gebhart/patrepeval huggingface dataset:
Direct detection of major histocompatibility complex class I binding to antigenic peptides using surface plasmon resonance. Peptide immobilization and characterization of binding specificity (1993)

We have developed model systems in which the binding of purified, genetically engineered, soluble analogues of major histocompatibility complex (MHC) class I molecules to immobilized antigenic peptides can be monitored in real time using surface plasmon resonance (SPR). Synthetic analogues of several peptides known to bind different mouse and human MHC class I molecules were prepared with cysteine residues substituted at appropriate positions. The analogue peptides were immobilized via the bifunctional reagent N-gamma-maleimidobutyryloxy-succinimide to amino groups generated on the dextran-modified gold surface of a biosensor flow cell. Using this approach, each position in the sequence of an H-2Ld-specific viral peptide, pMCMV (YPHFMPTNL), was used for coupling, and the resulting surfaces were tested for binding of the soluble analogue of H-2Ld, H-2Lds. In accord with our previously described H-2Ld/pMCMV three-dimensional structural model, only those residues of the peptide that remain exposed following binding (positions 4-8) can be replaced by cysteine and used for coupling. Stable binding of soluble MHC class I molecules, H-2Lds, H-2Dds, H-2Kbs, and HLA-A2s to their respective immobilized cognate peptides was detected by SPR. Specificity of the peptide/MHC interaction was characterized both by direct binding using immobilized peptides and by competition with peptides in solution, and in general was consistent with known immunological reactivity. Some peptides bound not only their cognate MHC molecule, but others at lower apparent affinity. Measurement of real time binding of MHC class I molecules to peptides immobilized through specific side chains suggests the application of a similar approach to the study of the interaction of peptides with a wide variety of peptide-binding macromolecules.
Surviving the first hours in sepsis: getting the basics right (an intensivist's perspective) (2011)

Severe sepsis is a major cause of morbidity and mortality, claiming between 36 000 and 64 000 lives annually in the UK, with a mortality rate of 35%. International guidelines for the management of severe sepsis were published in 2004 by the Surviving Sepsis Campaign and condensed into two Care Bundles. In 2010, the Campaign published results from its improvement programme showing that, although an absolute mortality reduction of 5.4% was seen over a 2 year period in line with increasing compliance with the Bundles, reliability was not achieved and Bundle compliance reached only 31%. This article explores current challenges in sepsis care and opportunities for further improvements. Basic care tasks [microbiological sampling and antibiotic delivery within 1 h, fluid resuscitation, and risk stratification using serum lactate (or alternative)] are likely to benefit patients most, yet are unreliably performed. Barriers include lack of awareness and robust process, the lack of supporting controlled trials, and complex diagnostic criteria leading to recognition delays. Reliable, timely delivery of more complex life-saving tasks (such as early goal-directed therapy) demands greater awareness, faster recognition and initiation of basic care, and more effective collaboration between clinicians and nurses on the front line, in critical care and in specialist support services, such as microbiology and infectious diseases. Organizations such as Survive Sepsis, the Surviving Sepsis Campaign and the Global Sepsis Alliance are working to raise awareness and promote further improvement initiatives. Future developments will focus on sepsis biomarkers and microarray techniques to rapidly screen for pathogens, risk stratification using genetic profiling, and the development of novel therapeutic agents targeting immunomodulation.
Building a user-derived interface (1984)

Many human-computer interfaces are designed with the assumption that the user must adapt to the system, that users must be trained and their behavior altered to fit a given interface. The research presented here proceeds from the alternative assumption: Novice behavior is inherently sensible, and the computer system can be made to adapt to it. Specifically, a measurably easy-to-use interface was built to accommodate the actual behavior of novice users. Novices attempted an electronic mail task using a command-line interface containing no help, no menus, no documentation, and no instruction. A hidden operator intercepted commands when necessary, creating the illusion of an interactive session. The software was repeatedly revised to recognize users' new commands; in essence, the interface was derived from user behavior. This procedure was used on 67 subjects. The first version of the software could recognize only 7 percent of all the subjects' spontaneously generated commands; the final version could recognize 76 percent of these commands. This experience contradicts the idea that user input is irrelevant to the design of command languages. Through careful observation and analysis of user behavior, a mail interface unusable by novices evolved into one that let novices do useful work within minutes.
Phase recovery and holographic image reconstruction using deep learning in neural networks (2017)

