gebhart/patrepeval huggingface dataset:
Effect of Adsorption of Succinic Acid on the Formation of Amorphous Calcium Phosphate (1994)

Adsorption of dissolved succinic acid on the formation of ACP and its stability were investigated in the synthetic process of ACP by the reaction of CaCl2-(NH4)2 HPO4-C4H6O4-NH4OH. The crystallization of ACP to HAp and amount of succinic acid adsorbed were affected by some conditions such as initial pH, temperature, aging time and concentration of succinic acid in the mother liquor. The largest amount of succinic acid was adsorbed to ACP when the ACP was produced at 0°C, initial pH 10 and concentration of succinic acid 6.0 mass% and aged at 25°C for 3h. From the result of infrared spectra of the ACP which adsorbed succinic acid, two peaks due to carboxylic acid were newly found at 1400cm-1 and 1550cm-1. These peaks were not found from the result for a mixture of ACP and succinic acid. The adsorbed succinic acid was decomposed at about 480°C and ACP was crystallized to Ca3(PO4)2 at above 600°C by heating.
Identification of Components of RNAi Pathways Using the Tandem Affinity Purification Method<I> (2005)

RNA interference (RNAi) is rapidly becoming a standard laboratory technique for understanding and regulating the function of specific genes in evolutionarily diverse organisms, including plants, Caenorhabditis elegans, Drosophila, and mammalian cells (1–10). RNAi is initiated by the conversion of doublestranded RNA (dsRNA) into 21- to 23-nucleotide (nt) fragments of dsRNA by Dicer enzymes. These short, interfering RNAs, or siRNAs as they are known, are incorporated into an RNAi effector complex, the RNA-induced silencing complex (RISC), which uses them as guides to target and destroy complementary messenger RNA (mRNA). Recent findings point to a tight connection between microRNA (miRNA) and RNAi molecular machineries. Recent study also has led to the unmasking of a widespread biological regulatory mechanism involving miRNAs (11–17), and there is a wide agreement that the core RNAi machinery carries out numerous cellular functions by an endogenous pathway important for normal development in many organisms, including gene regulation, virus resistance, and chromatin remodeling (1–17). Although some components of the RNAi cellular machinery have been identified, the overall picture is far from clear. We describe the tandem affinity purification (TAP) method (18–20) to isolate protein components of RISC in cultured Drosophila Schneider-2 (S2) cells. This purification method has allowed us to identify several RISC components, including Argonaute 2 (AGO2), the Drosophila homolog of fragile X mental retardation protein (dFMR1), and a DEAD-box RNA helicase Dmp68 (21,22). Identification of components of RNAi/miRNA pathways by the TAP method eliminates the need for large-scale sample preparation and overcomes, for example, the potential hazards associated with the use of a radioisotope, thereby placing the method within the scope of the average laboratory.
Meta Learning Shared Hierarchies (2017)

We develop a metalearning approach for learning hierarchically structured policies, improving sample efficiency on unseen tasks through the use of shared primitives---policies that are executed for large numbers of timesteps. Specifically, a set of primitives are shared within a distribution of tasks, and are switched between by task-specific policies. We provide a concrete metric for measuring the strength of such hierarchies, leading to an optimization problem for quickly reaching high reward on unseen tasks. We then present an algorithm to solve this problem end-to-end through the use of any off-the-shelf reinforcement learning method, by repeatedly sampling new tasks and resetting task-specific policies. We successfully discover meaningful motor primitives for the directional movement of four-legged robots, solely by interacting with distributions of mazes. We also demonstrate the transferability of primitives to solve long-timescale sparse-reward obstacle courses, and we enable 3D humanoid robots to robustly walk and crawl with the same policy.
Structural and Functional Implications of the Intron/Exon Organization of the Human Endothelial Cell Protein C/Activated Protein C Receptor (EPCR) Gene: Comparison With the Structure of CD1/Major Histocompatibility Complex 1 and 2 Domains (1999)

The endothelial cell protein C/activated protein C receptor (EPCR) is located primarily on the surface of the large vessels of the vasculature. In vitro studies suggest that it is involved in the protein C anticoagulant pathway. We report the organization and nucleotide sequence of the human EPCR gene. It spans approximately 6 kbp of genomic DNA, with a transcription initiation point 79 bp upstream of the translation initiation (Met) codon in close proximity to a TATA box and other promoter element consensus sequences. The human EPCR gene has been localized to 20q11.2 and consists of four exons interrupted by three introns, all of which obey the GT-AG rule. Exon I encodes the 5' untranslated region and the signal peptide, and exon IV encodes the transmembrane domain, the cytoplasmic tail, and the 3' untranslated region. Exons II and III encode most of the extracellular region of the EPCR. These exons have been found to correspond to those encoding the alpha1 and alpha2 domains of the CD1/major histocompatibility complex (MHC) class I superfamily. Flanking and intervening introns are of the same phase (phase I) and the position of the intervening intron is identically located. Secondary structure prediction for the amino acid sequence of exons II and III corresponds well with the actual secondary structure elements determined for the alpha1 and alpha2 domains of HLA-A2 and murine CD1.1 from crystal structures. These findings suggest that the EPCR folds with a beta-sheet platform supporting two alpha-helical regions collectively forming a potential binding pocket for protein C/activated protein C.
A 2.5 MHz 2D array with Z-axis electrically conductive backing (1997)

