gebhart/patrepeval huggingface dataset:
Synthetic DNA probes for detection of genes for enterotoxins A, B, C, D, E and for TSST‐1 in staphylococcal strains (1992)

A dot blot hybridization technique with oligonucleotide probes was developed for the specific detection of the TSST-1 gene and the staphylococcal enterotoxin (SE) genes A, B, C, D and E. For each toxin gene a probe sequence was chosen from the previously determined sequence. A total of 145 staphylococcal strains (133 Staphylococcus aureus and 12 coagulase-negative staphylococci (CNS) were studied by this genotypic method and by two phenotypic assays (gel immunodiffusion and ELISA). An excellent correlation (96%) was observed between the genotypic and phenotypic assays. DNA from two CNS strains hybridized with a probe without detection of the corresponding toxin (SEB for one strain and SEC for the other strain). One Staph. aureus strain was shown to be an SEC producer, but was not detected by the corresponding probe. Gene probe and immunological assays seem to be complementary methods for studies of staphylococcal strains producing (or potentially producing) TSST-1 or enterotoxins.
Independent Component Analysis Applied to fMRI Data (2004)

Methods for testing and validating independent component analysis (ICA) results in fMRI are growing in importance as the popularity of this model for studying brain function increases. We introduce...
Ethoprop depletion from soil as influenced by simulated rainfall. (1992)

Two field microplot tests were conducted in sandy soil to evaluate retention of ethoprop in relation to simulated rainfall levels. Ethoprop was applied at the equivalent of 13.5 kg a.i./ha, and simulated rainfall was added at rates of 2.5, 7.5, 15.0, and 22.5 cm over a 6-day period. Ethoprop concentration in the soil at 5-, 10-, and 40-day intervals indicated that it was depleted rapidly with increased rainfall levels. The 2.5-cm level of simulated rainfall reduced ethoprop concentration to one-half in the 0 to 15 cm depth within 10.7 days, whereas the 22.5 cm of rain shortened this period to 1.7 days. Soil samples taken 10 days after ethoprop treatment and inoculated with Meloidogyne javanica indicated that 2.5 cm of rain rendered the nematicide ineffective against M. javanica.
Local corticosteroid application blocks transmission in normal nociceptive C‐fibres (1990)

The effect of a locally applied depot form of a corticosteroid on the electrical properties of nerves was investigated in an experimental model. The segmental transmission in electrically stimulated A-fibres and in C-fibres of the plantar nerve in the anaesthetized rat was utilized. A drop of methylprednisolone acetate or vehicle constituent was placed on the dissected plantar nerve proximal to the stimulating electrodes after recording control responses (A-fibre volley in the sciatic nerve and C-fibre evoked reflex discharge in flexor motoneurons). The corticosteroid was found to suppress the transmission in thin unmyelinated C-fibres but not in myelinated A-beta fibres. The effect was found to be due to the corticosteroid per se. The effect was reversed when the corticosteroid was removed, which suggests a direct membrane action.
Controlled-release carbidopa-levodopa (Sinemet) in combination with standard Sinemet in advanced Parkinson's disease. (1989)

Twelve of 23 patients with Parkinson's disease and motor fluctuations who entered a double-blind study comparing controlled-release carbidopa/levodopa (Sinemet CR-4) with standard Sinemet (SS) continued into open label follow-up on a combination of CR-4 and SS (C/S); the rest continued on CR-4 alone. Significant improvement on C/S compared with CR-4 was noted for shorter duration and reduced disability of dyskinesias, and more hours "on" without dyskinesias (all p less than 0.05). Total number of hours "off" was improved on C/S over SS (p less than 0.01). Sinemet CR-4 proved to be better than C/S for sleep disturbance (p less than 0.05). Although the total number of tablets and doses per day of CR-4 was reduced during the C/S period, total levodopa dosage per day was not significantly changed from either of the previous periods. The C/S therapy for advanced parkinsonism can be more efficacious for fluctuators than either CR-4 or SS alone.
Activin type II receptors in embryonic dorsal root ganglion neurons of the chicken (2001)

