gebhart/patrepeval huggingface dataset:
Enhanced antilymphoma efficacy of CD19-redirected influenza MP1–specific CTLs by cotransfer of T cells modified to present influenza MP1 (2004)

To enhance the in vivo antitumor activity of adoptively transferred, CD19-specific chimeric antigen receptor (CAR)-redirected cytotoxic T lymphocytes (CTLs), we studied the effect of restimulating CAR(+) CTLs through their endogenous virus-specific T-cell antigen receptor (TcR) by the cotransfer of engineered T-cell antigen-presenting cells (T-APCs). Using influenza A matrix protein 1 (MP1) as a model antigen, we show that ex vivo-expanded CD4(+) and CD8(+) T-APCs expressing a hygromycin phosphotransferase-MP1 fusion protein (HyMP1) process and present MP1 to autologous human leukocyte antigen (HLA)-restricted, MP1-specific CD4(+) and CD8(+) CTL precursors. The MP1-specific CTLs are amenable to subsequent genetic modification to express a CD19-specific CAR, designated CD19R, and acquire HLA-unrestricted reactivity toward CD19(+) leukemia and lymphoma tumor targets while maintaining HLA-restricted MP1 specificity. The restimulation of MP1xCD19 dual-specific CTLs in vivo by the adoptive transfer of irradiated HyMP1(+) T-APCs resulted in the enhanced antilymphoma potency of bispecific effector cells, as measured by elimination of the biophotonic signal of established firefly luciferase-expressing Burkitt lymphoma xenografts in nonobese diabetic/severe combined immunodeficiency (NOD/scid) animals compared with control groups restimulated by Hy(+)MP1(neg) T-APCs. Engineered T-APCs are a novel and versatile antigen-delivery system for generating antigen-specific T cells in vitro and enhancing the in vivo effector functioning of CAR-redirected antitumor effector cells.
Multiresponsive Reversible Polymer Networks Based on Hydrogen Bonding and Metal Coordination (2011)

Side-chain-functionalized polymers containing hydrogen bonding and metal coordination sites have been synthesized using ring-opening metathesis polymerization. These polymers were cross-linked reversibly either selectively by using hydrogen bonding or metal coordination or simultaneously using both interactions through the addition of small molecule cross-linking agents. The hydrogen bonding motifs utilized for reversible cross-linking are based on cyanuric acid residues hydrogen bonded to 2,4-diaminotriazine-based cross-linking agents. The metal coordination motifs are based on palladated SCS pincer complexes coordinated to bispyridine cross-linking agents. By controlling the reversible cross-linking strategy, we were able to modulate (1) the rheology of the polymer networks from a free-flowing liquid to a highly elastic gel and vice versa and vary the dynamic moduli over 10 orders of magnitude and (2) the responsiveness of the networks to external stimuli such as temperature and ligand displacement agents. The hydrogen bonded cross-linking resulted in polymer networks that were thermally reversible whereas the metal coordinated cross-linked networks mainly showed chemoresponsive behavior. Since both interactions are fully orthogonal to each other, we successfully cross-linked the polymer using both interactions to obtain multiresponsive networks that exhibited both thermal and chemoresponsiveness. We were also able to selectively de-cross-link the hydrogen bonded cross-links of the multifunctionalized networks through competitive interactions at room temperature via the addition of a monotopic end-capping agent without affecting the metal coordinated cross-links. In contrast, the metal coordination could be de-cross-linked completely using a ligand displacement agent such as triphenylphosphine again without affecting the hydrogen bonded cross-links.
Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus‐prone mice (2010)

Syk inhibition suppresses the development of lupus skin and kidney disease in lupus-prone mice, suppresses established disease in lupus-prone mice, and may represent a valuable treatment for patients with SLE.
Studies on the purification of thrombopoietin from kidney cell culture medium. (1985)

