gebhart/patrepeval huggingface dataset:
Protein Kinase and Phosphatase Inhibitors: Applications in Neuroscience (2003)

Extracellular signals, including neurotransmitters, hormones, cytokines, and growth factors, produce many of their physiological effects by regulating the state of phosphorylation of specific proteins in target cells (Walaas and Greengard, 1991). Inhibitors of protein kinases and protein phosphatases are useful tools in evaluating the physiological roles of protein phosphorylation signaling mechanisms, and may ultimately find therapeutic applications. Available inhibitors include natural and synthetic compounds, peptides, and proteins (MacKintosh and MacKintosh, 1994). Natural inhibitors include endogenous protein inhibitors of protein kinases (e.g., the protein kinase inhibitor [PKI] of cyclic AMP [cAMP]-dependent protein kinase [PKA]) and protein phosphatases (e.g., inhibitor-1, inhibitor-2, and DARPP-32), as well as toxins produced by bacteria, fungi, plants, dinoflagellates, and insects. Synthetic inhibitors include peptide analogs derived from intramolecular pseudosubstrate inhibitory domains of protein kinases and phosphatases, derivatives of natural toxins, and analogs and inhibitors of endogenous activators (e.g., cAMP analogs) or substrates (e.g., ATP analogs). This chapter will review the most widely available inhibitors with demonstrated utility, including their basic properties and applications relevant to their use in neuroscience research.
Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. (1987)

The murine IgG3 monoclonal antibody (MoAb) 3F8, specific for the ganglioside GD2, activates human complement, is active in antibody-dependent cell-mediated cytotoxicity (ADCC), and can target specifically to human neuroblastoma in patients with metastatic disease. In a phase I study, 3F8 was administered intravenously (IV) to 17 patients with metastatic GD2 positive neuroblastoma or malignant melanoma at doses of 5, 20, 50, and 100 mg/m2. Serum 3F8 levels achieved were proportional to the dose of 3F8 infused. However, serum antimouse antibody levels did not increase with the amount of 3F8 administered. Toxicities included pain, hypertension, urticaria, and complement depletion. All acute side effects were controllable with symptomatic therapy. No long-term side effects were detected in patients observed for more than 14 months. None of the 17 patients received any antitumor therapy postantibody treatment. Antitumor responses occurred in seven of 17 patients. These ranged from complete clinical remissions to mixed responses. The murine monoclonal antibody (MoAb) 3F8 has clinical utility for the diagnosis and therapy of neuroblastoma and melanoma.
Generalizing Skills with Semi-Supervised Reinforcement Learning (2016)

Deep reinforcement learning (RL) can acquire complex behaviors from low-level inputs, such as images. However, real-world applications of such methods require generalizing to the vast variability of the real world. Deep networks are known to achieve remarkable generalization when provided with massive amounts of labeled data, but can we provide this breadth of experience to an RL agent, such as a robot? The robot might continuously learn as it explores the world around it, even while deployed. However, this learning requires access to a reward function, which is often hard to measure in real-world domains, where the reward could depend on, for example, unknown positions of objects or the emotional state of the user. Conversely, it is often quite practical to provide the agent with reward functions in a limited set of situations, such as when a human supervisor is present or in a controlled setting. Can we make use of this limited supervision, and still benefit from the breadth of experience an agent might collect on its own? In this paper, we formalize this problem as semisupervised reinforcement learning, where the reward function can only be evaluated in a set of "labeled" MDPs, and the agent must generalize its behavior to the wide range of states it might encounter in a set of "unlabeled" MDPs, by using experience from both settings. Our proposed method infers the task objective in the unlabeled MDPs through an algorithm that resembles inverse RL, using the agent's own prior experience in the labeled MDPs as a kind of demonstration of optimal behavior. We evaluate our method on challenging tasks that require control directly from images, and show that our approach can improve the generalization of a learned deep neural network policy by using experience for which no reward function is available. We also show that our method outperforms direct supervised learning of the reward.
Sleep and Apnea in the Elderly: Reliability and Validity of 24-Hour Recordings in the Home (1991)