The design, fabrication and initial testing of a prototype fully /spl lambda//2 sampled, 2500 element 2D phased array is presented. The array utilizes a unique Z-axis electrical conductivity backing layer to provide both acoustic attenuation and electrical interconnect for the signal channels. The electrical interconnect is designed to be in the acoustic shadow of the transducer elements so as to minimize the foot print of the array. A modular, demountable Pad Grid Array interconnect is used to connect to the backing of the array. Results are presented for measurements of the single element properties of electrical impedance, pulse echo waveform and spectrum, directivity, and cross talk.
Metoclopramide Treatment of Tardive Dyskinesia (1981)

Five patients with tardive dyskinesia (average age, 64 years) were treated with a central dopamine blocking agent, metoclopramide hydrochloride. The duration of symptoms ranged from four to 30 months. A pretreatment disability score was graded (0 to 4) for buccolingual, extremity, and truncal movements and for duration of tongue protrusion. A 59% improvement was achieved in total disability scores. Tongue protrusion demonstrated the most noticeable improvement. The average daily dosage ranged from a minimum of 20 mg to a maximum of 80 mg given in divided doses. Duration of follow-up ranged from three to eight months. Preliminary data suggest that metoclopramide may be effective in the treatment of tardive dyskinesia.
7-Aminopyrazolo[1,5-a]pyrimidines as Potent Multitargeted Receptor Tyrosine Kinase Inhibitors (2008)

7-Aminopyrazolo[1,5- a]pyrimidine urea receptor tyrosine kinase inhibitors have been discovered. Investigation of structure-activity relationships of the pyrazolo[1,5- a]pyrimidine nucleus led to a series of 6-(4- N, N'-diphenyl)ureas that potently inhibited a panel of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases. Several of these compounds, such as 34a, are potent inhibitors of kinase insert domain-containing receptor tyrosine kinase (KDR) both enzymatically (<10 nM) and cellularly (<10 nM). In addition, compound 34a possesses a favorable pharmacokinetic profile and demonstrates efficacy in the estradiol-induced murine uterine edema (UE) model (ED 50 = 1.4 mg/kg).
Reduced level of secretion and absence of subunit combination for the fibroin synthesized by a mutant silkworm, Nd(2). (1984)

Fibroin is normally composed of one H chain (350 kd) and one L chain (25 kd) which are connected by disulfide bond(s). However, the small amount of fibroin secreted into the lumen of the posterior silk gland of the Nd(2) (naked pupa) mutant does not contain L chain, although L chain mRNA is present and L chain is synthesized in the posterior silk gland cells of the mutant. In a hybrid silkworm, Nd(2)/Tamanashikasuri, where Tamanashikasuri is a normal producer of fibroin, L chain from the two alleles are distinguishable electrophoretically. It is demonstrated using this system that the L chain from the Nd(2) allele can combine normally with the H chain from Tamanashikasuri and the H-L complex is secreted normally. In another hybrid system, Nd(2)/J-131, where J-131 is a normal producer of fibroin, fibroin derived from the two alleles are distinguishable due to the different electrophoretic mobility of H chain. The fibroin derived from the J-131 allele is composed of H chain and L chain, while the fibroin derived from the Nd(2) allele is devoid of L chain, and its secretion is greatly reduced. We present evidence suggesting that the H chain derived from the Nd(2) allele is structurally abnormal and discuss how the H-L subunit structure is advantageous in the secretion of fibroin.
Identification of Compounds with Nanomolar Binding Affinity for Checkpoint Kinase-1 Using Knowledge-Based Virtual Screening (2004)

A virtual screen of a subsection of the AstraZeneca compound collection was performed for checkpoint kinase-1 (Chk-1 kinase) using a knowledge-based strategy. This involved initial filtering of the compound collection by application of generic physical properties followed by removal of compounds with undesirable chemical functionality. Subsequently, a 3-D pharmacophore screen for compounds with kinase binding motifs was applied. A database of approximately 200K compounds remained for docking into the active site of Chk-1 kinase, using the FlexX-Pharm program. For each compound that docked successfully into the binding site, up to 100 poses were saved. These poses were then postfiltered using a customized consensus scoring scheme for a kinase, followed by visual inspection of a selection of the docked compounds. This resulted in 103 compounds being ordered for testing in the project assay, and 36 of these (corresponding to four chemical classes) were found to inhibit the enzyme in a dose-response fashion with IC(50) values ranging from 110 nM to 68 microM.
Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing Data (2006)

