gebhart/patrepeval huggingface dataset:
Three-Dimensional Structures of Acidic and Basic Fibroblast Growth Factors (1991)

Members of the fibroblast growth factor (FGF) family of proteins stimulate the proliferation and differentiation of a variety of cell types through receptor-mediated pathways. The three-dimensional structures of two members of this family, bovine acidic FGF and human basic FGF, have been crystallographically determined. These structures contain 12 antiparallel beta strands organized into a folding pattern with approximate threefold internal symmetry. Topologically equivalent folds have been previously observed for soybean trypsin inhibitor and interleukins-1 beta and -1 alpha. The locations of sequences implicated in receptor and heparin binding by FGF are presented. These sites include beta-sheet strand 10, which is adjacent to the site of an extended sequence insertion in several oncogene proteins of the FGF family, and which shows sequence conservation among the FGF family and interleukin-1 beta.
Compression considerations in test access mechanism design (2005)

A low-cost test solution for core-based system-on-a-chip (SoC) comprises of test access mechanism (TAM) design – for facilitating access to the embedded cores – and the use of test data compression (TDC) methods – for reducing test resources. While most previous work has considered TAM design and TDC independently, this work analyzes the interrelations between the two, outlining that unless compression characteristics are integrated in the TAM design, test resource penalties may be incurred. This is due to the dependency of some TDC methods on test bus width and care bit density, both of which are related to test time, and hence to TAM design. Therefore, this paper analyzes the interactions between TDC and TAM, and highlights the compression characteristics which need to be considered in compression-driven TAM solutions for reducing test resource penalties. Furthermore, it also shows how an existing TAM design method can be enhanced toward a compression-driven solution.
A systematic genome-wide association analysis for inflammatory bowel diseases (IBD) (2007)

Two independent and hypothesis-free genome-wide association studies were carried out to find novel susceptibility genes for Crohn’s disease (CD), which is a chronic inflammatory disorder of the bowel. In a first sequence-based and “direct” scan, approximately 20,000 nonsynonymous SNPs, which result in a change in protein sequence, were typed. The second “indirect” map-based scan comprised about 100,000 evenly distributed SNPs.
Human keratinocyte migration on type IV collagen. Roles of heparin-binding site and alpha 2 beta 1 integrin. (1994)

Keratinocyte migration on type IV collagen involves the interaction of the alpha 2 beta 1 receptor with the Hep III region of the type IV collagen molecule.
A novel membrane antigen selectively expressed on terminally differentiated human B cells (1994)

A monoclonal antibody (MoAb) that defines a novel terminal B-cell-restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenström's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig-secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non-plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.
Reconstruction and Visualization of Fiber and Laminar Structure in the Normal Human Heart from Ex Vivo Diffusion Tensor Magnetic Resonance Imaging (DTMRI) Data (2007)

A visualization algorithm was developed to demonstrate the complex 3-dimensional orientation of the fibers and sheets in human myocardium.
Fundamentals of Operative Techniques in Neurosurgery (2010)

I. Operating Room Supplies, Instruments, and Equipment A. Neurological Institute Procedure Carts B. Neurological Institute Instrument Trays C. Supplies, Instruments, Equipment by Vendor II. Intra- and Extracranial Procedures A. Major Cranial Approaches B. Cranial Vascular Procedures C. Cranial Tumor Procedures D. Cranial Functional Procedures E. Cranial Trauma Procedures F. Cranial Infection Procedures G. Hydrocephalus Procedures H. Other Cranial Procedures III. Spinal Procedures A. Major Spinal Approaches B. Degenerative Disk Procedures C. Spinal Vascular Procedures D. Spinal Tumor Procedures E. Spinal Functional Procedures F. Spinal Trauma Procedures G. Spinal Infection Procedures H. Other Spinal Procedures I. Spinal Fusion Instrumentation IV. Pediatric Procedures A. Pediatric Vascular Procedures B. Pediatric Developmental Procedures C. Pediatric Spinal Procedures D. Pediatric Cranial Synostosis Procedures E. Pediatric Functional/Epilepsy Procedures F. Pediatric Trauma Procedures G. Other Pediatric Procedures V. Endovascular Procedures VI. Radiosurgical Procedures VII. Peripheral Nerve Procedures VIII. Minor Procedures
Orally Active and Potent Inhibitors of γ-Aminobutyric Acid Uptake (1985)