Two studies investigated the reliability and validity of measures of sleep and apnea using the home sleep monitoring system (HMS), which requires no instrumentation of the subject. From a pressure-sensitive pad on the subject's bed, signals from respiration and motility are recorded. These are scored for sleep and the occurrence of apneas, and the following measures are obtained: time in bed, total sleep time, number of awakenings from sleep, waking after sleep onset, sleep efficiency, and number of apneas. Overnight recordings of 14 adults were made concurrently with polysomnographic recordings in the New Haven Sleep Disorders Center. Significant agreement was found for each sleep measure and the apnea index. Four weekly 24-h recordings were made of eight elderly women, aged 62 to 90, in the home. There were significant individual differences and measurement reliability for each sleep measure and number of apneas. Some of the elderly showed highly episodic sleep patterns; and three of them showed high and variable apneas over the four weeks. These studies indicate the potential of the HMS for characterizing sleep in the elderly from nonintrusive, naturalistic observations in the home.
Trichoderma reesei cellobiohydrolases: why so efficient on crystalline cellulose? (1998)

28 Burmeister, W. P., Cottaz, S., Driguez, H., Palmieri, S. and Henrissat, B. (1997) Structure 5, 663-675 29 Damude, H. G., Withers, S. G., Kilburn, D. G., Miller, R. C. Jr. and Warren, R. A. J. (1995) Biochemistry 34, 2220-2224 30 Tenvisscha van Schletinga, A. C., Armand, S., Kalk, K. H., Isogai, A., Henrissat, B. and Dijkstra, B. W. (1995) Biochemistry 34, 15619-15623 31 Tews, I., Perrakis, A., Oppenheim, A., Dauter, Z., Wilson, K. S. and Vorgias, C. E. (1996) Nat. Struct. Biol. 3, 638-648
Transcranial magnetic stimulation in patients with epilepsy (1991)

We studied the effects of transcranial magnetic stimulation (TMS) applied in trains of 8- to 25-Hz stimuli on electroencephalographic epileptiform activity on eight patients being evaluated for epilepsy surgery. We performed the stimulation with a round water-cooled stimulation coil held flat on the scalp and centered over different positions of the International 10-20 System. We were unable to trigger seizures or induce epileptiform discharges arising from the epileptic focus in any of the eight patients with any of the stimulation protocols. However, we induced a partial motor seizure from the contralateral hemisphere to the exclusive temporal focus in the only patient stimulated with 100% maximal intensity. Precautions have to be taken when applying rapid TMS to patients because of the risk of seizure induction. Our results do not support the view that TMS specifically activates the epileptic foci.
6-Methylangelicins: a new series of potential photochemotherapeutic agents for the treatment of psoriasis (1984)

The possible presence of methylpsoralens as undesired inquinants in synthetic methylangelicins has been avoided through a synthetic pathway starting from umbelliferones carrying a methyl group in the 6-position. The new 6-methylangelicins show a high affinity toward DNA, forming in the dark a molecular complex; the complexed angelicins under UV-A irradiation photobind effectively to the macromolecule, forming only monoadducts. The new compounds show an evident antiproliferative activity by inhibiting DNA synthesis on Ehrlich cells; great differences, however, can be seen between the various compounds. All the compounds are lacking of skin erythemogenic activity. Some of the new 6-methylangelicins, evaluated in terms of mutagenic activity, demonstrate to be less effective than 8-methoxypsoralen (8-MOP), used for a comparison. On the basis of antiproliferative activity, lack of skin phototoxicity, and low mutagenicity, two compounds have been chosen for clinical evaluation. The compounds tested on seven psoriatic patients by topical application and UV-A irradiation proved to be more effective than 8-MOP, used in the same conditions.
Thermal stability and spin-transfer switchings in MgO-based magnetic tunnel junctions with ferromagnetically and antiferromagnetically coupled synthetic free layers (2009)

We prepared MgO-based magnetic tunnel junctions having a CoFeB/Ru/CoFeB synthetic free layer in which magnetizations of the CoFeB layers were ferromagnetically coupled (F-coupled Sy) or antiferromagnetically coupled (AF-coupled Sy). We studied spin-transfer switchings to evaluate their thermal stability (Δ0=KV/kBT) and intrinsic switching current density (JC0). Although the free layers of two types showed nearly equal JC0, the Δ0 of F-coupled Sy was observed to be twice that of AF-coupled Sy. This difference is attributable to the shape magnetic anisotropy of the free-layer cells. Results show that F-coupled Sy is superior to AF-coupled Sy for memory applications.
Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. (1994)

