gebhart/patrepeval huggingface dataset:
209. TCR Gene Editing in a Single Step of T Cell Activation To Redirect T Cell Specificity and Prevent GvHD (2015)

Transfer of T cell receptors (TCR) specific for tumor-associated antigens is a promising approach for cancer adoptive immunotherapy. Yet, TCR gene transfer into mature T cells results in competition for surface expression and inappropriate pairing between the exogenous and endogenous TCR chains, resulting in suboptimal activity and potentially harmful unpredicted specificities. Thus, we developed a TCR gene editing procedure, based on the knockout of the endogenous TCR genes by transient exposure to α and β chain specific Zinc Finger Nucleases (ZFNs), followed by the introduction of tumor-specific TCR genes (Provasi et al, Nat. Med. 2012). While successful, the complete editing requires multiple manipulation steps involving repeated cell activation cycles and transductions. To reduce the duration and complexity of cell product generation, we recently developed a ‘single TCR editing’ (SE) procedure, based on the disruption of the endogenous TCR α chain only followed by the transfer of the tumor specific TCR genes. This SE method generates redirected T cells fully devoid of their natural TCR repertoire in a single round of cell activation. We validated the SE protocol exploiting an HLA-A2 restricted TCR specific for NY-ESO-1 (expressed by a considerable proportion of high risk multiple myeloma). The SE strategy allowed rapid production of high numbers of tumor specific T cells enriched for an early differentiation phenotype. When fucntionaly tested (co-culture, γ-IFN and 51Cr release) against the U266 myeloma cell line (NY-ESO-1+HLA-A2+), all NY-ESO-1 redirected T cells showed a strikingly high killing activity. However, when we assess the alloreactive potential of the different redirected T cells in mixed lymphocyte reactions, we observed that the allogeneic lysis by SE T cells was markedly lower (p=0.05) than that of conventional TCR transfer cells (TR). These results were validated in NSG mice, where the genetically modified T cells were infused after the engraftment of the U266 myeloma. All animals treated with tumor specific T cells were completely myeloma-free at the time of sacrifice, demonstrating the powerful anti-tumor potential of the NY-ESO-1 redirected T cells. However, the overall survival of mice treated with TR vs SE cells was 26% vs 100% respectively (p<0,001) corresponding with a significant difference in acute and chronic GvHD occurrence (71% vs 0%, p<0,001). Consistently, histopathological analysis of human T cell infiltration in the organs revealed a significantly higher score in mice treated with TR cells (p<0.001). The relative simplicity of the SE protocol enables rapid generation of highly performing tumor specific T cells, fully devoid of their endogenous TCR repertoire, and thus incapable of participating in GvHD. Such single TCR edited cells thus potentially represent a further advance in adoptive immunotherapy for cancer.
Characterization of KIF7 gene in silico (2004)

Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) are Hedgehog family ligands, which play key roles in embryogenesis and carcinogenesis, especially in pancreatic cancer and gastric cancer. Drosophila Costal-2 (Cos2) is a Hedgehog signaling regulator, interacting with Smoothened (Smo), Cubitus interruptus (Ci), Fused (Fu) and microtubule. KIF27 is one of the mammalian orthologs for Drosophila Cos2. KIF7 gene is the paralog of KIF27 gene; however, complete coding sequence (CDS) of KIF7 remains elusive. Here we characterized human KIF7 gene by using bioinformatics. Human LOC374654 cDNA (NM_198525.1) was a 5'-truncated partial KIF7 cDNA, corresponding to the nucleotide position 1418-4538 of KIF7 complete CDS. KIF7 gene, consisting of 19 exons, was found to encode a 1343-amino-acid KIF7 protein. Human KIF7 showed 43.6% total-amino-acid identity with human KIF27. Kinesin motor catalytic (KISc) domain (codon 15-347 of KIF7) and novel KIF7-KIF27 homologous (KIF727H) domain (codon 699-1196 of KIF7) were well conserved between KIF7 and KIF27. Three coiled-coil regions were located within the KIF727H domain. KIF7 and KIF27 were N-type Kinesins with the KIF727H domain. KIF7 mRNA was expressed in embryonic stem (ES) cells, melanotic melanoma and Jurkat T cells, while KIF27 mRNA was expressed in testis, pancreatic islet, germ cell tumors and Jurkat T cells. This is the first report on the characterization of the KIF7 gene as well as on the identification of KIF727H domain.
Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals. (1983)

