gebhart/patrepeval huggingface dataset:
Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues. (1995)

Immunohistochemical analysis with the anti-Ret antibody was performed to investigate the expression of the c-ret proto-oncogene product (c-Ret protein) in embryonic, infant and adult rat tissues. During embryogenesis, the c-Ret expression became detectable by day 11.5 in the developing peripheral and central nervous systems as well as in the excretory system. In the peripheral nervous system of the trunk, it was expressed at high levels in the enteric neuroblasts and the autonomic and dorsal root ganglia. c-Ret positive cells appeared in the mesenchyme around the foregut and the dorsal aorta at day 11.5 and formed the myenteric plexus of the whole embryonic gut and the sympathetic trunk at later stages respectively. Examination of the cranial region revealed that the c-Ret protein was expressed in neural crest cells migrating from rhombomere 4 at day 11.5 and then became positive in the facial, glossopharyngeal and vagus cranial ganglia at day 12.5-13.5. After day 16.5 of gestation, the c-Ret expression was also observed in the trigeminal ganglion. In the central nervous system, the c-Ret protein was expressed in the neuroepithelial cells of the ventral neural tube (day 11.5-14.5), the motor neurons of the spinal cord (day 18.5) as well as in the embryonic neuroretina (day 18.5). In addition to the nervous system, the c-Ret expression was detected in the nephric duct (day 11.5), the ureteric bud (day 13.5) and the collecting ducts of the kidney (day 16.5). After birth, neurons in the nervous systems mentioned above continued to express the c-Ret protein at variable levels while no c-Ret expression was observed in the kidney of adult rats. Furthermore, the c-Ret expression was found in the acinar cells of the salivary gland, the epithelial cells of the thymus and the follicular dendritic cells of the spleen and lymph node in infant and adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)
From Cocaine to Ropivacaine: The History of Local Anesthetic Drugs (2001)

In 1850, about three centuries after the conquest of Peru by Pizzaro, the Austrian von Scherzer brought a sufficient quantum of coca leaves to Europe to permit the isolation of cocaine. As suggested by his friend Sigmund Freud, descriptions of the properties of the coca prompted the Austrian Koller to perform in 1884 the first clinical operation under local anesthesia, by administration of cocaine on the eye. The use of cocaine for local and regional anesthesia rapidly spread throughout Europe and America. The toxic effects of cocaine were soon identified resulting in many deaths among both patients and addicted medical staff. Local anesthesia was in a profound crisis until the development of modern organic chemistry which led to the synthesis of pure cocaine in 1891. New amino ester local anesthetics were synthesized between 1891 and 1930, such as tropocaine, eucaine, holocaine, orthoform, benzocaine, and tetracaine. In addition, amino amide local anesthetics were prepared between 1898 and 1972 including nirvaquine, procaine, chloroprocaine, cinchocaine, lidocaine, mepivacaine, prilocaine, efocaine, bupivacaine, etidocaine, and articaine. All of these drugs were ostensibly less toxic than cocaine, but they had differing amounts of central nervous system (CNS) and cardiovascular (CV) toxicity. Bupivacaine is of special interest because of its long duration of action and history of clinical application. Synthesized in 1957, the introduction of bupivacaine on the market in 1965 paralleled the progressive and cumulative reports of CNS and CV toxicity, leading to the restriction of its use and the identification of a special therapy-resistant CV toxicity. Numerous experimental studies were conducted to identify the fine cellular mechanism of this toxicity, which refines our understanding of the action of local anesthetics. The identification of optically active isomers of the mepivacaine family led to the selection of ropivacaine, a pure S-(-) enantiomer, whose toxicology was selectively and extensively studied before its introduction on the market in 1996. During the rapid and extensive use of ropivacaine in the clinic, unwanted side-effects have been found to be very limited.
ELISPOT Assay to Detect Cytokine‐Secreting Murine and Human Cells (1994)

