gebhart/patrepeval huggingface dataset:
Use of Immunoglobulin M Cross-Reactions in Differential Diagnosis of Human Flaviviral Encephalitis Infections in the United States (2002)

To define the virus specificity of the immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) among the medically important members of the Japanese encephalitis (JE) virus serocomplex of flaviviruses, 103 IgM-positive human serum samples from patients with confirmed West Nile (WN) virus, St. Louis encephalitis (SLE) virus, or JE virus infections were assembled and simultaneously tested against all three viral antigens in a standardized MAC-ELISA. Of the serum samples tested, 96 (93%) showed higher positive-to-negative absorbance ratios (P/Ns) with the infecting virus antigen compared to those obtained with the other two virus antigens. Of the seven specimens with higher P/Ns with heterologous virus antigens, six were from patients with SLE virus infections (the serum samples had higher levels of reactivity with WN virus antigen) and one was from a patient with a JE virus infection (this serum sample also had a higher level of reactivity with WN virus antigen). Not surprisingly, similar virus specificity was observed with WN virus-elicited IgM in cerebrospinal fluid. As shown in previous studies, a subset of these specimens was even less reactive in the MAC-ELISA with dengue virus, a member of a different flavivirus serocomplex. The degree of virus cross-reactivity did not appear to be related to days postonset, at least during the first 40 days of infection. Infections with WN virus could be correctly distinguished from infections with SLE virus on the basis of the observed anti-viral IgM cross-reactivities alone 92% of the time. Infections with SLE virus resulted in antibody that was more cross-reactive, so identification of SLE virus as the infecting agent by use of MAC-ELISA cross-reactivity alone was more problematic.
“Belts of Gold” and “Twenty-Pounders”: Robert Louis Stevenson’s Textualized Economies (2000)

A new model for gauging levels of soil disturbance (i.e. tillage) by analysing arable weed assemblages from archaeological contexts is applied to an extensive Roman-to-early medieval archaeobotanical sequence from the region west of Cologne. It tests the hypothesis that increasing use of the mouldboard plough, especially in a three-field system, would result in increased levels of soil disturbance which would be reflected in the kinds of weeds that grew in arable fields. The results point to clear differences in tillage regimes during the Roman period, providing support for the view that military sites were not provisioned by the same networks that supplied the civilian market. They also reveal generally low disturbance levels for the fifth and sixth centuries, indicating a continuing predominance of ard cultivation in the post-Roman period. The majority of seventh- to eighth-century samples had, however, been grown in 'high disturbance' conditions, a pattern that continued through the eighth and ninth centuries. Although use of the mouldboard plough within a fully developed three-field system may not have become widespread until the tenth or eleventh century, our evidence suggests that a plough capable of turning over the soil was in use in the Rhineland at a much earlier date.
l-Folic Acid Supplementation in Healthy Postmenopausal Women: Effect on Homocysteine and Glycolipid Metabolism (2005)

These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.
Controlled manipulation of nanoparticles with an atomic force microscope (1995)

We report on the application of the atomic force microscope (AFM) to manipulate and position nanometer-sized particles with nanometer precision. The technique, which can be regarded as a nanometer-scale analogy to atomic level manipulation with the scanning tunneling microscope, allowed us to form arbitrary nanostructures, under ambient conditions, by controlled manipulation of individual 30 nm GaAs particles. A whole new set of nanodevices can be fabricated particle-by-particle for studies of quantum effects and single electron tunneling. We also demonstrate a method, based on the AFM manipulation, to determine the true lateral dimensions of nano-objects, in spite of the tip-sample convolution.
Cancer Stem Cells: An Old Idea—A Paradigm Shift (2006)

