gebhart/patrepeval huggingface dataset:
Fluorinated tricyclic neuroleptics with prolonged action: 3-Fluoro-8-trifluoromethyl derivatives of 10-(4-methylpiperazino)- and 10-[4-(2-hydroxyethyl)piperazino]-10,11-dihydrodibenzo-[b,f]thiepin (1981)

A reaction of (4-fluoro-2-iodophenyl)acetic acid with 4-(trifluoromethyl)thiophenol gave the acid VIII which was cyclized with the reagent consisting from methanesulphonic acid and phosphorus pentoxide and afforded the methanesulphonic enol ester XIX . The alkaline hydrolysis resulted in 3-fluoro-8-trifluoromethyldibenzo[ b,f ]thiepin-10(11 H )-one ( XVI ) which was transformed via the alcohol XXIV to the chloro derivative XXV . Substitution reactions with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine resulted in the title compounds IV and V . These products are very potent cataleptic neuroleptic agents with a prolongation of duration of the effects comparable to that of isofloxythepin and tefluthixol. A series of further synthetic experiments aimed at alternative syntheses of the acid VIII and the ketone XVI ; their results were mostly not of use for preparative purpose but they led to isolation and characterization of a series of interesting heterocyclic products ( XVII , XVIII , XXII , XXIII , XXIX-XXXI , XXXVI-XXXIX ).
Recent Advances in Novel Drug Carrier Systems (2012)

This contribution book collects reviews and original articles from eminent experts working in the interdisciplinary arena of novel drug delivery systems and their uses. From their direct and recent experience, the readers can achieve a wide vision on the new and ongoing potentialities of different drug delivery systems. Since the advent of analytical techniques and capabilities to measure particle sizes in nanometer ranges, there has been tremendous interest in the use of nanoparticles for more efficient methods of drug delivery. On the other hand, this reference discusses advances in the design, optimization, and adaptation of gene delivery systems for the treatment of cancer, cardiovascular, pulmonary, genetic, and infectious diseases, and considers assessment and review procedures involved in the development of gene-based pharmaceuticals.
Identification of enhancer sequences 3’ of the rabbit Ig kappa L chain loci (1991)

The rabbit is useful for studies of Ig L chain gene expression because of a great disparity in expression of two isotypic forms of the kappa L chain. Normally, K1 is expressed at high levels and K2 is almost silent; expression of K2 increases in mutant or experimentally allotype-suppressed animals. The reasons for the preferential utilization of the K1 isotype have not been fully elucidated. We were interested in looking for second enhancers 3' of the C kappa genes because the absence of a 3' enhancer in the K2 locus could explain the preferential utilization of the K1 isotype. However, we found a strong region of enhancer activity about 7 kb downstream of the C kappa 2 gene. Sequences in this region are highly conserved between rabbit, man, and mouse. There also appears to be a homologous 3' enhancer region in the rabbit K1 locus. We also confirmed earlier reports that the rabbit K1 intron enhancer is inactive in transient transfections into mouse B cells but find that the same construct has low but significant activity in a human B cell line. In a comparable construct the K2 intron enhancer is without activity suggesting possible differential activity of the intronic enhancers.
A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico (2015)

This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1-50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2-4 years], 60% [5-20 years], and 93% [21-50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858.
Implantable pacing lead technology (1990)

Lead technology is reviewed, beginning with the first known permanent implant and continuing through today's state-of-the-art implant. Nondislodging transvenous leads and epimyocardial leads (sutureless, screw-in leads) are described. Conductors, insulation, and electrodes are discussed. The emphasis today appears to be on improving carbon, screw-in, porous, platinized and steroid eluting electrodes, while future developments may include very thin bipolar leads, higher pacing impedance electrodes, and easier to implant and explant devices.
Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation (2009)

Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation. (ClinicalTrials.gov number, NCT00174785.)
A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort (2014)

The association between the neuronal DDR and cognitive impairment, independent of AD pathology in the ageing brain, may be suggestive of a causal link via neuronal dysfunction.
Direction of chromosome rearrangements in Saccharomyces cerevisiae by use of his3 recombinational substrates. (1988)