The filter immunoplaque assay, otherwise called the enzyme-linked immunospot assay (ELISPOT), was initially developed to detect and quantitate individual antibody-secreting B cells. Recent modifications have improved the sensitivity of the ELISPOT assay such that cells producing as few as 100 molecules of specific protein per second can be detected. The ELISPOT assay utilizes two high-affinity cytokine-specific antibodies directed against different epitopes on the same cytokine molecule: either two monoclonal antibodies or a combination of one monoclonal antibody and one polyvalent antiserum. ELISPOT generates spots based on a colorimetric reaction that detects the cytokine secreted by a single cell. The spot represents a "footprint" of the original cytokine-producing cell. Spots are permanent and can be quantitated visually, microscopically, or electronically.
Oxidations by thionyl chloride. VI. Mechanism of the reaction with cinnamic acids (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidations by thionyl chloride. VI. Mechanism of the reaction with cinnamic acidsTatsuo Higa and Arnold J. KrubsackCite this: J. Org. Chem. 1975, 40, 21, 3037–3045Publication Date (Print):October 1, 1975Publication History Published online1 May 2002Published inissue 1 October 1975https://pubs.acs.org/doi/10.1021/jo00909a007https://doi.org/10.1021/jo00909a007research-articleACS PublicationsRequest reuse permissionsArticle Views1612Altmetric-Citations63LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Detection of Epstein–Barr virus‐specific memory CD4+T cells using a peptide‐based cultured enzyme‐linked immunospot assay (2013)

Approaches to evaluate T-cell responses to Epstein-Barr virus (EBV) include enzyme-linked immunospot (ELISPOT), which quantifies cells capable of immediate interferon-γ secretion upon antigen stimulation. However, evaluation of expandable EBV-specific memory T cells in an ELISPOT format has not been described previously. We quantified EBV-specific T-cell precursors with high proliferative capacity by using a peptide-based cultured interferon-γ ELISPOT assay. Standard and cultured ELISPOT responses to overlapping peptide pools (15-mers overlapping by 11 amino acids) covering the lytic (BZLF1 and BMRF1) and latent (EBNA1, EBNA3a, EBNA3b, EBNA3c, LMP1 and LMP2) EBV proteins were evaluated in 20 healthy subjects with remote EBV infection and, for comparison, in four solid organ transplant recipients. Cultured ELISPOT responses to both lytic and latent EBV antigens were significantly higher than standard ELISPOT responses. The distribution of EBV-specific T-cell responses detected in healthy virus carriers showed more consistent cultured ELISPOT responses compared with standard ELISPOT responses. T-cell responses quantified by cultured ELISPOT were mainly mediated by CD4+ T cells and a marked pattern of immunodominance to latent-phase antigens (EBNA1 > EBNA3 family antigens > LMP2 > LMP1) was shown. Both the magnitude and distribution of EBV-specific T-cell responses were altered in solid organ transplant recipients; in particular, cultured ELISPOT responses were almost undetectable in a lung-transplanted patient with EBV-associated diseases. Analysis of T-cell responses to EBV by ELISPOT assays might provide new insights into the pathogenesis of EBV-related diseases and serve as new tools in the monitoring of EBV infection in immunocompromised patients.
The inheritance of primary lymphoedema. (1985)

A family study is reported on 312 index patients who had primary lymphoedema with onset before 36 years. All had been investigated at St Thomas's Hospital, London, between 1965 and 1980. Most of the information was obtained by questionnaire, but 70 patients were also interviewed to check the reliability of the answers to the questionnaire. The frequency at birth of those who will develop primary lymphoedema is estimated to be about 1 in 6000, with a sex ratio of about one male to three females. Approximately 10% of children of index patients and 10% of sibs were affected when these relatives were at least five years older than the age of onset in the index patient. The proportion of female relatives affected was between two and four times that of males affected. The proportion of parents affected was about 10%. The proportion of grandparents, aunts, and uncles was about 2.5%. Where the index patient had an affected parent, the proportion affected of sibs and children was about 20%. The risk to relatives of male index patients was about 50% higher than for female index patients.
Miniature Fabry-Perot interferometers micromachined in silicon for use in optical fiber WDM systems (2002)

