gebhart/patrepeval huggingface dataset:
α-Helically constrained phage display library (2002)

The library described here is a collection of phages with six degenerate codons in gene VIII, specifying amino acids 12, 13, 15-17 and 19 of the major coat protein. The randomized positions are surface exposed in the wild-type protein and thus might be expected to tolerate a great diversity of side chains without compromising phage viability. In agreement with this supposition, the new library showed great diversity of amino acids at the randomized positions and diversity did not diminish noticeably during repeated subculture. Despite their diversity, however, the randomized positions should be strongly constrained conformationally because they lie in an extended alpha-helical portion of the protein, stabilized by numerous inter- and intra-subunit contacts--a presupposition corroborated by circular dichroism spectroscopy of many library members. To reflect this conformational homogeneity and the fact that random amino acids subtend a major fraction of the surface 'landscape' of the particle, we call the new construct an alpha landscape library. It can be used as a source of alpha-helical ligands and substitute antibodies.
Pleiotropic effects of statins (2015)

Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.
THE MECHANISM OF LYMPHOCYTE‐MEDIATED CYTOTOXICITY (1981)

Summary 1. Three classes of cytotoxic lymphocyte are discussed: thymus‐derived T cells, antibody‐dependent K cells and NK (natural killer) cells. Each of these cytotoxic lymphocytes has receptors allowing the formation of adhesions (contact) with a target cell (the cell to be killed). The type of receptor and the corresponding ligand on the target cell is different in each class. Cytotoxic T cells (and probably NK cells) react with a target cell antigen, in a manner rather like antibody‐antigen reactions (although not involving classical serum antibody). K cells have a receptor for the Fc part of immunoglobulin (IgG) and hence can make contact with antibody‐coated target cells. 2. It seems likely that all three classes of cytotoxic lymphocyte have a similar basic mechanism of killing, which is different from the membrane leakage occurring in complement‐mediated lysis. Much more information is available on cytotoxic T cells than on the other types of cell. 3. Cytotoxic T cell killing can be divided into two phases. A reversible phase in which the T cell is in contact with the target cell, but causes no apparent damage. This phase can vary from a few minutes up to several hours, when a single T cell interacts with a single target cell. If the T cell detaches or is inactivated the target cell survives. The second phase is irreversible, once the lethal event has occurred, and the target cell will progress to eventual lysis in the absence of the Tc cells. 4. The lethal event initiates a period of zeiosis (membrane blebbing) in the target cell, which is accompanied by increased effiux of 86 rubidium. Cell lysis occurs at a variable time after the initiation of zeiosis, when the soluble contents of the cytoplasm burst out of the target cell. The fact that both these phases are of variable length leads to the accumulation of cytoplasmic markers (such as 51 chromium) in the medium in an approximately linear fashion. 5. The nature of the lethal event is unknown, but it is suggested that it involves changes inside the target cell rather than at the target cell membrane. Remarkable long projections from the T cell (and also seen from K cells and NK cells), apparently arising as a result of the receptor‐ligand interaction, may be involved in the delivery of the lethal event.
Direct Haptic Volume Rendering in Lumbar Puncture Simulation (2012)

The preparation phase for surgical simulations often comprises the segmentation of patient data, which is needed for realistic visual and haptic rendering. Expert segmentation of 3D patient data sets can last from several hours to days. In this paper we introduce a direct haptic volume rendering approach for lumbar punctures. Preparation time spent for segmentation is much shorter and compared to our reference system nearly identical force output at the needle tip can be observed. The number of structures to be completely segmented by an expert is reduced from 11 to 3 tissues in abdominal data sets with 300 slices.
Clinical Perspectives onCryptococcus neoformansandCryptococcus gattii: Implications for Diagnosis and Management (2014)