The brain extraction of fifteen C-11-labeled compounds during a single capillary transit was studied in adult baboons by external detection of these tracers after injection into the internal carotid artery. The log Poct (partition coefficient for octanol/water) values of these compounds range from --0.7 to greater than 4.0. A parabolic relationship was found between the log Poct value of the C-11-labeled compounds and the fraction of the radiopharmaceutical entering the brain. Compounds with log Poct values between 0.9 and 2.5 were found to pass freely across the blood-brain barrier at a cerebral blood flow of 100 ml X min-1 X hg-1. An apparently decreased extraction of very lipophilic compounds was shown to be related to binding of the tracer to blood components and macromolecules (red blood cells, albumin, etc.). These data suggest that a radiopharmaceutical designed to measure blood flow should have a log Poct value of between 0.9 and 2.5.
Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer. (2013)

The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: A comparative histomorphometric study of ectopic bone formation (1990)

To investigate the bone formation ability of porous hydroxyapatite (HA) and tricalcium phosphate (TCP), ceramic discs were implanted with or without rat marrow cells into subcutaneous sites in syngeneic rats. The discs of HA and TCP had identical microstructures: pore size was 190-230 microns, porosity was 50-60%, and they were fully interconnected. Implants without marrow cells (discs themselves) did not show bone formation, whereas implants with marrow cells showed bone formation in the pores of the ceramics. The bone formation of both HA and TCP occurred initially on the surface of the ceramic and progressed towards the center of the pore. The de novo bone was quantitated from decalcified serial sections of the implants. One month after implantation with marrow cells, the percentage fractions of the pore area filled with bone for implanted HA and TCP were 16.9 and 15.1, respectively. At 2 months after implantation with marrow cells, the fractions of bone were 34.3 and 30.9, respectively. These results indicate that both HA and TCP ceramics can show comparable osteogenic ability in the presence of marrow cells.
Immunocytochemistry of M‐cadherin in mature and regenerating rat muscle (1994)

The cellular localization of M-cadherin may indicate that M-cadherin is involved in calcium-dependent adhesion between satellite cells and muscle fibers or, by means of interposed myoblasts, between the clustered myotubes in a regenerating muscle.
Maleic Anhydride CopolymersA Versatile Platform for Molecular Biosurface Engineering (2003)

A platform of thin polymer coatings was introduced for the functional modulation of immobilized bioactive molecules at solid/liquid interfaces. The approach is based on covalently attached alternating maleic acid anhydride copolymers with a variety of comonomers and extended through conversion of the anhydride moieties by hydrolysis, reaction with functional amines, and other conversions of the anhydride moieties. We demonstrate that these options permit control of the physicochemical constraints for bioactive molecules immobilized at interfaces to influence important performance characteristics of biofunctionalized materials for medical devices and molecular diagnostics. Examples concern the impact of the substrate-anchorage of fibronectin on the formation of cell-matrix adhesions, the orientation of endothelial cells according to lateral anti-adhesive micropatterns using grafted poly(ethylene oxide), and the spacer-dependent activity of immobilized synthetic thrombin inhibitors.
Heterologous Liver Perfusion in Treatment of Hepatic Failure (1965)

From the Department of Surgery, University of Kentucky Medical School, Lexington, Kentucky and the University of Puerto Rico Medical School, San Juan, Puerto Rico
CD-I Designers Guide (1992)

From the Publisher:
Aware that the Compact Disc Interactive will be one of the major forces of the 90s,this text is essential reading to understand and appreciate the technology. The information included in this text will provide specific production skills so that CD-I becomes a tool at your disposal. Starting with an overview of basic concepts such as interactivity,multimedia and compact disc,this text contains the most up-to-date information on the developing topic of CD-I. It gradually progresses to a detailed explanation of the specific technical skills required to produce CD-I programmes.
Single domain intrabodies against WASP inhibit TCR-induced immune responses in transgenic mice T cells (2013)

