gebhart/patrepeval huggingface dataset:
Luminescent Colloidal Silicon Suspensions from Porous Silicon (1992)

A procedure for generating colloidal suspensions of Si that exhibit luminescence, attributed to quantum confinement effects, is described. Samples of n- or p-type Si that have been electrochemically etched to form porous Si can be ultrasonically dispersed into methylene chloride, acetonitrile, methanol, toluene, or water solvents, forming a suspension of fine Si particles that luminesce. Transmission electron microscopy analyses show that the Si particles have irregular shapes, with diameters ranging from many micrometers to nanometers. Luminescent, composite polystyrene/Si films can be made by the addition of polystyrene to a toluene suspension of the Si nanoparticles and casting of the resulting solution onto a glass slide.
Association Between Genetic Variation in the ABCB1 Gene and Switching, Discontinuation, and Dosage of Antidepressant Therapy (2013)

The objective of this study was to investigate whether polymorphisms in the ABCB1 gene were associated with switching, with discontinuation of antidepressants within 45 days after starting therapy, and/or with dose change in a large prospective population-based cohort study. Between April 1, 1991, and December 31, 2007, there were 1257 incident users of antidepressants with known ABCB1 genotypes (1236C>T, 2677G>T/A, 3435C>T) in the population-based Rotterdam Study. Logistic regression models were used to estimate the genotype and haplotype effect on the risk of switching and discontinuation. In addition, the association between the haplotypes and the prescribed drug dosage was assessed per drug class. The separate polymorphisms in the ABCB1 gene were associated with increased risks of switching and discontinuation but reached only statistical significance for the association between the 3435C>T polymorphism and switching. In a model adjusted for age and sex, homozygous carriers of the T-T-T haplotype had an increased risk of switching (odds ratio, 4.22; 95% confidence interval, 1.30-13.7; P = 0.017) and discontinuation (odds ratio, 1.47; 95% confidence interval, 0.98-2.22; P = 0.063). Explained variance was 10.4% for switching and 2.5% for discontinuation. In contrast, no association was observed between the T-T-T haplotype and the prescribed dosage. In summary, this study showed that genetic variation in the ABCB1 gene might play a role in the risk of switching and discontinuation of antidepressant therapy but the clinical relevance is limited.
Enhanced resistance to nuclease degradation of nucleic acids complexed to asialoglycoprotein-polylysine carriers (1994)

We have previously shown targeting of DNA to hepatocytes using an asialoorosomucoid-polylysine (AsOR-PL) carrier system. The AsOR-PL conjugate condenses DNA and facilitates entry via specific receptor-ligand interactions. In these studies, our objective was to determine if AsOR-PL conjugates protect bound DNA from nuclease attack. Double-stranded plasmid or single-stranded oligonucleotide DNA, alone or bound to conjugate, was incubated under conditions mimicking those encountered during in vitro and in vivo transfections. The results showed that complexed DNA was effectively protected from degradation by serum nucleases. Degradation of single-stranded oligonucleotides was inhibited 3- to 6-fold in serum during 5 hours of incubation. For complexed plasmids, greater than 90% remained full-length during 1.5 and 3 hour incubations in serum or culture medium containing 10% serum, respectively. Uncomplexed plasmid was completely degraded after 15 minutes in serum or 60 minutes in medium. In cell lysates, the conjugate was not effective in inhibiting endonuclease activity; plasmids were readily converted from supercoiled to open circular and linear forms. However, the resultant nicked forms were substantially protected from further degradation during one hour of incubation compared to plasmid alone. Under all conditions complexed DNA did not readily dissociate from the conjugate. Overall, for both single and double-stranded DNA, AsOR-PL conjugates conferred substantial protection from nuclease degradation.
Optimal Cost Sampling for Decision Making with Multiple Regression Models (1989)