We have used a cDNA probe from a cloned rat liver Na+/taurocholate cotransporting polypeptide (Ntcp) to screen a human liver cDNA library. A 1,599-bp cDNA clone that encodes a human Na+/taurocholate cotransporting polypeptide (NTCP) was isolated. The human NTCP consists of 349 amino acids (calculated molecular mass of 38 kD) and exhibits 77% amino acid homology with the rat Ntcp. In vitro translation experiments indicate that the protein is glycosylated and has a molecular weight similar to the rat Ntcp. Injection of in vitro transcribed cRNA into Xenopus laevis oocytes resulted in the expression of Na(+)-dependent taurocholate uptake. Saturation kinetics indicated that the human NTCP has a higher affinity for taurocholate (apparent Km = 6 microM) than the previously cloned rat protein (apparent Km = 25 microM). NTCP-mediated taurocholate uptake into oocytes was inhibited by all major bile acid derivatives (100 microM), bumetanide (500 microM), and bromosulphophthalein (100 microM). Southern blot analysis of genomic DNA from a panel of human/hamster somatic cell hybrids mapped the human NTCP gene to chromosome 14.
Cloning and sequencing of a gene encoding a novel extracellular neutral proteinase from Streptomyces sp. strain C5 and expression of the gene in Streptomyces lividans 1326 (1992)

The gene encoding a novel milk protein-hydrolyzing proteinase was cloned on a 6.56-kb SstI fragment from Streptomyces sp. strain C5 genomic DNA into Streptomyces lividans 1326 by using the plasmid vector pIJ702. The gene encoding the small neutral proteinase (snpA) was located within a 2.6-kb BamHI-SstI restriction fragment that was partially sequenced. The molecular mass of the deduced amino acid sequence of the mature protein was determined to be 15,740, which corresponds very closely with the relative molecular mass of the purified protein (15,500) determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of the purified neutral proteinase was determined, and the DNA encoding this sequence was found to be located within the sequenced DNA. The deduced amino acid sequence contains a conserved zinc binding site, although secondary ligand binding and active sites typical of thermolysinlike metalloproteinases are absent. The combination of its small size, deduced amino acid sequence, and substrate and inhibition profile indicate that snpA encodes a novel neutral proteinase.
Identification of Fungal rDNA Associated with Soil Suppressiveness Against Heterodera schachtii Using Oligonucleotide Fingerprinting (2003)

ABSTRACT To understand the nature of a soil with suppressiveness against Heterodera schachtii, an rDNA analysis was used to identify fungi associated with H. schachtii cysts obtained from soils possessing various levels of suppressiveness. Because H. schachtii cysts isolated from these suppressive soils can transfer this beneficial property to nonsuppressive soils, analysis of the microorganisms associated with the cysts should lead to the identification of the causal organisms. Five soil treatments, generated by mixing different amounts of suppressive and fumigation-induced nonsuppressive soils, were infested with second-stage juveniles of H. schachtii and cropped with mustard-greens. Fungi were identified through an rDNA analysis termed oligonucleotide fingerprinting of ribosomal RNA genes (OFRG). Cysts obtained from soil mixtures consisting of 10 and 100% suppressive soil predominantly contained fungal rDNA with high sequence identity to Dactylella oviparasitica. The dominant fungal rDNA in the cysts isolated from the soil mixtures composed of 0.1 and 1% suppressive soil had high sequence identity to Fusarium oxysporum. Polymerase chain reaction (PCR) amplifications performed with sequence-selective primers corroborated the treatment-specific distribution of rDNA clones obtained by the OFRG analysis. When these sequence-selective PCR primers were used to examine H. schachtii cysts from biocidal soil treatments that produced various levels of suppressiveness, only the D. oviparasitica-like rDNA was consistently identified in the highly suppressive soils.
Pulmonary Hypertension after Splenectomy? (1999)

Patients who have had splenectomy may be at increased risk for developing pulmonary hypertension.
The effect of human tissue factor pathway inhibitor-2 on the growth and metastasis of fibrosarcoma tumors in athymic mice (2003)