3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].
Molecular principles of hair follicle induction and morphogenesis (2005)

Hair follicle (HF) development is the result of neuroectodermal-mesodermal interactions, and can be divided into morphologically distinguishable stages (induction, organogenesis and cytodifferentiation). The spacing, polarity and differentiation patterns of HFs are driven by interacting, self-assembling gradients of inhibitors and activators, which are established jointly by the skin epithelium and mesenchyme. For HF development to occur, the dominant-negative influence of inhibitors of the HF differentiation pathway must be locally counteracted by specific antagonists and/or overriden by stimulators of hair placode formation. Once a mesenchymal condensate of inductive fibroblasts has formed, it takes over control of most subsequent steps of HF organogenesis and of epithelial stem cell differentiation into distinct lineages. In this review we introduce the morphological characteristics, major underlying principles and molecular key players that control HF development. The focus is on recent insights into the molecular interactions leading to hair follicle induction, and we close with synthesizing a corresponding working hypothesis.
Self‐Healing Supramolecular Block Copolymers (2012)

Polymer, heal thyself! Supramolecular ABA triblock copolymers formed by dimerization of 2-ureido-4-pyrimidinone (UPy) end-functionalized polystyrene-b-poly(n-butyl acrylate) (PS-b-PBA) AB diblock copolymers have been synthesized, resulting in a self-healing material that combines the advantageous mechanical properties of thermoplastic elastomers and the dynamic self-healing features of supramolecular materials.
Decadal Survey White Paper: Probing Stellar Dynamics in Galactic Nuclei (2009)

Electromagnetic observations over the last 15 years have yielded a growing appreciation for the importance of supermassive black holes (SMBH) to the evolution of galaxies, and for the intricacies of dynamical interactions in our own Galactic center. Here we show that future low-frequency gravitational wave observations, alone or in combination with electromagnetic data, will open up unique windows to these processes. In particular, gravitational wave detections in the 10 −5 − 10 −1 Hz range will yield SMBH masses and spins to unprecedented precision and will provide clues to the properties of the otherwise undetectable stellar remnants expected to populate the centers of galaxies. Such observations are therefore keys to understanding the interplay between SMBHs and their environments.
Novel polyhydroxylated steroidal saponins from Allium giganteum. (1991)

From the bulbs of Allium giganteum, three new steroidal saponins, (25R)-3-O-acetyl-5α-spirostan-2α, 3β, 5α, 6β-tetraol 2-O-β-D-glucopyranoside (2), (25R)-5α-spirostan-2α, 3β, 5α, 6β-tetraol 2-O-β-D-glucopyranoside (3) and (25R)-3-O-benzoyl-5α-spirostan-2α, 3β, 5α, 6β-tetraol 2-O-β-D-glucopyranoside (4), have been isolated. The new saponins are unique in structure having the sugar moiety at the C-2 hydroxyl position on the steroidal skeleton.
Emx1 is a Marker for Pyramidal Neurons of the Cerebral Cortex (2001)

