gebhart/patrepeval huggingface dataset:
The dermatophytes (1995)

The etiologic agents of the dermatophytoses (ringworm) are classified in three anamorphic (asexual or imperfect) genera, Epidermophyton, Microsporum, and Trichophyton. Species capable of reproducing sexually belong in the teleomorphic genus, Arthroderma, of the Ascomycota. On the basis of primary habitat association, they may be grouped as geophilic (soil associated), zoophilic, and anthropophilic. Adaptation to growth on humans by most geophilic species resulted in diminished loss of sporulation, sexuality, and other soil-associated characteristics. The dermatophytes have the ability to invade keratinized tissue (skin, hair, and nails) but are usually restricted to the nonliving cornified layer of the epidermis because of their inability to penetrate viable tissue of an immunocompetent host. However, invasion does elicit a host response ranging from mild to severe. Acid proteinases, elastase, keratinases, and other proteinases reportedly act as virulence factors. The development of cell-mediated immunity correlated with delayed hypersensitivity and an inflammatory response is associated with clinical cure, whereas the lack of or a defective cell-mediated immunity predisposes the host to chronic or recurrent dermatophyte infection. Chronic dermatophytosis is mostly caused by Trichophyton rubrum, and there is some evidence that mannan produced by this fungus suppresses or diminishes the inflammatory response. Since dermatophytes cause a communicable disease, modes of transmission and control are discussed as well as a survey of recent trends in therapy. Collection of specimens, culture media, and tests for identification are also presented. Genetic studies have led to an understanding of incompatibility mechanisms, pleomorphism and variation, resistance to griseofulvin, and virulence. Molecular biology has contributed to our knowledge of the taxonomy and phylogenetic relationships of dermatophytes.
RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX (2002)

The function of DAXX, a highly conserved mammalian gene, has remained controversial; this is due, in part, to its identification in a variety of yeast two-hybrid screens. Targeted deletion in the mouse revealed that DAXX is essential for embryonic development. Furthermore, the increased levels of apoptosis observed in Daxx-knockout embryos and embryonic stem cell lines suggested that DAXX functions in an anti-apoptotic capacity. In contrast, overexpression studies showed that DAXX may promote apoptosis. Additional studies showed that, when overexpressed, DAXX could function as a transcriptional repressor. To clarify these matters, we have used RNAi to deplete endogenous DAXX and thereby assess DAXX function in cell lines previously tested in overexpression studies. Increased apoptosis was observed in DAXX-depleted cells, showing DAXX to be anti-apoptotic. The apoptosis induced by the absence of DAXX was rescued by Bcl-2 overexpression. In addition, transcriptional derepression was observed in RNAi-treated cells, indicating the ability of endogenous DAXX to repress gene expression and allowing for the identification of novel targets of DAXX repression, including nuclear factor kappaB (NF-kappaB)- and E2F1- regulated targets. Thus, depletion of DAXX by RNAi has verified the crucial role of endogenous DAXX as an anti-apoptotic regulator, and has allowed the identification of probable physiological targets of DAXX transcriptional repression.
Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. (1981)

A noncytotoxic dose of verapamil, a coronary vasodilator, enhances the cytotoxicity of vincristine (VCR) and vinblastine in P388 leukemia and its VCR-resistant subline, P388/VCR. When 2.2 to 6.6 microM verapamil was added along the VCR to the P388/VCR culture in vitro, VCR resistance was completely overcome. Verapamil in doses of 50 to 100 mg/kg administered daily for 10 days with VCR also enhances the chemotherapeutic effect of VCR in P388- and, especially, P388/VCR-bearing mice. When approximately 3 times the amount of VCR was given to a P388/VCR bearer as compared to a P388 bearer, VCR resistance was almost completely overcome in vivo with 50 to 100-mg/kg doses of verapamil. The amount of VCR incorporated into P388 cells was larger than that in P388/VCR cells. Verapamil (6.6 microM) enhanced the cellular level of VCR in P388 cells 2-fold and enhanced the level of VCR in P388/VCR cells 10-fold. The amount of VCR in P388/VCR cells reached the same level as that found in P388 cells. The overcoming of VCR resistance in vivo and in vitro could be explained by the effective accumulation of VCR by verapamil in P388/VCR cells mediated by the inhibition of a VCR efflux function of the cells, a mechanism which remains to be solved.
Targeted proteomic strategy for clinical biomarker discovery (2008)

