gebhart/patrepeval huggingface dataset:
Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors (2003)

High-capacity adenoviral (HC-Ad) vectors expressing B-domain-deleted human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A. Intravenous administration of these vectors into hemophilic FVIII-deficient immunodeficient SCID mice (FVIIIKO-SCID) at a dose of 5 x 10(9) infectious units (IU) resulted in efficient hepatic gene delivery and long-term expression of supraphysiologic FVIII levels (exceeding 15 000 mU/mL), correcting the bleeding diathesis. Injection of only 5 x 10(7) IU still resulted in therapeutic FVIII levels. In immunocompetent hemophilic FVIII-deficient mice (FVIIIKO), FVIII expression levels peaked at 75 000 mU/mL but declined thereafter because of neutralizing anti-FVIII antibodies and a cellular immune response. Vector administration did not result in thrombocytopenia, anemia, or elevation of the proinflammatory cytokine interleukin-6 (IL-6) and caused no or only transient elevations in serum transaminases. Following transient in vivo depletion of macrophages before gene transfer, significantly higher and stable FVIII expression levels were observed. Injection of only 5 x 10(6) HC-Ad vectors after macrophage depletion resulted in long-term therapeutic FVIII levels in the FVIIIKO and FVIIIKO-SCID mice. Intravenous injection of an HC-Ad vector into a hemophilia A dog at a dose of 4.3 x 10(9) IU/kg led to transient therapeutic canine FVIII levels that partially corrected whole-blood clotting time. Inhibitory antibodies to canine FVIII could not be detected, and there were no signs of hepatotoxicity or of hematologic abnormalities. These results contribute to a better understanding of the safety and efficacy of HC-Ad vectors and suggest that the therapeutic window of HC-Ad vectors could be improved by minimizing the interaction between HC-Ad vectors and the innate immune system.
Etalon/Grating Synchronized Scanning of a Narrowband Pulsed Dye Laser (1974)

A computer compatible digital scanning system has been developed to simplify the controls of a narrowband pulsed tunable dye laser so that operation is analogous to scanning a spectrometer. The system is an accessory to the nitrogen laser-pumped DL-Series dye laser which incorporates both grating and etalon as the wavelength selecting elements. The grating is rotated with a mechanical sine drive so that wavelength response is linear. Linewidth of the laser without etalon is 0.1A and scanning is achieved with a stepping motor. Inserting an etalon into the cavity reduces the linewidth to 0.01A and tuning is achieved by tilting the etalon. However, since the etalon wavelength change depends on the grating wavelength and decreases as the square of the tilt angle, wavelength synchronization to the grating becomes difficult. In our system a digital computation accurate to 0.01% linearizes the etalon response to match that of the grating. Single scans of 3A and multiple scans of 30A can be achieved without loss of wavelength synchronization. Analog and digital wavelength readout to 0.01A and computer compatibility are included. System details and sample data are presented.
Decellularized Native and Engineered Arterial Scaffolds for Transplantation (2003)

More than 570,000 coronary artery bypass grafts are implanted each year, creating an important demand for small-diameter vascular grafts. For patients who lack adequate internal mammary artery or saphenous vein, tissue-engineered arteries may prove useful. However, the time needed to tissue engineer arteries (7 weeks or more) is too long for many patients. Decellularized cadaveric human arteries are another possible source of vascular conduit, but limited availability and the potential for disease transmission limit their widespread use. In contrast, decellularized tissue-engineered arteries could serve as grafts for immediate implantation, as scaffolds onto which patients' cells could be seeded, or as carriers for genetically engineered cells to aid cell transplantation. The goal of this study was to quantify the effects of decellularization on vascular matrix and mechanical properties. Specifically, we compared cellular elimination, extracellular matrix retention, and mechanical characteristics of porcine carotid arteries before and after treatment with three decellularization methods. In addition, for the first time, tissue-engineered arteries were decellularized. Decellularized native arteries were also used as a scaffold onto which vascular cells were seeded. These studies identified a decellularization method for native and engineered arteries that maximized cellular elimination, without greatly compromising mechanical integrity. We showed that engineered tissues could be decellularized, and demonstrated the feasibility of reseeding decellularized vessels with vascular cells.
Effect of l-glutamate on 2-oxoglutarate decarboxylase in Euglena gracilis (1992)