We used the his3 recombinational substrates (his3 fragments) to direct large interchromosomal (translocations) and intrachromosomal (deletions and tandem duplications) rearrangements in the yeast Saccharomyces cerevisiae. In strains completely deleted for the wild-type HIS3 gene, his3 fragments, one containing a deletion of 5' amino acid coding sequences and the other containing a deletion of 3' amino acid coding sequences, were first placed at preselected sites by homologous recombination. His+ revertants that arose via spontaneous mitotic recombination between the two his3 fragments were selected. This strategy was used to direct rearrangements in both RAD52+ and rad52 mutant strains. Translocations occurred in the RAD52+ genetic background and were characterized by orthogonal field alternating gel electrophoresis of yeast chromosomal DNA and by standard genetic techniques. An unexpected translocation was also identified in which HIS3 sequences were amplified. Two types of tandem duplications of the GAL(7, 10, 1) locus were also directed, and one type was not observed in rad52 mutants. Recombination mechanisms are discussed to account for these differences.
Cross-Protective Immunity against Heterologous Streptococcus pneumoniae (2012)

sponsorship: MRC|G0600410, Medical Research Council|G0600410, Academy of Medical Sciences (AMS)|AMS-SGCL5-Cohen, Medical Research Council|G0600410, National Institute for Health Research|CL-2009-18-010
Peripheral and central mechanisms of cutaneous hyperalgesia (1992)

Hyperalgesia after cutaneous injury can be divided into two phenomena: Primary hyperalgesia occurs at the site of injury and is characterized by hyperalgesia to mechanical and heat stimuli. Secondary hyperalgesia occurs outside the injury site and is characterized by mechanical hyperalgesia only. Hyperalgesia in inflammatory processes corresponds to primary hyperalgesia. Hyperalgesia in referred pain and neuropathic pain resembles secondary hyperalgesia (Table 3). Evidence for the latter would be strengthened if hyperalgesia to cooling stimuli, which is observed in neuropathic pain, was also demonstrated in referred pain and in secondary hyperalgesia. Some of the more likely neural mechanisms to explain primary and secondary hyperalgesia are illustrated in Fig. 8. Primary hyperalgesia to heat stimuli has a counterpart in the sensitization of peripheral nociceptors to heat stimuli (Fig. 8A), leading to similar changes in central neurons. In addition, the enlargement of the mechanical receptive field of primary afferent nociceptors to include the site of injury may account for the primary hyperalgesia to mechanical stimuli (Fig. 8B). In the literature, there are some contradictions with respect to the stimulus modalities to which hyperalgesia and sensitization occur. In spite of the well-documented sensitization of primary afferent nociceptors to heat stimuli, there are few studies on its molecular mechanisms. On the other hand, there is pharmacological evidence for a peripheral mechanism of primary mechanical hyperalgesia, but little direct evidence that nociceptors can be sensitized to mechanical stimuli by injury. This contradiction should spawn further investigations into the mechanical response properties of nociceptors and into the molecular mechanisms of heat sensitization. Secondary hyperalgesia to mechanical stimuli is likely due to the sensitization of central pain signalling neurons (CPSNs). This sensitization could involve only input from nociceptors (Fig. 8C), since mechanical pain thresholds after a cutaneous injury are of the same order as those of nociceptors. Central sensitization could also be the result of enhanced connectivity between low-threshold mechanoreceptors and CPSNs (Fig. 8D). This form of sensitization may account for the pain to light touch associated with neuropathic pain. Receptive field plasticity is a prevalent property of dorsal horn neurons and probably plays a vital role with regard to hyperalgesia. The molecular mechanisms of synaptic plasticity are currently subject to intense experimental investigation and may provide new insights on the mechanisms of pain and hyperalgesia.
Polarity signals in epithelial cells (1993)

In simple epithelia, specialized vectorial functions such as transport and secretion are made possible by the segregation of proteins and lipids into opposite surface domains. This polarized distribution results from selective delivery to and retention at the appropriate domain. In the case of direct delivery, the sorting site for apical and basolateral proteins is the trans-Golgi network (TGN) where they are incorporated into distinct apical and basolateral vesicles that are targeted to the respective surfaces. The machinery that controls this simple process is in fact rather complicated. It involves many different steps from the recognition event (between 'sorting signal(s)' and 'sorting receptor(s)' to the formation of the vesicles, their budding, and the docking to the specialized plasma membrane domain. Here we summarize the latest developments in the sorting of apical and basolateral proteins, focusing in particular on the signals that are involved in this process and the current hypotheses about the mechanisms responsible for it, in both epithelia and in non-polarized cells.
Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses. (1989)

We determined the complete nucleotide sequence of an infectious proviral molecular clone (FIV-14) of the feline immunodeficiency virus (FIV). FIV-14 has a genome organization similar in complexity to other lentiviruses. In addition to three large open reading frames representing the gag, pol, and env genes, at least four small open reading frames are present in the pol-env intergenic, env, and env-3' long terminal repeat regions. Nucleotide and deduced amino acid sequence alignments of the FIV coding sequences with analogous sequences of other lentiviruses revealed significant identities only in the gag and pol genes. Phylogenetic tree analyses of gag and pol gene-encoded protein sequences demonstrate that FIV is more closely related to the ungulate lentiviruses, equine infectious anemia virus and visna virus, than to the primate lentiviruses, human and simian immunodeficiency viruses.
Three dimensional ICs, having four stacked active device layers (2003)