The techniques of silicon micromachining have been used to fabricate a second-generation Fabry-Perot interferometer for use in the near-infrared spectral region. These devices provide a sharp optical transmission peak which can be used as wavelength division demultiplexers in optical fiber communications systems. The wavelength tuning and parallelism control of the mirror elements are achieved electrostatically, by varying the voltage between control electrodes. This second-generation device includes a thin, etch-stopped corrugated diaphragm as the suspension for the movable element.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Antibody Humanization by CDR Grafting (2004)

The goal of antibody humanization is to engineer a monoclonal antibody (MAb) raised in a nonhuman species into one that is less immunogenic when administered to humans. The development of this technology had transformed the stagnant state of antibody therapeutics in the 1980s, when the major obstacle was the human anti-murine antibody (HAMA) response (1, 2). The HAMA response occurred in up to 50% of patients upon the administration of murine hybridoma-derived antibodies (3) and severely compromised the safety, efficacy, and biological half-life of these reagents. In addition, murine antibody constant regions are inefficient in directing suitable human immune effector functions for therapeutic effects. Efforts to produce human antibodies by hybridoma technology (4) and Epstein-Barr virus (EBV)-mediated B-lymphocyte transformation (5) have met with limited success, but their widespread application is hampered by the lack of robust human hybridoma fusion partners and the instability of EBV-transformed clones, respectively (see ref. 6–8 for review). Consequently, humanization technology was well-placed to exploit the plethora of murine MAbs against a variety of disease targets and turn them into effective clinical reagents.
Structure-activity relationships of 2-aminotetralins and 2-aminoindanes: inhibitory neuroeffector mechanisms in isolated guinea-pig ilea. (1982)

The ability of 2-aminotetralins (2-ATs), 2-aminoindanes (2-AIs), morphine (M) and clonidine (CLON) to alter neuroeffector transmission was studied on field-stimulated (FS) guinea-pig ilea (GPI). The activity of these compounds to inhibit K+, histamine (H), actylcholine (ACh), nicotine (Nic) and serotonin (5-HT) induced contractions was determined using superfused GPI segments. 2-ATs, 2-AIs, M and CLON dose-dependently inhibited contractions produced by low frequency stimulation through alpha-adrenergic, opioid or unknown receptor mediated mechanisms. 2-ATs inhibited ACh, Nic, 5-HT and FS, but not K+- or H-induced contractions. 2-ATs, 2-Ais and M were more potent than hexamethonium in inhibiting Nic-induced contractures. 2-AT and 2-AI-induced inhibition was not antagonized by naloxone or phentolamine. However, the inhibitory effects of 2-ATs. 2-AIs and M on FS-GPI were antagonized by increasing the concentration of Ca2+ ion in the media. These data are consistent with the supposition that 2-ATs, 2-AIs or M alter neuroeffector transmission through competitive changes in Ca2+ disposition in cholinergic neurons of guinea-pig isolated ilea. A discussion relating other biological actions of 2-ATs or 2-AIs (e.g. alpha-adrenergic mediated antinociception) to the observed inhibitory neuroeffector responses is provided.
Toward a quantitative description of large-scale neocortical dynamic function and EEG (2000)

A general conceptual framework for large-scale neocortical dynamics based on data from many laboratories is applied to a variety of experimental designs, spatial scales, and brain states. Partly distinct, but interacting local processes (e.g., neural networks) arise from functional segregation. Global processes arise from functional integration and can facilitate (top down) synchronous activity in remote cell groups that function simultaneously at several different spatial scales. Simultaneous local processes may help drive (bottom up) macroscopic global dynamics observed with electroencephalography (EEG) or magnetoencephalography (MEG). A local/global dynamic theory that is consistent with EEG data and the proposed conceptual framework is outlined. This theory is neutral about properties of neural networks embedded in macroscopic fields, but its global component makes several qualitative and semiquantitative predictions about EEG measures of traveling and standing wave phenomena. A more general “metatheory” suggests what large-scale quantitative theories of neocortical dynamics may be like when more accurate treatment of local and nonlinear effects is achieved. The theory describes the dynamics of excitatory and inhibitory synaptic action fields. EEG and MEG provide large-scale estimates of modulation of these synaptic fields around background levels. Brain states are determined by neuromodulatory control parameters. Purely local states are dominated by local feedback gains and rise and decay times of postsynaptic potentials. Dominant local frequencies vary with brain region. Other states are purely global, with moderate to high coherence over large distances. Multiple global mode frequencies arise from a combination of delays in corticocortical axons and neocortical boundary conditions. Global frequencies are identical in all cortical regions, but most states involve dynamic interactions between local networks and the global system. EEG frequencies may involve a “matching” of local resonant frequencies with one or more of the many, closely spaced global frequencies.
Enhanced Amyloidogenic Processing of the β-Amyloid Precursor Protein in Gene-targeted Mice Bearing the Swedish Familial Alzheimer's Disease Mutations and a “Humanized” Aβ Sequence (1996)