Although the concept that cancers arise from "stem cells" or "germ cells" was first proposed about 150 years ago, it is only recently that advances in stem cell biology have given new impetus to the "cancer stem cell hypothesis." Two important related concepts of this hypothesis are that (a) tumors originate in either tissue stem cells or their immediate progeny through dysregulation of the normally tightly regulated process of self-renewal. As a result of this, (b) tumors contain a cellular subcomponent that retains key stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation albeit aberrant that contributes to cellular heterogeneity. Recent experimental evidence in a variety of tumors has lent strong support to the cancer stem cell hypothesis that represents a paradigm shift in our understanding of carcinogenesis and tumor cell biology. This hypothesis has fundamental implications for cancer risk assessment, early detection, prognostication, and prevention. Furthermore, the current development of cancer therapeutics based on tumor regression may have produced agents that kill differentiated tumor cells while sparing the rare cancer stem cell population. The development of more effective cancer therapies may thus require targeting this important cell population.
Murine Peyer's patch T cell clones. Characterization of antigen-specific helper T cells for immunoglobulin A responses. (1982)

We successfully cloned antigen-specific T cells from murine gut-associated lymphoreticular tissue, i.e., Peyer's patches, which are dependent upon T cell growth factor and independent of antigen for continuous growth. These clones exhibit helper activity for IgA responses to sheep erythrocytes (SRBC) and have been designated T helper (Th) A. Two broad categories of Th A clones have been maintained in continuous culture. The first group supports IgM and largely IgA anti-SRBC plaque-forming cell (PFC) responses in both normal and SRBC-primed splenic B cell cultures, whereas the second group supports low IgM, IgG1, and IgG2 and high IgA PFC responses. Subclones derived from single cells maintain the parent helper properties when propagated in culture for long periods (greater than 7 mo). Cloned Th A cells are antigen specific and do not support polyclonal or immune responses to other thymus dependent antigens in normal B cell cultures. Th A cells require full histocompatibility for helper functions because addition of cloned Th A cells to B cell cultures from other H-2 types does not result in IgA responses. Cloned Th A cells are Thy-1.2+ and Lyt-1+ and Lyt-2-, Ig-, and I-A-. Th A cells bear Fc receptors for IgA and do not possess receptors for IgM or IgG isotypes. Thus, T cells that primarily promote IgA isotype responses have been isolated in high frequency from murine PP, an anatomical site of major importance for induction and regulation of the IgA response.
HORMONE-PRODUCING CULTURES OF ADRENAL AND PITUITARY TUMOR ORIGIN (1962)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Principles of Power Electronics (2023)

Substantially expanded and updated, the new edition of this classic textbook provides unrivalled coverage of the fundamentals of power electronics. Comprehensive coverage of foundational concepts in circuits, magnetics, devices, dynamic models, and control establishes a strong conceptual framework for further study. Extensive discussion of contemporary practical considerations, enhanced by real-world examples, prepares readers for design scenarios ranging from low-power dc/dc converters to multi-megawatt ac machine drives. New topics include SiC and GaN wide-bandgap materials, superjunction MOSFET and IGBT devices, advanced magnetics design, multi-level and switched-capacitor converters, RF converter circuits, and EMI. Over 300 new and revised end-of-chapter problems enhance and expand understanding of the material, with solutions for instructors. Unique in its breadth and depth, and providing a range of flexible teaching pathways at multiple levels, this is the definitive guide to power electronics for graduate and senior undergraduate students in electrical engineering, and practicing electrical engineers.
Modulation of Cell-adhesive Activity of Fibronectin by the Alternatively Spliced EDA Segment (1997)