The four-layer-stacked master slice is proposed as a system application for 3-D ICs. The master slice consists of a programmable logic array for logic circuits, a CMOS gate array for I/O interface buffer circuits, and a CMOS SRAM. Fabrication technologies for the four-layer-stacked 3-D IC are described. Laser beam recrystallization was carried out for the formation of three SOI (silicon-on-insulator) layers in the 3-D IC. Recrystallization without cracks in both SOI and vertical isolation layers was accomplished by adjusting laser annealing conditions. Microprobe Raman spectroscopy data indicated that a tensile stress of (3-6)*10/sup 9/ dyne/cm/sup 2/ was present in each SOI layer. Surface planarization of the vertical isolation layer was carried out with a combination of polystyrene spin coating and dry etching. An initial surface roughness of about 1.7 mu m was successfully reduced to less than 500 A, and the planarized surface did not interfere with either recrystallization or photolithography. NMOSFETs and PMOSFETs, fabricated in the four-layer-stacked 3-D IC, have been successfully operated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Femtogram on-column detection of nicotine by isotope dilution gas chromatography/negative ion detection mass spectrometry (1993)

A gas chromatographic method, utilizing detection by negative chemical ionization (NCI) mass spectrometry, is presented for the detection of nicotine. The method incorporates derivatization with heptafluorobutyric anhydride/pyridine to yield the ring-opened addition product, 1-[4-(3'-pyridyl)-4-heptafluorobutyryloxybutyl]-1- methylheptafluorobutanamide. The resulting heptafluorobutanamide is both relatively stable and an excellent electron scavenger. This methodology provides for the detection of nicotine at femtogram on-column levels, the measurement of nicotine over three orders of magnitude, and the minimization of contamination due to environmental nicotine.
Gender Differences in Sex‐Risk Behaviors, Economic Livelihood, and Self‐Concept Among Drug Injectors and Crack Smokers (1995)

The authors compared male and female substance abusers and found that female substance abusers were at increased risk for HIV, relative to males, through sex‐risk behaviors. Specifically, women were more likely to have had sexual relations with a drug injector and greater involvement in prostitution, including exchanging sex for drugs or money, than men. Women had fewer legitimate employment opportunities and were less likely to have received support through illegal sources, excluding prostitution, than men. Women bad significantly lower perceived self‐concept, greater depression, and more anxiety than men. Gender, economic means of support, and self‐concept were highly interrelated. These findings underscore the need for interventions that address the economically marginalized position of addicted women and their low self‐concept.
Rates of abuse of tramadol remain unchanged with the introduction of new branded and generic products: results of an abuse monitoring system, 1994-2004 (2005)

The data generated demonstrate that the abuse of tramadol remained very low despite new branded and generic formulations. Contrary to the hypothesis that cheaper generic drugs would lead to higher rates of abuse, we found no increase in abuse with the introduction of generic tramadol. Ultracet abuse rates, unlike those found with other widely used hydrocodone and oxycodone combination products, have been even lower than that observed for tramadol. Since the FDA has now mandated that proactive risk-management plans be implemented for new drugs, the tramadol risk-management plan may be useful as a prototypic model which can be modified to accommodate other drugs with abuse potential.
Voltammetry of covalently immobilized cytochrome c on self-assembled monolayer electrodes (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVoltammetry of covalently immobilized cytochrome c on self-assembled monolayer electrodesMaryanne Collinson, Edmond F. Bowden, and Michael J. TarlovCite this: Langmuir 1992, 8, 5, 1247–1250Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://doi.org/10.1021/la00041a004RIGHTS & PERMISSIONSArticle Views1363Altmetric-Citations196LEARN 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 InReddit PDF (492 KB) Get e-Alerts Get e-Alerts
Über die Herstellung von Oxyuvitinaldehyd aus p‐Kresol (1909)