Activin induces neuropeptide expression in chicken ciliary ganglion neurons. To determine if activin might also influence neuropeptide expression in developing sensory neurons, we examined whether type II activin receptors are expressed during embryonic development of the chicken dorsal root ganglia (DRG), and also examined the effects of activin on neuropeptide expression in cultured DRG neurons. Using reverse transcription polymerase chain reaction (rtPCR), we detected mRNAs for both the activin receptors type IIA (ActRIIA) and type IIB (ActRIIB) in DRG from embryonic day 7 through posthatch day 1. With in situ hybridization, we found that morphologically identifiable neurons express mRNAs for both ActRIIA and ActRIIB. With developmental age, a subset of neurons that hybridizes more intensely with riboprobes to these receptor mRNAs becomes evident. A similar pattern of expression is observed with immunocytochemical staining using antisera against activin type II receptors. To examine whether embryonic DRG cells respond to activin we treated dissociated cultures of DRG with activin A and assessed the expression of vasoactive intestinal peptide (VIP) and calcitonin gene related peptide (CGRP) mRNAs using semiquantitative rtPCR. Activin treatment results in an increase in VIP mRNA, but does not affect CGRP mRNA levels. These observations indicate that neurons in the embryonic chicken DRG can respond to activin and suggest that activin has the potential to play a role in the development and function of DRG sensory neurons.
A New Breast Carcinoma Antigen Defined by a Monoclonal Antibody2 (1985)

A new monoclonal antibody (MoAb), 3E1-2, to human breast carcinoma cells was made. With the use of the immunoperoxidase technique, 3E1-2 was tested on Formalin-fixed and fresh sections of 27 normal and 81 neoplastic tissues, including 37 carcinomas of the breast, 15 lung tumors, 5 colon tumors, and other tumors. Strong uniform staining of the cytoplasm and membrane occurred with the breast carcinoma, whereas with normal breast tissue less intense staining of the luminal membrane was seen; not all cells were reactive with the MoAb. Most other human tumors (with the exception of some lung, kidney, and uterine carcinomas) were nonreactive, and few normal tissues were reactive. The unique features of this new MoAb are: a) reaction with Formalin-fixed as well as fresh tissue; b) lack of a reaction with the cell surface of 43 established cell lines, including 10 lines derived from breast carcinoma cultures; c) variable staining patterns in different breast carcinomas, varying from all cells staining to dense cytoplasmic staining to minimal membrane staining of a few cells; d) a great differential in staining patterns between normal and neoplastic tissue (nonetheless, some normal tissues were 3E-1.2+). The antibody does not detect a tumor-specific antigen, but has a high carcinoma-to-normal breast ratio of staining. In addition, preliminary studies on the sera of 20 patients with carcinoma of the breast have shown that the antigen detected by 3E1-2 is elevated in their serum; 3E1-2 thus has the potential to be used for diagnosis of this disease.
Learning by Playing - Solving Sparse Reward Tasks from Scratch (2018)

We propose Scheduled Auxiliary Control (SAC-X), a new learning paradigm in the context of Reinforcement Learning (RL). SAC-X enables learning of complex behaviors - from scratch - in the presence of multiple sparse reward signals. To this end, the agent is equipped with a set of general auxiliary tasks, that it attempts to learn simultaneously via off-policy RL. The key idea behind our method is that active (learned) scheduling and execution of auxiliary policies allows the agent to efficiently explore its environment - enabling it to excel at sparse reward RL. Our experiments in several challenging robotic manipulation settings demonstrate the power of our approach.
Development of Potent Thrombin Receptor Antagonist Peptides (1996)

