gebhart/patrepeval huggingface dataset:
The absolute bioavailability and effect of food on the pharmacokinetics of zolmitriptan in healthy volunteers (1998)

At therapeutic doses zolmitriptan has good oral bioavailability in healthy volunteers and has dose-proportional pharmacokinetics that are not affected by food to any clinically relevant extent.
The human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses (1999)

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted by Clara cells of the bronchial epithelium, is a prime host factor that processes viral envelope glycoproteins and determines the infectivity of influenza A and Sendai viruses (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, The Journal of Biological Chemistry, 1992, Vol. 267, pp. 13573-13579). We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluid of the human respiratory tract, significantly inhibited induction of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multicycles of mouse-adapted influenza A virus replication in rat lungs in vivo. Recombinant MPI and the C- but not the N-terminal domain of MPI inhibited both the activity of tryptase Clara and the induction of virus infection by tryptase Clara. The 50% inhibitory concentrations of MPI and the C-terminal domain peptide (Pro50-Ala107) of MPI for tryptase Clara were 7.4 and 61.6 nM, respectively, with Sendai virus envelope glycoproteins as the substrate. Studies on deletion mutants of the C-terminal domain of MPI revealed that the minimal size of MPI required for the inhibition of tryptase Clara is the peptide Lys60-Ala107. Studies involving site-directed mutagenesis of the C-terminal domain of MPI indicated that the Leu72-Met73 site of MPI is the inhibitory site for tryptase Clara. Substitution of residue Leu72 with a basic amino acid significantly increased in the inhibitory activity of the C-terminal domain of MPI, but further substitution of residue Met73 with various amino acids in these mutants reduced the inhibitory activity. Since there is evidence suggesting that the concentration of MPI in respiratory fluid is insufficient for prevention of virus infection, the administration of MPI, the recombinant C-terminal domain of MPI, and their mutants, with residue Leu72 substituted with residues Arg72 and Lys72, may be useful for treatment of such pneumotropic virus infections.
Relationship between Polymorphism in the Angiotensinogen, Angiotensin-Converting Enzyme or Angiotensin II Receptor and Renal Progression in Japanese NIDDM Patients (1999)

We determined the relationship between the gene polymorphism of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), or angiotensin II receptor (AT1R) and the progression of diabetic nephropathy in a multicenter trial of ethnically homogeneous Japanese patients with non-insulin-dependent diabetes (NIDDM). Gene polymorphism of ACE I/D, AGT M235T and AT1R A1166C was determined by polymerase chain reaction amplification using allele-specific primers. Japanese NIDDM patients (n = 1,152) were selected from several diabetic clinics. All patients were divided into three groups as follows: (1) group I (n = 407): normoalbuminuric patients; (2) group II (n = 327): microalbuminuric patients, and (3) group III (n = 418): overt albuminuric patients. Clinical factors for investigation in all patients were the date of birth, gender, levels of urinary albumin excretion, findings of the ocular fundus, duration of diabetes, hemoglobin A1c and blood pressure. It appears that genetic polymorphisms in the renin-angiotensin systems, i.e. ACE or AT1R, may affect the progression to renal failure of patients (especially females) with NIDDM.
Combined ex vivo treatment with immunotoxins and mafosfamid: a novel immunochemotherapeutic approach for elimination of neoplastic T cells from autologous marrow grafts. (1985)

