gebhart/patrepeval huggingface dataset:
Extinction technique for optical storage using anisotropic color centers in alkali halides (1974)

An extinction technique is described for obtaining high-contrast images while effectively increasing sensitivity in photodichroic alkali halide crystals.
Insulitis and β-Cell Mass in the Natural History of Type 1 Diabetes (2015)

Descriptions of insulitis in human islets throughout the natural history of type 1 diabetes are limited. We determined insulitis frequency (the percent of islets displaying insulitis to total islets), infiltrating leukocyte subtypes, and β-cell and α-cell mass in pancreata recovered from organ donors with type 1 diabetes (n = 80), as well as from donors without diabetes, both with islet autoantibodies (AAb(+), n = 18) and without islet autoantibodies (AAb(-), n = 61). Insulitis was observed in four of four donors (100%) with type 1 diabetes duration of ≤1 year and two AAb(+) donors (2 of 18 donors, 11%). Insulitis frequency showed a significant but limited inverse correlation with diabetes duration (r = -0.58, P = 0.01) but not with age at disease onset. Residual β-cells were observed in all type 1 diabetes donors with insulitis, while β-cell area and mass were significantly higher in type 1 diabetes donors with insulitis compared with those without insulitis. Insulitis affected 33% of insulin(+) islets compared with 2% of insulin(-) islets in donors with type 1 diabetes. A significant correlation was observed between insulitis frequency and CD45(+), CD3(+), CD4(+), CD8(+), and CD20(+) cell numbers within the insulitis (r = 0.53-0.73, P = 0.004-0.04), but not CD68(+) or CD11c(+) cells. The presence of β-cells as well as insulitis several years after diagnosis in children and young adults suggests that the chronicity of islet autoimmunity extends well into the postdiagnosis period. This information should aid considerations of therapeutic strategies seeking type 1 diabetes prevention and reversal.
An effective method on blind speech separation in strong noisy environment (2005)

Researches in speech separation that have existed mostly concentrate on the noise-free or low noise situations. But speech communication in reality is usually interfered by strong noise. In this paper we present an effective blind speech separation method in strong noisy environment based on discrete wavelet transform (DWT) and independent component analysis (ICA). Firstly, denoising the strong noisy mixtures with DWT is performed, in which step de-noising is done reasonably in order to get little distorted speech mixtures. Then separate these mixtures by ICA to get each independent speech. Finally, further post processing that includes the normalization and post de-noising has been performed to improve the performance of the separated speeches, that obtains the final estimated sources. Simulation results exhibit a high level of separating results.
Linear-after-the-exponential polymerase chain reaction and allied technologies. Real-time detection strategies for rapid, reliable diagnosis from single cells. (2007)

Accurate detection of gene sequences in single cells is the ultimate challenge to polymerase chain reaction (PCR) sensitivity. Unfortunately, commonly used conventional and real-time PCR techniques are often too unreliable at that level to provide the accuracy needed for clinical diagnosis. Here we provide details of linear-after-the-exponential-PCR (LATE-PCR), a method similar to asymmetric PCR in the use of primers at different concentrations, but with novel design criteria to ensure high efficiency and specificity. Compared with conventional PCR, LATE-PCR increases the signal strength and allele discrimination capability of oligonucleotide probes such as molecular beacons and reduces variability among replicate samples. The analysis of real-time kinetics of LATE-PCR signals provides a means for improving the accuracy of single cell genetic diagnosis.
Coded aperture compressive temporal imaging (2013)

We use mechanical translation of a coded aperture for code division multiple access compression of video. We discuss the compressed video's temporal resolution and present experimental results for reconstructions of > 10 frames of temporal data per coded snapshot.
Mechanism of Idiosyncratic Drug Reactions: Reactive Metabolites Formation, Protein Binding and the Regulation of the Immune System (2002)