Human cryptococcosis is most commonly due to infection with Cryptococcus neoformans and C. gattii, with C. neoformans var. grubii (serotype A) accounting for the great majority of infections worldwide. Cryptococcosis is uncommon in hematopoietic stem cell transplantation; in a large multicenter study in the United States, only 2 of 306 cases were associated with hematopoietic stem cell transplantation, and 54 with solid organ transplantation (SOT). Any condition associated with prolonged or high-dose corticosteroid exposure predisposes to cryptococcosis. Other than malignancy and organ transplantation, such conditions include connective tissue disorders (e.g., systemic lupus erythematosus and vasculitides), chronic obstructive pulmonary disease, and sarcoidosis. Visual loss is one of the most serious, debilitating sequelae (if not the most serious) of central nervous system (CNS) cryptococcosis. Rapid diagnosis and treatment is the key to achieving good outcomes. Molecular tests can distinguish between C. neoformans and C. gattii but are seldom required for diagnosis of cryptococcosis due to either species. A decrease in susceptibility to azole drugs, especially fluconazole, was noted among isolates of C. neoformans var. grubii from patients with AIDS, in parallel with widespread use of fluconazole prior to the advent of highly active antiretroviral therapy (HAART). The major determinants of outcome include neurological status, intracranial pressure (ICP), the presence of cerebral mass lesions, and cryptococcal load at presentation.
Diene-transmissive hetero-Diels–Alder reaction of cross-conjugated azatrienes: a novel and efficient method for the synthesis of ring-fused nitrogen heterocycles (1997)

A diene-transmissive hetero-Diels–Alder reaction of cross- conjugated azatrienes, which provides a novel and efficient synthetic method for ring-fused, nitrogen-heterocyclic frameworks such as quinazolin-2-ones and pyrimido[5,4-c]- pyridazin-6-ones, is described for the first time.
The Role of IL-1 in the Immune System (2003)

Interleukin-1 (IL-1) is a proinflammatory cytokine that plays an important role in inflammation and host responses to infection (for reviews, see refs. 1–3). The original identification of IL-1 as an endogenous pyrogen, lymphocyte-activating factor, hemopoietin-1, and osteoclast-activating factor, serves to demonstrate its pleiotropic activity (4). IL-1, produced by cell types such as macrophages, monocytes, and synovial lining cells, induces inflammation by activating synovial cells, endothelial cells, lymphocytes, and macrophages. Upon activation, these cells produce a variety of chemokines, cytokines, and inflammatory mediators (5), including IL-1 itself, IL-6, tumor necrosis factor-α (TNF-α), IL-8, and cyclooxygenase (COX)-2; these molecules cause infiltration of leukocytes into inflammatory sites, increase the permeability of blood vessel walls, and induce fever (1,2,6).
Pore space reconstruction of vuggy carbonates using microtomography and multiple‐point statistics (2007)

To reconstruct complex porous media, such as carbonates, we propose a two‐step approach to combine different types of images: microtomography at the resolution of a few microns to resolve large pores and vugs, with statistically reconstructed high‐resolution images for smaller features. Two‐dimensional (2‐D) thin sections provide multiple‐point statistics which describe the statistical relation between multiple spatial locations that can be used to generate 3‐D images with accurate connectivity. These statistical reconstructions are combined with images directly measured by microtomography. The integrated method is tested on carbonates for which 3‐D images of disconnected vugs are captured, while 2‐D thin sections characterize the small‐scale structure. The integrated images have permeabilities computed using the lattice Boltzmann method that are similar to laboratory‐measured values.
Generation and analysis of 280,000 human expressed sequence tags. (1996)