The high complexity and large dynamic range of blood plasma proteins currently prohibit the sensitive and high-throughput profiling of disease and control plasma proteome sample sets large enough to reliably detect disease indicating differences. To circumvent these technological limitations we describe here a new two-stage strategy for the mass spectrometry (MS) assisted discovery, verification and validation of disease biomarkers. In an initial discovery phase N-linked glycoproteins with distinguishable expression patterns in primary normal and diseased tissue are detected and identified. In the second step the proteins identified in the initial phase are subjected to targeted MS analysis in plasma samples, using the highly sensitive and specific selected reaction monitoring (SRM) technology. Since glycosylated proteins, such as those secreted or shed from the cell surface are likely to reside and persist in blood, the two-stage strategy is focused on the quantification of tissue derived glycoproteins in plasma. The focus on the N-glycoproteome not only reduces the complexity of the analytes, but also targets an information-rich subproteome which is relevant for remote sensing of diseases in the plasma. The N-glycoprotein based biomarker discovery and validation workflow reviewed here allows for the robust identification of protein candidate panels that can finally be selectively monitored in the blood plasma at high sensitivity in a reliable, non-invasive and quantitative fashion.
Amino Acid Sequence in Constitutionally Isomeric Tetrapeptide Amphiphiles Dictates Architecture of One-Dimensional Nanostructures (2014)

The switching of two adjacent amino acids can lead to differences in how proteins fold thus affecting their function. This effect has not been extensively explored in synthetic peptides in the context of supramolecular self-assembly. Toward this end, we report here the use of isomeric peptide amphiphiles as molecular building blocks to create one-dimensional (1D) nanostructures. We show that four peptide amphiphile isomers, with identical composition but a different sequence of their four amino acids, can form drastically different types of 1D nanostructures under the same conditions. We found that molecules with a peptide sequence of alternating hydrophobic and hydrophilic amino acids such as VEVE and EVEV self-assemble into flat nanostructures that can be either helical or twisted. On the other hand, nonalternating isomers such as VVEE and EEVV result in the formation of cylindrical nanofibers. Furthermore, we also found that when the glutamic acid is adjacent to the alkyl tail the supramolecular assemblies appear to be internally flexible compared to those with valine as the first amino acid. These results clearly demonstrate the significance of peptide side chain interactions in determining the architectures of supramolecular assemblies.
Biomechanical pulping of aspen chips: energy savings resulting from different fungal treatments (1990)

Besides increasing paper strength, fungal treatments can also reduce the electrical energy needed for fiberizing chips during mechanical pulping. Fungal species, chip movement, and treatment duration affected the extent of energy savings. This paper reports that four-week-long treatment with white-rot fungi, including Phlebia species or Pholiota mutabilis, in a stationary wire tray bioreactor resulted in at least 35% energy savings for pulping chips to 100 mL CSF in a 300-mm-diameter disc refiner. With Phanerochaete chrysosporium in a rotating-drum bioreactor, the optimal treatment duration was four weeks. Treatment with a brown-rot fungus also resulted in energy savings. Over the range of fungi and conditions tested, neither chip weight loss nor lignin loss correlated with energy savings. Some treatments giving the least chip weight loss ({lt}5%) saved the most energy. Wood modifications responsible for energy savings differed from those that increased strength. Treatments that saved the most energy did not necessarily give the highest strength properties.
Cytotoxic activities of recombinant soluble murine lymphotoxin-alpha and lymphotoxin-alpha beta complexes (1997)

