gebhart/patrepeval huggingface dataset:
Structure of the Threonine-Rich Extensin from Zea mays (1990)

Chymotryptic digestion of a threonine-rich hydroxyproline-rich glycoprotein (THRGP) purified from the cell surface of a Zea mays cell suspension culture gave a peptide map dominated by the hexadecapeptide TC5: Thr-Hyp-Ser-Hyp-Lys-Pro-Hyp-Thr-Pro-Lys-Pro-Thr-Hyp-Hyp-Thr-Tyr, in which the repetitive motif Ser-Hyp-Lys-Pro-Hyp-Thr-Pro-Lys is homologous with the dominant decamer of P1-type dicot extensins: Ser-Hyp-Hyp-Hyp-Hyp-Thr-Hyp-Val-Tyr-Lys, modified by a Lys for Hyp substitution at residue 3, a Val-Tyr deletion at residues 8 and 9, and incomplete post-translational modification of proline residues. One of the minor peptides (TC1) contained the 8-residue sequence: Thr-Hyp-Ser-Hyp-Hyp-Hyp-Hyp-Tyr corresponding to the C-terminal tail (judging from the recently isolated maize cDNA clone MC56) which is homologous with the major repetitive motif of the ;P3' class of dicot extensins. Direct peptide sequencing defined potential glycosylated regions on the THRGP corresponding to clone MC56 and showing that glycosylated and nonglycosylated domains alternate with high regularity. The THRGP is not in the polyproline-II conformation, judging from circular dichroic spectra, but nevertheless is an extended rod, from electron microscopic data. HF-solvolysis of cell walls from maize coleoptile, root, and root tip released deglycosylated THRGP detected on sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots with high titer rabbit polyclonal antibodies raised against the intact THRGP. In a quantitative enzyme-linked immunosorbent assay, these antibodies cross-reacted 20% with tomato P1 extensin, and 18% with anhydrous hydrogen fluoride-deglycosylated P1. These results, together with other previously published data, show that maize THRGP is homologous with the dicot P1 extensins and, as such, is the first extensin isolated from a graminaceous monocot.
Developments in the treatment of hemophilia B: focus on emerging gene therapy (2013)

Hemophilia B is a genetic disorder that is characterized by a deficiency of clotting factor IX (FIX) and excessive bleeding. Advanced understanding of the pathophysiology of the disease has led to the development of improved treatment strategies that aim to minimize the acute and long-term complications of the disease. Patients with hemophilia B are ideal candidates for gene therapy, mostly because a small increase in protein production can lead to significantly decreased bleeding diathesis. Although human clotting FIX was cloned and sequenced over 30 years ago, progress toward achieving real success in human clinical trials has been slow, with long-term, therapeutically relevant gene expression only achieved in one trial published in 2011. The history of this extensive research effort has revealed the importance of the interactions between gene therapy vectors and multiple arms of the host immune system at multiple stages of the transduction process. Different viral vector systems each have unique properties that influence their ability to deliver genes to different tissues, and the data generated in several clinical trials testing different vectors for hemophilia have guided our understanding toward development of optimal configurations for treating hemophilia B. The recent clinical success implementing a novel adeno-associated virus vector demonstrated sufficient FIX expression in patients to convert a severe hemophilia phenotype to mild, an achievement which has the potential to profoundly alter the impact of this disease on human society. Continued research should lead to vector designs that result in higher FIX activity at lower vector doses and with reduced host immune responses to the vector and the transgene product.
Numerical Simulation of the Pulsating Catheter Pump: A Left Ventricular Assist Device (1999)