We report the generation of 319,311 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' and 3' ends of 194,031 human cDNA clones. Our goal has been to obtain tag sequences from many different genes and to deposit these in the publicly accessible Data Base for Expressed Sequence Tags. Highly efficient automatic screening of the data allows deposition of the annotated sequences without delay. Sequences have been generated from 26 oligo(dT) primed directionally cloned libraries, of which 18 were normalized. The libraries were constructed using mRNA isolated from 17 different tissues representing three developmental states. Comparisons of a subset of our data with nonredundant human mRNA and protein data bases show that the ESTs represent many known sequences and contain many that are novel. Analysis of protein families using Hidden Markov Models confirms this observation and supports the contention that although normalization reduces significantly the relative abundance of redundant cDNA clones, it does not result in the complete removal of members of gene families.
Distortion-tolerant 3D recognition of occluded objects using computational integral imaging (2006)

In a computational three-dimensional (3D) volumetric reconstruction integral imaging (II) system, volume pixels (voxels) of the scene are reconstructed plane by plane. Therefore, foreground occluding objects and background occluded objects can be reconstructed separately when there is enough spatial separation between the occluding object and the occluded object. Using volumetric computational II reconstruction, we are able to recognize distorted and occluded objects with correlation based recognition algorithms. We present experimental results which show recognition of 3D rotated and occluded targets in a reconstructed scene. We also show the ability of the proposed technique to recognize distorted and occluded 3D non-training targets.
Three-dimensional mask effects and source polarization impact on OPC model accuracy and process window (2007)

As semiconductor technology moves toward and beyond the 65 nm lithography node, the importance of Optical Proximity Correction (OPC) models grows due to the lithographer's need to ensure high fidelity in the mask- to-silicon transfer. This, in turn, causes OPC model complexity to increase as NA increases and minimum feature size on the mask decreases. Subtle effects, that were considered insignificant, can no longer be ignored. Depending on the imaging system, three dimensional mask effects need to be included in OPC modeling. These effects can be used to improve model accuracy and to better predict the final process window. In this paper, the effects of 3D mask topology on process window are studied using several 45 nm node mask structure types. Simulations are conducted with and without a polarized illumination source. The benefits of using an advanced model algorithm, that comprehends 3D mask effects, will be discussed. To quantify the potential impact of this methodology, relative to current best known practices, all results are compared to those obtained from a model using a conventional thin film mask.
Ligand-Based Drug Design Methodologies in Drug Discovery Process: An Overview (2006)

Ligand-based drug design represents an important research field in the drug discovery and optimisation process. This review provides an overview about the theoretical background of the quantitative structure activity relationship (QSAR) models.
Rapid and Sensitive Immunoassay for the Measurement of Serum S100B Using Isoform-specific Monoclonal Antibody (1999)

S100 is an acidic calcium-binding protein with a molecular weight of 21 000, originally discovered by Moore (1) in the bovine brain. Today, >14 different S100 members are known (2), of which S100A1 and S100B are the most studied (3)(4)(5)(6). Because a high concentration of S100B is present in the brain, S100 has been studied for use as a biochemical marker for central nervous system pathology. Numerous studies in the literature have suggested the clinical usefulness of measuring this protein in cerebrospinal fluid (7)(8)(9)(10)(11), and in recent years, serum S100B has been reported as a useful marker for early detection of metastases of melanoma and cerebral complications from head injury, cardiac surgery, and acute stroke (12)(13)(14)(15)(16)(17)(18)(19)(20)(21).

With the advent of therapeutic treatments for stroke that either dissolve the clot or protect the brain, early diagnosis of stroke and the identification of appropriate patients for intervention are increasingly important. Existing assays lack sensitivity and ease of use and usually require ≥3 h to perform. We have, therefore, developed an ELISA that is rapid, highly sensitive, and S100B specific. This ELISA was used to retrospectively assess S100B concentrations in the serum of stroke patients.

Human S100B cDNA (Genome System), amplified by PCR, was cloned into vector pET28a (Novagen) and expressed in Escherichia coli BL-21 (DE3)pLysS (Novagen). Recombinant human S100B (rS100B) was isolated from host cells that were induced with 1 mmol/L isopropylthio-β-galactoside for 2 h at 37 °C and were lysed with a native buffer system. S100B was purified with an Ni-NTA affinity column.