The use of linezolid with medications that increase concentrations of serotonin in the central nervous system may result in serotonin toxicity. Prescribers must weigh risks and benefits of this combination. Patients and prescribers should be cognizant of signs and symptoms of serotonin toxicity and should initiate appropriate measures if such symptoms develop.
The Chemistry of Conducting Polythiophenes (1998)

Directing the structure and function of polythiophenes (PTs) can lead to remarkable enhancements in the electronic and photonic properties of the resultant materials, as discussed in this comprehensive review of the chemistry and synthesis of PTs. The Figure illustrates the use of heteroatom-functionalized PTs as chemical sensors: upon ion complexation PT conjugation is greatly reduced, leading to a sensory response.
Atomic View of a Toxic Amyloid Small Oligomer (2012)

Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein αB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: β-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the β-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.
Structural and Functional Changes in Proteins Induced by Free Radical‐mediated Oxidative Stress and Protective Action of the Antioxidants N‐tert‐Butyl‐α‐phenylnitrone and Vitamin Ea (1998)

The free radical theory of aging proposes that reactive oxygen species (ROS) cause oxidative damage over the lifetime of the subject. It is the cumulative and potentially increasing amount of accumulated damage that accounts for the dysfunctions and pathologies seen in normal aging. We have previously demonstrated that both normal rodent brain aging and normal human brain aging are associated with an increase in oxidative modification of proteins and in changes in plasma membrane lipids. Several lines of investigation indicate that one of the likely sources of ROS is the mitochondria. There is an increase in oxidative damage to the mitochondrial genome in aging and a decreased expression of mitochondrial mRNA in aging. We have used a multidisciplinary approach to the characterization of the changes that occur in aging and in the modeling of brain aging, both in vitro and in vivo. Exposure of rodents to acute normobaric hyperoxia for up to 24 h results in oxidative modifications in cytosolic proteins and loss of activity for the oxidation-sensitive enzymes glutamine synthetase and creatine kinase. Cytoskeletal protein spin labeling also reveals synaptosomal membrane protein oxidation following hyperoxia. These changes are similar to the changes seen in senescent brains, compared to young adult controls. The antioxidant spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) was effective in preventing all of these changes. In a related study, we characterized the changes in brain protein spin labeling and cytosolic enzyme activity in a series of phenotypically selected senescence-accelerated mice (SAMP), compared to a resistant line (SAMR1) that was derived from the same original parents. In general, the SAM mice demonstrated greater oxidative changes in brain proteins. In a sequel study, a group of mice from the SAMP8-sensitive line were compared to the SAMR1-resistant mice following 14 days of daily PBN treatment at a dose of 30 mg/kg. PBN treatment resulted in an improvement in the cytoskeletal protein labeling toward that of the normal control line (SAMR1). The results of these and related studies indicate that the changes in brain function seen in several different studies may be related to the progressive oxidation of critical brain proteins and lipids. These components may be critical targets for the beneficial effects of gerontotherapeutics both in normal aging and in disease of aging.
Enhancement of In Vitro Capillary Tube Formation by Substrate Nanotopography (2007)

Endothelial progenitor cells are cultured on nanotopographic substrates with a line-grating geometry and respond to these substrates through aligned and elongated morphology, reduced proliferation, and increased migration relative to flat substrates. The cells also form supercellular band structures, which lead to enhanced capillary tube formation upon the addition of matrigel. These results suggest that substrate nanotopography can be used to create organized vascular structures in vitro. Image taken at 250 × magnification. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2008/c2487_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Serum protein binding and the role of increased alpha 1‐acid glycoprotein in moderately obese male subjects. (1984)

Serum protein and lipid concentrations as well as the serum protein binding of propranolol, diazepam and phenytoin were measured in normal weight and obese volunteers. Concentrations of alpha 1-acid glycoprotein (AAG) in the obese subjects were double that of the lean controls. Conversely, concentrations of high density lipoproteins (HDL) were decreased in the obese group. The serum binding of propranolol was increased in the obese subjects and correlated with serum AAG concentrations. Diazepam binding was slightly decreased in the obese as a result of lower serum albumin concentrations and elevated free fatty acids. The binding of phenytoin was comparable in all of the volunteers. These findings point out some of the complex pathophysiologic changes associated with obesity which may in turn influence drug disposition and hence drug therapy in the obese patient.
Apolipoprotein E Is Localized to the Cytoplasm of Human Cortical Neurons: A Light and Electron Microscopic Study (1994)