Human lymphotoxin-alpha (LT alpha) is found in a secreted form and on the surface of lymphocytes as a complex with a second related protein called lymphotoxin-beta (LT beta). Both secreted human LT alpha and TNF have similar biological activities mediated via the TNF receptors, whereas the cell surface LT alpha beta complex binds to a separate receptor called the LT beta receptor (LT beta R). The murine LT alpha and LT beta (mLT alpha and mLT beta) proteins have never been characterized. When recombinant mLT alpha was produced by either of several methods, the protein had a very low specific activity relative to that of human LT alpha in the conventional WEHI 164 cytotoxicity bioassay. The weak activity observed was inhibited by a soluble murine TNF-R55 Ig fusion protein (mTNF-R55-Ig), but not by mLT beta R-Ig. Coexpression of both mLT alpha and a soluble version of mLT beta in insect cells led to an LT alpha beta form that was cytotoxic in the WEHI 164 assay via the LT beta R. To determine whether natural mLT alpha-like forms with cytotoxic activity comparable to that of secreted human LT alpha were secreted from primary spleen cells, splenic lymphocytes were activated in various ways, and their supernatants were analyzed for cytotoxic activity. Using specific Abs to distinguish between mTNF and mLT, a TNF component was readily detected; however, there was no evidence for a secreted mLT alpha cytotoxic activity using this assay. Combined, these observations suggest that secreted mLT alpha may not play a role in the mouse via interactions with TNF-R55, and the ramifications of this hypothesis are discussed.
Worsening of Macrophage Activation Syndrome in a Patient with Adult Onset Still’s Disease after Initiation of Etanercept Therapy (2001)

The macrophage activation syndrome (MAS) is a rare, potentially fatal, clinical syndrome, which has been described in childhood rheumatic disorders. MAS is defined by a prolonged period of fevers, pancytopenia, and hypertriglyceridemia (with or without hypofibrinogenemia). Histopathological examination of bone marrow, spleen, or lymph nodes shows hemophagocytosis by mononuclear phagocytes. In patients with Still's disease, observed triggering events for MAS have included both infectious processes and pharmacological agents, such as parenteral gold and nonsteroidal anti-inflammatory drugs. We report the case of a young woman with adult-onset Still's disease (AOSD), complicated by an Epstein-Barr virus infection and subsequent MAS, whose course worsened after administration of the soluble tumor necrosis factor-alpha receptor, etanercept. Subsequent treatment with pulse corticosteroids and cyclosporine A induced a dramatic clinical improvement. Treatment data regarding the use of etanercept in AOSD are lacking; given our experience and recent reports in children with Still's disease, we would suggest caution using this agent in patients with AOSD, particularly when complicated by MAS.
Initiation and processing of two kappa immunoglobulin germ line transcripts in mouse B cells. (1990)

The splicing patterns and sequences of two processed kappa immunoglobulin germ line mRNAs are presented. A 1.1-kilobase (kb) mRNA appeared to be derived from splicing of the previously characterized 8.4-kb germ line transcript, while a 0.8-kb mRNA was the splice product of a second 4.7-kb germ line transcript that initiated 50 base pairs upstream of J kappa 1. The interaction of the two kappa germ line promoters with nuclear binding factors is also examined. The potential role of these germ line transcripts in establishing the rearrangement potential of the locus is discussed.
Cytoplasmic expression of a reporter gene by co-delivery of T7 RNA polymerase and T7 promoter sequence with cationic liposomes (1993)