A thrombocytopoiesis-stimulating factor (TSF) has been purified from human embryonic kidney (HEK) cell culture medium. In the initial purification step, crude HEK cell culture medium was fractionated with saturated ammonium sulfate (step I). The proteins precipitated by 40% to 60% and 60% to 80% ammonium sulfate saturation increased the percent of sulfur 35 incorporation into platelets of assay mice (P less than 0.01). The ammonium sulfate-precipitated proteins that contained significant TSF activity were further refined on Sephadex G-75 columns (step II). The fraction containing the highest specific activity (greatest 35S incorporation into platelets of assay mice per milligram of protein) was further purified by diethylaminoethyl (DEAE)-cellulose column chromatography (step III). TSF activity was eluted from the columns between 0.3 and 1.0 mol/L NaCl. Additional Sephadex chromatography of post-DEAE-chromatographic preparations further increased the purity of the TSF (step IV). TSF from this four-step procedure was further processed on a DEAE-high-performance liquid chromatography (HPLC) column (step Va) or size exclusion (SE)-HPLC columns (step Vb). After HPLC, the activity was localized in a region corresponding to a retention time of 6 to 8 minutes for the DEAE-HPLC, but longer times were found after SE-HPLC. TSF was further purified by additional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and SE-HPLC (step VI). The final product had significant TSF activity and represented a purification of approximately 500,000-fold. It was also shown that the isoelectric pH of partially purified TSF was 4.7 and the molecular weight of the more highly purified preparation was approximately 32,000. After extraction by a combination of chromatographic procedures, a single homogeneous product was obtained.
Fusion of the Human Gene for the Polyubiquitination Coeffector UEV1 with Kua, a Newly Identified Gene (2000)

UEV proteins are enzymatically inactive variants of the E2 ubiquitin-conjugating enzymes that regulate noncanonical elongation of ubiquitin chains. In Saccharomyces cerevisiae, UEV is part of the RAD6-mediated error-free DNA repair pathway. In mammalian cells, UEV proteins can modulate c-FOS transcription and the G2-M transition of the cell cycle. Here we show that the UEV genes from phylogenetically distant organisms present a remarkable conservation in their exon-intron structure. We also show that the human UEV1 gene is fused with the previously unknown gene Kua. In Caenorhabditis elegans and Drosophila melanogaster, Kua and UEV are in separated loci, and are expressed as independent transcripts and proteins. In humans, Kua and UEV1 are adjacent genes, expressed either as separate transcripts encoding independent Kua and UEV1 proteins, or as a hybrid Kua-UEV transcript, encoding a two-domain protein. Kua proteins represent a novel class of conserved proteins with juxtamembrane histidine-rich motifs. Experiments with epitope-tagged proteins show that UEV1A is a nuclear protein, whereas both Kua and Kua-UEV localize to cytoplasmic structures, indicating that the Kua domain determines the cytoplasmic localization of Kua-UEV. Therefore, the addition of a Kua domain to UEV in the fused Kua-UEV protein confers new biological properties to this regulator of variant polyubiquitination.
Ultrasonic spot welding of aluminum sheet/carbon fiber reinforced polymer – joints (2007)

Abstract Current demands on light weight constructions lead to an increasing use of light weight metals such as aluminum or magnesium alloys as well as fiber reinforced polymers (FRP). Suitable welding methods are necessary to join these dissimilar material groups and to integrate them in engineering structures. At the Institute of Materials Science and Engineering the ultrasonic metal welding technique was successfully applied to realize aluminum sheet/carbon‐fiber‐reinforced polymer (CFRP) ‐ joints. The welding during this process occurs in two steps: First the ultrasonic shear waves lead to a softening and displacement of the polymer matrix out of the welding zone. In the second step a direct weld between the load bearing carbon fibers of the CFRP and the aluminum alloy sheet is generated. A welding time of less than 5 s and no damage of the carbon fibers are important advantages of the process. Actually tensile shear strengths of about 30 MPa were achieved for the joints. By means of light microscopic and SEM investigations the bonding mechanisms can be described in detail. Possible application fields of such welds can be seen in the automotive or in the aircraft industry.
Isolation and properties of a low molecular mass endoglucanase from Trichoderma reesei (1992)