ABSTRACT This paper develops an explicit relationship between sample size, sampling error, and related costs for the application of multiple regression models in observational studies. Graphs and formulas for determining optimal sample sizes and related factors are provided to facilitate the application of the derived models. These graphs reveal that, in most cases, the imprecision of estimates and minimum total cost are relatively insensitive to increases in sample size beyond n =20. Because of the intrinsic variation of the regression model, even if larger samples are optimal, the relative change in the total cost function is small when the cost of imprecision is a quadratic function. A model‐utility approach, however, may impose a lower bound on sample size that requires the sample size be larger than indicated by the estimation or cost‐minimization approaches. Graphs are provided to illustrate lower‐bound conditions on sample size. Optimal sample size in view of all considerations is obtained by the maximin criterion, the maximum of the minimum sample size for all approaches.
Parallel coprocessor for Kohonen's self-organizing neural network (2003)

A new efficient integrated circuit implementation of the Self-Organising Feature Map algorithm is described. The fully digital hardware is designed for high speed parallel processing and modular expandability. The hardware implementation acts as a neural coprocessor which uses synchronous, bit-serial arithmetic. It includes functional units which perform the Euclidean distance computation, the minimum distance search, the memory controlling, and the updating function. The on-chip learning facilitates fully autonomous operation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Comparison of Continuous Thalamic Stimulation and Thalamotomy for Suppression of Severe Tremor (2000)

Thalamic stimulation and thalamotomy are equally effective for the suppression of drug-resistant tremor, but thalamic stimulation has fewer adverse effects and results in a greater improvement in function.
Composition in Distributional Models of Semantics (2010)

Vector-based models of word meaning have become increasingly popular in cognitive science. The appeal of these models lies in their ability to represent meaning simply by using distributional information under the assumption that words occurring within similar contexts are semantically similar. Despite their widespread use, vector-based models are typically directed at representing words in isolation, and methods for constructing representations for phrases or sentences have received little attention in the literature. This is in marked contrast to experimental evidence (e.g., in sentential priming) suggesting that semantic similarity is more complex than simply a relation between isolated words. This article proposes a framework for representing the meaning of word combinations in vector space. Central to our approach is vector composition, which we operationalize in terms of additive and multiplicative functions. Under this framework, we introduce a wide range of composition models that we evaluate empirically on a phrase similarity task.
Antisense Oligonucleotides (1997)

The therapeutic use of oligonucleotides represents a new paradigm for drug discovery. The technology focuses on a class of chemicals, oligonucleotides, that have not been studied as potential drugs before and uses them to intervene in processes that, likewise, have not been studied as sites at which drugs might act. Although the field is still in its infancy, it has generated considerable enthusiasm because of the potential specificity of oligonucleotide drugs and the breadth of potential applications.
Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction (2015)

Intracellular trafficking of viruses can be influenced by a variety of inter-connected cellular sorting and degradation pathways involving endo-lysosomal vesicles, the ubiquitin-proteasome system, and autophagy-based or endoplasmic reticulum-associated machinery. In the case of recombinant adeno-associated viruses (AAV), proteasome inhibitors are known to prevent degradation of ubiquitinated AAV capsids, thereby leading to increased nuclear accumulation and transduction. However, the impact of other cellular degradation pathways on AAV trafficking is not well understood. In the current study, we screened a panel of small molecules focused on modulating different cellular degradation pathways and identified eeyarestatin I (EerI) as a novel reagent that enhances AAV transduction. EerI improved AAV transduction by an order of magnitude regardless of vector dose, genome architecture, cell type, or serotype. This effect was preceded by sequestration of AAV within enlarged vesicles that were dispersed throughout the cytoplasm. Specifically, EerI treatment redirected AAV particles toward large vesicles positive for late endosomal (Rab7) and lysosomal (LAMP1) markers. Notably, MG132 and EerI (proteasomal and endoplasmic reticulum-associated degradation inhibitors, respectively) appear to enhance AAV transduction by increasing the intracellular accumulation of viral particles in a mutually exclusive fashion. Taken together, our results expand on potential strategies to redirect recombinant AAV vectors toward more productive trafficking pathways by deregulating cellular degradation mechanisms.
Direct manipulation techniques for 3D objects using 2D locator devices (1987)