Expression of bacteriophage T7 RNA polymerase in mammalian cells can efficiently drive the transcription of a foreign gene controlled by the T7 promoter (Elroy-Stein et al., Proc. Natl. Acad. Sci. USA. 86, 6126-6130, 1989). We have tested the hypothesis that purified T7 RNA polymerase can be co-delivered into mammalian cells together with a reporter gene (chloramphenicol acetyltransferase, CAT) controlled by the T7 promoter (pT7-EMC-CAT) using DC-chol cationic liposomes. Indeed, significant level of CAT activity was observed in human lung adenocarcinoma (A549-1) cells which had been incubated with a complex of T7 RNA polymerase, pT7-EMC-CAT DNA and DC-chol cationic liposomes. The expression was specific in that T3 RNA polymerase could not replace the T7 RNA polymerase, and that co-delivered T7 RNA polymerase did not enhance the expression of a CAT gene controlled by the SV40 early promoter. The system was optimized in terms of enzyme, DNA and liposome concentrations. Time course experiment indicated that the expression of the T7 system was about 8-10 hours sooner than the SV40 system, consistent with the notion that T7 RNA polymerase does not enter into the nucleus and the transcription takes place in the cytoplasm of the transfected cells. The expression of the T7 system was transient; it declined after 30 hours post transfection, probably due to turnover of the phage enzyme in the mammalian cells. The expression system described here should be useful for gene transfer experiments which require a fast but transient expression of a foreign gene. We have also compared our delivery system with a commercial reagent, Lipofectin, which has been used to deliver T3 or T7 RNA polymerase with a reporter plasmid encoding the T3 or T7 promoter.
Lipoprotein lipase induces catabolism of normal triglyceride-rich lipoproteins via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in vitro. A process facilitated by cell-surface proteoglycans (1993)

Bovine milk lipoprotein lipase (LPL) induced binding, uptake, and degradation of 125I-labeled normal human triglyceride-rich lipoproteins by cultured mutant fibroblasts lacking LDL receptors. The induction was dose-dependent and occurred whether LPL and 125I-lipoproteins were added to incubation media simultaneously or LPL was allowed to bind to cell surfaces, and unbound LPL was removed by washing prior to the assay. Lipolytic modification of lipoproteins did not appear to be necessary for increased catabolism because the effect of LPL was not prevented by inhibitors of LPL's enzymatic activity, p-nitrophenyl N-dodecylcarbamate or phenylmethylsulfonyl fluoride. However, the effect was abolished by boiling LPL prior to the assay suggesting that major structural features of LPL were required. Also, LPL-induced binding to cells was blocked by an anti-LPL monoclonal antibody but not by antibodies that are known to block apolipoprotein E- or B-100-mediated binding to low density lipoprotein (LDL) receptors. This indicates that LPL itself mediated 125I-lipoprotein binding to cells. Cellular degradation of 125I-lipoproteins was partially or completely blocked by two previously described ligands for the LDL receptor-related protein/alpha 2-macroglobulin receptor (LRP): activated alpha 2-macroglobulin (alpha 2M*), and the 39-kDa receptor-associated protein. These data implicated LRP as mediating LPL-induced lipoprotein degradation and were confirmed by showing that LPL's effects were prevented by an immunoaffinity-isolated polyclonal antibody against LRP. Furthermore, LPL promoted binding of 125I-lipoproteins to highly purified LRP in a solid-phase assay. Heparin or heparinase treatment of cells markedly decreased LPL-induced binding, uptake, and degradation of lipoproteins, but had no effect on catabolism of alpha 2M*. Thus, cell-surface proteoglycans were obligatory participants in the effects of LPL but were not required for LRP-mediated catabolism of alpha 2M*. Taken together, these in vitro findings establish that through interaction with cell-surface proteoglycans, LPL induces catabolism of normal human triglyceride-rich lipoproteins via LRP.
Glioblastoma Multiforme and the Epidermal Growth Factor Receptor (2005)

Glioblastoma multiforme is one of the most aggressive and recalcitrant cancers. A tumor that can be identified radiographically can sometimes be resected, yielding a putatively clean magnetic resonance image postoperatively, but tumor cells are invariably present in areas of the brain that are at a considerable distance from the site of initial diagnosis. The delivery of radiotherapy to a field encompassing the tumor and a margin of 2 to 3 cm increases survival, but not substantially. Systemic treatment may be beneficial, but therapy with nitrosoureas and the methylating agent temozolomide increases survival only slightly. Virtually all patients with glioblastoma multiforme . . .
Real-time Vision-based Hand Gesture Recognition Using Haar-like Features (2007)