The pulsating catheter (PUCA) pump, a left ventricular assist device, consists of a hydraulically or pneumatically driven membrane pump, extracorporeally placed and mounted to a valved catheter. The catheter is introduced into an easily accessible artery and positioned with its distal tip in the left ventricle. Blood is aspirated from the left ventricle during systole and ejected into the ascending aorta during diastole. A numerical model of the PUCA pump has been developed to determine the internal diameter of the PUCA pump catheter that allows a certain blood flow. The model considers a limitation of mechanical blood damage and determines the accompanying pressure and flow profile for driving the pump. For a flow of 5 L/min, a catheter with an internal diameter of at least 6. 95 mm is required. For 3 L/min, the minimal diameter is 5.50 mm. The latter catheter can be introduced in the axillary artery, the former via the aorta during an open thorax surgical procedure. To validate the numerical model, 2 different PUCA pump configurations were tested in vitro. Results showed a good resemblance between model and in vitro behavior of the PUCA pump.
Redox control of resistance to cis-diamminedichloroplatinum (II) (CDDP): protective effect of human thioredoxin against CDDP-induced cytotoxicity. (1996)

Thioredoxin is a small ubiquitous protein with multiple biological functions, including cellular defense mechanisms against oxidative stress. In the present study, we investigated the role of human thioredoxin (hTRX) in the acquisition of cellular resistance to cis-diamminedichloroplatinum (II) (CDDP). The expression and activity of hTRX in Jurkat T cells was dose-dependently enhanced by exposure to CDDP, as determined by immunoblot analysis and insulin reducing assay. Furthermore, chloramphenicol acetyltransferase analysis using the hTRX promoter-reporter gene construct revealed that treatment of Jurkat cells with CDDP caused transcriptional activation of the hTRX gene, which might be mediated through increased generation of intracellular reactive oxygen intermediates. To examine the biological significance of hTRX induction, we established hTRX-overexpressing derivatives of L929 fibrosarcoma cells by stable transfection with the hTRX cDNA. The clones, which constitutively expressed the exogenous hTRX, displayed increased resistance to CDDP-induced cytotoxicity, compared with the control clones. After exposure to CDDP, the control cells showed a significant increase in the intracellular accumulation of peroxides, whereas the hTRX-transfected cells did not. Taken together, these results suggest that overexpressed hTRX is responsible for the development of cellular resistance to CDDP, possibly by scavenging intracellular toxic oxidants generated by this anticancer agent.
OX40L–OX40 Signaling in Atopic Dermatitis (2021)

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L-OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L-OX40 axis as a promising target for the treatment of atopic dermatitis.
Assessment of heart rate variability derived from finger-tip photoplethysmography as compared to electrocardiography (2008)

Heart rate variability (HRV) is traditionally derived from RR interval time series of electrocardiography (ECG). Photoplethysmography (PPG) also reflects the cardiac rhythm since the mechanical activity of the heart is coupled to its electrical activity. Thus, theoretically, PPG can be used for determining the interval between successive heartbeats and heart rate variability. However, the PPG wave lags behind the ECG signal by the time required for transmission of pulse wave. In this study, finger-tip PPG and standard lead II ECG were recorded for five minutes from 10 healthy subjects at rest. The results showed a high correlation (median = 0.97) between the ECG-derived RR intervals and PPG-derived peak-to-peak (PP) intervals. PP variability was accurate (0.1 ms) as compared to RR variability. The time domain, frequency domain and Poincaré plot HRV parameters computed using RR interval method and PP interval method showed no significant differences (p < 0.05). The error analysis also showed insignificant differences between the HRV indices obtained by the two methods. Bland-Altman analysis showed high degree of agreement between the two methods for all the parameters of HRV. Thus, HRV can also be reliably estimated from the PPG based PP interval method.
Cryopyrin-associated periodic syndromes: background and therapeutics (2010)

Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations of the gene encoding the NLR family protein NLRP3, which together with caspase-1 and adaptor proteins constitutes a protein complex termed the inflammasome. In innate immune reactions, a variety of stimuli activate the NLRP3 inflammasome, triggering caspase-1 to process proIL-1 and thus to produce mature IL-1. Excessive production of IL-1 by monocytes/macrophages is the central pathophysiology of CAPS, and daily injection of the IL-1 receptor antagonist anakinra rapidly ameliorates the inflammatory symptoms in most cases. Furthermore, double-blind, placebo-controlled clinical trials have recently confirmed the efficacy and safety of rilonacept, a fusion protein of the IL-1 receptor and IgG Fc, and canakinumab, a human anti-IL-1 monoclonal antibody, as novel long-lasting agents for treating CAPS.
Nutritional support of bone marrow transplant recipients: a prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program. (1987)