Article Free Access Share on Direct manipulation techniques for 3D objects using 2D locator devices Authors: Gregory M. Nielson Arizona State University Arizona State UniversityView Profile , Dan R. Olsen Brigham Young University Brigham Young UniversityView Profile Authors Info & Claims I3D '86: Proceedings of the 1986 workshop on Interactive 3D graphicsJanuary 1987 Pages 175–182https://doi.org/10.1145/319120.319134Online:01 January 1987Publication History 65citation1,344DownloadsMetricsTotal Citations65Total Downloads1,344Last 12 Months57Last 6 weeks23 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 AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Mitochondria Targeted Nanoscale Zeolitic Imidazole Framework-90 for ATP Imaging in Live Cells (2017)

Zeolitic imidazole frameworks (ZIFs) are an emerging class of functional porous materials with promising biomedical applications such as molecular sensing and intracellular drug delivery. We report herein the first example of using nanoscale ZIFs (i.e., ZIF-90), self-assembled from Zn<sup>2+</sup> and imidazole-2-carboxyaldehyde, to target subcellular mitochondria and image dynamics of mitochondrial ATP in live cells. Encapsulation of fluorescent Rhodamine B (RhB) into ZIF-90 suppresses the emission of RhB, while the competitive coordination between ATP and the metal node of ZIF-90 dissembles ZIFs, resulting in the release of RhB for ATP sensing. With this method, we are able to image mitochondrial ATP in live cells and study the ATP level fluctuation in cellular glycolysis and apoptosis processes. The strategy reported here could be further extended to tune nanoscale ZIFs inside live cells for targeted delivery of therapeutics to subcellular organelles for advanced biomedical applications.
Electron microscopic structure of purified, active γ-secretase reveals an aqueous intramembrane chamber and two pores (2006)

Gamma-secretase is an intramembrane-cleaving aspartyl protease required for the normal development of metazoans because it processes Notch within cellular membranes to release its signaling domain. More than two dozen additional substrates of diverse functions have been reported, including the Notch ligands Delta and Jagged, N- and E-cadherins, and a sodium channel subunit. The protease is causally implicated in Alzheimer's disease because it releases the neurotoxic amyloid beta-peptide (Abeta) from its precursor, APP. Gamma-secretase occurs as a large complex containing presenilin (bearing the active site aspartates), nicastrin, Aph-1, and Pen-2. Because the complex contains at least 18 transmembrane domains, crystallographic approaches to its structure are difficult and remote. We recently purified the human complex essentially to homogeneity from stably expressing mammalian cells. Here, we use EM and single-particle image analysis on the purified enzyme, which produces physiological ratios of Abeta40 and Abeta42, to obtain structural information on an intramembrane protease. The 3D EM structure revealed a large, cylindrical interior chamber of approximately 20-40 A in length, consistent with a proteinaceous proteolytic site that is occluded from the hydrophobic environment of the lipid bilayer. Lectin tagging of the nicastrin ectodomain enabled proper orientation of the globular, approximately 120-A-long complex within the membrane and revealed approximately 20-A pores at the top and bottom that provide potential exit ports for cleavage products to the extra- and intracellular compartments. Our reconstructed 3D map provides a physical basis for hydrolysis of transmembrane substrates within a lipid bilayer and release of the products into distinct subcellular compartments.
Using a Convenient, Quantitative Model for Torsional Entropy To Establish Qualitative Trends for Molecular Processes That Restrict Conformational Freedom (1998)