The homeobox-containing gene, Emx1, a mouse homologue of Drosophila empty spiracles, is specifically expressed in the developing telencephalic cortex. It has been reported that Emx1 transcripts and the protein product are localized in most cells of the cerebral cortex during the process of proliferation, migration, differentiation and maturation. We provide evidence here, based on a multitude of experimental approaches in developing rats, in support of the hypothesis that the expression of this gene is restricted to pyramidal neurons. Specifically, we found that, similar to pyramidal neurons, cells expressing Emx1 are distributed in all cortical layers, except layer I. Using in situ hybridization and immunocytochemistry at the light and electron microscope levels, we have shown that the density, distribution, soma shape and ultrastructural features of these cells were identical to those of pyramidal neurons. Double-labelling experiments confirmed that the vast majority of Emx1-expressing cells also contained glutamate, a marker of pyramidal neurons. We also found that this gene is expressed by most glutamate-containing neurons in dissociated cortical cell cultures and the vast majority of cells in radially arranged clones of pyramidal cells in the cortices of chimeric mice. Thus, the homeobox gene Emx1 can be reliably used as a marker of the pyramidal cell lineage.
Growth of large periodic arrays of carbon nanotubes (2003)

Large periodic arrays of carbon nanotubes have been grown by plasma-enhanced hot filament chemical vapor deposition on periodic arrays of nickel dots that were prepared by polystyrene nanosphere lithography. A single layer of self-assembled polystyrene spheres was first uniformly deposited on a silicon wafer as a mask, and then electron beam vaporization was used to deposit a nickel layer through the mask. The size of and spacing between the nickel dots are tunable by varying the diameter of the polystyrene spheres, which consequently determines the diameter and site density of carbon nanotubes. The technique can be scaled up at much lower cost than electron beam lithography.
Glyphosate-Resistant Italian Ryegrass (Lolium multiflorum) in California: Distribution, Response to Glyphosate, and Molecular Evidence for an Altered Target Enzyme (2008)

Selection by herbicides has resulted in widespread evolution of herbicide resistance in agricultural weeds. In California, resistance to glyphosate was first confirmed in rigid ryegrass in 1998. Objectives of this study were to determine the current distribution and level of glyphosate resistance in Italian ryegrass, and to assess whether resistance could be due to an altered target site. Seeds were sampled from 118 populations and seedlings were treated with glyphosate at 866 g ae ha −1 . Percentage of survivors ranged from 5 to 95% in 54 populations. All plants from 64 populations died. One susceptible (S) population, four putatively resistant (R) populations, and one S accession from Oregon were used for pot dose–response experiments, shikimic acid analyses, and DNA sequencing. Seedlings were treated with glyphosate at eight rates, ranging from 108 to 13,856 g ae ha −1 . Shoot biomass was evaluated 3 wk after treatment and fit to a log-logistic regression equation. On the basis of GR 50 (herbicide rate required to reduce growth by 50%) values, seedlings from putatively R populations were roughly two to 15 times more resistant to glyphosate than S plants. Shikimic acid accumulation was similar in all plants before glyphosate treatment, but at 4 and 7 DAT, S plants from California and Oregon accumulated approximately two and three times more shikimic acid, respectively, than R plants. Sequencing of a cDNA fragment of the EPSPS coding region revealed two different codons, both of which encode proline at amino acid position 106 in S individuals. In contrast, all R plants sequenced exhibited missense mutations at site 106. Plants from one population revealed a mutation resulting in a proline to serine substitution. Plants from three R populations exhibited a mutation corresponding to replacement of proline with alanine. Our results indicate that glyphosate resistance is widespread in Italian ryegrass populations of California, and that resistance is likely due to an altered target enzyme.
The art and practical wisdom of student affairs leadership (2002)

Abstract The author argues that practical wisdom is the highest achievement of professional practice and examines how practical wisdom is gained and nurtured in professional life.
Lead(II) Complex Formation with l-Cysteine in Aqueous Solution (2015)