The ELISA buffers were as follows: plate-coating buffer (100 mmol/L carbonate buffer, pH 9.6); phosphate-buffered …
Continuous and noninvasive estimation of arterial blood pressure using a photoplethysmographic approach (2004)

Arterial blood pressure is one of the most important physiological parameters for the noninvasive diagnosis and monitoring of cardiovascular diseases. This study examines the relationships between arterial blood pressure and certain features of the photoplethysmographic (PPG) signals obtained from 15 young healthy subjects. Width of 1/2 pulse amplitude, width of 2/3 pulse amplitude, systolic upstroke time and diastolic time of the pulse were selected as features of the PPG signals. The experiment involved three sessions: rest, step-climbing exercise, and recovery from exercise. It was found that the diastolic time has higher correlation with systolic blood pressure (SBP) and diastolic blood pressure (DBF) than other features. The mean differences between the estimated and the measured blood pressure using a standard device are 0.21 mm Hg for SBP and 0.02 mm Hg for DBF. The corresponding standard deviations are 7.32 mm Hg for SBP and 4.39 mm Hg for DBF. The preliminary results indicate that it is possible to use the photoplethysmography only for cuffless and continuous estimation of arterial blood pressure.
Determinants of rat albumin promoter tissue specificity analyzed by an improved transient expression system. (1987)

The 150-base-pairs region located upstream of the transcriptional start site of the rat albumin gene contains all of the critical sequences necessary for this gene's tissue-specific expression in rat hepatoma cells. In transient expression assays using an improved CAT system or direct mRNA analysis we were able to detect a faithful transcription from the albumin promoter in albumin-negative dedifferentiated H5 hepatoma cells which was 250-fold weaker than in differentiated H4II hepatoma cells producing albumin. This strong tissue specificity could be completely overcome through the cis action of a non-tissue-specific enhancer. Two upstream regions from nucleotides -151 to -119 and from -118 to -94, were required for efficient transcription in H4II cells. Each region contained a sequence motif highly conserved among different species. The effect of the -151/-119 region was strictly tissue specific, while the -118/-94 region was also involved in the low level of transcription observed in H5 cells. Finally, sequences between the CCAAT box and the TATA box also contributed to the overall tissue specificity of rat albumin gene transcription.
Adaptive Rate Pacing Controlled by the Right Ventricular Preelection Interval: Clinical Experience With a Physiological Pacing System (1992)

In the Precept pacing system, the right ventricular intracardiac impedance waveform is used to evaluate either of two indicators of metabolic demand relative right ventricular stroke volume and preejection interval (PEI). PEI is known to reliably parallel contractility changes, which is reflective of physical and emotional stress. The stability and dynamic behavior of PEI were tested in ten patients with a Precept pacing system under various forms of exercise and during postural changes. Although significant patient-to-patient variability of the sensor values was observed, reflecting individual physiological differences, the chronic stability of PEI was excellent in the total device experience of 147 months. In all patients, PEI shortened significantly during bicycle ergometry from a mean value of 137.7 +/- 17.8 (range 96-162) to a mean value of 103.0 +/- 21.6 (range 92-109) (P less than 0.05). Low level bicycle exercise of short duration resulted in a prompt decrease in PEI and increase in pacing rate in all patients. There were no uniform postural responses overall, although some posture related rate changes were observed in two patients. We conclude that the first generation of a PEI based pacing system holds promise for adaptive rate pacing.
Corn Stover Silage Versus Corn Silage for Milk Production (1921)

