obtained by mail. Differences were demonstrated in SF-36 subscale scores provided by mail and telephone for the same individuals. (non- author abstract)
MRI and quantitative autoradiographic studies following bolus injections of unlabeled and 14C‐labeled gadolinium‐diethylenetriaminepentaacetic acid in a rat model of stroke yield similar distribution volumes and blood‐to‐brain influx rate constants (2010)

In previous studies on a rat model of transient cerebral ischemia, the blood and brain concentrations of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) following intravenous bolus injection were repeatedly assessed by dynamic contrast-enhanced (DCE)-MRI, and blood-to-brain influx rate constants (K(i)) were calculated from Patlak plots of the data in areas with blood-brain barrier (BBB) opening. For concurrent validation of these findings, after completing the DCE-MRI study, radiolabeled sucrose or α-aminoisobutyric acid was injected intravenously, and the brain disposition and K(i) values were calculated by quantitative autoradiography (QAR) assay employing the single-time equation. To overcome two of the shortcomings of this comparison, the present experiments were carried out with a radiotracer virtually identical to Gd-DTPA, Gd-[(14)C]DTPA, and K(i) was calculated from both sets of data by the single-time equation. The protocol included 3 h of middle cerebral artery occlusion and 2.5 h of reperfusion in male Wistar rats (n = 15) preceding the DCE-MRI Gd-DTPA and QAR Gd-[(14)C]DTPA measurements. In addition to K(i) , the tissue-to-blood concentration ratios, or volumes of distribution (V(R) ), were calculated. The regions of BBB opening were similar on the MRI maps and autoradiograms. Within them, V(R) was nearly identical for Gd-DTPA and Gd-[(14)C]DTPA, and K(i) was slightly, but not significantly, higher for Gd-DTPA than for Gd-[(14)C]DTPA. The K(i) values were well correlated (r = 0.67; p = 0.001). When the arterial concentration-time curve of Gd-DTPA was adjusted to match that of Gd-[(14)C]DTPA, the two sets of K(i) values were equal and statistically comparable with those obtained previously by Patlak plots (the preferred, less model-dependent, approach) of the same data (p = 0.2-0.5). These findings demonstrate that this DCE-MRI technique accurately measures the Gd-DTPA concentration in blood and brain, and that K(i) estimates based on such data are good quantitative indicators of BBB injury.
Chemically synthesized peptides of hepatitis B surface antigen duplicate the d/y specificities and induce subtype-specific antibodies in chimpanzees. (1983)

Synthetic peptides, predicted from the nucleotide sequence of the S gene of hepatitis B virus were analyzed in terms of the established specificities of the hepatitis B surface antigen. The analysis indicated that the group-specific alpha antigen is composed of at least three nonoverlapping sequences and that a relatively hydrophilic region of the surface antigen protein, spanning amino acid residues 110-137, specifies the major d and y subtype system. The d/y subtype appears to depend on changes in one or more variable amino acids at positions 127, 131, and 134 of the hepatitis B surface antigen protein. Peptide 49 (consisting of amino acid sequences of the y subtype for the region 110-137), coupled to a carrier protein and mixed with an adjuvant, stimulated a brisk anti-y response in chimpanzees, the relevant model of human response to hepatitis B virus immunization and infection. Experimental challenge with homologous hepatitis B virus resulted in a pattern of partial protection. The results offer promise for the application of chemically synthesized peptides as vaccines in the prophylaxis of hepatitis B virus disease.
Stromal Depletion Goes on Trial in Pancreatic Cancer (2010)

For decades, surgeons and pathologists have likened pancreatic tumors to rocks. That’s because a dense, fibrotic mass called the stroma surrounds the cancer cells in the tumor. Such stroma, consisting of connective tissue, fibroblasts, leukocytes, and blood vessels, accompanies most solid tumors, but its extent and compactness are exceptional in pancreatic cancer. And since pancreatic cancer is exceptional also in its deadliness, researchers have wondered whether the stroma is at least partly responsible. Some recent studies now make that case. They argue for the idea that the stroma is blocking drug penetration and contributing to tumor survival, and that drugs that punch holes in the stromal barrier can be effective. “It’s hard to get drug into a rock,” said Robert Wolff, M.D., an oncologist at the University of Texas M. D. Anderson Cancer Center in Houston. “If you can soften up the rock, you may be able to get a better therapeutic index.” Skeptics remain, but several combination therapies are now in clinical trials to test this “stromal depletion hypothesis.” And some oncologists, including Wolff, are already giving certain patients a stromatargeted drug in an off-label indication, outside clinical trials.
How Citrate Ligands Affect Nanoparticle Adsorption to Microparticle Supports (2012)