Phase recovery from intensity-only measurements forms the heart of coherent imaging techniques and holography. In this study, we demonstrate that a neural network can learn to perform phase recovery and holographic image reconstruction after appropriate training. This deep learning-based approach provides an entirely new framework to conduct holographic imaging by rapidly eliminating twin-image and self-interference-related spatial artifacts. This neural network-based method is fast to compute and reconstructs phase and amplitude images of the objects using only one hologram, requiring fewer measurements in addition to being computationally faster. We validated this method by reconstructing the phase and amplitude images of various samples, including blood and Pap smears and tissue sections. These results highlight that challenging problems in imaging science can be overcome through machine learning, providing new avenues to design powerful computational imaging systems.
Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11 (1994)

Using gene targeting, we have created mice with a disruption in the homeobox-containing gene hoxd-11. Homozygous mutants are viable and the only outwardly apparent abnormality is male infertility. Skeletons of mutant mice show a homeotic transformation that repatterns the sacrum such that each vertebra adopts the structure of the next most anterior vertebra. Defects are also seen in the bones of the limb, including regional malformations at the distal end of the forelimb affecting the length and structure of phalanges and metacarpals, inappropriate fusions between wrist bones, and defects at the most distal end in the long bones of the radius and ulna. The phenotypes show both incomplete penetrance and variable expressivity. In contrast to the defects observed in the vertebral column, the phenotypes in the appendicular skeleton do not resemble homeotic transformations, but rather regional malformations in the shapes, length and segmentation of bones. Our results are discussed in the context of two other recent gene targeting studies involving the paralogous gene hoxa-11 and another member of the Hox D locus, hoxd-13. The position of these limb deformities reflects the temporal and structural colinearity of the Hox genes, such that inactivation of 3' genes has a more proximal phenotypic boundary (affecting both the zeugopod and autopod of the limb) than that of the more 5' genes (affecting only the autopod). Taken together, these observations suggest an important role for Hox genes in controlling localized growth of those cells that contribute to forming the appendicular skeleton.
Periodic Recurrence of Gangrenous Dermatitis Associated with Clostridium Septicum in a Broiler Chicken Operation (1996)

The association of gangrenous dermatitis (GD) of chickens with Clostridium septicum infection was well documented in the United States during the 1960s (Bickford AA: 1971, Proc 20th Western Poult Dis Conf, pp. 6, 7). At about the same time, GD was recognized as a source of considerable economic loss to broiler production operations in the United Kingdom and Australia. 1,3 Subsequently, the potentiating role of immunosuppression induced by infectious bursal disease virus (IBDV) and other viral agents was recognized. Reduction of losses caused by GD requires control procedures for IBDV and other immunosuppressive agents. Recent reports have suggested that there may be an increased incidence of the clostridial diseases of chickens in the United States. Among these diseases, GD associated with C. septicum is a major concern. At the California Veterinary Diagnostic Laboratory System (CVDLS), Turlock Branch, the diagnosis of this disease was once as frequent as 5% of all diagnostic cases (Bristow DL: 1971, Proc 20th Western Poult Dis Conf, p. 11). After producers implemented procedures to limit the effects of IBDV, the diagnosis of GD became a rare event in California. This report documents an unusual annual recurrence of C. septicum-associated GD over 3 consecutive years in a single house of a multiple-house broiler facility. The ranch involved in this report is situated on flat delta valley terrain and consists of 8 broiler houses. The houses are similar in design but differ in size. Three houses are 10,000 sq ft, 3 are 15,000 sq ft, and 2 are 17,500 sq ft. Feed sources, feed delivery systems, ventilation systems, and litter management procedures are uniform on the ranch. A single well serves as the water source for all houses, and hot-water brooding is practiced in all houses. The ranch is operated on a year-round all-in, all-out basis. On February 3, 1993, 7 dead 43-day-old broiler chickens were submitted from house 5 (15,000 sq ft) to CVDLS, Turlock Branch, for necropsy. Mortality in the house had increased suddenly to about 1% per day. Stocking density in all three 15,000-sq-ft buildings had been 19,000 chicks at placement. This density is approximately 8.5% higher than normal for these houses. Climatic conditions were normal for winter with characteristically high humidities and cool temperatures. Litter conditions in the house were described as old and wet. On January 18, 1994, a similar group of 6 dead broiler chickens was submitted from house 5. A sudden increase in mortality had occurred in this house only. The birds were
Silica-Coated Nanocomposites of Magnetic Nanoparticles and Quantum Dots (2005)