We evaluated a novel ex vivo "purging" protocol for selective elimination of neoplastic T cells from human marrow by using a sensitive clonogenic assay. Immunotoxins (IT) were synthesized by conjugating ricin (R) to four different monoclonal antibodies (MoAb) directed against distinct markers of T cell lineage. Treatment with anti-p67-R produced effective elimination of leukemic T cells from human marrow. The cyclophosphamide congener mafosfamid (ASTA Z 7577) markedly enhanced the target cell cytotoxicity of IT and extended the final level of clonogenic kill 2 to 3 logs. Our data show that anti-p67-R in combination with mafosfamid resulted in a maximum elimination of 6.2 logs of neoplastic T cells with minimal toxicity to normal bone marrow progenitors. The efficiency of this protocol was not reduced in the presence of excess normal bone marrow cells. Similar findings were obtained by using a cocktail of four different anti-T cell IT. This approach is unique in combining both immunologic (IT) and chemical (mafosfamid) strategies for more effective ex vivo bone marrow purging in autologous bone marrow transplantation for T cell acute lymphoblastic leukemia/lymphoblastic lymphoma.
A Biomimetic Total Synthesis of (−)-Spirotryprostatin B and Related Studies (2000)

The prenylated natural products spirotryprostatin A and B derived from the Trp-Pro diketopiperazine also feature an oxidative rearrangement of the indole to form a spirooxindole. Synthetically, formation of the oxindole ring was stereoselectively accomplished by reaction of the appropriate indole precursor with N-bromosuccinimide. For optimum results, the oxidation should be carried out prior to diketopiperazine cyclization. In this manner, we have synthesized the tetrahydro- and dihydro- analogues of spirotryprostatin B in four steps from L-tryptophan methyl ester. The dihydro derivative was then converted to spirotryprostatin B by unsaturation of the pyrrolidine ring to a pyrroline, thus unambiguously confirming the structure of the natural product.
Impact of self-heating and thermal coupling on analog circuits in SOI CMOS (1998)

This paper examines the influence of the static and dynamic electrothermal behavior of silicon-on-insulator (SOI) CMOS transistors on a range of primitive analog circuit cells. In addition to the more well-known self-heating close-range thermal coupling effects are also examined. Particular emphasis is given to the impact of these effects on drain current mismatch due to localized temperature differences. Dynamic electrothermal behavior in the time and frequency domains is also considered, measurements and analyses are presented for a simple amplifier stage, current mirrors, a current output D/A converter, and ring oscillators fabricated in a 0.7-/spl mu/m SOI CMOS process. It is shown that circuits which rely strongly on matching, such as the current mirrors or D/A converter, are significantly affected by self-heating and thermal coupling. Anomalies due to self-heating are also clearly visible in the small-signal characteristics of the amplifier stage. Self-heating effects are less significant for fast switching circuits. The paper demonstrates how circuit-level simulations can be used to predict undesirable nonisothermal operating conditions during the design stage.
II. Regulation of neuropeptide receptors in enteric neurons (1998)

Neuropeptides exert their diverse biological effects by interacting with G protein-coupled receptors (GPCRs). In this review we address the question, What regulates the ability of a target cell, in particular a neuron, to respond to a neuropeptide? Available evidence from studies of many GPCRs in reconstituted systems and transfected cell lines indicates that much of this regulation occurs at the level of the receptor and serves to alter the capacity of the receptor to bind ligands with high affinity and to couple to heterotrimeric G proteins. Although some of the knowledge gained from these studies is applicable to the regulation of neuropeptide receptors on neurons, at present there are far more questions than answers.
Clinical use of a pronuclear stage score following intracytoplasmic sperm injection: impact on pregnancy rates under the conditions of the German embryo protection law (2000)

The German embryo protection law does not allow embryo selection, but only selection of pronuclear stage (PN) oocytes. Only as many PN oocytes are allowed to be selected as are planned to be transferred. Therefore, a clinically applicable score to assess the quality of PN oocytes would be helpful. A recently published score was used under the conditions of the German embryo protection law in 74 non-selected, consecutive intracytoplasmic sperm injection cycles. Only criteria which could be evaluated at the PN stage were included, i.e. not criteria which could only be assessed after pronuclear membrane breakdown or the first cleavage division. Supernumerary PN oocytes were cryopreserved after selection. A mean PN score of <13 (sum of scores of all selected PN oocytes/number of selected PN oocytes) led to a pregnancy rate of 4%, a mean PN score of > or =13 to a pregnancy rate of 22%. Embryo morphology and cumulative PN were correlated (r = 0.52, P < 0.05). The negative predictive value was 92% at a threshold of 13 for the mean PN score. The use of this and perhaps additional scoring systems of PN stage oocytes might help to offer patients in Germany the transfer of two selected PN oocytes, which would reduce the multiple pregnancy rate.
Explicit local exchange-correlation potentials (1971)