Although standard supportive care for bone marrow transplant (BMT) recipients includes total parenteral nutrition (TPN), it has not been shown that this is the most appropriate method of nutritional support. To determine whether current BMT recipients require TPN during the early recovery period, we conducted a prospective, randomized clinical trial comparing TPN and an individualized enteral feeding program (counseling, high protein snacks and/or tube feeding). Nutritional assessment included measurement of serum proteins, anthropometry, and body composition analysis. For the latter, total body water and extracellular fluid were measured by standard radioisotope dilution techniques and used to quantitate body cell mass and body fat plus extracellular solids (FAT + ECS). In 27 TPN patients, body composition 28 days after BMT, expressed as a percentage of baseline, was body cell mass, 100%, extracellular fluid, 108%, FAT + ECS, 108%, and in 30 enteral feeding program patients, was body cell mass, 93%, extracellular fluid, 104%, and FAT + ECS, 94%. Only the difference in FAT + ECS was statistically significant (p less than 0.01). Compared to the enteral feeding program, TPN was associated with more days of diuretic use, more frequent hyperglycemia, and more frequent catheter removal (prompted by catheter-related complications), but less frequent hypomagnesemia. There were no significant differences in the rate of hematopoietic recovery, length of hospitalization, or survival, but nutrition-related costs were 2.3 times greater in the TPN group. We conclude that TPN is not clearly superior to individualized enteral feeding and recommend that TPN be reserved for BMT patients who demonstrate intolerance to enteral feeding.
Real-time voice and data integration in token ring LAN (2002)

Analytical and simulation models developed for the voice and data integrated token ring local area network (LAN) based on the IEEE 802.5 standard are presented. In the model, a simple concept termed the equivalent load representation is introduced to handle both voice and data traffic in the network. This technique can be extended to handle multimedia services in a token ring network. Using extensive simulation of the network, the integrity of the model was verified. From the simulation, the following results were derived: (a) optimal range for voice packet length; (b) relationship between voice packet delay and number of voice stations; (c) maximum number of voice stations supported by the network; (d) relationship between data and voice traffic in the same network; and (e) statistical characteristics of voice packet delay. Both the analytical and simulation models derived provide practical design rules for implementing voice/data integrated service in a token ring network using existing technology and standards.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Lithium stimulation of HPP‐CFC and stromal growth factor production in murine dexter culture (1992)

We have previously reported that the addition of lithium chloride (LiCl) to murine Dexter cultures results in increased numbers of progenitor and mature hematopoietic cells of the granulocyte, macrophage, and megakaryocyte lineages. We now report the effect of various levels of LiCl on the high proliferative potential colony-forming cell (HPP-CFC) in Dexter culture and on the induction of growth factors from Dexter stromal cells. LiCl (4 mEq/L) stimulated supernatant HPP-CFC for the first 4 weeks of culture (150-275%), and stimulated stromal HPP-CFC at week 3 (170-222%). Higher levels of lithium (8 and 12 mEq/L) selectively stimulated supernatant HPP-CFC, macrophage, and eosinophil production, whereas granulocytes and granulocyte-macrophage colony-forming cells (CFU-C) were inhibited. mRNA expression was evaluated from week 4 Dexter cultures that received a pulse or continuous exposure to lithium and had received either 0 or 1,100 cGy irradiation. Four mEq/L LiCl stimulated increased expression of G-CSF, GM-CSF, IL-6, and, in the nonirradiated stroma continuously exposed to lithium, CSF-1 mRNA. In general, the higher levels of lithium stimulated increased mRNA expression for these same growth factors. mRNA for the recently described Steel factor was decreased with increasing levels of lithium added to either normal or irradiated stroma. Bioassays of conditioned medium (cm) from irradiated cultures against the FDC-P1 and T1165 cell lines indicated cytokine activity, which was blocked by antibodies to GM-CSF and IL-6, respectively. Altogether these data show that lithium stimulates Dexter HPP-CFC, and this stimulation appears to be mediated by multiple growth factors that are induced from stromal cells.
Evidence against an early signalling role for ceramide in Fas-mediated apoptosis (1997)