Fibronectin (FN) has a complex pattern of alternative splicing at the mRNA level. One of the alternatively spliced segments, EDA, is prominently expressed during biological processes involving substantial cell migration and proliferation, such as embryonic development, malignant transformation, and wound healing. To examine the function of the EDA segment, we overexpressed recombinant FN isoforms with or without EDA in CHO cells and compared their cell-adhesive activities using purified proteins. EDA+ FN was significantly more potent than EDA- FN in promoting cell spreading and cell migration, irrespective of the presence or absence of a second alternatively spliced segment, EDB. The cell spreading activity of EDA+ FN was not affected by antibodies recognizing the EDA segment but was abolished by antibodies against integrin alpha5 and beta1 subunits and by Gly-Arg-Gly-Asp-Ser-Pro peptide, indicating that the EDA segment enhanced the cell-adhesive activity of FN by potentiating the interaction of FN with integrin alpha5beta1. In support of this conclusion, purified integrin alpha5beta1 bound more avidly to EDA+ FN than to EDA- FN. Augmentation of integrin binding by the EDA segment was, however, observed only in the context of the intact FN molecule, since the difference in integrin-binding activity between EDA+ FN and EDA- FN was abolished after limited proteolysis with thermolysin. Consistent with this observation, binding of integrin alpha5beta1 to a recombinant FN fragment, consisting of the central cell-binding domain and the adjacent heparin-binding domain Hep2, was not affected by insertion of the EDA segment. Since the insertion of an extra type III module such as EDA into an array of repeated type III modules is expected to rotate the polypeptide up to 180 degrees at the position of the insertion, the conformation of the FN molecule may be globally altered upon insertion of the EDA segment, resulting in an increased exposure of the RGD motif in III10 module and/or local unfolding of the module. Our results suggest that alternative splicing at the EDA exon is a novel mechanism for up-regulating integrin-binding affinity of FN operating when enhanced migration and proliferation of cells are required.
Metabolism and in vitro antiretroviral activities of bis(pivaloyloxymethyl) prodrugs of acyclic nucleoside phosphonates (1993)

Bis(pivaloyloxymethyl) [bis(pom)] derivatives of various acyclic nucleoside phosphonates--9-(2-phosphonylmethoxyethyl)adenine (PMEA), 9-(2-phosphonylmethoxypropyl)adenine (PMPA), and 9-(2-phosphonylmethoxypropyl)diaminopurine (PMPDAP)--were found to exhibit 9- to 23-fold greater antiviral activity than their corresponding unmodified compounds. The cytotoxicity of the bis(pom) analogs was also increased by various degrees, thus altering the therapeutic indexes of these compounds. Metabolic studies using [3H]bis(pom)PMEA and [3H]PMEA as model compounds suggested a > 100-fold increase in the cellular uptake of the bis(pom) derivative and formation of active diphosphorylated metabolite. However, the bis(pom) derivatives were chemically unstable and highly susceptible to serum-mediated hydrolysis, factors which limit their potential utility for intracellular drug delivery.
THE EFFECT OF CHINESE HERBAL MEDICINE CONTAINING ACONITINE ON THE PAIN RELIEF IN INTERSTITIAL CYSTITIS PATIENTS. - A PRELIMINARY STUDY - (2009)

You have accessJournal of Urology1 Apr 2009THE EFFECT OF CHINESE HERBAL MEDICINE CONTAINING ACONITINE ON THE PAIN RELIEF IN INTERSTITIAL CYSTITIS PATIENTS. - A PRELIMINARY STUDY - Takayuki Tsuchida, Tatsuya Miyamoto, Takashi Yamagishi, Satoru Kira, Kenji Kayanuma, Yaburu Haneda, Hideki Kobayashi, Hidenori Zakoji, Isao Araki, and Masayuki Takeda Takayuki TsuchidaTakayuki Tsuchida More articles by this author , Tatsuya MiyamotoTatsuya Miyamoto More articles by this author , Takashi YamagishiTakashi Yamagishi More articles by this author , Satoru KiraSatoru Kira More articles by this author , Kenji KayanumaKenji Kayanuma More articles by this author , Yaburu HanedaYaburu Haneda More articles by this author , Hideki KobayashiHideki Kobayashi More articles by this author , Hidenori ZakojiHidenori Zakoji More articles by this author , Isao ArakiIsao Araki More articles by this author , and Masayuki TakedaMasayuki Takeda More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(09)60078-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "THE EFFECT OF CHINESE HERBAL MEDICINE CONTAINING ACONITINE ON THE PAIN RELIEF IN INTERSTITIAL CYSTITIS PATIENTS. - A PRELIMINARY STUDY -." The Journal of Urology, 181(4S), pp. 23–24 © 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 181Issue 4SApril 2009Page: 23-24 Advertisement Copyright & Permissions© 2009 by American Urological AssociationMetricsAuthor Information Takayuki Tsuchida More articles by this author Tatsuya Miyamoto More articles by this author Takashi Yamagishi More articles by this author Satoru Kira More articles by this author Kenji Kayanuma More articles by this author Yaburu Haneda More articles by this author Hideki Kobayashi More articles by this author Hidenori Zakoji More articles by this author Isao Araki More articles by this author Masayuki Takeda More articles by this author Expand All Advertisement PDF downloadLoading ...
Potential mechanisms and implications for the formation of tau oligomeric strains (2016)