The effect of tricarboxylic acid-cycle intermediates and related compounds on 2-oxoglutarate decarboxylase activity was investigated. The addition of L-glutamate to Euglena cells grown on glucose/(NH4)2SO4 medium resulted in an increase in 2-oxoglutarate decarboxylase activity, which was abolished by the simultaneous addition of cycloheximide. Immunochemical titration, immunoblot analysis and labelling in vivo with antibody raised against 2-oxoglutarate decarboxylase showed that the increase in 2-oxoglutarate decarboxylase activity was due to synthesis of new protein and not to activation of pre-existing protein. The experimental results reported here demonstrate that L-glutamate is assimilated by the pathway, via 2-oxoglutarate, that consists of L-glutamate-oxaloacetate aminotransferase, 2-oxoglutarate decarboxylase and succinate semialdehyde dehydrogenase, rather than by the gamma-aminobutyrate shunt, consisting of L-glutamate decarboxylase and gamma-aminobutyrate aminotransferase.
Opioid receptor interactions and conformations of the 6.alpha. and 6.beta. epimers of oxymorphamine. Solid-state conformation of 6.alpha.-oxymorphamine (1985)

The affinities of the oxymorphamine epimers for mu and delta opioid receptors were determined in vitro. The 6 alpha and 6 beta epimers are potent mu-selective ligands with similar receptor-binding profiles. The relatively undramatic effect of C-6 chirality on receptor interactions is intriguing in view of the recently demonstrated profound influence of C-6 chirality on ring-C solution conformations (ring C is a chair conformer in the beta epimer but adopts a twist-boat conformation in the alpha epimer) and prompted the determination of the crystal structure of alpha-oxymorphamine. The crystal structure showed that ring C in this epimer also adopts a twist-boat conformation in the solid state. Molecular modeling of the oxymorphamines in the preferred ring-C conformations (alpha = boat, beta = chair) demonstrated that the 6-amino groups project to spatial loci significantly more proximal (0.35 A) than would be the case (2.2 A) if both epimers adopted chair conformations for ring C. Consequently, although the epimeric oxymorphamines differ in ring-C conformation, the principle potential heteroatomic binding sites in each epimer are oriented similarly, which may be partly responsible for the lack of dramatic differences in receptor binding profiles.
Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication (2007)

Our findings uncovered a new role for nucleolin in cell division, and highlight the importance of nucleolar proteins for centrosome duplication.
Localization of UvrA and Effect of DNA Damage on the Chromosome of Bacillus subtilis (2002)

We found that the nucleotide excision repair protein UvrA, which is involved in DNA damage recognition, localizes to the entire chromosome both before and after damage in living Bacillus subtilis cells. We suggest that the UvrA(2)B damage recognition complex is constantly scanning the genome, searching for lesions in the DNA. We also found that DNA damage induces a dramatic reconfiguration of the chromosome such that it no longer fills the entire cell as it does during normal growth. This reconfiguration is reversible after low doses of damage and is dependent on the damage-induced SOS response. We suggest that this reconfiguration of the chromosome after damage may be either a reflection of ongoing DNA repair or an active mechanism to protect the cell's genome. Similar observations have been made in Escherichia coli, indicating that the alteration of chromosome structure after DNA damage may be a widespread phenomenon.
Medicinal Foodstuffs. XXIX. Potent Protective Effects of Sesquiterpenes and Curcumin from Zedoariae Rhizoma on Liver Injury Induced by D-Galactosamine/Lipopolysaccharide or Tumor Necrosis Factor-.ALPHA.. (2002)