We have investigated whether the increases in ceramide levels that occur during apoptosis in SKW 6.4 cells induced by anti-Fas antibody depend on the activation of caspases. Using cells prelabelled to equilibrium with [14C]acetate, it was shown that the amount of ceramide approximately doubled after 24 h incubation with anti-Fas, but the time course of ceramide changes was slower than that of anti-Fas-induced cell death. Complete inhibition of the effects of anti-Fas on cell death and on ceramide production was observed when the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-(O-methyl)fluoromethane (zVAD.fmk) was added together with anti-Fas, but N-benzyloxycarbonyl-Phe-Ala-fluoromethane (a structurally similar cathepsin B inhibitor) had no effect. Treatment of cells with the Ca2+-ionophore A23187 also doubled ceramide levels, but in this case the effect was complete within 2 h, was not blocked by zVAD.fmk and was not associated with increases in nuclear fragmentation. These results suggest that ceramide is not an upstream messenger in Fas-mediated apoptosis and may instead be produced as a consequence of processes downstream of the activation of caspases and increases in cytosolic calcium concentration.
Cyclopentenone Prostaglandins as Potential Inducers of Phase II Detoxification Enzymes (2000)

Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes, such as glutathione S-transferases (GSTs). In the present study, we developed a cell culture system that potently responds to phenolic antioxidants and found that antitumor prostaglandins (PGs) are potential inducers of GSTs. We screened primary hepatocytes and multiple cell lines for inducing GST activity upon incubation with the phenolic antioxidant (tert-butylhydroquinone) and found that rat liver epithelial RL34 cells most potently responded. Based on an extensive screening of diverse chemical agents on the induction of GST activity in RL34 cells, the J2 series of PGs, 15-deoxy-Delta(12,14)-prostaglandin J2 (15-deoxy-Delta(12,14)-PGJ2) in particular, were found to be potential inducers of GST. Enhanced gene expression of Class pi GST isozyme (GSTP1) by 15-deoxy-Delta(12,14)-PGJ2 was evident as a drastic elevation of the mRNA level. Hence, we examined the molecular mechanism underlying the 15-deoxy-Delta(12, 14)-PGJ2-induced GSTP1 gene expression. From functional analysis of various deletion mutant genes, we found that the 15-deoxy-Delta(12, 14)-PGJ2 reponse element was localized in a region containing a GSTP1 enhancer I (GPEI) that consists of two imperfect phorbol 12-O-tetradecanoylphorbol-13-acetate response elements. When the GPEI was combined with the minimum GSTP1 promoter, the element indeed showed an enhancer activity in response to 15-deoxy-Delta(12, 14)-PGJ2. Point mutations of either of the two imperfect 12-O-tetradecanoylphorbol-13-acetate response elements in GPEI completely abolished the enhancer activity. Gel mobility shift assays demonstrated that 15-deoxy-Delta(12,14)-PGJ2 specifically stimulated the binding of nuclear proteins including the transcription factor c-Jun, but not Nrf2, to GPEI. These results suggest that 15-deoxy-Delta(12,14)-PGJ2 induces the expression of the rat GSTP1 gene through binding of proteins, including c-Jun, to a specific GPEI.
Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells (2015)