The information available on the feeding value of corn stover silage is limited and no experimental data has been reported comparing corn stover silage, made from cured corn stalks, with corn silage, as feeds for milk production. Rusk, of the Illinois Experiment Station, successfully maintained breeding beef cows through the winter on corn stover silage, and one pound of cotton seed meal daily. Long, of the Missouri Station reports that breeding beef cows gained in weight on a ration of corn stover silage and wheat straw. In Wisconsin very little of the corn is husked as standing corn. The stalks are needed for feed and are usually harvested with the grain to be made into silage or are fed separate in the dry form. Claims have been made that corn stover silage, that is the stalks with ears removed, is equal in feeding value to ordinary corn silage. I t was the purpose of the experiment reported here to obtain information that would corroborate or refute these claims, with reference to milk production.
Prevalence of Gram-Negative Rods in the Normal Pharyngeal Flora (1975)

We obtained throat cultures from 100 randomly selected people free from any chronic upper or lower respiratory disease who did not work in a hospital and who had not experienced any acute illness or received any antibacterial therapy in the 4 weeks preceding culture. Eighteen percent harbored either a species of Enterobacteriaceae or Pseudomonas aeruginosa in their pharynx. In all cases, colony counts were low, the majority being detected in broth media selective for Gram-negative rods. There were no clear-cut age or sex distributions of Gram-negative pharyngeal carriage. These data imply that, in at least some cases, isolation of Gram-negative rods from sputum of untreated patients may be a normal finding, and that in some patients with pulmonary infection, the pretreatment, upper respiratory tract flora may serve as the source of subsequent superinfection with Gram-negative rods.
Time-reversal checkpointing methods for RTM and FWI (2012)

ABSTRACT Time-domain seismic simulation can form the basis of reverse time depth migration and full-waveform inversion. These applications need to temporally crosscorrelate a forward simulation state with an adjoint simulation state and therefore need to be able to access each time step of a forward simulation in time-reverse order. This requires saving all forward states for all times (which can require more memory than is typically available on a computer system for many problems of interest), or the ability to checkpoint information and rapidly recompute forward simulation states as needed. Prior work has suggested how to do the latter by optimally choosing which forward simulation time steps to checkpoint, thereby enabling the most efficient reuse of memory buffers and minimizing recomputation. The optimal trade-off between memory usage and recomputation can be further improved under the assumption that the information needed to do temporal crosscorrelation is smaller than the information required to restart a simulation from a given time step. This assumption is true for many geophysical problems of interest. The modification can yield a reduction in the memory requirement and recomputation time. The tested examples applied to isotropic elastic reverse time migration and anisotropic viscoelastic full-waveform inversion.
Tools for User-Centred Design (2013)

User-Centred Design aims to involve users at all stages of the design of products. Some of the basic principles are briefly considered together with their relationship to ergonomics. Tools for the application of User-Centred Design are discussed including specific tools such as digital human modelling, personas, manikin characters, inclusive design and human behavioural modelling.
Fluorescence-Modified Superparamagnetic Nanoparticles: Intracellular Uptake and Use in Cellular Imaging (2006)

This report describes the preparation and characterization of new magnetic fluorescent nanoparticles and our success in using them to label living cells. The bifunctional nanoparticles possess a magnetic oxide core composed of a dimercaptosuccinic acid (DMSA) ligand at the surface and a covalently attached fluorescent dye. The nanoparticles exhibited a high affinity for cells, which was demonstrated by fluorescence microscopy and magnetophoresis. Fluorescence microscopy was used to monitor the localization patterns of magnetic nanoparticles associated with cells. We observed two types of magnetic labeling: adsorption of the nanoparticles on the cell membrane (membranous fluorescence) and internalization of the nanoparticles inside the cell (intracellular vesicular fluorescence). After internalization, nanoparticles were confined inside endosomes, which are submicrometric vesicles of the endocytotic pathway. We demonstrated that endosome movement could be piloted inside the cell by external magnetic fields such that small fluorescent chains of magnetic endosomes were formed in the cell cytoplasm in the direction of the applied magnetic field. Finally, by measuring the critical cellular magnetic load (quantitated by magnetophoresis), we have demonstrated the potential of this new magneto-fluorescent nanoagent for medical use.