gebhart/patrepeval huggingface dataset:
Immunochromatographic Strip Test for Rapid Detection of Diphtheria Toxin: Description and Multicenter Evaluation in Areas of Low and High Prevalence of Diphtheria (2002)

An immunochromatographic strip (ICS) test was developed for the detection of diphtheria toxin by using an equine polyclonal antibody as the capture antibody and colloidal gold-labeled monoclonal antibodies specific for fragment A of the diphtheria toxin molecule as the detection antibody. The ICS test has been fully optimized for the detection of toxin from bacterial cultures; the limit of detection was approximately 0.5 ng of diphtheria toxin per ml within 10 min. In a comparative study with 915 pure clinical isolates of Corynebacterium spp., the results of the ICS test were in complete agreement with those of the conventional Elek test. The ICS test was also evaluated for its ability to detect toxigenicity from clinical specimens (throat swabs) in two field studies conducted within areas of the former USSR where diphtheria is epidemic. Eight hundred fifty throat swabs were examined by conventional culture and by use of directly inoculated broth cultures for the ICS test. The results showed 99% concordance (848 of 850 specimens), and the sensitivity and specificity of the ICS test were 98% (95% confidence interval, 91 to 99%) and 99% (95% confidence interval, 99 to 100%), respectively.
New prodrugs of acyclic nucleosides with antiviral activity. (1988)

More than 130 acyclic purine and pyrimidine nucleoside derivatives have been synthesized. Structure-activity relationships among a selected group of 6- and 9-substituted guanine derivatives will be discussed. By introduction of secondary aliphatic (e.g. isopropyl or secondary butyl) ether groups into acyclic nucleosides such as aciclovir and ganciclovir new lipophilic prodrugs with modified physical and improved pharmacokinetic properties have been obtained. Several compounds with isopropylether groups in the side-chain and/or in the 6-position (among these the 6-deoxy derivative Hoe 602) of the purine moiety displayed excellent antiviral activity when tested in vivo against herpes simplex virus type 1 infection in mice.
Studies on the Metabolism of Unsaturated Fatty Acids. XIV.1 Purification and Properties of NADPH-Dependent trans-2-Enoyl-CoA Reductase of Escherichia coli K-12 (1984)

NADPH-dependent trans-2-enoyl-CoA reductase was purified to homogeneity from Escherichia coli. The molecular weight of the native enzyme was estimated to be 80,000 by gel filtration and that of the subunit was estimated to be 40,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme was most active toward trans-2-hexenoyl-CoA and trans-2-octenoyl-CoA but was less active toward longer chain substrates, whereas the Km values decreased progressively with increasing carbon chain length of substrates. The reductase appears to have a functional thiol group. The enzyme activity was rapidly decreased by p-hydroxymercuribenzoate and 5,5'-dithiobis(2-nitrobenzoic acid), and slowly by N-ethylmaleimide. The enzyme was protected from inhibition by these SH-reagents by the addition of NADPH. The enzyme was also inhibited by saturated acyl-CoA esters.
Mitigation of 21st century Antarctic sea ice loss by stratospheric ozone recovery (2012)

We investigate the effect of stratospheric ozone recovery on Antarctic sea ice in the next half‐century, by comparing two ensembles of integrations of the Whole Atmosphere Community Climate Model, from 2001 to 2065. One ensemble is performed by specifying all forcings as per the Representative Concentration Pathway 4.5; the second ensemble is identical in all respects, except for the surface concentrations of ozone depleting substances, which are held fixed at year 2000 levels, thus preventing stratospheric ozone recovery. Sea ice extent declines in both ensembles, as a consequence of increasing greenhouse gas concentrations. However, we find that sea ice loss is ∼33% greater for the ensemble in which stratospheric ozone recovery does not take place, and that this effect is statistically significant. Our results, which confirm a previous study dealing with ozone depletion, suggest that ozone recovery will substantially mitigate Antarctic sea ice loss in the coming decades.
Influence of human T-cell leukemia virus type I tax and rex on interleukin-2 gene expression (1993)