The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of different effector mechanisms across the spectrum of H7N9 disease and recovery. We find that a diversity of response mechanisms contribute to resolution and survival. Patients discharged within 2-3 weeks have early prominent H7N9-specific CD8(+) T-cell responses, while individuals with prolonged hospital stays have late recruitment of CD8(+)/CD4(+) T cells and antibodies simultaneously (recovery by week 4), augmented even later by prominent NK cell responses (recovery >30 days). In contrast, those who succumbed have minimal influenza-specific immunity and little evidence of T-cell activation. Our study illustrates the importance of robust CD8(+) T-cell memory for protection against severe influenza disease caused by newly emerging influenza A viruses.
Self-Assembled Two-Dimensional Block Copolymers on Pre-patterned Templates with Laser Interference Lithography (2007)

We present an experimental result of the self-assembling for cylindrical nanostructures of PS-b-PMMA block copolymers (BCPs) on pre-patterned templates. The templates are fabricated by two-beam interference lithography at 325 nm into negative SU-8 photoresist. To align the BCPs nanostructures perpendicular the surface of templates, homopolymer polystyrene (hPS) layer is brushed on the patterns for modifying the interfacial energies. Thus, precisely control the localization and orientation of PS-b-PMMA nanostructures on patterned substrates is achieved.
Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase. (1993)

RNA-dependent protein kinase is a M(r) 68,000 protein in human cells (p68 kinase) or a M(r) 65,000 protein in murine cells (p65 kinase). p65/p68 is a serine/threonine kinase induced by interferon treatment and generally activated by double-stranded RNAs. Once activated, the known function of this kinase is inhibition of protein synthesis through phosphorylation of the eukaryotic initiation factor 2. Here we have investigated the potential for tumorigenicity in mice of murine NIH 3T3 clones expressing human p68 kinase, either the wild-type or a mutant inactive kinase with a single amino acid substitution in the invariant lysine-296 in the catalytic domain II. Expression of the mutant p68 kinase was correlated with a malignant transformation phenotype, giving rise to the production of large tumors of at least 1 cm in diameter within 7-12 days in all inoculated mice. In contrast, no tumor growth was observed for several weeks in mice inoculated with NIH 3T3 cell clones expressing either the wild-type recombinant p68 kinase or only the endogenous p65 kinase, the murine analogue of the p68 kinase. These results suggest that functional p65/p68 kinase (recently called PKR), by a still undefined mechanism, may also act as a tumor suppressor. Consequently, one of the pathways by which interferon inhibits tumor growth might be through its capacity to induce the enhanced expression of this kinase.
Novel Electrospun Polylactic Acid Nanocomposite Fiber Mats with Hybrid Graphene Oxide and Nanohydroxyapatite Reinforcements Having Enhanced Biocompatibility (2016)

Graphene oxide (GO) and a nanohydroxyapatite rod (nHA) of good biocompatibility were incorporated into polylactic acid (PLA) through electrospinning to form nanocomposite fiber scaffolds for bone tissue engineering applications. The preparation, morphological, mechanical and thermal properties, as well as biocompatibility of electrospun PLA scaffolds reinforced with GO and/or nHA were investigated. Electron microscopic examination and image analysis showed that GO and nHA nanofillers refine the diameter of electrospun PLA fibers. Differential scanning calorimetric tests showed that nHA facilitates the crystallization process of PLA, thereby acting as a nucleating site for the PLA molecules. Tensile test results indicated that the tensile strength and elastic modulus of the electrospun PLA mat can be increased by adding 15 wt % nHA. The hybrid nanocomposite scaffold with 15 wt % nHA and 1 wt % GO fillers exhibited higher tensile strength amongst the specimens investigated. Furthermore, nHA and GO nanofillers enhanced the water uptake of PLA. Cell cultivation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and alkaline phosphatase tests demonstrated that all of the nanocomposite scaffolds exhibit higher biocompatibility than the pure PLA mat, particularly for the scaffold with 15 wt % nHA and 1 wt % GO. Therefore, the novel electrospun PLA nanocomposite scaffold with 15 wt % nHA and 1 wt % GO possessing a high tensile strength and modulus, as well as excellent cell proliferation is a potential biomaterial for bone tissue engineering applications.