The 80% aqueous acetone extract of Zedoariae Rhizoma was found to show a protective effect against D-galactosamine (D-GalN)/lipopolysaccharide-induced acute liver injury in mice. To clarify the active compounds, the principal constituents were examined and 11 sesquiterpenes (furanodiene, curdione, neocurdrione, dehydrocurdione, germacrone, 13-hydroxygermacrone, curcumenol, isocurcumenol, aerugidiol, zedoarondiol, and curcumenone) and a diarylheptanoid (curcumin) were found to inhibit the increase in serum aspartate aminotransaminase and alanine aminotransaminase at a dose of 50 mg/kg p.o. in agreement with the previous in vitro studies, except for dehydrocurdione, aerugidiol, and zedoarondiol. In particular, curdione, neocurdione, curcumenol, and isocurcumenol potently inhibited the increase at a dose of 12.5 mg/kg p.o. Furthermore, the eight sesquiterpenes, furanodiene, curdione, neocurdione, dehydrocurdione, germacrone, 13-hydroxygermacrone, curcumenol, and curcumenone, also showed a protective effect against D-GalN/tumor necrosis factor-alpha-induced liver injury in mice at a dose of 50 mg/kg p.o.
Histological typing of nasopharyngeal carcinoma. (1978)

There is little agreement about correlations between histological type and the epidemiological and biological characteristics of NPC. This is largely due to variations in terminology and diagnostic criteria. The use of the terminology and definitions proposed by WHO would facilitate and improve international comparisons.
rePLay: A Hardware Framework for Dynamic Program Optimization (1999)

In this paper, we propose a new framework for enhancing application performance through execution-guided optimization. The rePLay Framework uses information gathered at run-time to optimize an application&amp;apos;s instruction stream. Some of these optimizations persist temporarily for only a single execution, others persist between runs. The heart of the rePLay Framework is a trace-cache like device called the frame cache, used to store optimized regions of the original executable. These regions, called frames, are large, single-entry, single-exit regions spanning many basic blocks in the program&amp;apos;s dynamic instruction stream. Optimizations are performed on these frames by a flexible optimizer contained within the processor. A rePLay configuration with a 256-entry frame cache, using realistically-sized frame constructor and frame sequencer achieves an average frame size of 88 instructions with 68% coverage of the dynamic istream, an average frame completion rate of 97.81%, and a frame predict...
Cytokine-mediated enhancement of epidermal growth factor receptor expression provides an immunological approach to the therapy of pancreatic cancer (1997)

The increased expression of epidermal growth factor receptor induced by tumor necrosis factor alpha renders pancreatic cancer cells more susceptible to antibody-dependent cellular cytotoxicity by a mAb specific for this receptor. Laboratory studies with athymic mice bearing xenografts of human pancreatic cancer cells demonstrated a cytokine-induced ability of the mAb to cause significant tumor regression. In a phase I/II clinical trial, 26 patients with unresectable pancreatic cancer were enrolled into three cohorts receiving variable amounts of the antibody together with a constant amount of tumor necrosis factor alpha. With increasing doses of antibody, the growth of the primary tumor was significantly inhibited. This was reflected by a longer median survival, with one complete remission lasting for 3 years obtained with the highest dose of antibody employed. Thus, a combination of the cytokine, tumor necrosis factor alpha, with a mAb to the epidermal growth factor receptor offers a potentially useful approach for the treatment of pancreatic cancer.
Current strategies for the treatment of diffuse large B cell lymphoma (2005)

Although improvement has been made in low-risk patients, much work has to be done for patients with high-risk lymphoma. It may come with a better definition of genetic abnormalities specifically associated with refractoriness to chemotherapy.
Rational design and synthesis of 1,5-disubstituted tetrazoles as potent inhibitors of the MDM2-p53 interaction (2016)

Using the computational pharmacophore-based ANCHOR.QUERY platform a new scaffold was discovered. Potent compounds evolved inhibiting the protein-protein interaction p53-MDM2. An extensive SAR study was performed based on our four-point pharmacophore model, yielding derivatives with affinity to MDM2 in the nanomolar range. Their binding affinity with MDM2 was evaluated using both fluorescence polarization (FP) assay and 2D-NMR-HSQC experiments.
Transport-aware IP routers: A built-in protection mechanism to counter DDoS attacks (2003)