The possibilities of the Hohenberg-Kohn-Sham local density theory are explored in view of recent advances in the theory of the interacting electron gas. The authors discuss and provide numerical data for the effective exchange-correlation potentials mu xc for ground state problems and Vxc for excitation spectra. The potential mu xc(r) is written as a factor beta ( rho (r)), which depends on the local density rho (r), times the Kohn-Sham-Gaspar potential mu x=-e2kF/ pi . The factor beta , which is represented by a simple analytical formula, varies between 1 for very high densities and about 1.5 for very low densities, where mu xc thus approaches the Slater approximation. The potential Vxc is given in the form of a table. The explicit predictions of the approximate theories are mapped in their linearized versions. The theory is also developed for the case when the ion cores are treated separately, and the local density approximation is applied only to the valence electrons.
Synthesis, crystal structure and properties of the first trinuclear copper(ii) cryptate bridged by an imidazole anion (2002)

The trinuclear copper(II) cryptate [Cu3L(im)(Br)2](ClO4)3·H2O was studied, where im denotes the imidazolate anion and L is a reduced form cryptand which was synthesized by [2 + 3] Schiff-base condensation of tris(2-aminopropyl)amine with 2,6-diformylpyridine followed by reduction with NaBH4. An ES-MS spectrum confirms the presence of a Cu3L core and its dimer in the cryptate. X-Ray analysis shows that the three copper(II) centers are arranged in an isosceles triangles. Cu(1) is located in a N4Br coordination environment with a square pyramidal configuration. Cu(2) and Cu(3) showed square planar configurations with N3Br and N4 coordination environments, respectively. Two nitrogens of an imidazole anion acting as a bridging ligand link Cu(1) and Cu(3). A weak interaction was found between Cu(2) and Br(1). Both intermolecular hydrogen bonds and the weak interaction between two molecules of cryptates via ClO4− resulted in the formation of a dimer of the cryptate. The magnetic interaction in the dimer was also studied.
DeCAF: A Deep Convolutional Activation Feature for Generic Visual Recognition (2013)

We evaluate whether features extracted from the activation of a deep convolutional network trained in a fully supervised fashion on a large, fixed set of object recognition tasks can be re-purposed to novel generic tasks. Our generic tasks may differ significantly from the originally trained tasks and there may be insufficient labeled or unlabeled data to conventionally train or adapt a deep architecture to the new tasks. We investigate and visualize the semantic clustering of deep convolutional features with respect to a variety of such tasks, including scene recognition, domain adaptation, and fine-grained recognition challenges. We compare the efficacy of relying on various network levels to define a fixed feature, and report novel results that significantly outperform the state-of-the-art on several important vision challenges. We are releasing DeCAF, an open-source implementation of these deep convolutional activation features, along with all associated network parameters to enable vision researchers to be able to conduct experimentation with deep representations across a range of visual concept learning paradigms.
Galanin inhibits leptin expression and secretion in rat adipose tissue and 3T3-L1 adipocytes (2004)