The X region of human T-cell leukemia virus type I (HTLV-I) encodes two proteins that regulate viral gene expression. The tax protein is the product of the transactivator gene and has been shown to up-regulate the expression of some cellular genes controlling T-cell replication, including that of the interleukin-2 (IL-2) T-cell growth hormone and the alpha chain of its receptor (IL-2R). Several studies have shown that tax transactivation of the IL-2R alpha-chain promoter is mediated by binding sites for the transcriptional activator NF-kappa B, and this mechanism has also been implicated in the tax activation of IL-2 promoter activity. The rex gene product of HTLV-I regulates viral protein production by influencing mRNA expression and has been implicated in the stabilization of IL-2R alpha-chain mRNA. In the present studies, the ability of the tax and rex proteins to transactivate IL-2 gene expression has been reinvestigated. The ability of the tax protein to transactivate IL-2 promoter activity appears, at least in part, to be mediated by the recognition sequence for a DNA-binding complex known as CD28RC. Consistent with this hypothesis is the observation that tax-mediated activation of IL-2 gene expression is resistant to the immunosuppressive affects of cyclosporin A, a property postulated for the CD28RC binding complex. Unexpectedly, this tax-mediated up-regulation of IL-2 expression is synergized by the presence of the rex protein. These findings demonstrate that transactivation of IL-2 gene expression by tax is augmented by mechanisms distinct from NF-kappa B and raise the possibility that rex, as well as tax, contributes to the oncogenic capability of HTLV-I by altering the expression of the IL-2 gene in T cells infected with this retrovirus.
Targeting CD20+ Aggressive B-cell Non–Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice (2014)

The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20(+) B-NHL in vitro and in vivo. CAR(+) exPBNK had significantly enhanced in vitro cytotoxicity, compared with CAR(-) exPBNK against CD20(+) Ramos (P < 0.05), Daudi, Raji, and two rituximab-resistant cell lines, Raji-2R and Raji-4RH (P < 0.001). As expected, there was no significant difference against CD20(-) RS4;11 and Jurkat cells. CD107a degranulation and intracellular IFNγ production were also enhanced in CAR(+) exPBNK in response to CD20(+) B-NHL -: specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain(-/-) (NSG) mice, the luciferase signals measured in the CAR(+) exPBNK-treated group were significantly reduced, compared with the signals measured in the untreated mice and in mice treated with the CAR(-) exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (P < 0.001) and reduced tumor size, compared with those of the untreated and the CAR(-) exPBNK-treated mice (P < 0.05). These preclinical data suggest that ex vivo-exPBNK modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor-risk CD20(+) hematologic malignancies.
The Consensus 5' Splice Site Motif Inhibits mRNA Nuclear Export (2015)

In eukaryotes, mRNAs are synthesized in the nucleus and then exported to the cytoplasm where they are translated into proteins. We have mapped an element, which when present in the 3'terminal exon or in an unspliced mRNA, inhibits mRNA nuclear export. This element has the same sequence as the consensus 5'splice site motif that is used to define the start of introns. Previously it was shown that when this motif is retained in the mRNA, it causes defects in 3'cleavage and polyadenylation and promotes mRNA decay. Our new data indicates that this motif also inhibits nuclear export and promotes the targeting of transcripts to nuclear speckles, foci within the nucleus which have been linked to splicing. The motif, however, does not disrupt splicing or the recruitment of UAP56 or TAP/Nxf1 to the RNA, which are normally required for nuclear export. Genome wide analysis of human mRNAs, lncRNA and eRNAs indicates that this motif is depleted from naturally intronless mRNAs and eRNAs, but less so in lncRNAs. This motif is also depleted from the beginning and ends of the 3'terminal exons of spliced mRNAs, but less so for lncRNAs. Our data suggests that the presence of the 5'splice site motif in mature RNAs promotes their nuclear retention and may help to distinguish mRNAs from misprocessed transcripts and transcriptional noise.
Enzymatic Nanolithography of Polyaniline Nanopatterns by Using Peroxidase‐Modified Atomic Force Microscopy Tips (2009)

A new enzyme nanolithography strategy for creating conducting polymer nanostructures through the modification of AFM tips with peroxidase is described. Scanning of the modified tip in the presence of aniline and hydrogen peroxide is used for biocatalytic patterning of different polyaniline nanostructures (see figure).
Pyrido[2,3‐d]pyrimidines and Pyrimido[5′,4′:5,6]pyrido[2,3‐d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
Germline transgenesis of zebrafish using the medaka Tol1 transposon system (2008)

Tol1 is a DNA-based transposable element first identified from an albino mutant medaka fish. It has been demonstrated to function as an efficient gene transfer vector in mammalian cells. We now demonstrate Tol1 germline transgenesis in zebrafish. A construct containing the green fluorescence protein (GFP) reporter gene inserted between the Tol1 arms was microinjected together with Tol1 transposase mRNA into fertilized eggs. Sustained GFP expression was observed in 88% of 1-month-old fish, suggesting efficient transposon integration into somatic cells. Eleven of 24 adult GFP-positive fish yielded GFP-positive progeny. Sequencing analysis of Tol1 insertion sites in GFP-positive progeny confirmed Tol1 transposition-mediated integrations into zebrafish chromosomes. We also observed functional independence of the Tol1 transposase-substrate system from that of Tol2, another medaka-derived transposon. Coupled with its previously demonstrated maximal cargo capacity of >20 kb, Tol1 could serve as a useful addition to the zebrafish genetic engineering toolbox.
Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca2+-Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands (1999)