The culmination of many years of increasing research into the toxicity of tau aggregation in neurodegenerative disease has led to the consensus that soluble, oligomeric forms of tau are likely the most toxic entities in disease. While tauopathies overlap in the presence of tau pathology, each disease has a unique combination of symptoms and pathological features; however, most study into tau has grouped tau oligomers and studied them as a homogenous population. Established evidence from the prion field combined with the most recent tau and amyloidogenic protein research suggests that tau is a prion-like protein, capable of seeding the spread of pathology throughout the brain. Thus, it is likely that tau may also form prion-like strains or diverse conformational structures that may differ by disease and underlie some of the differences in symptoms and pathology in neurodegenerative tauopathies. The development of techniques and new technology for the detection of tau oligomeric strains may, therefore, lead to more efficacious diagnostic and treatment strategies for neurodegenerative disease. [Formula: see text].
Controlled Synthesis and Inclusion Ability of a Hyaluronic Acid Derivative Bearing β-Cyclodextrin Molecules (2006)

A new synthetic route to beta-cyclodextrin-linked hyaluronic acid (HA-CD) was developed. This was based on the preparation of a HA derivative selectively modified with adipic dihydrazide (HA-ADH) and a beta-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction. The CD-polysaccharide was fully characterized in terms of chemical integrity and purity by high-resolution NMR spectroscopy. The complexation ability of the grafted CD was further demonstrated by isothermal titration calorimetry using sodium adamantane acetate (ADAc) and Ibuprofen as model guest molecules. The thermodynamic parameters for the complexation of these negatively charged guest molecules by the beta-CD grafted on negatively charged HA were shown to be largely influenced by the ionic strength of the aqueous medium.
Inhibition of Serum- and Ras-Stimulated DNA Synthesis by Antibodies to Phospholipase C (1990)

Several immunologically distinct isozymes of inositol phospholipid-specific phospholipase C (PLC) have been purified from bovine brain. Murine NIH 3T3 fibroblasts were found to express PLC-gamma, but the expression of PLC-beta was barely detectable by radioimmunoassay or protein immunoblot. A mixture of monoclonal antibodies was identified that neutralizes the biological activity of both endogenous and injected purified PLC-gamma. When co-injected with oncogenic Ras protein or PLC-gamma, this mixture of antibodies inhibited the induction of DNA synthesis that characteristically results from the injection of these proteins into quiescent 3T3 cells. However, when oncogenic Ras protein or PLC-gamma was co-injected with a neutralizing monoclonal antibody to Ras, only the DNA synthesis induced by the Ras protein was inhibited--that induced by PLC was unaffected. These results suggest that the Ras protein is an upstream effector of PLC activity in phosphoinositide-specific signal transduction and that PLC-gamma activity is necessary for Ras-mediated induction of DNA synthesis.
Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicles (2009)