The lack-of service differentiation and resource isolation by current IP routers exposes their vulnerability to Distributed Denial of Service (DDoS) attacks (Garber, 2000), causing a serious threat to the availability of Internet services. Based on the concept of layer-4 service differentiation and resource isolation, where the transport-layer information is inferred from the IP headers and used for packet classification and resource management, we present a transport-aware IP (tIP) router architecture that provides fine-grained service differentiation and resource isolation among different classes of traffic aggregates. The tIP router architecture consists of a fine-grained Quality-of-Service (QoS) classifier and an adaptive weight-based resource manager. A two-stage packet-classification mechanism is devised to decouple the fine-grained QoS lookup from the usual routing lookup at core routers. The fine-grained service differentiation and resource isolation provided inside the tIP router is a powerful built-in protection mechanism to counter DDoS attacks, reducing the vulnerability of Internet to DDoS attacks. Moreover, the tIP architecture is stateless and compatible with the Differentiated Service (DiffServ) infrastructure. Thanks to its scalable QoS support for TCP control segments, the tIP router supports bidirectional differentiated services for TCP sessions.
Identification, cloning, and characterization of a novel human T-cell- specific tyrosine kinase located at the hematopoietin complex on chromosome 5q (1993)

Abstract Signal transduction through the T-cell receptor and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Because neither the T-cell receptor nor cytokine receptors contain intrinsic kinase domains, signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified. To identify unique T-cell tyrosine kinases, we used polymerase chain reaction-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. We have cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866 bp encoding a protein with a predicted size of 72 Kd, which is in keeping with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. EMT contains both SH2 and SH3 domains, as do many other intracellular kinases. EMT does not contain the N-terminal myristylation site or the negative regulatory tyrosine phosphorylation site in its carboxyterminus that are found in the SRC family of tyrosine kinases. EMT is related to the B-cell progenitor kinase (BPK), which has recently been implicated in X-linked hypogammaglobulinemia, to the TECI mammalian kinase, which has been implicated in liver neoplasia, to the more widely expressed TECII mammalian kinase, and to the Drosophila melanogaster Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human homologue of a recently identified murine interleukin-2 (IL-2)-inducible T cell kinase (ITK). However, unlike ITK, EMT message and protein levels do not vary markedly on stimulation of human IL-2-responsive T cells with IL-2. Taken together, it seems that EMT is a member of a new family of intracellular kinases that includes BPK, TECI, and TECII. EMT was localized to chromosome 5q31–32, a region that contains the genes for several growth factors and receptors as well as early activation genes, particularly those involved in the hematopoietic system. Furthermore, the 5q31–32 region is implicated in the genesis of the 5q- syndrome associated with myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400 WORDS)
Significance of porosity and compliance of microporous, polyurethane-based microarterial vessel on neoarterial wall regeneration (1997)

The microporous structure of artificial vascular grafts, which increases compliance and porosity simultaneously, may enhance neoarterial regeneration. In order to differentiate these effects, three models of segmented polyurethane grafts (inner diameter, 1.5 mm; wall thickness, 100 microns) with or without micropores fabricated using an excimer laser ablation technique, were prepared, and their neoarterial regenerative potentials were studied upon implantation: Model I (microporous, permeable, compliant); Model II (smooth-surfaced, impermeable, compliant); and Model III (smooth-surfaced, impermeable, noncompliant). In Models I and II, the pore or groove size (diameter, 100 microns) and pore or groove arrangement were fixed, and consequently their compliances were almost identical. Irrespective of model, the luminal surfaces were coated with benzophenone-derivatized gelatin and subsequently photocured. Twenty grafts (length, 20 mm) of each model were implanted in the aortas of rats. Predetermined implantation periods were 4, 12, and 24 weeks. Total patency rate decreased in the order Model I (100%), II (87%), and III (59%) grafts. All patent grafts were completely endothelialized after 12 weeks of implantation, irrespective of model. After 12- and 24-week implantations, in Model I grafts, the neoarterial wall was thin, and smooth muscle cells (SMCs) were of the contractile phenotype. In Model II grafts, the neoarterial wall exhibited considerable thickening. In Model III grafts, the neoarterial wall exhibited marked thickening, and SMCs were of the synthetic phenotype. The neoarterial wall thickness at the midportion of the grafts after 24 weeks of implantation increased in the order Model I (48 +/- 8 microns), II (146 +/- 87 microns), and III (385 +/- 21 microns) grafts. These results strongly suggest that compliance matching and porosity synergistically resulted in neoarterial wall restoration without appreciable thickening.
Searching for new reactivity (Nobel lecture). (2002)

