gebhart/patrepeval huggingface dataset:
Effects of deuterium anneal on MOSFETs with HfO2 gate dielectrics (2003)

The effects of high-temperature (600/spl deg/C) anneal in a dilute deuterium (N/sub 2/ : D/sub 2/= 96 : 4) atmosphere was first investigated and evaluated in comparison to high-temperature forming gas (N/sub 2/ : H/sub 2/= 96 : 4) anneal (600/spl deg/C) and nonanneal samples. The high-temperature deuterium anneal was as effective as the forming gas anneal in improving MOSCAP and MOSFET characteristics such as the C-V curve, drain current, subthreshold swing, and carrier mobility. These can be attributed to the improved interface quality by D/sub 2/ atoms. However, unlike the forming gas anneal, the deuterium anneal provided the hafnium oxide (HfO/sub 2/) gate dielectric MOSFET with better reliability characteristics such as threshold voltage (V/sub T/) stability under high voltage stress.
Bubbles: a unifying framework for low-level statistical properties of natural image sequences (2003)

Recently, different models of the statistical structure of natural images have been proposed. These models predict properties of biological visual systems and can be used as priors in Bayesian inference. The fundamental model is independent component analysis, which can be estimated by maximization of the sparsenesses of linear filter outputs. This leads to the emergence of principal simple cell properties. Alternatively, simple cell properties are obtained by maximizing the temporal coherence in natural image sequences. Taking account of the basic dependencies of linear filter outputs permit modeling of complex cells and topographic organization as well. We propose a unifying framework for these statistical properties, based on the concept of spatiotemporal activity "bubbles."A bubble means here an activation of simple cells (linear filters) that is contiguous both in space (the cortical surface) and in time.
Identification and characterization of the promoter of fibroblast activation protein (2010)

Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein belonging to the serine protease family. It is selectively expressed by tumor stromal fibroblasts and transiently in the fibroblasts of healing wounds. FAP has been shown to modulate growth, differentiation, adhesion, and metastasis of tumor cells. Despite the importance of FAP in cancer, the mechanisms that govern its expression have not been defined. In this study, we determined the transcription start site of the FAP gene and identified a 2-kb segment with promoter activity in cells expressing FAP. Truncation of this fragment revealed that the core promoter activity resided in a 245-bp fragment surrounding the transcription start site. Electrophoretic mobility shift assay showed that EGR1 binds to the FAP promoter. Mutation of the EGR1 site within this fragment significantly decreased the promoter activity of FAP and eliminated EGR1 binding. Down-regulation of EGR1 resulted in a significant reduction in endogenous FAP mRNA expression. These findings identify the basal transcriptional requirements of FAP gene expression and show EGR1 is an important regulator of FAP expression.
Direct Evidence for Circulating apoSAA as the Precursor of Tissue AA Amyloid Deposits (1988)

A precursor product study was carried out using tritiated, undenatured murine high-density lipoprotein (HDL)-apoSAA, to assess whether circulating HDL-apoSAA is the precursor of tissue AA amyloid deposits. The quantity of label accumulating in AA over a 24-h period was determined per unit weight of spleen. In addition a mathematical assessment of the quantity of label that should have accumulated in splenic AA within 24 h was made, based on the half-life of circulating apoSAA, the rate of change of the specific activity of circulating apoSAA, and rate of deposition of splenic AA. The observed result was approximately 47% of the theoretically predicted value. The latter did not include extraction efficiencies of AA peptide from spleen nor losses which might have occurred during column fractionation of splenic extracts. The observed and predicted results are therefore in remarkably good agreement and indicate that circulating apoSAA is the major source of protein for splenic AA amyloid deposition.
Inhibiting Alternative Pathway Complement Activation by Targeting the Factor D Exosite (2012)

By virtue of its amplifying property, the alternative complement pathway has been implicated in a number of inflammatory diseases and constitutes an attractive therapeutic target. An anti-factor D Fab fragment (AFD) was generated to inhibit the alternative complement pathway in advanced dry age-related macular degeneration. AFD potently prevented factor D (FD)-mediated proteolytic activation of its macromolecular substrate C3bB, but not proteolysis of a small synthetic substrate, indicating that AFD did not block access of the substrate to the catalytic site. The crystal structures of AFD in complex with human and cynomolgus FD (at 2.4 and 2.3 Å, respectively) revealed the molecular details of the inhibitory mechanism. The structures show that the AFD-binding site includes surface loops of FD that form part of the FD exosite. Thus, AFD inhibits FD proteolytic function by interfering with macromolecular substrate access rather than by inhibiting FD catalysis, providing the molecular basis of AFD-mediated inhibition of a rate-limiting step in the alternative complement pathway.
Integrative Epidemiology: From Risk Assessment to Outcome Prediction (2005)