Optimal culture conditions for obtaining low molecular mass endoglucanase (EG) from culture fluids of Trichoderma reesei were determined. The purification of this unglycosylated EG in a two-step procedure is described. In contrast to most cellulases, this EG did not bind to ConA-affinity columns. The unglycosylated fraction of the culture fluid proteins was further purified by preparative isoelectric focusing. Conditions relevant to an enzyme assay for this EG were determined (pH optimum 5.8, temperature optimum 52 degrees C).
Novel uniaxial force sensor based on visual information for minimally invasive surgery (2014)

This paper presents an innovative approach of utilising visual feedback to determine physical interaction forces with soft tissue during Minimally Invasive Surgery (MIS). This novel force sensing device is composed of a linear retractable mechanism and a spherical visual feature. The sensor mechanism can be adapted to endoscopic cameras used in MIS. As the distance between the camera and feature varies due to the sliding joint, interaction forces with anatomical surfaces can be computed based on the visual appearance of the feature in the image. Hence, this device allows the measurement of forces without introducing new stand-alone sensors. A mathematical model was derived based on validation data tests and preliminary experiments were conducted to verify the model's accuracy. Experimental results confirm the effectiveness of our vision based approach.
Anticancer effect of mastic on human oral cancer cells (2016)

Objectives: Mastic is a resinous extract from the stem and main leaves of Pistacia lentiscus, grown only in the Chios island of Greece. Mastic has antibacterial, anti-inflammatory, anticancer, and anti-ulcer activities. Although mastic has been widely studied, its inhibitory effect against cancer cells, especially oral cancer cells, has not been elucidated. The purpose of this study was to assess the anticancer effects of mastic on human oral cancer YD-10B cells. Methods: YD-10B cells were cultured in 0, 1, 2, 5, and 10 mg/mL mastic for 24 h. Cell count, viability, morphology, colony-forming assay, and DAPI staining were analyzed. Results: Mastic treatment of YD-10B cells resulted in a dose-dependent inhibition of cell growth, and almost all the cells in the 10 mg/mL culture were dead (P<0.05). Mastic treatment induced a morphological change and nuclear fragmentation in the YD-10B cells, and inhibited colony formation of YD-10B cells in a dose-dependent manner. Conclusions: These results indicate that mastic exhibited anticancer effects on the YD-10B cells through changes in cell morphology and apoptosis.
One-Step, Room Temperature, Colorimetric Detection of Mercury (Hg2+) Using DNA/Nanoparticle Conjugates (2008)

Introduction of Hg2+ into an aqueous solution containing oligonucleotide-tethered gold nanoparticle probes and a linker oligonucleotide with a number of thymine−thymine (T−T) mismatches results in the formation of particle aggregates at room temperature with a concomitant colorimetric response. The high selectivity of this detection system is attributed to Hg2+-mediated formation of T−Hg2+−T base pairs as evidenced by an increase in a sharp melting temperature.
Immobilization of Pectin Fragments on Solid Supports:  Novel Coupling by Thiazolidine Formation (2002)

As a prerequisite to solid-phase and sequence analyses and for the study of the fine structure of pectin, we have developed oriented and chemoselective methodologies to couple model pectin fragments onto a solid support. Polyethylene glycol polyacrylamide (PEGA) resins were selected due to their excellent swelling properties in a wide range of solvents, including water, and their easy accessibility to enzymes. Following appropriate derivatization of amino-terminated PEGA resins, oligomers of alpha-D-galacturonic acid (GalA), up to the trimer, were anchored to the support through their reducing end. In addition to reductive amination, the strategies included the formation of an oxime bond, a glycosyl hydrazide, and a pyroglutamyl ring. Further, we developed a new immobilization approach based on the formation of a thiazolidine ring. All methods proved efficient and did not require modification of the GalA oligomers prior to coupling. In addition, very mild conditions and few steps for derivatization of the support were required. Immobilization by thiazolidine ring and oxime bond formation were the preferred methods, given the stability of the linkages formed, their compatibility with aqueous solvents, the few number of steps required, and their potential for application to larger pectin fragments. Thiazolidine and pyroglutamyl anchoring were developed further by the insertion of a disulfide bond which allowed release of the saccharides under mild, selective conditions.
Therapeutic Antibody Targeting of CD97 in Experimental Arthritis: the Role of Antigen Expression, Shedding, and Internalization on the Pharmacokinetics of Anti-CD97 Monoclonal Antibody 1B2 (2009)