The processing of the beta-amyloid precursor protein (APP) in vivo has been characterized in a novel animal model that recapitulates, in part, the APP genotype of a familial form of Alzheimer's disease (AD). A gene-targeting strategy was used to introduce the Swedish familial AD mutations and convert mouse Abeta to the human sequence. The mutant APP is expressed at normal levels in brain, and cleavage at the mutant beta-secretase site is both accurate and enhanced. Furthermore, human Abeta production is significantly increased to levels 9-fold greater than those in normal human brain while nonamyloidogenic processing is depressed. The results on Abeta production extend similar findings obtained in cell culture to the brain of an animal and substantiate Abeta as a etiological factor in Swedish familial AD. These animals provide several distinguishing features over others created by conventional transgenic methodologies. The spatial and temporal expression patterns of human Abeta are expected to be faithfully reproduced because the gene encoding the mutant APP remains in its normal chromosomal context. Thus, the neuropathological consequences of human Abeta overproduction can be evaluated longitudinally in the absence of potential mitigating effects of APP overexpression or presence of the mouse Abeta peptide.
1-Benzyl-3-(5‘-hydroxymethyl-2‘-furyl)indazole (YC-1) Derivatives as Novel Inhibitors Against Sodium Nitroprusside-Induced Apoptosis (2002)

Antiapoptotic agents based on 1-benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole (22, YC-1) derivatives were explored for effective treatment of sepsis and septic shock. We found that compound 22, 1-benzyl-3-(5'-methoxymethyl-2'-furyl)indazole (27), and 1-phenyl-3-(5'-hydroxymethyl-2'-furyl)indazole (23) were the most effective inhibitors of sodium nitroprusside-induced vascular smooth muscle cell apoptosis. These three compounds are proposed as potential therapeutic agents for the treatment of sepsis.
Estimating evolutionary rate of local protein binding surfaces: a Bayesian Monte Carlo approach (2005)

To infer protein function by matching local surface patterns, an effective scoring matrix for evaluating surface similarity is critical. In this study, we develop an evolution model of binding surfaces using a continuous time Markov process. We develop a Bayesian Markov chain Monte Carlo method to estimate the substitution rates of amino acid residues with specialized move sets. We then develop scoring matrices of residue similarity specific to a functional site and show how they can be used to identify similar binding surfaces, and how such information can be used for predicting biological roles of proteins. Our method is especially effective in extracting evolutionary information from the phylogeny of sequences homologous to a protein structure, all of which may be of unknown functions.
Immunotherapy of murine sarcomas using lymphokine activated killer cells: optimization of the schedule and route of administration of recombinant interleukin-2. (1986)