Residual ligands from colloidal synthesis of nanoparticles influence adsorption of nanoparticles to supports and may complicate fabrication of nanoparticle-decorated microparticles. In this work, we studied the adsorption of completely ligand-free metal nanoparticles and controlled ligand-functionalized nanoparticles to chemically inert microparticle supports. Adsorption of ligand-free silver nanoparticles to barium sulfate microparticle supports is a quantitative, nonreversible process following Freundlich adsorption isotherm. However, adsorption efficiency is very sensitive to ligand concentration applied during laser-based synthesis of silver nanoparticles: exceeding a specific threshold concentration of 50 μmol/L citrate equal to a nanoparticle ligand surface coverage of about 50%, results in an almost complete prevention of nanoparticle adsorption because of electrosteric repulsion by ligand shell. Laser-based synthesis of nanoparticle-decorated microparticles is demonstrated with a variety of metal nanoparticles (Ag, Au, Pt, Fe) and supporting microparticles (calcium phosphate, titanium dioxide, barium sulfate) with application potential in heterogeneous catalysis or biomedicine where ligand control offers extra value, like enhanced catalytic activity or biocompatibility.
Increased production of interleukin 6 and interleukin 8 in scleroderma fibroblasts. (1998)

Increased production of IL-6 and IL-8 by scleroderma fibroblasts suggests that these cells may have been stimulated by certain cytokines in vivo.
Colloidal Assembly Route for Responsive Colloidosomes with Tunable Permeability (2007)

We present a robust and straightforward approach for fabricating a novel colloidosome system where colloidal particles are assembled to form colloidal shells on the surface of stimuli-responsive microgel scaffolds. We demonstrate that the structural properties of the colloidal shells can be controlled through the colloidal particle size and modulus, and the state of supporting microgel particles. This technique offers a new way to engineer colloidosomes, enabling fine control over their permeability over a wide range of length scales.
Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines (2016)

Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 4-((6-([1,1'-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC<sub>50</sub> 0.044 μM) but was ∼2000-fold less active toward CDK1 (IC<sub>50</sub> 86 μM). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor-kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.
Siamese Instance Search for Tracking (2016)

In this paper we present a tracker, which is radically different from state-of-the-art trackers: we apply no model updating, no occlusion detection, no combination of trackers, no geometric matching, and still deliver state-of-the-art tracking performance, as demonstrated on the popular online tracking benchmark (OTB) and six very challenging YouTube videos. The presented tracker simply matches the initial patch of the target in the first frame with candidates in a new frame and returns the most similar patch by a learned matching function. The strength of the matching function comes from being extensively trained generically, i.e., without any data of the target, using a Siamese deep neural network, which we design for tracking. Once learned, the matching function is used as is, without any adapting, to track previously unseen targets. It turns out that the learned matching function is so powerful that a simple tracker built upon it, coined Siamese INstance search Tracker, SINT, which only uses the original observation of the target from the first frame, suffices to reach state-of-the-art performance. Further, we show the proposed tracker even allows for target re-identification after the target was absent for a complete video shot.
A pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration. (1999)

Comparison between groups and over time demonstrated that both nasal routes resulted in significantly higher CSF concentrations relative to corresponding plasma levels, and that nasal-atomizer administration produced significantly higher CSF concentrations compared to the drop approach.
A modified anaerobic method of sweat collection (1984)

In an attempt to devise a method for collecting large volumes of thermally induced sweat with less epidermal contamination and evaporative water loss, we developed an anaerobic sweat collector by using a sheet of polyethylene film placed over a thin layer of Vaseline and paraffin oil on the skin. To test the validity of the new method, sweat samples collected every 5 min from the new collector (sweat A) were compared with those obtained from a second collector using no oil (sweat B) and scraped sweat for concentrations of adenosine 3',5'-cyclic monophosphate (cAMP), protein, glucose, urea, lactic acid, calcium, sodium, potassium, and cholesterol. The concentration of sweat ingredients in scraped sweat was often far greater than could be expected from evaporative water loss alone. When compared with sweat A, sweat B also had higher concentrations of these ingredients in the initial samples, indicating epidermal contamination, which was especially marked in cAMP, protein, urea, cholesterol, and calcium. Concomitant with a rise in plasma glucose following the administration of a glucose bolus, the sweat glucose significantly increased, indicating the plasma as a major source of sweat glucose. We conclude that the new sweat collector is instrumental in collecting large volumes of the cleanest possible human sweat.
Autonomic neuromuscular junctions: current developments and future directions. (1986)

(1) The autonomic neuromuscular junction has been defined, with emphasis on the role of muscle effector bundles and en passage release of transmitter from extensive terminal nerve varicosities to diffuse to muscle across variable and often wide junctional clefts. (2) A multiplicity of neurotransmitters is described in the autonomic nervous system, including purines, peptides, amino acids and monoamines. The ultrastructural identification, projections, roles and interactions of the different nerve types have been discussed. (3) It has been suggested that the part played by peripheral neuroeffector control mechanisms has been underestimated and includes cotransmission, pre- and post-junctional neuromodulation, and the participation of locally released agents. (4) A time-lapse film was shown of the formation of autonomic neuromuscular junctions in culture, introducing questions relating to long-term 'trophic' influences in the autonomic nervous system.