CD97 is a member of the EGF-TM7 family of adhesion class receptors, with a proposed role in inflammatory cell recruitment. Neutralization of murine CD97 with the anti-mCD97 mAb 1B2 was efficacious in prevention of murine collagen-induced arthritis, a model with features resembling rheumatoid arthritis. Here, the therapeutic potential of neutralizing CD97 in arthritis was studied with emphasis on the 1B2 pharmacokinetics. Mice with established arthritis were treated with anti-mCD97 or anti-TNF-alpha serum. Ab pharmacokinetics and biodistribution were studied in diseased and nondiseased mice using labeled 1B2. The impact of CD97 expression on Ab pharmacokinetics was studied using CD97 knockout mice. Treatment with 1B2 showed an efficacy comparable to anti-TNF-alpha treatment. Pharmacokinetic analysis of 1B2 in wild-type and CD97 knockout mice indicated a dose-dependent Ab clearance, due to specific interaction with CD97. Biodistribution studies showed accumulation of 1B2 in spleen and lung. In vitro studies using murine splenocytes revealed that CD97 when bound to Ab was internalized. Moreover, soluble CD97 was detected in the supernatant, suggesting Ag shedding. Finally, in arthritic mice, higher levels of soluble CD97 were found and 1B2 treatment led to specific targeting of inflamed paws, resulting in a higher clearance rate of 1B2 in arthritic mice than in wild-type mice. In conclusion, our data support a therapeutic value of CD97 neutralization in experimental arthritis. The pharmacokinetic profile of the 1B2 Ab illustrates the complexity of Ab elimination from an organism and stresses the importance of understanding Ag-Ab interactions when developing therapeutic mAbs.
Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study (2004)

Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.
The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. (1994)

Inhibition of DNA synthesis prevents mitotic entry through the action of the S-phase checkpoint. We have isolated S-phase arrest-defective (sad) mutants that show lethality in the presence of the DNA synthesis inhibitor hydroxyurea (HU). Several of these mutants show phenotypes consistent with inappropriate mitotic entry in the presence of unreplicated DNA, indicating a defect in the S-phase checkpoint. sad1 mutants are additionally defective for the G1 and G2 DNA damage checkpoints, and for DNA damage-induced transcription of RNR2 and RNR3. The transcriptional response to DNA damage requires activation of the Dun1 protein kinase. Activation of Dun1 in response to replication blocks or DNA damage is blocked in sad1 mutants. The HU sensitivity of sad1 mutants is suppressed by mutations in CKS1, a subunit of the p34CDC28 kinase, further establishing a link between cell cycle progression and lethality. sad1 mutants are allelic to rad53, a radiation-sensitive mutant. SAD1 encodes an essential protein kinase. The observation that SAD1 controls three distinct checkpoints suggests a common mechanism for cell cycle arrest at these points. Together, these observations implicate protein phosphorylation in the cellular response to DNA damage and replication blocks.
Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with Ulcerative Colitis and Recurrent  Clostridium difficileInfection (2012)

We report a case of ulcerative colitis (UC) and recurrent Clostridium difficile infection (CDI) where the patient was on immunomodulatory therapy and had successful CDI eradication after fecal transplantation. This is the first case report in the literature documenting successful C. difficile eradication in an immunosuppressed patient. We feel that fecal transplantation should be studied as a treatment option in these patients.
mRNA precursor splicing in vivo: sequence requirements determined by deletion analysis of an intervening sequence. (1985)