A peptide-based structure-activity study is reported leading to the discovery of novel potent thrombin receptor antagonists. Systematic substitution of nonproteogenic amino acids for the second and third residues of the human thrombin receptor "tethered ligand" sequence (SFLLR) led to a series of agonists with enhanced potency. The most potent pentapeptide agonist identified was Ser-p-fluoroPhe-p-guanidinoPhe-Leu-Arg-NH2, 9 (EC50 approximately 0.04 microM for stimulation of human platelet aggregation, approximately 10-fold more potent than the natural pentapeptide). Systematic substitution of the NH2-terminal Ser in 9 with neutral hydrophobic NH2-acyl groups led to partial agonists and eventually antagonists with unprecedented potency (greater than 1000-fold increase over the previously reported antagonist 3-mercaptopropionyl-Phe-Cha-Cha-Arg-Lys-Pro-Asn-Asp-Lys-NH2). In the series of NH2-acyl tetrapeptide antagonists, N-transcinnamoyl-p-fluoroPhe-p-guanidinoPhe-Leu-Arg-NH 2, 41 (BMS-197525), was identified as the tightest binding (IC50 approximately 8 nM) and most potent with an IC50 approximately 0.20 microM for inhibition of SFLLRNP-NH2-stimulated platelet aggregation. Systematic single substitutions in 41 indicated that, in addition to the NH2-terminal acyl group, the side chains at the second and third positions were also responsible for important and specific receptor interactions. The p-fluoroPhe and p-guanidinoPhe residues in the second and third positions of 41 were observed to be optimal in both the agonist and antagonist series. In the case of antagonists, however, an appropriately positioned positively charged group (i.e., protonated base) at the third residue was required. In contrast, such a substitution was not required for potent agonist activity. An even more potent antagonist resulted when 41 was extended at the C-terminus by a single Arg residue giving rise to analog 90 (BMS-200261) which had an IC50 approximately 20 nM for inhibition of SFLLRNP-NH2-stimulated platelet aggregation. When the C-terminal Arg of 90 was replaced by an Orn-(Ndelta-propionyl) residue, the resulting antagonist 91 (BMS-200661) was suitable for use in radioligand binding assays (Kd = 10-30 nM). Antagonist activity observed for selected compounds was verified through secondary assays in that these analogs prevented SFLLRNP-NH2-stimulated GTPase activity in platelet membranes and Ca2+ mobilization in cultured human smooth muscle cells and mouse fibroblasts. Furthermore, this inhibition occurred at concentrations that had no effect on thrombin catalytic activity indicating a specific activity attributable to receptor binding and not enzyme inhibition.
Patterns of cortical reorganization in complex regional pain syndrome (2003)

This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic pain.
Studies of thrombin-induced proteoglycan release in the degradation of human and bovine cartilage. (1994)

Because fibrin is commonly observed within arthritic joints, studies were undertaken to determine whether purified coagulation and fibrinolytic proteases degrade cartilage in vitro and to seek evidence for the activation of coagulation in arthritic joints through measurements of the levels of inhibitor-enzyme complexes and several other proteins associated with coagulation and fibrinolysis. The concentrations of 13 plasma proteins and complexes of thrombin and Factor Xa with antithrombin III were measured in synovial fluids recovered at the time of knee replacement surgery. All zymogens necessary to constitute the coagulation cascade were present. Thrombin and the combination of prothrombin plus prothrombinase induced proteoglycan release from both normal and arthritic cartilages. Factor Xa and plasmin induced release from diseased cartilage only, and urokinase, tissue plasminogen activator, and activated protein C were without effect at the levels used. At saturating levels of thrombin (> or = 2.0 microM) 80% of the proteoglycan content of normal cartilage was released within 24 h. Thrombin, which is cationic, reversibly binds cartilage with Kd = 7.0 +/- 1.0 microM and Bmax = 820 +/- 70 ng/mg of human cartilage. Levels of thrombin-antithrombin III complexes in synovial fluids and arthritis were 4-fold higher in osteo (OA) and 43-fold higher in rheumatoid (RA) than in controls (0.98 nM). Factor Xa-antithrombin III complex levels were threefold lower in OA and fivefold higher in RA than in controls (0.24 nM). These elevated levels of enzyme-inhibitor complexes imply a history of activation of coagulation within the joint, especially in RA. Since thrombin degrades cartilage in vitro and had been generated in vivo, as inferred by the existence of thrombin-antithrombin III complexes, intraarticular activation of coagulation may both contribute to the pathology of arthritis and comprise a target for therapy and diagnosis.
Microfluidic Serial Dilution Circuit (2006)

In vitro evolution of RNA molecules requires a method for executing many consecutive serial dilutions. To solve this problem, a microfluidic circuit has been fabricated in a three-layer glass-PDMS-glass device. The 400-nL serial dilution circuit contains five integrated membrane valves: three two-way valves arranged in a loop to drive cyclic mixing of the diluent and carryover, and two bus valves to control fluidic access to the circuit through input and output channels. By varying the valve placement in the circuit, carryover fractions from 0.04 to 0.2 were obtained. Each dilution process, which is composed of a diluent flush cycle followed by a mixing cycle, is carried out with no pipeting, and a sample volume of 400 nL is sufficient for conducting an arbitrary number of serial dilutions. Mixing is precisely controlled by changing the cyclic pumping rate, with a minimum mixing time of 22 s. This microfluidic circuit is generally applicable for integrating automated serial dilution and sample preparation in almost any microfluidic architecture.
All children who experience epileptic falls do not necessarily have Lennox-Gastaut syndrome... but many do (2011)