Quantum dots (QDs) and magnetic nanoparticles (MPs) are of interest for biological imaging, drug targeting, and bioconjugation because of their unique optoelectronic and magnetic properties, respectively. To provide for water solubility and biocompatibility, QDs and MPs were encapsulated within a silica shell using a reverse microemulsion synthesis. The resulting SiO2/MP-QD nanocomposite particles present a unique combination of magnetic and optical properties. Their nonporous silica shell allows them to be surface modified for bioconjugation in various biomedical applications.
The Accumulation of Man6GlcNAc2-PP-dolichol in theSaccharomyces cerevisiae Δalg9 Mutant Reveals a Regulatory Role for the Alg3p α1,3-Man Middle-arm Addition in Downstream Oligosaccharide-lipid and Glycoprotein Glycan Processing (2000)

N-Glycans in nearly all eukaryotes are derived by transfer of a precursor Glc(3)Man(9)GlcNAc(2) from dolichol (Dol) to consensus Asn residues in nascent proteins in the endoplasmic reticulum. The Saccharomyces cerevisiae alg (asparagine-linked glycosylation) mutants fail to synthesize oligosaccharide-lipid properly, and the alg9 mutant, accumulates Man(6)GlcNAc(2)-PP-Dol. High-field (1)H NMR and methylation analyses of Man(6)GlcNAc(2) released with peptide-N-glycosidase F from invertase secreted by Deltaalg9 yeast showed its structure to be Manalpha1,2Manalpha1,2Manalpha1, 3(Manalpha1,3Manalpha1,6)-Manbeta1,4GlcNAcbeta1, 4GlcNAcalpha/beta, confirming the addition of the alpha1,3-linked Man to Man(5)GlcNAc(2)-PP-Dol prior to the addition of the final upper-arm alpha1,6-linked Man. This Man(6)GlcNAc(2) is the endoglycosidase H-sensitive product of the Alg3p step. The Deltaalg9 Hex(7-10)GlcNAc(2) elongation intermediates were released from invertase and similarly analyzed. When compared with alg3 sec18 and wild-type core mannans, Deltaalg9 N-glycans reveal a regulatory role for the Alg3p-dependent alpha1,3-linked Man in subsequent oligosaccharide-lipid and glycoprotein glycan maturation. The presence of this Man appears to provide structural information potentiating the downstream action of the endoplasmic reticulum glucosyltransferases Alg6p, Alg8p and Alg10p, glucosidases Gls1p and Gls2p, and the Golgi Och1p outerchain alpha1,6-Man branch-initiating mannosyltransferase.
The Renoprotective Potential of Pentoxifylline in Chronic Kidney Disease (2005)