Proadrenomedullin N-terminal 20 peptide (PAMP) is a 20-amino acid hypotensive peptide expressed in the adrenal medulla. We investigated the localization and function of PAMP receptors in the human adrenal gland. Autoradiography showed the presence of [125I]PAMP-binding sites in both zona glomerulosa and adrenal medulla that were displaced by cold PAMP and PAMP(12-20) but not by other preproadrenomedullin-derived peptides. PAMP, but not PAMP(12-20), counteracted, in a concentration dependent manner, both aldosterone response of zona glomerulosa cells and catecholamine response of adrenal medulla cells to BAYK-8644, the selective agonist of voltage-activated Ca2+ channels, as well as to K+ and angiotensin II. PAMP(12-20) partially reversed this antisecretagogue effect of PAMP. Collectively, these findings suggest (1) that PAMP inhibits Ca2+-dependent, agonist-stimulated aldosterone and catecholamine secretion, acting via specific receptors and through a mechanism involving the impairment of Ca2+ influx; and (2) that PAMP(12-20) acts as a weak antagonist of PAMP receptors, thereby suggesting that both C- and N-terminal sequences of the PAMP molecule are required for this peptide to exert its antisecretagogue action on the human adrenal gland.
Protein and amino acid composition of hair from mice carrying the naked (N) gene (1984)

Summary The protein and amino acid compositions of hair from mice carrying the naked ( N ) gene were compared with those of wild-type (+ / +) mouse hair using two-dimensional polyacrylamide gel electrophoresis and amino acid analysis. In samples obtained from N /+ mice, the numbers of positions of the low-sulphur (LS), high-sulphur (HS) and high tyrosine (HT) protein spots were indistinguishable from those observed in + / + samples but the amount of HT protein was reduced in N / + hair. In samples obtained from N /N mice the protein spots were fewer than, and perhaps different from, those in samples from the other two genotypes; all protein classes were represented but the HS and HT protein content appeared to be less than that in + / + and N / + hair. Amino acid analyses of hair samples showed that the HS contents of + / + and N / + hair were approximately the same, whereas the HT protein content of N / + hair was about half that in + / + hair. N / N hair contained less half-cystine and tyrosine than + / + and N / + hairs, but because the contents of proline, threonine and glycine were unexpectedly high, it appears that protein components of unusual composition are present in N / N hair. It was concluded that the gene at the N locus is involved only indirectly in the synthesis of the structural proteins found in mouse hair.
Activation of factor XI in plasma is dependent on factor XII [see comments] (1993)

The activation of factor XI initiates the intrinsic coagulation pathway. Until recently it was believed that the main activator of factor XI is factor XIIa in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface. Two recent reports have presented evidence that in a purified system factor XI is activatable by thrombin together with the soluble polyanion dextran sulfate. To assess the physiological relevance of these findings we studied the activation of factor XI in normal and factor XII-deficient plasma. We used either kaolin/cephalin or dextran sulfate as a surface for the intrinsic coagulation pathway, tissue factor to generate thrombin via the extrinsic pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is rapidly cleaved on incubation with kaolin. The kinetics appear to be exponential with half the maximum cleavage at 5 minutes. Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. Tissue factor (1:500) added to plasma did not induce cleavage of factor XI during a 90-minute incubation, although fibrin formation within 30 seconds indicated that thrombin was generated via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to 50% prothrombin activation) directly to factor XII deficient or normal plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to instantaneous fibrinogen cleavage, but again no cleavage of factor XI was observable. We conclude that in plasma surroundings factor XI is not activated by thrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable.
Flattening maps for the visualization of multibranched vessels (2005)

In this paper, we present two novel algorithms which produce flattened visualizations of branched physiological surfaces, such as vessels. The first approach is a conformal mapping algorithm based on the minimization of two Dirichlet functionals. From a triangulated representation of vessel surfaces, we show how the algorithm can be implemented using a finite element technique. The second method is an algorithm which adjusts the conformal mapping to produce a flattened representation of the original surface while preserving areas. This approach employs the theory of optimal mass transport. Furthermore, a new way of extracting center lines for vessel fly-throughs is provided.
A new robot architecture for tele-echography (2003)

This paper presents a slave robot carrying an ultrasound probe for remote echographic examination. This robot is integrated in a master-slave system called robotic tele-echography (TER). The system allows an expert operator to perform a remote diagnosis from echographic data he acquires on a patient located in a distant place. The originality of this robot lies in its architecture: the cable-driven robot is lightweight and semirigid, and it is positioned on the patient body. In this paper, we describe the clinical application, the system architecture, the second implementation of the robot, and experiments performed with this prototype.
Cardiac gap junctions in rat ventricle: localization using site-directed antibodies and laser scanning confocal microscopy. (1990)