Interleukin-2 (IL-2) at high doses or at low doses in concert with lymphokine-activated killer (LAK) cells can produce regression of established pulmonary and hepatic metastases from a variety of tumors in mice. IL-2 appears to mediate its antitumor effect through the generation of LAK cells in vivo from endogenous lymphocytes and by the stimulation of host and transferred LAK cell proliferation in tissues. In this paper we have investigated different strategies for IL-2 administration to determine which regimen produced maximal in vivo proliferation and optimal immunotherapeutic efficacy of LAK cells. Tissue expansion of lymphoid cells was assessed using an assay of in vivo labeling of dividing cells by the thymidine analogue, 5-[125I]iododeoxyuridine. The therapeutic effect of the different IL-2 administration protocols was determined by evaluating their efficacy in the treatment of established, 3-day pulmonary metastases from sarcomas in mice. The selection of IL-2 injection regimens for evaluation was based upon pharmacokinetic studies of IL-2 in mice. A single i.v. or i.p. dose yielded high peak IL-2 levels that could be measured for only a few hours after injection, while IL-2 given i.p. thrice daily produced titers that were detectable throughout the study periods (greater than or equal to 6 units/ml of serum after 100,000 units of IL-2 i.p. thrice daily). Using the proliferation and therapy models, we tested the same cumulative daily doses of IL-2 administered by i.v. or i.p. once daily, or i.p. thrice daily regimens. The i.p. thrice daily protocol stimulated greater lymphoid cell proliferation in the lungs, for example, than did the other regimens. Similarly, 300,000 units of IL-2 divided i.p. thrice daily were more successful in reducing metastases (n = 16) than was the entire dose given i.v. once daily (n = 190; P less than 0.05) or i.p. once daily (n = 71; P less than 0.05). When compared to the i.p. or i.v. once daily protocols, the i.p. thrice daily regimen for IL-2 also produced greater proliferation of exogenous LAK cells, as well as a more effective therapeutic outcome when IL-2 was combined with transferred LAK cells. Thus, sustained, lower levels of IL-2 were more effective than brief, high peak titers for stimulation of proliferation and antitumor activity. We then evaluated the effect of duration of IL-2 treatment as well as the number of LAK cell injections in the two models.(ABSTRACT TRUNCATED AT 400 WORDS)
Erythropoietin expression in primary rat Sertoli and peritubular myoid cells (2001)

Kidney and liver are the major organs of erythropoietin (Epo) synthesis. However, Epo messenger RNA (mRNA) has been detected in several organs, such as brain, lung, and testis. Furthermore, functional Epo receptors have been demonstrated on different cell types, including rat Leydig cells. The aim of the study was to identify testicular cells expressing Epo mRNA and to quantitate its levels by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Besides whole testis, Epo transcripts were found in Sertoli and peritubular myoid cells, while no signal was detected in Leydig cells. Exposure of Sertoli cells to CoCl(2) led to an increase of Epo mRNA level. Semiquantitative competitive RT-PCR presented an increase in the level of Epo mRNA in Sertoli cells stimulated by follicle-stimulating hormone, while exposure of peritubular myoid cells cultures to testosterone reduced Epo mRNA expression. Due to the blood-testis barrier, basal expression of Epo suggests a not yet defined function of this hormone in testis.
The stem-loop structure at the 3' end of histone mRNA is necessary and sufficient for regulation of histone mRNA stability. (1987)

Chimeric genes were made by fusing mouse histone genes with a human alpha-globin gene. The genes were introduced into mouse L cells and the stability of the chimeric mRNAs was measured when DNA synthesis was inhibited. An mRNA containing all the globin coding sequences and the last 30 nucleotides of the histone mRNA was degraded at the same rate as histone mRNA.
Highly conformal film growth by chemical vapor deposition. II. Conformality enhancement through growth inhibition (2009)

The authors present a novel strategy for enhancing conformality in chemical vapor deposition (CVD) based on the concept of growth inhibition. In Part I, they showed how surface site blocking was responsible for the increase in conformality observed at higher pressures in high vapor pressure precursors. In this work, they apply this concept to enhance conformality by considering a secondary species that acts as an inhibitor of the precursor. The experimental results obtained for the growth of TiB2 from Ti(BH4)3dme (dme=dimethoxyethane), with dme acting as the growth inhibitor, agree well with the models, based on a first order adsorption/desorption kinetics, and show how this strategy greatly enhances the conformality of nonconformal precursors. Finally, they show how multiple surface mechanisms including surface site blocking, associative desorption, long surface residence time of by-products, or coadsorption of two reactants can induce growth inhibition. Consequently, this strategy can be potentially applied to many existing CVD systems, provided suitable molecular inhibitors are identified.