Mixing liposomes with hydrophilic particles induces fusion of the liposome onto the particle surface. Such supported bilayers have been studied extensively as models of the cell membrane, while their applications in drug delivery have not been pursued. In this communication, we report liposome fusion on mesoporous particles as a synergistic means to simultaneously load and seal cargo within the porous core. We find fusion of a cationic lipid (DOTAP) on an anionic silica particle loads an anionic fluorescent dye (calcein) into the particle to a concentration exceeding 100x that in the surrounding medium. The loaded "protocell" particles are taken up efficiently by Chinese hamster ovary cells, where, due to a reduced pH within endosomal compartments, calcein is effectively released. Compared to some other nanoparticle systems, protocells provide a simple construct for cargo loading, sealing, delivery, and release. They promise to serve as useful vectors in nanomedicine.
Exome-Scale Discovery of Hotspot Mutation Regions in Human Cancer Using 3D Protein Structure (2016)

The impact of somatic missense mutation on cancer etiology and progression is often difficult to interpret. One common approach for assessing the contribution of missense mutations in carcinogenesis is to identify genes mutated with statistically nonrandom frequencies. Even given the large number of sequenced cancer samples currently available, this approach remains underpowered to detect drivers, particularly in less studied cancer types. Alternative statistical and bioinformatic approaches are needed. One approach to increase power is to focus on localized regions of increased missense mutation density or hotspot regions, rather than a whole gene or protein domain. Detecting missense mutation hotspot regions in three-dimensional (3D) protein structure may also be beneficial because linear sequence alone does not fully describe the biologically relevant organization of codons. Here, we present a novel and statistically rigorous algorithm for detecting missense mutation hotspot regions in 3D protein structures. We analyzed approximately 3 × 10(5) mutations from The Cancer Genome Atlas (TCGA) and identified 216 tumor-type-specific hotspot regions. In addition to experimentally determined protein structures, we considered high-quality structural models, which increase genomic coverage from approximately 5,000 to more than 15,000 genes. We provide new evidence that 3D mutation analysis has unique advantages. It enables discovery of hotspot regions in many more genes than previously shown and increases sensitivity to hotspot regions in tumor suppressor genes (TSG). Although hotspot regions have long been known to exist in both TSGs and oncogenes, we provide the first report that they have different characteristic properties in the two types of driver genes. We show how cancer researchers can use our results to link 3D protein structure and the biologic functions of missense mutations in cancer, and to generate testable hypotheses about driver mechanisms. Our results are included in a new interactive website for visualizing protein structures with TCGA mutations and associated hotspot regions. Users can submit new sequence data, facilitating the visualization of mutations in a biologically relevant context. Cancer Res; 76(13); 3719-31. ©2016 AACR.
Bladder emptying by intermittent electrical stimulation of the pudendal nerve (2006)

Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with alpha-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 +/- 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 +/- 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 +/- 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 +/- 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.
The p85 Subunit of Phosphatidylinositol 3-Kinase Associates with the Fc Receptor γ-Chain and Linker for Activitor of T Cells (LAT) in Platelets Stimulated by Collagen and Convulxin (1998)

There is extensive evidence to show that phosphatidylinositol 3-kinase plays an important role in signaling by the immune family of receptors, which has recently been extended to include the platelet collagen receptor, glycoprotein VI. In this report we present two potential mechanisms for the regulation of this enzyme on stimulation of platelets by collagen. We show that on stimulation with collagen, the regulatory subunit of phosphatidylinositol 3-kinase associates with the tyrosine-phosphorylated form of the adapter protein linker for activator of T Cells (LAT) and the tyrosine-phosphorylated immunoreceptor tyrosine-based activation motif of the Fc receptor gamma-chain (a component of the collagen receptor complex that includes glycoprotein VI). The associations of the Fc receptor gamma-chain and LAT with p85 are rapid and supported by the Src-homology 2 domains of the regulatory subunit. We did not obtain evidence to support previous observations that the regulatory subunit of phosphatidylinositol 3-kinase is regulated through association with the tyrosine kinase Syk. The present results provide a molecular basis for the regulation of the p85/110 form of phosphatidylinositol 3-kinase by GPVI, the collagen receptor that underlies activation.