Lennox-Gastaut syndrome (LGS) is a severe, chronic, epileptic encephalopathy, primarily with childhood onset, which is characterised by a triad of features: multiple seizure types, including tonic seizures that may appear late in the course of the disorder; abnormal EEG features with slow spike-wave discharges; and cognitive impairment. Recognition of LGS is problematic, since the seizure types and EEG features that characterise it are not pathognomonic and often change over time. Furthermore, although seizures associated with LGS may occur de novo, the appearance of core LGS seizures may be preceded by prolonged periods of other seizure types, including myoclonic seizures, partial seizures, or infantile spasms. This has led some authors to postulate that a continuum between LGS and other types of childhood epilepsy may exist. Accurate diagnosis requires careful assessment of both clinical and EEG features, in order to distinguish LGS from other childhood epilepsy syndromes, such as atypical benign partial epilepsy of childhood, Dravet syndrome or epilepsies with predominantly myoclonic-astatic seizures. Since there is no biological marker that can be used to confirm diagnosis of LGS and because of the multiple aetiologies that could lead to its development, early referral to a specialist team may prove to be crucial for facilitating both diagnosis and management. Such an approach ensures that patients receive the appropriate treatment at the correct time, providing the best opportunity for the clinical course and overall prognosis to be improved. Effective management of LGS requires regular reappraisal of the evolving symptoms and features, and adjustment of the treatment accordingly.
Exposure to Room Light before Bedtime Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans (2010)

These findings indicate that room light exerts a profound suppressive effect on melatonin levels and shortens the body's internal representation of night duration. Hence, chronically exposing oneself to electrical lighting in the late evening disrupts melatonin signaling and could therefore potentially impact sleep, thermoregulation, blood pressure, and glucose homeostasis.
Mechanotransduction through the cytoskeleton (2002)

We constructed a model cytoskeleton to investigate the proposal that this interconnected filamentous structure can act as a mechano- and signal transducer. The model cytoskeleton is composed of rigid rods representing actin filaments, which are connected with springs representing cross-linker molecules. The entire mesh is placed in viscous cytoplasm. The model eukaryotic cell is submitted to either shock wave-like or periodic mechanical perturbations at its membrane. We calculated the efficiency of this network to transmit energy to the nuclear wall as a function of cross-linker stiffness, cytoplasmic viscosity, and external stimulation frequency. We found that the cytoskeleton behaves as a tunable band filter: for given linker molecules, energy transmission peaks in a narrow range of stimulation frequencies. Most of the normal modes of the network are spread over the same frequency range. Outside this range, signals are practically unable to reach their destination. Changing the cellular ratios of linker molecules with different elastic characteristics can control the allowable frequency range and, with it, the efficiency of mechanotransduction.
Design of interchain disulfide bonds in the framework region of the Fv fragment of the monoclonal antibody B3 (1994)

The Fv fragments are the smallest units of antibodies that retain the specific antigen binding characteristics of the whole molecule and are being used for the diagnosis and therapy of human diseases. These are noncovalently associated heterodimers of the heavy (VH) and the light (VL) chain variable domains, which, without modification, tend to dissociate, unfold, and/or nonspecifically aggregate. The fragment is usually stabilized by producing it as a single chain recombinant molecule in which the two chains are linked by means of a short polypeptide linker. An alternative strategy is to connect the two chains by means of an interchain disulfide bond. We used molecular graphics and other modeling tools to identify two possible interchain disulfide bond sites in the framework region of the Fv fragment of the monoclonal mouse antibody (mAb) B3. The mAb B3 binds to many human cancer cells and is being used in the development of a new anticancer agent. The two sites identified are VH44-VL105 and VH111-VL48. (VH44-VL100 and VH105-VL43 in the numbering scheme of Kabat et al., "Sequence of Proteins of Immunological Interest," U.S. DHHS, NIH publication No. 91-3242, 1991). This design was recently tested using the chimeric protein composed of a truncated form of Pseudomonas exotoxin and the Fv fragment of mAb B3 with the engineered disulfide bond at VH44-VL105 (Brinkmann et al., Proc. Natl. Acad. Sci. U.S.A. 90:7538, 1993). The chimeric toxin was found to be just as active as the corresponding single chain counterpart and considerably more stable. Because these disulfide bond sites are in the framework region, they can be located from sequence alignment alone. We expect that the disulfide bond at these sites will stabilize the Fv fragment of most antibodies and the antigen-specific portion of the T-cell receptors, which are homologous.
Cytokine-induced enhancement of ICAM-1 expression results in increased vulnerability of tumor cells to monocyte-mediated lysis (1991)