Current interventions with proven efficacy, such as glycemic and blood pressure control, dietary protein restriction, and angiotensin II blockade, slow the progression of chronic kidney disease (CKD); however, whether long-term cessation of CKD progression is possible remains unclear. Because of the pathogenetic complexity of this condition, multidrug interventions with the least adverse effects should be investigated as the next step in attempts to stop CKD progression. Pentoxifylline, a non-selective phosphodiesterase inhibitor with indiscernible toxicity, exerts potent inhibitory effects against cell proliferation, inflammation, and extracellular matrix accumulation, all of which play important roles in CKD progression. Pentoxifylline monotherapy markedly reduces proteinuria in patients with membranous nephropathy. Moreover, limited human studies have proven pentoxifylline efficacy in reducing proteinuria in patients with diabetes receiving angiotensin-converting enzyme inhibitors, and in patients with nephrotic syndrome secondary to lupus nephritis despite immunosuppressive therapy. Further clinical trials are necessary to examine whether pentoxifylline can improve renal outcomes in patients receiving interventions of proven efficacy.
Magnetic Position and Orientation Tracking System (1979)

Three-axis generation and sensing of quasi-static magneticdipole fields provide information sufficient to determine both the position and orientation of the sensor relative to the source. Linear rotation transformations based upon the previous measurements are applied to both the source excitation and sensor output vectors, yielding quantities that are linearly propotional to small changes in the position and orientation. Changes are separated using linear combinations of sensor output vectors, transformed to the desired coordinate frame, and used to update the previous measurements. Practical considerations for a head-tracking application are discussed.
Art in organic synthesis (1970)

Partial table of contents: Adrenosterone. Adriamycine. Aflatoxines. Ajmaline. Aldosterone. B-Amyrine. Anguidine. Basketene. Benzene Dimer. Benzene Oxides. Benzvalene. Bicyclo [8.8.8]hexacosane, out-in, in-in. Biotin. Carpetimycin A. Catenane. Cecropia Juvenile Hormone. Cephalotaxene. Chaenorhine. Damsin. Delta Acid. Diamond Structures. Dihydromevinoline, Compactin. Dihydroperiphyllene. Elaiomycin. Elaiophylin. Epiandrosterone. Eriolanin. Erythromycin. Estrone. Fenestrane. Friedelin. Frullanolide. Garryine. Geissoschizoline. Gibberilic Acid. Helicenes. Hexaazabenzene. Histrionicotoxin. Hooplane. Iceane. Insulin. Iridomyrmecin. Iso-retronecanol. Kekulene. Kopsane. Lasalocid A. Leucotrienes. Lincosamine. Lipoic Acid. Marasmic Acid. Mavacurine. Maysine. Methelenomycin. Methynolide. Methmycin. Methynolide. Nenitzescu Hydrocarbon. Nonactin. Octalene. [5]Paracyclophane. Pentalene Dianion. Pentaprismane. Quinghaosu (Artemisinin). Quadrone. Quassin. Quinine. Reserpine. Retigeranic Acid. Rifamycine S. Sexipyridine. Showdomycin. Tetracyclines. Tetrahedrane, Tetra-t-Butyl. Thromboxane B2?. Vernelopin. Vermiculene. Verrucarol. Vinblastin, Vincristine. Vitamin A. Vitamin B12?. Zoanthocanthin. Index.
Lambert-Eaton Myasthenic Syndrome (2004)

Lambert-Eaton myasthenic syndrome (LEMS) is an idiopathic or paraneoplastic syndrome producing antibodies against presynaptic voltage-gated P/Q calcium channels. This decreases calcium entry into the presynaptic terminal, which prevents binding of vesicles to the presynaptic membrane and acetylcholine release. LEMS is most often associated with small cell lung cancer, although idiopathic presentations comprise approximately 40% of the cases. The most common initial complaint is proximal muscle weakness involving the lower extremities more than the upper extremities. Depressed deep tendon reflexes and autonomic dysfunction are frequently present. Involvement of the bulbar or respiratory muscles is rare. Diagnosis is confirmed by electrophysiological testing, which demonstrates small compound muscle action potentials and facilitation with exercise or 20-Hz repetitive stimulation. A serum test for voltage-gated calcium channel antibodies is commercially available. Treatment involves removing the cancer associated with the disease. If cancer is not found, immunosuppressive medications and acetylcholinesterase inhibitors are used with moderate success. Patients with idiopathic LEMS should be screened every 6 months with chest imaging for cancer.
Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids (2000)