In addition to serving as a fat depot, adipose tissue is also considered as an important endocrine organ that synthesizes and secretes a number of factors. Leptin is an adipocyte-derived hormone that plays a vital role in energy balance. Expression of leptin is regulated by dietary status and hormones. In the present study, we report that galanin, an orexigenic peptide, inhibits leptin expression and secretion in rat adipose tissue and in 3T3-L1 adipocytes. Treatment with galanin (25 micro g/animal) induced approximately 46% down-regulation of leptin secretion at 15 min, followed by 40, 37 and 47% decreases in leptin secretion at 1, 2 and 4 h respectively. Although Northern blot analysis of adipose tissue from the same animals showed that leptin mRNA expression in adipose tissue was unaffected by galanin treatment for 2 h, galanin treatment for 4 h led to decline of leptin mRNA expression in a dose-dependent manner. Meanwhile, treating the rats with galanin had no effect on leptin mRNA expression in the hypothalamus. The inhibitory action of the galanin on leptin mRNA and protein levels was also observed in vitro. When incubated with 10 nM galanin for 48 h, leptin mRNA expression and protein secretion also decreased in 3T3-L1 adipocytes. On the other hand, galanin was found not only to express in rat adipose tissue, but also to increase about 8-fold after fasting. Based on these data, we speculate that increased galanin expression in rat adipose tissue after fasting may be involved in reducing leptin expression and secretion in fasting rats.
Efficient Synthesis of Phosphorylated Prodrugs with Bis(POM)-phosphoryl Chloride (2004)

An efficient method for the synthesis of phosphorylated prodrugs is described. The preparation of various bis-pivaloyloxymethyl (POM) phosphate triesters was accomplished in moderate to good yields with the use of bis(POM) phosphoryl chloride under mild conditions.
Towards a generic per-fee-link framework (2007)

Low value electronic content is not being offered following a model in which the content is accessed clicking in a new sort of links called per-fee-links. The goal of these links is making the (micro)payment of a web content as simple as possible: just by clicking on a link. Despite this model has been proposed as an approach to pay low-value content on the web, we do not find any existing framework following that model. As a response to this need, we propose a new framework based on three main components. First, a session-oriented protocol that is independent of the application protocol used (HTTP, FTP ...). It does not only support the per-fee-links model but also other models such as pay-per-data, pay-per-time, etc. Second, we describe how to define a per-fee-link. Finally, we mention the set of functions that should be supported by a wallet in this framework.
Analysis of Heart Rate Variability Five Minutes Before the Onset of Paroxysmal Atrial Fibrillation (1999)

We observed abrupt changes in sympathovagal balance in the last 5 minutes preceding an episode of atrial fibrillation. This can be related to a double behavior in the neurogenic drive: in Type A episodes there is an increase of the LF spectrum, LF:HF ratio, and a decrease of the HF spectrum consistent with an increase of neurogenic sympathetic drive; in Type B episodes there is a reduction of the LF spectrum, LF/HF ratio, and an increase of HF spectrum consistent with an enhancement of the neurogenic parasympathetic drive. In some patients, we found that the two mechanisms operate during different hours of the day and that sometimes there is an increase of sympathetic tone, and in the same instances an increase of parasympathetic tone. Heart-rate variability measures fluctuation in autonomic inputs to the heart rather than the mean level of autonomic impulse; autonomic imbalance is probably more important than the vagal or sympathetic drive alone.
The orientation of the major coat protein of bacteriophage f1 in the cytoplasmic membrane of Escherichia coli. (1981)

The orientation of the major coat (B) protein of the bacteriophage f1, an integral membrane protein in the cytoplasmic membrane of infected Escherichia coli, was examined. Pyridoxal 5'-phosphate and [3H]NaBH4 were used to label the cytoplasmic membrane proteins in spheroplasts and membrane vesicles of E. coli infected with bacteriophage f1. Under the conditions described, tritium incorporation was almost completely dependent on the presence of pyridoxal 5'-phosphate and little if any of the cytoplasmic proteins were labeled when the reaction was applied to intact spheroplasts. The major coat protein was isolated from the cytoplasmic membranes labeled in this manner and the chymotryptic peptides were analyzed for the presence of tritium in the pyridoxamine 5'-phosphate conjugate. When the proteins were labeled in the intact spheroplast, only the NH2-terminal chymotryptic peptide of the coat protein was labeled. If the proteins were labeled during osmotic lysis of the spheroplasts or in isolated vesicles, the chymotryptic peptide containing the COOH terminus of the coat protein as well as the NH2-terminal peptide was labeled. The NH2-terminal peptide was labeled to approximately the same extent as occurred in the intact spheroplast. These results are consistent with the hypothesis that the mature f1 coat protein asymmetrically spans the cytoplasmic membrane of the infected host with its NH2 terminus exposed on the outside and COOH terminus exposed on the cytoplasmic surface.
A live, attenuated recombinant West Nile virus vaccine (2006)