Pretreatment of the human melanoma cell line, A375, and the human colon carcinoma cell line, HT-29, with certain cytokines was found to increase the vulnerability of these cells to monocyte-mediated killing. This activity was found to correlate with increased expression of intercellular adhesion molecule-1 (ICAM-1) on the tumor cells and was blocked by anti-ICAM-1 antibodies. Both IFN-gamma and TNF induced large increases in the ICAM-1 expression on both cell lines and increased the susceptibility of the tumor cells to monocyte-mediated killing. IFN-alpha and IL-1 beta, however, induced only small increases in ICAM-1 expression and enhanced the lysis of the A375 cells but not the HT-29 cells by monocytes. These differences may be the result of a higher basal expression of ICAM-1 found on the A375 cells when compared with the HT-29 cells. These data indicate that regulation of ICAM-1 expression on tumor cells can alter the vulnerability of these cells to lysis by monocytes.
TNIK, a Novel Member of the Germinal Center Kinase Family That Activates the c-Jun N-terminal Kinase Pathway and Regulates the Cytoskeleton (1999)

Germinal center kinases (GCKs) compose a subgroup of the Ste20 family of kinases. Here we describe the cloning and characterization of a novel GCK family kinase, Traf2- and Nck-interacting kinase (TNIK) that interacts with both Traf2 and Nck. TNIK encodes a polypeptide of 1360 amino acids with eight spliced isoforms. It has 90% amino acid identity to the Nck-interacting kinase in both the N-terminal kinase domain and the C-terminal germinal center kinase homology region. The homology drops to 53% in the intermediate region. TNIK specifically activates the c-Jun N-terminal kinase pathway when transfected into Phoenix-A cells (derivatives of 293 cells), similar to many GCKs. However, in contrast to other GCKs, this activation is mediated solely by the GCK homology region of TNIK. In addition, in Phoenix-A, NIH-3T3, and Hela cells, overexpression of wild type TNIK, but not the kinase mutant form of TNIK, results in the disruption of F-actin structure and the inhibition of cell spreading. Furthermore, TNIK can phosphorylate Gelsolin in vitro. This is the first time that a GCK family kinase is shown to be potentially involved in the regulation of cytoskeleton.
Extracellular Vesicle (EV) Array: microarray capturing of exosomes and other extracellular vesicles for multiplexed phenotyping (2013)

The limit of detection (LOD) was determined on exosomes derived from the colon cancer cell line LS180. It clarified that supernatant from only approximately 10(4) cells was needed to obtain signals or that only 2.5×10(4) exosomes were required for each microarray spot (~1 nL). Phenotyping was performed on plasma (1-10 µL) from 7 healthy donors, which were applied to the EV Array with a panel of antibodies against 21 different cellular surface antigens and cancer antigens. For each donor, there was considerable heterogeneity in the expression levels of individual markers. The protein profiles of the exosomes (defined as positive for CD9, CD63 and CD81) revealed that only the expression level of CD9 and CD81 was approximately equal in the 7 donors. This implies questioning the use of CD63 as a standard exosomal marker since the expression level of this tetraspanin was considerably lower.
Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors. (1998)

Several members of the Ly-49 receptor family inhibit NK cell-mediated lysis of targets expressing appropriate MHC class I molecules. Ly-49D and Ly-49H, two Ly-49 molecules that lack immunoreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic domains, associate with mouse DAP12, a molecule that possesses an immunoreceptor tyrosine-based activation motif (ITAM). Cotransfection of either Ly-49D or Ly-49H with DAP12 induces surface expression of both Ly-49 and DAP12. The Ly-49/DAP12 complex was coimmunoprecipitated from the transfected cells, demonstrating a physical association of DAP12 with Ly-49D or Ly-49H in the plasma membrane. Stimulation of transfectants with Abs recognizing either Ly-49D or Ly-49H results in cellular activation, as assessed by induction of tyrosine phosphorylation of multiple cellular substrates.