This paper proposes a two level approach to solve the problem of real-time vision-based hand gesture classification. The lower level of the approach implements the posture recognition with Haar-like features and the AdaBoost learning algorithm. With this algorithm, real-time performance and high recognition accuracy can be obtained. The higher level implements the linguistic hand gesture recognition using a context-free grammar-based syntactic analysis. Given an input gesture, based on the extracted postures, the composite gestures can be parsed and recognized with a set of primitives and production rules.
Modification of Polyhydroxyalkanoates (PHAs) (2014)

The excellent biodegradability, compatibility and versatile structural composition of polyhydroxyalkanotes (PHAs) have secured their significance for industrial applications. More importantly, these polymers can also play a critical role in biomedical applications such as a 3D scaffold for tissue engineering, bio-adhesive, surgical sutures, implants and anticoagulant films. Unfortunately, their hydrophobicity, crystallinity and lack of surface ligand groups potentially limit their applications in this area. Hence, the future of these biodegradable polymers as biomedical device components is strongly dependent on successful modifications to tailor their properties and characteristics. Chemical, physical and enzymatic approaches have been explored for polymer modifications, resulting in a uniquely transformed PHA endowed with functionalized reactive groups and/or enhanced properties such as thermal stability, elasticity, improved hydrophilicity and degradability. While chemical modification processes provide a large degree of freedom in controlling and designing modified PHAs in bulk quantities to suit a particular function, most often they have to contend with the drawback of toxic impurities that require difficult downstream processing. Physical or enzymatic modifications are therefore considered to be alternative methods that involve no toxic compounds. A number of modified PHAs are easily prepared by physical methods and have been successfully applied in diverse applications where neat PHAs may have easily failed. However, the current concern over environmental degradation and deterioration coupled with elevated health hazards discourage the use of high energy radiation and co-initiator chemicals in physical methods, pushing the emerging environmentally friendly enzyme catalyzed process to the center stage of the modification arena. In this chapter, the chemical, physical and enzymatic processes typically employed for polymer modification and functionalization are discussed.
TAUTOMERISM AND FLUORESCENCE OF LUMAZINE (1987)

Abstract— The fluorescence properties of lumazine, 1‐methyl‐lumazine (1‐ML) and 3‐methyl‐lumazine (3‐ML) in aqueous solution are pH dependent. Emissions with the following maxima were attributed to the four ionic species of lumazine: dianion (483 nm), monoanion (467 nm), neutral (380 nm) and monocation (505 nm). Neutral lumazine emitted, besides, a fluorescence at 481 nm with a large Stokes shift (10 000 cm ‐1 ). As a similar emission is observed with 3‐ML but not with 1‐ML, we suggest as emitting species the N(8)‐H‐phototautomer resulting from the N(l) to N(8) proton transfer in the excited state. At pH 10, the fluorescence quantum yield of 3‐ML, Q f = 0.24 ± 0.02 was higher than that of 1‐ML, Q f = 0.015 ± 0.002. At this pH, lumazine is a mixture of N(l)‐deprotonated and N(3)‐deprotonated monoanions, the emitting properties being principally due to the N(l)‐deprotonated species, Q f = 0.24 ± 0.02. The evaluation of the ionization constants in the excited state are discussed in relation to the tautomeric nature of the emitting species.
Benzamil blockade of brain Na+channels averts Na+-induced hypertension in rats (1998)

To determine the possible involvement of brain amiloride-sensitive Na+ channels in Na(+)-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na+ channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na(+)-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na(+)-induced hypertension, such as renovascular hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal sympathetic discharge, and plasma vasopressin concentration induced by an acute increase in cerebrospinal Na+ concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol.kg-1.day-1) for 7 days attenuated Na(+)-induced chronic hypertension in both deoxycorticosterone acetate-salt and stroke-prone spontaneous hypertensive rats, accompanied by reduction of urinary excretion of vasopressin and norepinephrine but not in renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol.kg-1.day-1) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+ channels are expected to function as one of the Na+ receptors in the brain and to be involved in the pressor mechanism of Na(+)-induced hypertension.