Antibodies were raised to three synthetic peptides, each constructed to match a different cytoplasmic region of the 43kD protein of the cardiac gap junction. These antibodies have all been used for immunohistochemical localization of gap junctions in the rat ventricle. Each is shown to have different staining characteristics which provide supporting evidence for the model proposed for the configuration of the gap junction protein within the membrane. Laser scanning confocal microscopy has confirmed that the localization of ventricular myocyte gap junctions is solely within intercalated disks. This technique is demonstrated to provide a greater overview of the three dimensional arrangement of the junctions than other microscopical techniques. Larger gap junctions occur typically at the periphery of the disk, with smaller junctions situated in the central zone. The analysis of the number and distribution of gap junctions over large volumes of myocardial tissue (three-dimensional tomography) is now feasible with this approach, and may be used to delineate conduction pathways.
Transfecting Mammalian Cells: Optimization of Critical Parameters Affecting Calcium-Phosphate Precipitate Formation (1996)

DNA-calcium phosphate co-precipitates arise spontaneously in supersaturated solutions. Highly effective precipitates for transfection purposes, however, can be generated only in a very narrow range of physico-chemical conditions that control the initiation and growth of precipitate complexes. The concentrations of calcium and phosphate are the main factors influencing characteristics of the precipitate complex, but other parameters, such as temperature, DNA concentration and reaction time are important as well. An example for this is the finding that almost all of the soluble DNA in the reaction mix can be bound into an insoluble complex with calcium phosphate in <1 min. Extending the reaction time to 20 min results in aggregation and/or growth of particles and reduces the level of expression. With improved protocols we gained better reproducibility and higher efficiencies both for transient and for stable transfections. Up to 60% of cells stained positive for beta-gal and transient production of secreted proteins was improved 5- to 10-fold over results seen with transfections using standard procedures. Similar improvements in efficiency (number of recombinant cell colonies) were observed with stable transfections, using co-transfected marker plasmids for selection. Transient expression levels 2 days after DNA transfer and titers obtained from stable cell lines, emerging weeks later, showed strong correlation.
A scheme to construct global file system (2002)

Pervasive computing compels applications to store files on the Internet. We propose a scheme to organize heterogeneous file servers scattered around the Internet into a unified file system that provides a file service as a whole. There are three main features associated with the file system. First, its architecture is of high scalability, which ensures the system can be extended to a large scale. Second, the file names in the system are location-independent. Third, several measures have been taken in the system, such as caches and proximity-based algorithms for file location, to improve the file access performance. The scheme has been implemented in CSFS (Campus Star File System). By now, the prototype development of CSFS has finished.
Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis (1999)

In the present study, we demonstrate that systemic IL-4 treatment ameliorates disease progression of established CIA. Although clinical disease progression of established CIA. Although clinical disease progression was only arrested and not reversed, clear protection against cartilage and bone destruction was noted. This is in accord with findings in both human RA and animal models of RA that show that inflammation and tissue destruction sometimes are uncoupled processes. Of great importance is that, although inflammation was still present, strong reduction in serum COMP was found after exposure to IL-4. This indicated that serum COMP levels reflected cartilage damage, although a limited contribution of the inflamed synovium cannot be excluded. Increased serum IL-1Ra level (twofold) was found after systemic treatment with IL-4, but it is not likely that this could explain the suppression of CIA. We and others have reported that high dosages of IL-1Ra are needed for marked suppression of CIA. As reported previously, lower dosages of IL-4 did not reduce clinical disease severity of established CIA. Of importance is that combined treatment of low dosages of IL-4 and IL-10 appeared to have more potent anti-inflammatory effects, and markedly protected against cartilage destruction. Improved anti-inflammatory effect was achieved with IL-4/prednisolone treatment. In addition, synergistic effects were found for the reduction of cartilage and bone destruction. This indicates that systemic IL-4/prednisolone treatment may provide a cartilage and bone protective therapy for human RA.
Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex (2008)

Ever since the groundbreaking work of Ramon y Cajal, the cerebellar cortex has been recognized as one of the most regularly structured and wired parts of the brain formed by a rather limited set of distinct cells. Its rather protracted course of development, which persists well into postnatal life, the availability of multiple natural mutants, and, more recently, the availability of distinct molecular genetic tools to identify and manipulate discrete cell types have suggested the cerebellar cortex as an excellent model to understand the formation and working of the central nervous system. However, the formulation of a unifying model of cerebellar function has so far proven to be a most cantankerous problem, not least because our understanding of the internal cerebellar cortical circuitry is clearly spotty. Recent research has highlighted the fact that cerebellar cortical interneurons are a quite more diverse and heterogeneous class of cells than generally appreciated, and have provided novel insights into the mechanisms that underpin the development and histogenetic integration of these cells. Here, we provide a short overview of cerebellar cortical interneuron diversity, and we summarize some recent results that are hoped to provide a primer on current understanding of cerebellar biology.