e n z n l d e h y d e herstellen kxnn, wenn man D i a l k y I -:t n i 1 in e nrit F o r m a1 tl e I1 ?tl uud N i t r o s o d i iii e t h J 1 a n i 1 in tinter geeigneten Jledingungen i n Renktion bringt.i Y i r wollten diese Merhode xuf p -K r e s o l an\ventleii; (la ljei den ersten Versucben die -1nsl)euten an € I n i n o s x l i c ~l a l d e h y cl wenig befriedigend waren, $0 stiidierten w i r zuerst die Ein:i-irkung von 1 ; o r m n l d e h y d xiif p -K r e s o l .IIierbei fanden v i r , dn13 unter gewissen Redingungen nicht das von .\lnnnsse2)nus den beiden I<omponenteu gewonnene H o m o s n l i g e n i II entsteht, sondern eine Verbindung, die 1 blolekiil Formaldehyd nieiir r 11 t h i I t.Dieser Forninldeli~tl konnte eutweder :ils Kr~~tt:tllforriialdeliytl vorhnnden sein, oder er war i n Form einer Alkoholgruppe i n das Molekul eingetreten.Die neue Verbiudiing gibt nun beini Erhitzen iiir sich oder niit rerdunnten
Nonlinear State Estimation in the Presence of Multiple Steady States (1996)

This paper concerns the problem of state estimation in nonlinear deterministic processes. For moderately nonlinear deterministic processes, the inadequacy of full-order Luenberger observer and extended Luenberger observer with constant gain is shown analytically and through numerical simulation of a chemical reactor. The results indicate that the convergence of an extended Luenberger observer with constant gain may be poorer than that of a simple linear Luenberger observer. A nonlinear observer design method with varying gain is applied to a classical exothermic stirred-tank reactor with multiple steady states. Under significant observer-initialization errors and several observer gains, the global asymptotic convergence of the nonlinear observer is demonstrated through numerical simulations. In the presence of the multiple steady states, the nonlinear observer converges to the same steady-state operating point at which the reactor operates, irrespective of the observer initial conditions.
Tyrosine Phosphorylation of the κ-Opioid Receptor Regulates Agonist Efficacy (2000)

To explore the role of highly conserved tyrosine residues in the putative cytoplasmic domains of the seven-transmembrane G protein-coupled opioid receptors, we expressed the rat kappa-opioid receptor (KOR) in Xenopus oocytes and then activated the intrinsic insulin receptor tyrosine kinase. KOR activation by the agonist produced a strong increase in potassium current through coexpressed G protein-gated inwardly rectifying potassium channels (K(IR)3). Brief pretreatment with insulin caused a 60% potentiation of the KOR-activated response. The insulin-induced increase in kappa-opioid response was blocked by the tyrosine kinase inhibitor genistein. In contrast, insulin had no effect on the basal activity of K(IR)3, suggesting that KOR is the target of the tyrosine kinase cascade. Mutation of tyrosine residues to phenylalanines in either the first or second intracellular loop of KOR to produce KOR(Y87F) and KOR(Y157F) had no effect on either the potency or maximal effect of. However, neither KOR(Y87F)- nor KOR(Y157F)-mediated responses were potentiated by insulin treatment. Insulin pretreatment shifted the dose-response curve for activation of KOR by increasing the maximal response without changing the EC(50) value for. These results suggest that insulin increases the efficacy of KOR activation by phosphorylating two tyrosine residues in the first and second intracellular loops of the receptor. Thus, tyrosine phosphorylation may provide an important mechanism for modulation of G protein-coupled receptor signaling.
The Electric Field Induced In A Spherical Volume Conductor By A Magnetic Coil (2005)

A computer model is developed to predict the induced current density in brain from an arbitrary magnetic stimulator coil arrangement. The head is modeled as a uniform spherical conductor, and a least squares fit to an analytical solution of Laplace's equation is used to solve the boundary value problem. This method requires much less computational time and storage compared to finite element methods, yet provides accurate results for homogeneous models having simple geometry. The results for a double-square shaped stimulator coil are presented.
Treatment of Open Sternal Wounds with the Vacuum-Assisted Closure System: A Safe, Reliable Method (2002)

Missoula, Mont. John W. Harlan, M.D. 900 North Orange Street, Suite 106 Missoula, Mont. 59802 Received for publication April 26, 2000; revised March 12, 2001.
Chemical synthesis of insect cuticular hydrocarbons (2010)

The external cuticle of insects is covered by a waxy layer composed of mixtures of hydrophobic lipids that include long-chain alkanes, alkenes, wax esters, fatty acids, alcohols, aldehydes, and sterols. The primary purpose of this layer is to maintain water balance and prevent desiccation, as described in Chapter 6, but many of the cuticular lipid components have important secondary roles as intraspecific contact chemical signals (pheromones). These roles include species and sex recognition during reproductive interactions, and nestmate recognition and other colony organization functions in social insects. Thus, these compounds are essential mediators of insect behaviors. Cuticular compounds are also exploited by parasitoids and predators as interspecific contact cues (kairomones) to aid in host location.