A non-quantum-mechanical, readily applied model is described that estimates torsional entropy (Stor, the entropy associated with torsional motions about a single bond) quantitatively. Using this model, torsional entropies are evaluated for a variety of molecular arrangements. Qualitative trends emerge from these estimates that are consistent with chemical intuition. The entropy associated with torsional motion is not constant: values of Stor range from 0 to 15 J mol-1 K-1 and are sensitive to details of the bond around which the torsion occurs Important characteristics include the bond length, the hybridization, the symmetry, the sizes of these atoms or groups of atoms, and the extent of conjugation to adjacent bonds. These values are relatively independent of one another in a number of important cases, and therefore the total change in conformational entropy for a given process may be estimated by adding changes in entropy due to restricting torsions around individual bonds. A model that permits quantitative estimations of changes in conformational entropy will be useful in a wide range of chemical and biochemical applications that include the design of tight-binding polyvalent pharmaceuticals and stable multiparticlemolecular assemblies, as well as in the kinetic and thermodynamic analysis of almost any chemical reaction that involves the restriction of the torsions of rotors.
SASAPOS Cascades of Perfluorinated Aromatic Carboxylic Acids: Low‐Temperature Decarboxylation Triggered by Electrostatic Effects of Polycationic Ligand Sets (2004)

Abstract Polycationically substituted derivatives of benzoic and phthalic acids were synthesized for the first time via SASAPOS cascades of the corresponding perfluoro(di)carboxylic acids or acyl chlorides (SASAPOS: s elf‐ a ctivated s ilyl‐ a ssisted p oly‐ o nio s ubstitution). The carboxylic acids decarboxylate with extreme ease (e.g. at room temperature or below) via the corresponding carboxylates. Electrostatically highly stabilized phenylanion derivatives figure as potent electrofuges in these reactions. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)
Abstract 6278: Burden of Chronic Renal Insufficiency in the General Population and Added Predictive Power of GFR to BNP and NT-proBNP in Detection of Altered Ventricular Structure and Function (2008)

Background: Chronic renal insufficiency (CRI) is a strong predictor of increased mortality in the presence of heart failure (HF) and its prevalence has been increasing in the US. In addition, CRI is a major contributing factor to the progression of HF as it is associated with chronic volume overload, accelerated atherosclerosis and hypertension (HTN). The first aim of the current study was to evaluate the prevalence of CRI in an adult general population. The second aim was to address whether calculated glomerular filtration rate (cGFR) adds value to the cardiac biomarkers BNP and NT-proBNP in detecting early cardiac structural and functional impairments in the general population. Methods: From 1997 to 1999 medical history, physical examination, echocardiography, BNP (Biosite) and NT-proBNP (Roche) and serum creatinine (SCr) were obtained in 1,982 randomly selected residents of Olmsted County, MN &gt;= 45 years (range 45 – 96 years). GFR was calculated using the Cockroft Gault equation. CRI was defined as a GFR &lt; 60 ml/min. Cardiac structure and function were evaluated by in-depth echocardiographic examination. Results: The prevalence of cardiovascular co-morbidities was coronary atherosclerosis 12%, HTN 29.5% and diabetes mellitus 7.5%. The prevalence of CRI was 22.8% when cGFR was used for its detection. Importantly, by Chi-Square model, cGFR significantly increased the ability of BNP in detecting left ventricular hypertrophy (LVH) (p=0.004), increased relative wall thickness (p=0.0036), diastolic dysfunction (DDF) (p=0.0001) and HTN (p=0.0002). Similarly, when combined with NT-proBNP, cGFR increased the predictive power of detecting DDF (p=0.0001) and HTN (p=0.0366). Conclusion: This study reports a higher than predicted prevalence of CRI in this general US population equal to 23% and closely associated with the prevalence of HTN (29.5%). Importantly, this study also demonstrates that cGFR has additive predictive power when used in combination with two cardiac biomarkers of cardiac dysfunction and remodeling, BNP and NT-proBNP. These studies underscore the increasing burden of CRI in the general population and the utility of assessing cardiorenal function by combining renal and cardiac biomarkers in assessment of cardiac structure and function.
Free-space switching for optical fibre networks (1996)