To define the extent of intervening sequence required for splicing higher eukaryotic mRNA precursors in vivo, we constructed deletions within the second intervening sequence of the human G gamma-globin gene that progressively approach the donor or acceptor splice sites. Most of the intervening sequence can be deleted with no effect on splicing. At the donor splice site, 6 bases of intervening sequence are sufficient for accurate and efficient splicing. At the acceptor splice site, 20 bases are sufficient for accurate and efficient splicing, and 16 bases are sufficient for accurate splicing but at a reduced level. However, 15 bases are insufficient for splicing at a significant level. The effect of deletions ending near the acceptor splice site is independent of whether an A-G dinucleotide is introduced into the acceptor splice site region by the deletion.
Cooperative B7-1/2 (CD80/CD86) and B7-DC Costimulation of CD4+ T Cells Independent of the PD-1 Receptor (2003)

B7-DC is a recently discovered member of the B7 family that binds to PD-1 and is selectively expressed by dendritic cells (DCs). It has been shown to either costimulate or inhibit T cell responses. To assess the role of B7-DC in DC-T cell interactions, DCs from B7-DC knockout (KO) mice were generated and compared with DCs from wild-type (WT) and B7-1/B7-2 double KO mice. B7-1/B7-2-deficient DCs, while strongly diminished in their ability to stimulate naive CD4+ T cells, nonetheless retain partial activity. DCs from B7-DC KO mice are diminished in their ability to activate CD4+ T cells, demonstrating that DC-expressed B7-DC serves a predominantly stimulatory rather than inhibitory function in the initiation of T cell responses. B7-DC costimulates expression of CD40L with faster kinetics than B7-1 and displays potent synergy with B7-1 and B7-2 for T cell proliferation and cytokine production, indicating that these B7 family members work in concert to stimulate T cells. Finally, costimulation with B7-DC alone or in conjunction with B7-1 is PD-1 independent, indicating that B7-DC costimulates T cells via a second receptor.
FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study (2003)

Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.
Stable DNA transformation in the obligate intracellular parasite Toxoplasma gondii by complementation of tryptophan auxotrophy. (1994)

The protozoan parasite Toxoplasma gondii infects a wide range of vertebrate hosts and is an important opportunistic pathogen in immunocompromised humans. Although Toxoplasma is amenable to both biochemical and cellular experimental approaches, the molecular basis of its success as an intracellular parasite is poorly understood. To provide a system for molecular genetic analyses, we have developed a stable DNA transformation system for Toxoplasma based on complementation of its naturally occurring tryptophan auxotrophy. Complementation was accomplished by expressing the Escherichia coli trpB gene, encoding the beta subunit of tryptophan synthase (EC 4.2.1.20), the enzyme that catalyzes the formation of tryptophan from indole plus serine. Transformants were obtained by electroporation of a plasmid, called SAG1/trpB, containing the trpB gene flanked by Toxoplasma surface antigen 1 (SAG1) gene sequences and selection for growth on indole. Transformants were obtained with circular forms of the SAG1/trpB plasmid with efficiencies of 10(-4) per cell. Transformation with either circular or linear SAG1/trpB resulted in integration into the genome at distinct, nonhomologous sites. Trp+ transformants typically contained tandemly repeated copies of the SAG1/trpB plasmid and were stable in the absence of continued selection. The Trp phenotype provides a dominant selectable marker that should allow expression of foreign or altered genes in Toxoplasma and facilitate molecular analyses of genes important for intracellular survival.
Resonant Tunnelling Diodes and High Electron Mobility Transistors Integrated on GaAs Substrates (2006)

AlGaAs/InGaAs high electron mobility transistors (HEMTs) and AlAs/GaAs resonant tunnelling diodes (RTDs) are integrated on GaAs substrates. Molecular beam epitaxy is used to grow the RTD on the HEMT structure. The current–voltage characteristics of the RTD and HEMT are obtained on a two-inch wafer. At room temperature, the peak-valley current ratio and the peak voltage are about 4.8 and 0.44 V, respectively. The HEMT is characterized by a gate length of 1 μm, a maximum transconductance of 125 mS/mm, and a threshold voltage of -1.0 V. The current–voltage characteristics of the series-connected RTDs are presented. The current–voltage curves of the parallel connection of one RTD and one HEMT are also presented.