The bacteriophage P1 Cre/loxP system has become a powerful tool for in vivo manipulation of the genomes of transgenic mice. Although in vitro studies have shown that Cre can catalyze recombination between cryptic "pseudo-loxP" sites in mammalian genomes, to date there have been no reports of loxP-site infidelity in transgenic animals. We produced lines of transgenic mice that use the mouse Protamine 1 (Prm1) gene promoter to express Cre recombinase in postmeiotic spermatids. All male founders and all Cre-bearing male descendents of female founders were sterile; females were unaffected. Sperm counts, sperm motility, and sperm morphology were normal, as was the mating behavior of the transgenic males and the production of two-celled embryos after mating. Mice that expressed similar levels of a derivative transgene that carries an inactive Cre exhibited normal male fertility. Analyses of embryos from matings between sterile Cre-expressing males and wild-type females indicated that Cre-catalyzed chromosome rearrangements in the spermatids that lead to abortive pregnancies with 100% penetrance. Similar Cre-mediated, but loxP-independent, genomic alterations may also occur in somatic tissues that express Cre, but, because of the greater difficulty of assessing deleterious effects of somatic mutations, these may go undetected. This study indicates that, following the use of the Cre/loxP site-specific recombination systems in vivo, it is prudent to eliminate or inactivate the Cre recombinase gene as rapidly as possible.
Performance enhancement of long-distance simultaneous measurement of strain and temperature based on a fiber Raman laser with an etched FBG (2005)

The performance enhancement of long-distance remote simultaneous measurement of strain and temperature based on a fiber Raman laser is proposed and demonstrated by an etched fiber Bragg grating (FBG) fixed on a quartz plate. An all-FBG-based Raman fiber laser with a high extinction ratio of more than /spl sim/50 dB is clearly obtained. After reducing the cladding diameter of the FBG to enhance the strain sensitivity, its half segment is fixed firmly on a quartz plate to respond to temperature only, while the other half of the etched FBG is free to respond to both temperature and strain. The lasing wavelength shift and separation occur with the temperature and strain change, respectively. The strain sensitivity is significantly enhanced to be approximately 1.6 times higher than that of a conventional FBG. A simple and effective technique for simultaneous measurement of strain and temperature for long-distance sensing applications of more than 50 km is readily achieved.
Complex and Context Dependent Regulation of Hematopoiesis by TGF‐β Superfamily Signaling (2009)

The transforming growth factor (TGF)-beta superfamily of growth factors, including the TGF-betas, activins, and bone morphogenetic proteins (BMPs), provide cells with a broad spectrum of regulatory signals through the intracellular Smad pathway. Since loss-of-function studies of a majority of the TGF-beta superfamily members result in embryonic lethality, much of our current knowledge of the TGF-beta superfamily's role in hematopoiesis is generated from studies performed in vitro, or in very early stages of embryonic development. TGF-beta is well documented as a potent inhibitor of hematopoietic stem cell (HSC) proliferation in vitro, while its role in vivo is largely unknown. BMP signaling is crucial for the initiation of hematopoiesis in the developing embryo, although its role in adult hematopoiesis remains elusive. More recently we and others have used conditional knockout models to unravel the role of several components of TGF-beta family signaling in adult hematopoiesis. Here we review the currently known functions for the major factors of this signaling family in embryonic and adult hematopoietic regulation and discuss the context dependency and complexity that permeate this regulation.