Drug-induced adverse reactions, especially type B reactions, represent a major clinical problem. They also impart a significant degree of uncertainty into drug development because they are often not detected until the drug has been released onto the market. Type B reactions are also termed idiosyncratic drug reactions by many investigators due to their unpredictable nature and our lack of understanding of the mechanisms involved. It is currently believed that the majority of these reactions are immune-mediated and are caused by immunogenic conjugates formed from the reaction of a reactive metabolite of a drug with cellular proteins. It has been shown that most drugs associated with idiosyncratic reactions form reactive metabolites to some degree. Covalent binding of reactive metabolites to cellular proteins has also been shown in many cases. However, studies to reveal the role of reactive metabolites and their protein-adducts in the mechanism of drug-induced idiosyncratic reactions are lacking. This review will focus on our current understanding and speculative views on how a reactive metabolite of a drug might ultimately lead to immune-mediated toxicity.
The role of antigen-presenting cells in the regulation of delayed-type hypersensitivity. I. Spleen dendritic cells. (1992)

A previously unreported mechanism for the induction of delayed-type hypersensitivity (DTH) was studied in detail. The subcutaneous injection (without adjuvant) of spleen dendritic cells (DC) pulsed with keyhole limpet haemocyanin (KLH) into syngeneic BALB/c mice caused DTH when the ear was later injected with the same antigen. When KLH-pulsed DC were transferred intravenously, DTH was not induced, although the titre of anti-KLH antibodies rose after such transfer. The intravenous transfer of KLH-pulsed DC into mice immunized subcutaneously with KLH in complete Freund's adjuvant (CFA) at the same time (in the sensitization phase), but not when the ear was challenged with KLH (in the effector phase), had a suppressive effect on DTH, in an H-2-restricted way. When radiolabelled DC were transferred intravenously, they migrated into the spleen, but when transferred by subcutaneous injection, they stayed in the skin or migrated into the lymph nodes. In splenectomized mice immunized with KLH, the intravenous transfer of KLH-pulsed DC did not cause production of anti-KLH antibodies and did not suppress DTH. These findings suggest that the anatomical sites in which antigens are presented (i.e. the spleen or lymph nodes) rather than the type of cell that first presents antigens to the immune system governs whether DTH or antibody production is induced. Antibody production was induced when antigens were presented in the spleen.
Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. (1996)

Nucleosome-specific T helper (Th) cells provide major histocompatibility complex class II-restricted, cognate help to nephritogenic antinuclear autoantibody-producing B cells in lupus. However, the lupus Th cells do not respond when components of the nucleosome, such as free DNA or histones, are individually presented by antigen-presenting cells. Thus critical peptide epitopes for the pathogenic Th cells are probably protected during uptake and processing of the native nucleosome particle as a whole. Therefore, herein we tested 145 overlapping peptides spanning all four core histones in the nucleosome. We localized three regions in core histones, one in H2B at amino acid position 10-33 (H2B(10-33)), and two in H4, at position 16-39 (H4(16-39)) and position 71-94 (H4(71-94)), that contained the peptide epitopes recognized by the pathogenic autoantibody-inducing Th cells of lupus. The peptide autoepitopes also triggered the pathogenic Th cells of (SWR x NZB)F1 lupus mice in vivo to induce the development of severe lupus nephritis. The nucleosomal autoepitopes stimulated the production of Th1-type cytokines, consistent with immunoglobulin IgG2a, IgG2b, and IgG3 being the isotypes of nephritogenic autoantibodies induced in the lupus mice. Interestingly, the Th cell epitopes overlapped with regions in histones that contain B cell epitopes targeted by autoantibodies, as well as the sites where histones contact with DNA in the nucleosome. Identification of the disease-relevant autoepitopes in nucleosomes will help in understanding how the pathogenic Th cells of spontaneous systemic lupus erythematosus emerge, and potentially lead to the development of peptide-based tolerogenic therapy for this major autoimmune disease.
Decreased Visual Function after Patchy Loss of Retinal Pigment Epithelium Induced by Low-Dose Sodium Iodate (2009)

Stable, patchy RPE loss was observed with a low concentration of NaIO(3). The OKR measurement showed changes in visual function earlier than the cued WM test and before histologic findings were observed.
Learning and making decisions when costs and probabilities are both unknown (2001)