In this paper, we advance the concept of integrative epidemiology. Our unifying premise is that the same genes that are implicated in cancer risk may also be involved in a person's propensity to carcinogenic exposure and/or to modulation of therapeutic outcome. In the coming years, molecular epidemiology will play an increasingly prominent role in early detection of cancer and in identifying genetically high-risk subgroups that might benefit disproportionately from more intensive screening or chemoprevention interventions. Molecular epidemiology is also integral to pharmacogenetic research, by constructing genetic profiles that could be used to individualize therapy and to understand the functional consequences of chemoprevention, chemotherapy, or radiotherapy response. At the level of risk assessment, the focus might be on germline polymorphisms in candidate genes; for early detection, epigenetic events in these same or other genes may be relevant; and tumor tissue expression levels, loss of heterozygosity, genomic amplification, rearrangements, or somatic mutations in the same classes of genes may determine outcome. We will provide examples of how changes in the function of a single gene can contribute to susceptibility to carcinogenic exposure, predisposition to cancer development, patient prognosis, and prediction of outcome.
Design, Synthesis, and Pharmacological Characterization of (+)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY354740):  A Potent, Selective, and Orally Active Group 2 Metabotropic Glutamate Receptor Agonist Possessing Anticonvulsant and Anxiolytic Properties (1997)

2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (9) was designed as a conformationally constrained analog of glutamic acid. For 9, the key torsion angles (tau 1 and tau 2) which determine the relative positions of the alpha-amino acid and distal carboxyl functionalities are constrained where tau 1 = 166.9 degrees or 202 degrees and tau 2 = 156 degrees, respectively. We hypothesized that 9 would closely approximate the proposed bioactive conformation of glutamate when acting at group 2 metabotropic glutamate receptors (mGluRs). The racemic target molecule (+/-)-9, its C2-diastereomer (+/-)-16, and its enantiomers (+)-9 (LY354740) and (-)-9 (LY366563) were prepared by an efficient, stereocontrolled, and high-yielding synthesis from 2-cyclopentenone. Our hypothesis that 9 could interact with high affinity and specificity at group 2 mGluRs has been supported by the observation that (+/-)-9 (EC50 = 0.086 +/- 0.025 microM) and its enantiomer (+)-9 (EC50 = 0.055 +/- 0.017 microM) are highly potent agonists for group 2 mGluRs in the rat cerebral cortical slice preparation (suppression of forskolin-stimulated cAMP formation) possessing no activity at other glutamate receptor sites (iGluR or group 1 mGluR) at concentrations up to 100 microM. Importantly, the mGluR agonist effects of (+)-9 are evident following oral administration in mice in both the elevated plus maze model of anxiety (ED50 = 0.5 mg/kg) and in the ACPD-induced limbic seizure model (ED50 = 45.6 mg/kg). Thus, (+)-9 is the first orally active group 2 mGluR agonist described thus far and is an important tool for studying the effects of compounds of this class in humans.
Network of coupled promoting motions in enzyme catalysis (2002)

A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.
Temperature Effect on Activation Rate Constants in ATRP: New Mechanistic Insights into the Activation Process (2009)

Activation rate constants (kact) for a variety of initiators for Cu-mediated ATRP were measured with Cu(I)Br(PMDETA) at various temperatures (i.e., −40 to +60 °C). Reactions of less active alkyl halides were more accelerated by increased temperatures than reactions of more active initiators. Straight Eyring and Arrhenius plots were obtained, from which the activation parameters (i.e., ΔH⧧, ΔS⧧, Ea, and ln A) were determined. The activation enthalpies ΔH⧧ are in between 26.0 and 38.7 kJ mol−1 with highly negative activation entropies (ΔS⧧ = −156 to −131 J mol−1 K−1), which indicate greatly ordered structures of the transition states for these reactions.
Flip‐angle measurement by magnetization inversion: Calibration of magnetization nutation angle in hyperpolarized 3He magnetic resonance imaging lung experiments (2010)

The aim of this work was to establish a new, fast, and robust method of flip-angle calibration for magnetic resonance imaging of hyperpolarized (3) He. The method called flip-angle measurement with magnetization inversion is based on acquiring images from periodically inverted longitudinal magnetization created using the spatial modulation of magnetization technique. By measuring the width of the area where the magnetization was inverted by the spatial modulation of magnetization preparation in phase images, the flip angle can be generated using a simple equation. To validate and establish the limits of the proposed method, flip-angle measurement with magnetization inversion acquisitions were simulated and applied to proton and hyperpolarized (3) He phantoms. Then, the calibration procedure was applied during hyperpolarized (3) He magnetic resonance imaging in a healthy volunteer. The advantage of the flip-angle measurement with magnetization inversion method compared with the conventional method based on the assessment of radiofrequency-decay is that it is free of errors induced by relaxation due to oxygen, by imperfect excitation slice profile and by any diffusion of (3) He into and out of the slice. Another advantage is that it does not require image processing with external software and therefore can be performed using the implemented tools on the magnetic resonance workstation.
Three-dimensional imaging of the human retina by high-speed optical coherence tomography (2003)