Human tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz inhibitor that inhibits the plasmin- and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor progression, invasion, and metastasis. To directly assess its role in tumor growth and metastasis in vivo, we stably transfected HT-1080 fibrosarcoma cells expressing either fully active wild-type human TFPI-2 (WT) or inactive R24Q TFPI-2 (QT) and examined their ability to form tumors and metastasize in athymic mice in comparison to mock-transfected cells (MT). MT and QT fibrosarcoma tumors grew 2 to 3 times larger than WT tumors. Tumor metastasis was confined to the lung and was observed in 75% of mice treated with either MT or QT cells, whereas only 42% of mice treated with WT cells developed lung metastases. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of each tumor group revealed 3- to 6-fold lower levels of murine vascular endothelial growth factor gene expression in WT tumors in relation to either MT or QT tumors. Comparative tumor gene expression analysis revealed that several human genes implicated in oncogenesis, invasion, metastasis, apoptosis, and angiogenesis had significantly altered levels of expression in WT tumors. Our collective data demonstrate that secretion of inhibitory TFPI-2 by a highly metastatic tumor cell markedly inhibits its growth and metastasis in vivo by regulating pericellular extracellular matrix (ECM) remodeling and angiogenesis.
High Resolution of Human Chromosomes (1976)

G-band prophase chromosomes from synchronized cells permit a high degree of resolution not previously attained in the study of chromosome structure and birth defects in man.
Incorporation of unnatural amino acid derivatives into a peptide bond via an oxime ester catalysed by papain or lipase (1996)

In the presence of an oxime in the reaction solution, papain and lipase P (Pseudomonas from Amano) catalysed the stereoselective transesterification of an N-protected amino acid or peptide ester to form an active (oxime) ester which in turn underwent peptide bond formation with several natural and unnatural amino acid derivatives (proline, N-methylglycine, N-methylalanine, α-methylphenylalanine).
Cyclosporine A toxicity and effect of the S-adenosylmethionine (1999)

We studied the simultaneous changes undergone by the main indicators of hepatotoxicity, nephrotoxicity and diabetogenicity in rats treated with cyclosporine A (CyA) for one, two, three and four weeks, using the dose of 10 and 20 mg/kg/day. The effects of the drug on the biliary excretion of several biliary compounds as well as on the bile flow fractions dependent and independent- of the biliary secretion of bile acids and glutathione were also studied. A further aim of this research was to evaluate the hepatoprotective effect of S-adenosylmethionine (SAMe) against the action of CyA. Our results show that CyA treatment alters hepatic, renal and pancreatic functions rapidly and simultaneously; the changes were slightly more intense with the higher dose but they did not become more pronounced when the treatment was prolonged for 4 weeks. The cholestatic effect of the drug is a multifactorial phenomena and develops accompanied by simultaneous decreases in the biliary secretion of bile acids, lipid, glutathione and proteins. SAMe plus CyA cotreatment antagonizes the main hepatotoxic effects of CyA in this species. This hepatoprotective effect of SAMe could be related to its regulatory function as regards membrane lipid composition and fluidity and to its key role in promoting the hepatic synthesis of thiol compounds.
Deletion of phenylalanine 508 causes attenuated phosphorylation‐dependent activation of CFTR chloride channels (2000)