The lead(II) complexes formed with the multidentate chelator l-cysteine (H2Cys) in an alkaline aqueous solution were studied using 207Pb, 13C, and 1H NMR, Pb LIII-edge X-ray absorption, and UV–vis spectroscopic techniques, complemented by electrospray ion mass spectrometry (ESI-MS). The H2Cys/PbII mole ratios were varied from 2.1 to 10.0 for two sets of solutions with CPbII = 0.01 and 0.1 M, respectively, prepared at pH values (9.1–10.4) for which precipitates of lead(II) cysteine dissolved. At low H2Cys/PbII mole ratios (2.1–3.0), a mixture of the dithiolate [Pb(S,N-Cys)2]2– and [Pb(S,N,O-Cys)(S-HCys)]− complexes with average Pb–(N/O) and Pb–S distances of 2.42 ± 0.04 and 2.64 ± 0.04 Å, respectively, was found to dominate. At high concentration of free cysteinate (>0.7 M), a significant amount converts to the trithiolate [Pb(S,N-Cys)(S-HCys)2]2–, including a minor amount of a PbS3-coordinated [Pb(S-HCys)3]− complex. The coordination mode was evaluated by fitting linear combinations of EXAFS oscillations to the experimental spectra and by examining the 207Pb NMR signals in the chemical shift range δPb = 2006–2507 ppm, which became increasingly deshielded with increasing free cysteinate concentration. One-pulse magic-angle-spinning (MAS) 207Pb NMR spectra of crystalline Pb(aet)2 (Haet = 2-aminoethanethiol or cysteamine) with PbS2N2 coordination were measured for comparison (δiso = 2105 ppm). The UV–vis spectra displayed absorption maxima at 298–300 nm (S– → PbII charge transfer) for the dithiolate PbS2N(N/O) species; with increasing ligand excess, a shoulder appeared at ∼330 nm for the trithiolate PbS3N and PbS3 (minor) complexes. The results provide spectroscopic fingerprints for structural models for lead(II) coordination modes to proteins and enzymes.
Basic Concepts in Population Modeling, Simulation, and Model‐Based Drug Development (2012)

Modeling is an important tool in drug development; population modeling is a complex process requiring robust underlying procedures for ensuring clean data, appropriate computing platforms, adequate resources, and effective communication. Although requiring an investment in resources, it can save time and money by providing a platform for integrating all information gathered on new therapeutic agents. This article provides a brief overview of aspects of modeling and simulation as applied to many areas in drug development.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e6; doi:10.1038/psp.2012.4; advance online publication 26 September 2012.
Effect of Protein Binding on the Pharmacological Activity of Highly Bound Antibiotics (2008)

During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma protein binding values are applied in the analysis. The aim of this study was to evaluate this approach by experimentally measuring free, unbound concentrations for antibiotics with reportedly high protein binding and their corresponding antimicrobial activities in media containing commonly used protein supplements. Free, unbound ceftriaxone and ertapenem concentrations were determined in bacterial growth medium with and without bovine/human serum albumin, as well as adult bovine serum and human plasma using in vitro microdialysis. The corresponding antimicrobial activity was determined in MIC and time-kill curve experiments using Escherichia coli ATCC 25922 and Streptococcus pneumoniae ATCC 6303 as test strains. A semimechanistic maximum effect model was simultaneously fitted to the data and respective EC(50) (concentration at half-maximum effect) values compared. Protein binding differed significantly for ceftriaxone (P < 0.05) between human plasma (76.8 +/- 11.0%) and commercially available bovine (20.2 +/- 8.3%) or human serum albumin (56.9 +/- 16.6%). Similar results were obtained for ertapenem (human plasma, 73.8 +/- 11.6%; bovine serum albumin, 12.4 +/- 4.8%; human serum albumin, 17.8 +/- 11.5%). The MICs and EC(50)s of both strains were significantly increased (P < 0.05) for ceftriaxone when comparing human and bovine serum albumin, whereas the EC(50)s were not significantly different for ertapenem. Free, unbound antibiotic concentrations differed substantially between plasma and protein supplements and correlated well with antimicrobial efficacy. Therefore, free, active concentrations should be measured in the test system instead of correcting for literature protein binding values.
Controlled Grafting of Well-Defined Epoxide Polymers on Hydrogen-Terminated Silicon Substrates by Surface-Initiated ATRP at Ambient Temperature (2004)