Conventional optical coherence tomography is based on A-scans, i.e., the fast scan direction is the z-direction. While this technique has been successfully demonstrated for two-dimensional cross sectional imaging of various tissues, it is rather slow if three-dimensional information is to be obtained. We report on a new technique that combines the transverse scanning approach of a confocal scanning laser ophthalmoscope with the depth sectioning capability of OCT. A stable high-frequency carrier is generated by use of an acousto optic modulator, and high frame rate is obtained by using a resonant scanning mirror for the priority scan (x-direction). Our prototype instrument records 64 transverse images consisting of 256x128 pixels in 1.2 seconds, thus providing the fastest retinal 3D OCT scanning system reported so far. We demonstrate the capabilities of our system by measuring and imaging the fovea and the optic nerve head region of healthy human volunteers in vivo.
Factors affecting the physical stability (aggregation) of peptide therapeutics (2017)

The number of biological therapeutic agents in the clinic and development pipeline has increased dramatically over the last decade and the number will undoubtedly continue to increase in the coming years. Despite this fact, there are considerable challenges in the development, production and formulation of such biologics particularly with respect to their physical stabilities. There are many cases where self-association to form either amorphous aggregates or highly structured fibrillar species limits their use. Here, we review the numerous factors that influence the physical stability of peptides including both intrinsic and external factors, wherever possible illustrating these with examples that are of therapeutic interest. The effects of sequence, concentration, pH, net charge, excipients, chemical degradation and modification, surfaces and interfaces, and impurities are all discussed. In addition, the effects of physical parameters such as pressure, temperature, agitation and lyophilization are described. We provide an overview of the structures of aggregates formed, as well as our current knowledge of the mechanisms for their formation.
The T-cell receptor is not hardwired to engage MHC ligands (2012)

The bias of αβ T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-γ chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.
Monitoring and visualization techniques for MR‐guided laser ablations in an open MR system (1998)

Our purpose was to develop temperature-sensitive MR sequences and image-processing techniques to assess their potential of monitoring interstitial laser therapy (ILT) in brain tumors (n = 3) and liver tumors (n = 7). ILT lasted 2 to 26 minutes, whereas images from T1-weighted fast-spin-echo (FSE) or spoiled gradient-recalled (SPGR) sequences were acquired within 5 to 13 seconds. Pixel subtraction and visualization of T1-weighted images or optical flow computation was done within less than 110 msec. Alternating phase-mapping of real and imaginary components of SPGR sequences was performed within 220 msec. Pixel subtraction of T1-weighted images identified thermal changes in liver and brain tumors but could not evaluate the temperature values as chemical shift-based imaging, which was, however, more affected by susceptibility effects and motion. Optical flow computation displayed the predicted course of thermal changes and revealed that the rate of heat deposition can be anisotropic, which may be related to heterogeneous tumor structure and/or vascularization.
Folded cavity SOI microring sensors for high sensitivity and real time measurement of biomolecular binding (2008)

We demonstrate folded waveguide ring resonators for biomolecular sensing. We show that extending the ring cavity length increases the resonator quality factor, and thereby enhances the sensor resolution and minimum level of detection, while at the same time relaxing the tolerance on the coupling conditions to provide stable and large resonance contrast. The folded spiral path geometry allows a 1.2 mm long ring waveguide to be enclosed in a 150 microm diameter sensor area. The spiral cavity resonator is used to monitor the streptavidin protein binding with a detection limit of approximately 3 pg/mm(2), or a total mass of approximately 5 fg. The real time measurements are used to analyze the kinetics of biotin-streptavidin binding.
Matrix-binding proteins of Staphylococcus aureus: functional analysis of mutant and hybrid molecules (1999)