In cell-attached patches stimulated with cAMP agonists, the single-channel open probability (Po) of the phenylalanine 508-deleted cystic fibrosis transmembrane conductance regulator (DeltaF508-CFTR) channel, the most common disease-associated mutation in cystic fibrosis, was abnormally low (a functional defect). To investigate the mechanism for the poor response of DeltaF508-CFTR to cAMP stimulation, we examined, in excised inside-out patches, protein kinase A (PKA)-dependent phosphorylation activation and ATP-dependent gating of wild-type (WT) and DeltaF508-CFTR channels expressed in NIH3T3 mouse fibroblasts. For WT-CFTR, the activation time course of CFTR channel current upon addition of PKA and ATP followed a sigmoidal function with time constants that decreased as [PKA] was increased. The curvilinear relationship between [PKA] and the apparent activation rate suggests an incremental phosphorylation-dependent activation of CFTR at multiple phosphorylation sites. The time course of PKA-dependent activation of DeltaF508-CFTR channel current also followed a sigmoidal function, but the rate of activation was at least 7-fold slower than that with WT channels. This result suggests that deletion of phenylalanine 508 causes attenuated PKA-dependent phosphorylation of the CFTR chloride channel. Once DeltaF508-CFTR channels were maximally activated with PKA, the mutant channel and WT channel had indistinguishable steady-state Po values, ATP dose-response relationships and single-channel kinetics, indicating that DeltaF508-CFTR is not defective in ATP-dependent gating. By measuring whole-cell current density, we compared the number of functional channels in WT- and DeltaF508-CFTR cell membrane. Our data showed that the estimated channel density for DeltaF508-CFTR was approximately 10-fold lower than that for WT-CFTR, but the cAMP-dependent whole-cell current density differed by approximately 200-fold. We thus conclude that the functional defect (a decrease in Po) of DeltaF508-CFTR is as important as the trafficking defect (a decrease in the number of functional channels in the plasma membrane) in cystic fibrosis pathogenesis.
The Existence of a Temperature-Driven Solid Solution for 0 < x < 1 in LixFePO4 (2006)

Abstract not Available.
Simultaneous nitrification and denitrification with electricity generation in dual‐cathode microbial fuel cells (2011)

Abstract BACKGROUND: Nitrogen removal using microbial fuel cells (MFCs) is of great interest owing to the potential benefits of bioenergy production. In this study, simultaneous nitrification and denitrification in dual‐cathode MFCs was investigated. RESULTS: The dual‐cathode MFCs investigated were capable of generating electricity and removing nitrogen, influenced by operating methods, nitrogen loading rates and external resistance. Depending on the ammonium concentration in the anode chamber, 84–97% of the ammonium nitrogen was removed via nitrification in the aerobic cathode. The removals of nitrate and total nitrogen were relatively low (∼50%) at the influent ammonium concentration of 80 mg NH 4 + ‐N L −1 , but were significantly improved to more than 90% at a lower ammonium input (40 and 20 mg NH 4 + ‐N L −1 ). When the electrode couples were electrically connected for different purposes, with high power output from the anode/aerobic cathode and high current generation from the anode/anoxic cathode, nitrogen removal was also improved. An investigation of aeration suggested that factors other than carbon supply, possibly inefficient reactor configuration, also limited the performance of the developed MFC. CONCLUSION: The experimental results demonstrated that the proposed pathway was feasible with effective nitrogen and organic removal. This study provided valuable information for the further development of a continuously operated dual‐cathode MFC system. Copyright © 2011 Society of Chemical Industry
Ink-jet fabrication of electronic components (2007)

Nanosized metallic particles dispersed in a polymeric matrix have been used conventionally as a paste or ink to print electrically active patterns on different substrates. The potential of ink-jet printing in this field is clearly important but the challenge to date has been how to achieve prints of low volume resistivity from the very low viscosity ink required for ink-jet printing. In this study, ink-jet printing techniques were used to directly deposit metallic conductive patterns to produce wiring boards, antennas, electrodes and so forth. In these methods, aqueous solutions of metal salt and reducing agent were ink-jet printed consecutively onto the substrate, where an immediate chemical reduction transformed the metal cations into very fine metallic particles. The best performing reducing agent for ink-jet metal deposition was found to be ascorbic acid at neutral pH. Using this chemistry, nanosized silver patterns, composed of particles in the size range 10–200 nm, were successfully formed using a standard office ink-jet thermal-head printer. Deposited layers of silver with high electrical conductance up to 1.89 × 105 S m−1 and sheet resistance up to 0.5 Ω/□ were printed whilst higher conductivities might be expected using more appropriate devices.
Possibility of Synthesizing an Organic Superconductor (1964)

London's idea that superconductivity might occur in organic macromolecules is examined in the light of the BCS theory of superconductivity. It is shown that the criterion for the occurrance of such a state can be met in certain organic polymers. A particular example is considered in detail. From a realistic estimation of the matrix elements and density of states in this polymer it is concluded that superconductivity should occur even at temperatures well above room temperature. The physical reason for this remarkable high transition temperature is discussed. It is shown further that the superconducting state of these polymers should be distinguished by certain unique chemical properties which could have considerable biological significance.