In many data mining domains, misclassification costs are different for different examples, in the same way that class membership probabilities are example-dependent. In these domains, both costs and probabilities are unknown for test examples, so both cost estimators and probability estimators must be learned. After discussing how to make optimal decisions given cost and probability estimates, we present decision tree and naive Bayesian learning methods for obtaining well-calibrated probability estimates. We then explain how to obtain unbiased estimators for example-dependent costs, taking into account the difficulty that in general, probabilities and costs are not independent random variables, and the training examples for which costs are known are not representative of all examples. The latter problem is called sample selection bias in econometrics. Our solution to it is based on Nobel prize-winning work due to the economist James Heckman. We show that the methods we propose perform better than MetaCost and all other known methods, in a comprehensive experimental comparison that uses the well-known, large, and challenging dataset from the KDD'98 data mining contest.
Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet beta-cells. (1994)

Insulin secretion from pancreatic islets is controlled by peptides as well as by nutrients. We report here a novel, extraordinarily potent peptidergic regulation of insulin secretion. A 27-residue form of pituitary adenylate cyclase activating polypeptide (PACAP27) as low as 10(-14) to 10(-13) M stimulated insulin release from rat islets in a glucose-dependent manner. PACAP27 also increased cytosolic free Ca2+ concentration ([Ca2+]i) in islet beta-cells. Nitrendipine, a blocker of the L-type Ca2+ channel, abolished both [Ca2+]i and insulin responses. Vasoactive intestinal peptide, a peptide exhibiting 68% amino acid homology with PACAP, also increased [Ca2+]i in beta-cells but only at concentrations in the nanomolar range, indicating that PACAP27 is 4 logs more potent. A 38-residue form of the peptide (PACAP38) stimulated insulin release and increased beta-cell [Ca2+]i in a manner similar to that of PACAP27. PACAP-like immunoreactivity was demonstrated in pancreatic nerve fibers, islets, and capillaries. The results indicate that PACAP is a physiologically occurring peptide in pancreas and that PACAP, in a glucose-dependent manner, activates beta-cells presumably via a high affinity PACAP-selective receptor, raises [Ca2+]i by increasing the activity of L-type Ca2+ channels, and consequently stimulates insulin release. PACAP appears to be by far the most potent insulinotropic peptide known.
Relationships at the Heart of Semantic Web: Modeling, Discovering, Validating and Exploiting Complex Semantic Relationship (2002)

During the last decade, the emphasis has been on finding relevant documents or content, an objective which most of today's search and browsing techniques address. We believe during the next decade, the emphasis will shift from documents and entities to relationships-that of discovering or validating contextually relevant, meaningful and possibly complex relationships amongst the entities that documents mention and describe. This also is likely to be the next area of focus for the Semantic Web community after it makes progress in addressing the current areas of emphasis on ontology representation, semantic metadata extraction for automatic annotation, query processing and inferencing. Relationships are fundamental to semantics-they associate meanings to words, terms and entities. Semantic Web intends to associate annotations (i.e., metadata) with all Web-accessible resources such that programs can associate 'meaning with data' to interpret them, and to process (access, invoke, utilize, and analyze) them automatically, resulting in higher scalability and better productivity. In this talk, we will look at a more comprehensive set of relationships that may be based not only on what is contained in or directly derived from data (or represented as part of resource modeling and annotations), but may be based on information extraction, external and prior knowledge and user defined computations. We also present some recent techniques for discovering indirect (i.e., transitive) and virtual (i.e., user-defined) yet meaningful (i.e., contextually relevant) relationships based on a set of patterns and paths between entities of interest, domain-specific computations and user defined relationships. In particular, we will discuss modeling, representation and computation or validation of three types of complex semantic relationships: (a) multi-ontology relationships and the issue of 'loss of information' investigated in the OBSERVER project, (b) Rho operator for semantic associations which seeks to identify contextually relevant and relevancy ranked indirect relationships or paths between entities using semantic metadata and relevant knowledge, and (c) ISCAPEs which allows interactive, human-directed knowledge validation of hypothesis involving user-defined relationships and operations in a multi-ontology, multi-agent InfoQuilt system.
Synthesis of Arylsubstituted Imidazolin-2-one Analogues (2004)

Herein we reported a one-pot synthesis of arylsubstituted imidazolin-2-ones by the cyclization of α-aminoacetophenone hydrochloride analogues 2 with arylisocyanates 3. Compared with other known synthetic route, this method resulted in higher yield.
Cloning of Interferon-Stimulated Gene 17: The Promoter and Nuclear Proteins That Regulate Transcription (1999)