West Nile (WN) virus is an important cause of febrile exanthem and encephalitis. Since it invaded the U.S. in 1999, >19,000 human cases have been reported. The threat of continued epidemics has spurred efforts to develop vaccines. ChimeriVax-WN02 is a live, attenuated recombinant vaccine constructed from an infectious clone of yellow fever (YF) 17D virus in which the premembrane and envelope genes of 17D have been replaced by the corresponding genes of WN virus. Preclinical tests in monkeys defined sites of vaccine virus replication in vivo. ChimeriVax-WN02 and YF 17D had similar biodistribution but different multiplication kinetics. Prominent sites of replication were skin and lymphoid tissues, generally sparing vital organs. Viruses were cleared from blood by day 7 and from tissues around day 14. In a clinical study, healthy adults were inoculated with 5.0 log(10) plaque-forming units (PFU) (n = 30) or 3.0 log10 PFU (n = 15) of ChimeriVax-WN02, commercial YF vaccine (YF-VAX, n = 5), or placebo (n = 30). The incidence of adverse events in subjects receiving the vaccine was similar to that in the placebo group. Transient viremia was detected in 42 of 45 (93%) of ChimeriVax-WN02 subjects, and four of five (80%) of YF-VAX subjects. All subjects developed neutralizing antibodies to WN or YF, respectively, and the majority developed specific T cell responses. ChimeriVax-WN02 rapidly elicits strong immune responses after a single dose, and is a promising candidate warranting further evaluation for prevention of WN disease.
Physiology of the Neurotrophins (1996)

The neurotrophins are a small group of dimeric proteins that profoundly affect the development of the nervous system of vertebrates. Recent studies have established clear correlations between the survival requirements for different neurotrophins of functionally distinct subsets of sensory neurons. The biological role of the neurotrophins is not limited to the prevention of programmed cell death of specific groups of neurons during development. Neurotrophin-3 in particular seems to act on neurons well before the period of target innervation and of normally occurring cell death. In animals lacking functional neurotrophin or receptor genes, neuronal numbers do not seem to be massively reduced in the CNS, unlike in the PNS. Finally, rapid actions of neurotrophins on synaptic efficacy, as well as the regulation of their mRNAs by electrical activity, suggest that neurotrophins might play important roles in regulating neuronal connectivity in the developing and in the adult central nervous system.
Caffeine improves barrier function in male skin (2006)

The influence of androgens, especially testosterone and its effector dihydrotestosterone, results in a constitutive disadvantage for male skin, e.g. reduced viability of hair at the scalp and reduced epidermal permeability barrier repair capacity. Dihydrotestosterone can act, among others, as an adenyl cyclase inhibitor. Caffeine on the other hand is an inexpensive and (in regular doses) harmless substance used in various cosmetic products, which can act as a phosphodiesterase inhibitor. To prove the hypothesis that caffeine as a phosphodiesterase inhibitor is able to override testosterone-induced effects on barrier function, we performed a double-blind placebo controlled study with healthy volunteers. In this study, 0.5% caffeine in a hydroxyethylcellulose gel preparation (HEC) was applied on one forearm, HEC without caffeine on the other forearm of male and female volunteers for 7 days and transepidermal water loss (TEWL) was measured before and at the end of the treatment period. Basal TEWL did not differ significantly between male and female subjects but the application of caffeine significantly reduced TEWL in male skin compared with female skin. We conclude that caffeine is beneficial for barrier function in male skin.