The fibrinogen-binding protein ClfA and the collagen-binding protein Cna are surface-associated adhesins of Staphylococcus aureus. ClfA has a dipeptide repeat region R composed mainly of serine and aspartate residues, more than 40 of which are required along with the 28-residue region W, the LPXTG motif and region M to display the ligand-binding region A on the cell surface in a functional form. Cna has a 61-residue region W and at least one 187-residue region B linking the collagen-binding region A to peptidoglycan. A cna mutant of S. aureus lacking region B was shown to bind collagen at the same level as wild-type Cna+ cells, indicating that region B is not necessary for ligand binding. Furthermore, altering the number of B repeats did not influence the level of collagen binding. In order to study the ability of C-terminal domains of Cna and ClfA to support functional ligand-binding activity of different adhesins, chimeric proteins were constructed and expressed in S. aureus. Surprisingly, the presence of a single Cna B domain and a nonapeptide linker located between ClfA region A and Cna region WM failed to support fibrinogen binding by S. aureus cells, despite the fact that ClfA region A was detected on the bacterial surface by immunoblotting. In contrast, the ClfA region A-Cna region B hybrid expressed as a recombinant protein in Escherichia coli did bind fibrinogen in Western ligand blots and in an ELISA-type assay. It is concluded that Cna region B cannot support functional display of ClfA region A on the bacterial cell surface. However, the ClfA dipeptide repeat region R and region WM did promote functional surface expression of the Cna collagen-binding domain in a hybrid Cna-ClfA protein.
Pilot Studies on the Use of 3,5-Diiodothyropropionic Acid, a Thyroid Hormone Analog, in the Treatment of Congestive Heart Failure (2002)

After an initial safety study in 7 normal volunteers, a randomized double-blind comparison was made between 3,5-diiodothyropropionic acid (DITPA) and placebo in 19 patients with moderately severe congestive failure. In heart failure patients receiving the drug for 4 weeks, cardiac index was increased (p = 0.04) and systemic vascular resistance index was decreased (p = 0.02). Systolic cardiac function was unchanged but isovolumetric relaxation time was decreased significantly, suggesting improvement in diastolic function. Total serum cholesterol (p = 0.005) and triglycerides (p = 0.01) also were decreased significantly. DITPA could represent a useful new agent for treatment of congestive heart failure.
Initiation of TCR signaling: regulation within CD3 dimers (2003)

The number of possible T cell activation outcomes resulting from T cell receptor (TCR) engagement suggests that the TCR is able to differentially activate a myriad of signaling pathways depending on the nature of the stimulus. The complex structural organization of the TCR itself could underlie this diversity of responses. Assembly and stoichiometric studies have helped us to shed some light on the initiation of TCR signaling. The TCR is composed of TCR and CD3 dimers. Changes in the interaction between CD3 subunits within the CD3 dimers and in the interaction of these dimers with the TCR heterodimer could be the triggering mechanism that initiates the first activation events. One of the hallmarks of these early changes in TCR conformation is the induced recruitment of the adapter protein Nck to a proline-rich sequence of the cytoplasmic tail of CD3epsilon, but there may be others. According to our most recent observations, the TCR is organized in pre-existing clusters within plasma membrane microdomains, exhibiting a complexity above and beyond that of dimer composition complexity. How the presence of TCR in clusters influences TCR avidity and propagation of TCR signals is something that has yet to be investigated.
Strategic directions in storage I/O issues in large-scale computing (1996)

article Free Access Share on Strategic directions in storage I/O issues in large-scale computing Authors: Garth A. Gibson Carnegie Mellon Univ., Pittsburgh, PA Carnegie Mellon Univ., Pittsburgh, PAView Profile , Jeffrey Scott Vitter Duke Univ., Durham, NC Duke Univ., Durham, NCView Profile , John Wilkes Hewlett-Packard Labs, Palo Alto, CA Hewlett-Packard Labs, Palo Alto, CAView Profile Authors Info & Claims ACM Computing SurveysVolume 28Issue 4Dec. 1996 pp 779–793https://doi.org/10.1145/242223.242300Published:01 December 1996Publication History 54citation1,518DownloadsMetricsTotal Citations54Total Downloads1,518Last 12 Months33Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
A Multilocus Genotyping Assay for Candidate Markers of Cardiovascular Disease Risk (1999)

A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed to facilitate evaluation of complex genetic risk factors in large cohorts. We have designed a prototype assay for genotyping a panel of 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated in the development and progression of cardiovascular disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, and the alleles are genotyped simultaneously using an array of immobilized, sequence-specific oligonucleotide probes. This multilocus assay was applied to two types of cohorts. Population frequencies for the markers were estimated using 496 unrelated individuals from a family-based cohort, and the observed values were consistent with previous reports. Linkage disequilibrium between consecutive pairs of markers within the apoCIII, LPL, and ELAM genes was also estimated. A preliminary analysis of single and pairwise locus associations with severity of atherosclerosis was performed using a composite cohort of 142 individuals for whom quantitative angiography data were available; evaluation of the potentially interesting associations observed will require analysis of an independent and larger cohort. This assay format provides a research tool for studies of multilocus genetic risk factors in large cardiovascular disease cohorts, and for the subsequent development of diagnostic tests.
Prospective Evaluation of the Argon Laser in the Treatment of Trichiasis (1992)

We report the results of argon-laser treatment in 60 consecutive eyelids with focal, symptomatic trichiasis. Permanence of eyelash destruction compared favorably with that reported for cryosurgery; complications were limited to minimal contour abnormalities and hypopigmentation.