Intrabody technology provides a novel approach to decipher the molecular mechanisms of protein function in cells. Single domains composed of only the variable regions (V(H) or V(L)) of antibodies are the smallest recombinant antibody fragments to be constructed thus far. In this study, we developed transgenic (Tg) mice expressing the V(H) or V(L) single domains derived from a monoclonal antibody raised against the N-terminal domain of Wiskott-Aldrich syndrome protein (WASP), which is an adaptor molecule in immune cells. In T cells from anti-WASP V(H) and V(L) single domain Tg mice, interleukin-2 production induced by T cell receptor (TCR) stimulation were impaired, and specific interaction between the WASP N-terminal domain and the Fyn SH3 domain was strongly inhibited by masking the binding sites in WASP. These results strongly suggest that the V(H)/VL single domain intrabodies are sufficient to knockdown the domain function of target proteins in the cytosol.
Photochemistry of S-Phenacyl Xanthates (2011)

Various synthetically readily accessible S-phenacyl xanthates are shown to undergo photoinitiated homolytic scission of the C-S bond in the primary step. The resultant fragments, phenacyl and xanthic acid radicals, recombine to form symmetrical 1,4-diketones and xanthogen disulfides, respectively, in high to moderate chemical yields in chemically inert solvents. They can also be efficiently trapped by a hydrogen-atom-donating solvent to give acetophenone and xanthic acid derivatives. The latter compound is in situ thermally converted to the corresponding alcohol in high chemical yields. S-Phenacyl xanthates could thus be utilized as synthetic precursors to the above-mentioned compounds or as photoremovable protecting groups for alcohols in which the xanthate moiety represents a photolabile linker. The photochemically released phenacyl radical fragments efficiently but reversibly add to the thiocarbonyl group of the parent xanthate molecule. The kinetics of this degenerative reversible addition-fragmentation transfer (RAFT)/macromolecular design via the interchange of xanthates (MADIX) mechanism was studied using laser flash photolysis (LFP) and density functional theory (DFT) calculations. The rate constants of the RAFT addition step, k(add) ∼ 7 × 10(8) M(-1) s(-1), and phenacyl radical addition to a double bond of 1,1-diphenylethylene, k(add) ∼ 10(8) M(-1) s(-1), in acetonitrile were experimentally determined by LFP. In addition, photoinitiation of the methyl methacrylate polymerization by S-phenacyl xanthate is demonstrated. The polydispersity index of the resulting poly(methyl methacrylate) was found to be ∼1.4. We conclude that S-phenacyl xanthates can serve simultaneously as photoinitiators as well as RAFT/MADIX agents in polymerization reactions.
A Mechanism for Inhibition of Factor VIII Binding to Phospholipid by von Willebrand Factor (1995)

von Willebrand factor (vWf) acts as a carrier for blood coagulation factor VIII (fVIII) in the circulation. The amino-terminal 272 residues of mature vWf contain a high affinity fVIII binding site. Upon thrombin activation, fVIII is released from vWf, thereby allowing its binding to phospholipid which is required for its procoagulant activity. Although phospholipid and vWf compete for fVIII binding, it was previously suggested that their binding sites are not closely juxtaposed within the fVIII protein because only amino-terminal vWf proteolytic fragments larger than SPIII-T4 (1-272) were able to block the binding of fVIII to phospholipid. We have demonstrated, however, that SPIII-T4 is able to inhibit fVIII binding to phosphatidylserine (PS) in a dose-dependent fashion, but only at concentrations higher than those used in previous experiments. Our demonstration that the Kd values for vWf and SPIII-T4 for fVIII are 0.52 nM and 48 nM, respectively, explain this discrepancy. Inhibition (> 95%) of SPIII-T4 binding to fVIII by a purified recombinant fVIII C2 domain polypeptide demonstrated that SPIII-T4 binds directly to C2, as we had previously shown for vWf. The similarity of the C2 binding sites for vWf and SPIII-T4 was further confirmed by the identical inhibitory effects of synthetic peptides and monoclonal antibodies (mAbs) on vWf-fVIII or SPIII-T4 fVIII binding. In both cases, binding was inhibited by synthetic peptide 2303-2332, containing a PS binding site, and by mAb NMC-VIII/5 Fab' (epitope within C2 residues 2170-2327). We propose that vWf, via residues 1-272, and PS compete for fVIII binding because they recognize overlapping sites within fVIII C2 domain residues 2303-2332.
Aldose reductase functions as a detoxification system for lipid peroxidation products in vasculitis (1999)