The processes for the selective oxidation of olefins have long been among the most useful tools for day-to-day organic synthesis. Herein, the focus is on the asymmetric-epoxidation (AE) and asymmetric-dihydroxylation (AD) reactions developed by Sharpless and co-workers. The reactions have a wide scope, are simple to run, and involve readily available starting materials. Ligand-accelerated catalysis is crucial to these reactions and might be the agent for uncovering more catalytic processes. In addition to the selectivity benefits of catalysis, the phenomenon of turnover (amplification) raises its potential impact. The author and his co-workers developed small, highly enantioselective catalysts that were unfettered by the "lock-and-key" selectivity of Natures enzymes, and tolerant of substrates throughout the entire range of olefin substitution patterns.
Cutaneous phototoxic occurrences in patients receiving Photofrin® (1990)

Incidence of cutaneous phototoxic reactions induced by intravenous injection of Photofrin polyporphyrin was assessed in a series of 180 patients (266 injections) undergoing photodynamic therapy (PDT) at Roswell Park Cancer Institute during the period 1986-1989. In addition to the usual verbal questions regarding phototoxic reactions solicited at follow-up, forty-two patients in this group also responded to a written questionnaire designed to solicit answers to specific questions. Photofrin doses ranged from 0.5 to 2.0 mg/kg. Overall, 20-40% of patients reported some type of phototoxic response.
T7 DNA polymerase in automated dideoxy sequencing (1988)

T7 DNA polymerase with chemically inactivated 3'-5' exo-nuclease activity, as well as unmodified T7 DNA polymerase, were used for sequencing by the dideoxy method in an automated system with fluorescence labelled primer and on-line detection of laser-excited reaction products. An analysis of signal intensity variations in the C track revealed that low C signals were usually preceded by a T in the sequence. This effect was modified by surrounding nucleotides. Signal intensities were more uniform with T7 polymerase than with the Klenow fragment of DNA polymerase I. Some sequences ambiguous with the Klenow enzyme could easily be evaluated with the T7 enzyme. One sequence could only be read by the unmodified T7 polymerase, while both the Klenow fragment and the chemically modified T7 enzyme gave uninterpretable data.
Neutralization of Heparin in Plasma by Platelet Factor 4 and Protamine Sulphate (1978)

The neutralization of heparin by protamine sulphate and platelet factor 4 (PF 4 ) has been studied using kaolin cephalin clotting time (KCCT), thrombin clotting time (TCT) and anti‐Xa assays to measure residual heparin levels. Protamine sulphate and purified PF 4 had almost equivalent neutralizing ability on a weight basis regardless of which assay system was used. Plasma samples that were heparinized in vitro could be totally and readily neutralized by both agents in all of the assay systems used. However, when heparinized plasma samples were obtained following intravenous injection of the drug different results for neutralization were obtained depending on the heparin assay used. When residual heparin was measured by anti‐Xa assay partial neutralization of heparin was observed even in the presence of a large excess of neutralizing agent. The same in vivo derived heparinized plasma samples had no heparin activity following neutralization if residual heparin was measured by KCCT and TCT assays. Further ion exchange chromatography experiments demonstrated that the heparin‐like activity that could not be neutralized in the anti‐Xa assay was not adsorbed by the resin ECTEOLA‐cellulose, and therefore could not be removed from plasma by this technique. These results suggest, therefore, that part of the plasma anti‐Xa activity produced following intravenous injection of heparin differs from the anti‐Xa activity obtained following addition of the drug to plasma in vitro .