A member of the interferon-stimulated gene (ISG) family encodes a 17-kDa ubiquitin homolog called ISG17 that is induced in the bovine uterine endometrium by interferon-tau (IFN-tau) during early pregnancy. The bovine (b) ISG17 cDNA shares 30% identity with a tandem ubiquitin repeat and 70% identity with human (h) ISG15. The present experiments were designed to sequence the bISG17 gene, compare general structure with the hISG15 gene, and to identify transcription factors that were induced by IFN-tau in bovine endometrial (BEND) cells. The promoter of the bISG17 gene was similar to the hISG15 gene in placement of a tandem IFN-stimulatory response element (ISRE) at position -90, but unique in the presence of three additional ISREs at positions -123, -332, and -525. IFN-tau (25 nM) induced nuclear proteins in BEND cells that interacted with a tandem bISG17 ISRE in electrophoretic mobility shift assay (EMSA). IFN-regulatory factor-1 (IRF-1) bound to this ISRE based upon supershift EMSA using antiserum against IRF-1. IFN-tau activated STAT-1 (signal transducer and activator of transcription-1) and -2 by 0.5 h, and IRF-1 by 2 h in BEND cells. It is concluded that the bISG17 gene is similar to the hISG15 gene, retains an ISRE that interacts with IRF-1, and is possibly induced initially by the STATs and later by IRF-1 in response to IFN-tau during early pregnancy.
High resolution radar target identification (2003)

The application of neural networks to the synthetic aperture radar (SAR) automatic target recognition (ATR) problem is discussed. In particular, initial studies investigating the use of an ART-2 self organizing neural-network in a 2-D SAR ATR system are summarized. The performance of the new neural net pattern-matching algorithm is compared with that of the baseline correlation pattern matching algorithm developed previously. This comparison includes evaluating the ability of the pattern matcher to reject nontargets (clutter discretes) and to classify the remaining detections into tank/APC/Howitzer categories.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Bacterial expression of a neutralizing mouse monoclonal antibody Fab fragment to a 150-kilodalton surface antigen of Entamoeba histolytica. (1999)

A mouse monoclonal antibody (MAb) (EH3015, IgG1 with a K light chain) prepared by hybridoma technology recognizes a 150-kD surface antigen of Entamoeba histolytica and inhibits adherence and cytotoxicity of the ameba to mammalian cells. The genes encoding the light chain and the Fd region of the heavy chain of the MAb were cloned and expressed in Escherichia coli. The plasmid used was designed for the expression of Fab with a hexa-histidine tag in the periplasmic space. Recombinant Fab fragments were purified and analyzed by an indirect immunofluorescence antibody test and Western immunoblot. The specificity of the recombinant Fab fragment was comparable with the parent whole IgG. In addition, the Fab fragments significantly inhibited the adherence of E. histolytica to erythrocytes. These results suggest that the production of a neutralizing MAb in Escherichia coli is practical and efficient with this expression system.
Amphiphilic copolymers for liquid bandage application studies (2010)

This research pertains to a new class of liquid bandage polymers which are promising for assisting advanced wound healing by serving as substrates to promote cell viability and proliferation. Amphiphilic nitrogen-containing polymer poly (3-methacryloyloxypropyltris (trimethylsiloxy)silane-co-N-isopropylacrylamide) (poly (TRIS-co-NIPAM)) was synthesized and investigated with further comparison to several different wound care polymers including commercialized 3M Nexcare No Sting Liquid Bandage. Cell viability on different polymers was tested on fetal human skin fibroblasts (HSFs) and neonatal human epidermal keratinocytes (HEKs). Test results were quantified by Sulforhodamine B (SRB) in vitro cytotoxicity assay. It was demonstrated that both HSFs and HEKs survive better on the poly (TRIS-co-NIPAM) film as the cell seeding substrate compared to other candidate polymer formulations, as well as to the commercial 3M No Sting Liquid Bandage polymer. Thus we conclude that wound healing could be accelerated by this new class of liquid bandage polymer, particularly for early-stage wounds..
Elucidation of Acid-induced Unfolding and Aggregation of Human Immunoglobulin IgG1 and IgG2 Fc (2011)