To clarify the localization of the glial protein apolipoprotein E (apoE) in human cortical neurons, we employed specific immunoelectron microscopy using a monoclonal antibody to human apoE in surgical specimens of temporal lobe. The specimens were rapidly fixed after excision from five patients undergoing surgery for medically intractable seizures, and postmortem material was also taken from one Alzheimer's disease patient for comparison. Strong apoE immunoreactivity was observed in many astrocytes filling the perinuclear cytoplasm and distal processes completely. Some cortical neurons were also apoE-immunoreactive. ApoE immunoreactivity of neurons was less intense than glial cells and was distributed in a punctate fashion confined to the region of the cell body and proximal dendrites, but not distal processes. These findings suggest that apoE, which is presumably synthesized and stored by astrocytes, may be taken up by cortical neurons in younger adult humans. The presence of apoE in some human neurons may allow apoE to affect neuronal metabolism. Isoform-specific interactions with microtubule-associated proteins, such as tau or MAP2C, could influence the rate of pathology in neurodegenerative diseases such as Alzheimer's disease.
Antibody Multispecificity Mediated by Conformational Diversity (2003)

A single antibody was shown to adopt different binding-site conformations and thereby bind unrelated antigens. Analysis by both x-ray crystallography and pre-steady-state kinetics revealed an equilibrium between different preexisting isomers, one of which possessed a promiscuous, low-affinity binding site for aromatic ligands, including the immunizing hapten. A subsequent induced-fit isomerization led to high-affinity complexes with a deep and narrow binding site. A protein antigen identified by repertoire selection made use of an unrelated antibody isomer with a wide, shallow binding site. Conformational diversity, whereby one sequence adopts multiple structures and multiple functions, can increase the effective size of the antibody repertoire but may also lead to autoimmunity and allergy.
High-performance spider webs: integrating biomechanics, ecology and behaviour (2010)

Spider silks exhibit remarkable properties, surpassing most natural and synthetic materials in both strength and toughness. Orb-web spider dragline silk is the focus of intense research by material scientists attempting to mimic these naturally produced fibres. However, biomechanical research on spider silks is often removed from the context of web ecology and spider foraging behaviour. Similarly, evolutionary and ecological research on spiders rarely considers the significance of silk properties. Here, we highlight the critical need to integrate biomechanical and ecological perspectives on spider silks to generate a better understanding of (i) how silk biomechanics and web architectures interacted to influence spider web evolution along different structural pathways, and (ii) how silks function in an ecological context, which may identify novel silk applications. An integrative, mechanistic approach to understanding silk and web function, as well as the selective pressures driving their evolution, will help uncover the potential impacts of environmental change and species invasions (of both spiders and prey) on spider success. Integrating these fields will also allow us to take advantage of the remarkable properties of spider silks, expanding the range of possible silk applications from single threads to two- and three-dimensional thread networks.
Controlled Drug Delivery (2000)

Advances in controlled release drug delivery systems have been largely based on advances in functional polymers. However, the future of controlled release dosage forms will likely be heavily dependent upon an increased understanding of protein chemistry and cell biology principles. As our understanding increases on how cells function in normal and disease states and what limits the actions of potential therapeutics, the possibility of designing delivery technologies into a therapeutic offers tremendous potential for clinical interventions with maximal efficacy and minimal side effects. Genes and gene products and peptide and protein drugs will be the drugs of choice in the future due to their exquisitely specific bioactivities. Delivery approaches for these classes of therapeutics will likely come in many forms, some of which may be radically new. As in the current millennium, the success of delivery approaches in the next millenium will require interdisciplinary approaches.
Vaccine Protection of Rhesus Macaques Against Simian Immunodeficiency Virus Infection (1990)

Rhesus macaques (Macaca mulatta) immunized with an inactivated whole SIVmac vaccine and muramyl dipeptide (MDP), incomplete Freund's adjuvant (IFA), or aqueous suspension were challenged intravenously with 0.1 TCID50 of cell-free SIVmac. Whereas virus was readily recovered from the peripheral blood lymphocytes of 10 of 10 nonvaccinated controls following this challenge dose, virus was not recovered from the three animals that received the vaccine with MDP nor from one of two animals that received the vaccine with IFA and one of three animals that received the aqueous vaccine. The animals that were protected against challenge were those that had detectable SIV antibody response to the envelop, both the outer glycoprotein (gp120) and the truncated transmembrane glycoprotein (gp31). Protected monkeys tended to have higher titers of syncytial inhibition antibody prior to challenge. An anamnestic response after challenge was observed only in the vaccinated monkeys that became infected. Vaccinated animals that became challenge-infected tended to live longer than infected controls. These results confirm those at two other primate centers and indicate that killed whole SIV vaccines can protect against low challenge doses of SIV and prevent early death in those monkeys that do become infected. The mechanism of this protection remains undetermined. This finding adds optimism to the possibility of an eventual AIDS vaccine.