Controlled grafting of well-defined epoxide polymer brushes on the hydrogen-terminated Si(100) substrates (Si−H substrates) was carried out via the surface-initiated atom-transfer radical polymerization (ATRP) at room temperature. Thus, glycidyl methacrylate (GMA) polymer brushes were prepared by ATRP from the α-bromoester functionalized Si−H surface. Kinetic studies revealed a linear increase in GMA polymer (PGMA) film thickness with reaction time, indicating that chain growth from the surface was a controlled “living” process. The graft polymerization proceeded more rapidly in the dimethylformamide/water (DMF/H2O) mixed solvent medium than in DMF, leading to much thicker PGMA growth on the silicon surface in the former medium. The chemical composition of the GMA graft-polymerized silicon (Si-g-PGMA) surfaces were characterized by X-ray photoelectron spectroscopy (XPS). The fact that the epoxide functional groups of the grafted PGMA were preserved quantitatively was revealed in the reaction with ethylenediamine. The “living” character of the PGMA chain end was further ascertained by the subsequent growth of a poly(pentafluorostyrene) (PFS) block from the Si-g-PGMA surface, using the PGMA brushes as the macroinitiators.
Erwinia chrysanthemi l-asparaginase: epitope mapping and production of antigenically modified enzymes (1994)

This study shows that the antigenicity of Erwinia chrysanthemi L-asparaginase can be reduced by site-directed mutagenesis. Ten B-cell epitopes of the enzyme were identified using synthetic hexapeptides and polyclonal antisera from rabbits and mice. The region 282GIVPPDEELP292 near the C-terminus was an immunodominant epitope. Binding of two hexapeptides (283IVPPDE288 and 287DEELPG292) to the antibodies was dependent on Pro285, and Pro286, since their replacement by almost any other amino acid resulted in reduced binding. The other residues were less important for binding the antibodies, as binding was relatively unaffected by amino acid substitutions. Three site-directed mutant enzymes, P285T (proline-285-->threonine etc.), P286Q and E288A, were expressed in Escherichia coli. The purified enzymes had subunit M(r) values of 35,000. The pI values of P285T, P286Q and the wild-type enzymes were 8.6, and that for the mutant E288A was 9.2. The kcat. and Km values for the mutants P286Q and E288A with L-asparagine and L-glutamine were comparable with those of the wild-type enzyme. The Km values for the mutant P285T with both substrates was similar to that of the wild-type enzyme, whereas the kcat. was reduced by 2-fold with L-asparagine and by 4-fold with L-glutamine. The change proline-->threonine reduced the antigenicity of the enzyme by 8-fold, as shown in sandwich e.l.i.s.a.s. using monoclonal antibodies raised against the wild-type enzyme.
Ablation of Kv3.1 and Kv3.3 Potassium Channels Disrupts Thalamocortical Oscillations In Vitro and In Vivo (2008)

The genes Kcnc1 and Kcnc3 encode the subunits for the fast-activating/fast-deactivating, voltage-gated potassium channels Kv3.1 and Kv3.3, which are expressed in several brain regions known to be involved in the regulation of the sleep-wake cycle. When these genes are genetically eliminated, Kv3.1/Kv3.3-deficient mice display severe sleep loss as a result of unstable slow-wave sleep. Within the thalamocortical circuitry, Kv3.1 and Kv3.3 subunits are highly expressed in the thalamic reticular nucleus (TRN), which is thought to act as a pacemaker at sleep onset and to be involved in slow oscillatory activity (spindle waves) during slow-wave sleep. We showed that in cortical electroencephalographic recordings of freely moving Kv3.1/Kv3.3-deficient mice, spectral power is reduced up to 70% at frequencies <15 Hz. In addition, the number of sleep spindles in vivo as well as rhythmic rebound firing of TRN neurons in vitro is diminished in mutant mice. Kv3.1/Kv3.3-deficient TRN neurons studied in vitro show approximately 60% increase in action potential duration and a reduction in high-frequency firing after depolarizing current injections and during rebound burst firing. The results support the hypothesis that altered electrophysiological properties of TRN neurons contribute to the reduced EEG power at slow frequencies in the thalamocortical network of Kv3-deficient mice.