Understanding the underlying mechanisms of Fc aggregation is an important prerequisite for developing stable and efficacious antibody-based therapeutics. In our study, high resolution two-dimensional nuclear magnetic resonance (NMR) was employed to probe structural changes in the IgG1 Fc. A series of (1)H-(15)N heteronuclear single-quantum correlation NMR spectra were collected between pH 2.5 and 4.7 to assess whether unfolding of C(H)2 domains precedes that of C(H)3 domains. The same pH range was subsequently screened in Fc aggregation experiments that utilized molecules of IgG1 and IgG2 subclasses with varying levels of C(H)2 glycosylation. In addition, differential scanning calorimetry data were collected over a pH range of 3-7 to assess changes in C(H)2 and C(H)3 thermostability. As a result, compelling evidence was gathered that emphasizes the importance of C(H)2 stability in determining the rate and extent of Fc aggregation. In particular, we found that Fc domains of the IgG1 subclass have a lower propensity to aggregate compared with those of the IgG2 subclass. Our data for glycosylated, partially deglycosylated, and fully deglycosylated molecules further revealed the criticality of C(H)2 glycans in modulating Fc aggregation. These findings provide important insights into the stability of Fc-based therapeutics and promote better understanding of their acid-induced aggregation process.
The effects of ancrod, the coagulating enzyme from the venom of Malayan pit viper (A. rhodostoma) on prothrombin and fibrinogen metabolism and fibrinopeptide A release in man. (1978)

The action of ancrod on fibrinogen and prothrombin metabolism was studied in six healthy individuals by the use of 131I-fibrinogen and 125I-prothrombin and by measurement of blood levels of fibrinopeptide A. Two untreated healthy controls were studied at the same time. Rapid defibrinogenation occurred during the initial 3 hr ancrod infusion, and fibrinogen levels were maintained near zero throughout the study. Large quantities of non-thrombin-clottable TCA-precipitable 131I material could be demonstrated in the circulation, reaching a maximum 3 to 6 hr after ancrod infusion and clearing with a half-life of 6 hr. Gel filtration of 6 hr plasmas demonstrated the presence of complexes larger than fibrinogen, as well as degradation products of fibrinogen-fibrin. Prothrombin concentration and metabolism were unchanged by ancrod treatment. Fibrinopeptide A levels in the ancrod group were greather than 4,000 ng/ml during the initial defibrinogenation, declined to greater than 80 ng/ml, and then increased to high levels after 3 days. These studies provide explanations of previous observations concerning the specificity of ancrod and demonstrate that rapid clotting of fibrinogen and dissolution of fibrin can occur in vivo without recruitment of the classic coagulation mechanism.
Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1 (2011)

Plasmodium falciparum malaria is a major cause of mortality and severe morbidity. Its virulence is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family is central to both. Here, we present evidence of a P. falciparum evasion mechanism not previously documented: the masking of PfEMP1-specific IgG epitopes by nonspecific IgM. Nonspecific IgM binding to erythrocytes infected by parasites expressing the PfEMP1 protein VAR2CSA (involved in placental malaria pathogenesis and protective immunity) blocked subsequent specific binding of human monoclonal IgG to the Duffy binding-like (DBL) domains DBL3X and DBL5ε of this PfEMP1 variant. Strikingly, a VAR2CSA-specific monoclonal antibody that binds outside these domains and can inhibit IE adhesion to the specific VAR2CSA receptor chondroitin sulfate A was unaffected. Nonspecific IgM binding protected the parasites from FcγR-dependent phagocytosis of VAR2CSA(+) IEs, but it did not affect IE adhesion to chondroitin sulfate A or lead to C1q deposition on IEs. Taken together, our results indicate that the VAR2CSA affinity for nonspecific IgM has evolved to allow placenta-sequestering P. falciparum to evade acquired protective immunity without compromising VAR2CSA function or increasing IE susceptibility to complement-mediated lysis. Furthermore, functionally important PfEMP1 epitopes not prone to IgM masking are likely to be particularly important targets of acquired protective immunity to P. falciparum malaria.