The problems of point-to-point communication have essentially been solved by advances in semiconductor laser and optical fibre technologies. Direct optical signal amplification has also become possible in recent years using Erbium-doped fibres [1], and uninterrupted glass fibre lengths of over 6000km are now being installed [2]. But the technologies used for signal routeing have yet to catch up with the huge potential bandwidths that optical fibres offer. The research outlined in this dissertation relates to the optical implementation of freespace routeing architectures for communication networks. These systems potentially allow hundreds or even thousands of signals to be optically routed through each other in a compact 3-dimensional volume, incurring very little crosstalk. This is achieved by the use of programmable computer-generated holograms (CGHs) displayed on a ferroelectric liquid crystal (FLC) spatial light modulator (SLM). The SLM provides fast 2-dimensional binary modulation of coherent light and acts as a dynamically reconfigurable diffraction pattern. The dissertation outlines the optical design and implementation of three such free-space switching architectures, where the SLM is used to deflect input signals to the required outpuJs in a bandwidth independent 'optically-transparent' manner. Experimental investigations of a broadband I-to-I5 fibre selector switch, a tuneable wavelength filter, and the initial experimental characterisation of a full N-to-M fibre crossbar switch are presented. These transparent switches offer a more compatible approach for routeing high bandwidth optical signals than existing electronic switch designs. The target applications for this FLCSLM technology are reconfigurationally unintensive operations involving very high optical modulation frequencies, where switch failures would be expensive. Applications include circuit-switching of broadband or wavelength-multiplexed data, and network management or restoration. The diffractive nature of CGHs makes them extremely robust in their operation and therefore well suited to the above applications. The dynamic CGH patterns used to perform the routeing are shift invariant and do not fail catastrophically if individual SLM pixels stop working. The optical efficiencies and crosstalk noise rejection are only limited by the diffraction efficiencies of the CGH-SLM. Relevant theoretical efficiency limits are derived and compared with experimental measurements. Better than -30dB crosstalk rejection is demonstrated by the I-to-I5 switch, and measurements suggest that less than 6dB insertion loss will be possible in future iterations, even with considerably more fibre ports.
Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+T cell response primed by DNA immunization (2005)

CD25(+) Treg cells suppress priming and/or expansion of antigen-specific CD8(+) T cells during DNA immunization and the peak CD8(+) T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8(+) T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects.
Identification and mapping of neutralizing epitopes of human parvovirus B19 by using human antibodies (1991)

We identified and mapped the regions responsible for neutralization in the human parvovirus B19 structural protein by using region-specific human antibodies derived from seropositive blood donors. The region-specific antibodies were purified by using affinity columns coupled with synthetic peptides of the hydrophilic regions including the beta-turn structure deduced by the predicted secondary structure of VP2. Fifteen highly specific antibodies against the synthetic peptides were obtained. Ten of them were able to precipitate the radiolabeled virus. Six of them proved to be able to protect the colony-forming unit erythroid cells in human bone marrow cell cultures from injury by the virus. The sequences recognized by the six neutralizing antibodies were sites corresponding to amino acids 253 to 272, 309 to 330, 325 to 346, 359 to 382, 449 to 468, and 491 to 515 from the amino-terminal portion of VP2. These observations suggest that the neutralizing epitopes were distributed in the region from amino acid 253 in the amino-terminal portion of VP2 to the carboxyl terminus of VP2.
Automated Fabrication of Mobility Aids: Clinical Demonstration of the UCL Computer Aided Socket Design System (1989)

1Research Prosthetist with Prosthetics Research Study, 720 Broadway, Seattle, Washington 98122; (206) 328-3116 2Director and Principal Investigator of Prosthetics Research Study in Seattle
ChemInform Abstract: Ge1‐xMnx‐Diluted Magnetic Semiconductor Nanostructures for Spintronics (2013)

Abstract Review: emphasis on the growth and structural properties of Ge:Mn thin films and quantm dots; 50 refs.