Giant cell arteritis (GCA) is a systemic vasculitis preferentially affecting large and medium-sized arteries. Inflammatory infiltrates in the arterial wall induce luminal occlusion with subsequent ischemia and degradation of the elastic membranes, allowing aneurysm formation. To identify pathways relevant to the disease process, differential display-PCR was used. The enzyme aldose reductase (AR), which is implicated in the regulation of tissue osmolarity, was found to be upregulated in the arteritic lesions. Upregulated AR expression was limited to areas of tissue destruction in inflamed arteries, where it was detected in T cells, macrophages, and smooth muscle cells. The production of AR was highly correlated with the presence of 4-hydroxynonenal (HNE), a toxic aldehyde and downstream product of lipid peroxidation. In vitro exposure of mononuclear cells to HNE was sufficient to induce AR production. The in vivo relationship of AR and HNE was explored by treating human GCA temporal artery-severe combined immunodeficiency (SCID) mouse chimeras with the AR inhibitors Sorbinil and Zopolrestat. Inhibition of AR increased HNE adducts twofold and the number of apoptotic cells in the arterial wall threefold. These data demonstrate that AR has a tissue-protective function by preventing damage from lipid peroxidation. We propose that AR is an oxidative defense mechanism able to neutralize the toxic effects of lipid peroxidation and has a role in limiting the arterial wall injury mediated by reactive oxygen species.
Left frontal hypoactivation in depression. (1991)

Baseline resting electroencephalogram activity was recorded with 3 different reference montages from 15 clinically depressed and 13 control subjects. Power in all frequency bands was extracted by fast Fourier transformation. There was a significant Group X Hemisphere interaction in the mid-frontal region, for the alpha band power only. Depressed subjects had less left-sided activation (i.e., more alpha activity) than did normal control subjects. This pattern of diminished left-sided frontal activation is interpreted as indicating a deficit in approach mechanisms in depressed subjects.
A control strategy of three-phase PWM inverter with fluctuating input voltage (2003)

A digital control strategy for the three-phase PWM inverter is proposed for a sinusoidal output with a fluctuating input voltage. The pulse width is computed by sampling and predicting the fluctuating input voltage every time the pulse generates. Three predictive methods are proposed. The errors and the waveform distortion of the output voltage are analyzed and discussed, along with the proposed predictive methods. The validity of the control method was experimentally verified using a microprocessor-based control system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A method for typing polymorphism at the HLA‐A locus using PCR amplification and immobilized oligonucleotide probes (1994)

We have developed a simple and rapid method for DNA typing of the HLA-A locus using PCR amplification and hybridization of the PCR product, labeled with biotinylated primers, to an array of immobilized oligonucleotide probes in a single hybridization reaction (reverse dot or line blot). A single primer set (RAP1007 and DB337) is used to specifically amplify a 990-bp fragment containing the HLA-A locus exons 1, 2, and 3 from genomic DNA. This primer set is locus-specific and amplifies all HLA-A alleles. A set of 51 sequence-specific oligonucleotide (SSO) probes, 25 for exon 2 and 26 for exon 3, was immobilized to a nylon membrane by UV-crosslinking oligonucleotide probes containing a poly-thymidine "tail" added with terminal transferase. In the line blot format, all 50 SSO probes plus a control probe are immobilized on a single nylon membrane strip. The probe array was used for typing in a hybridization reaction with DNA amplified from a variety of samples. These probes can identify 37 homozygous HLA-A alleles. In the analysis of heterozygous samples, 604 heterozygous types out of 633 (95.4%) possible heterozygous probe patterns can be detected as a unique probe reactivity pattern. A simple computer program has been developed to assign the alleles and genotypes based on the probe hybridization pattern.
Development and evaluation of candidate recombinant Salmonella-vectored Salmonella vaccines (2010)

Attenuated Salmonella Enteriditis (ΔSE) recombinant vaccine vectors incorporating a Salmonella flagellar filament protein (fliC) subunit, a putative cell-mediated epitope, for expression of the lamB gene (encoding a maltose outer membrane porin), with or without co-expression of a putative immune-enhancing CD154 oligopeptide, were developed and compared with wild-type Salmonella Enteriditis (experiments 1 and 2) or the attenuated ΔSE empty vector (experiment 3) as initial vaccine candidates against Salmonella infection. A total of 3 experiments were performed to assess the infection and clearance rate of each of these constructs. Each construct or Salmonella Enteriditis was orally administered to broiler chicks at day of hatch by oral gavage (~10(8) cfu/chick). In experiments 1 to 3, liver-spleen and cecal tonsils were removed aseptically for recovery of wild-type Salmonella Enteriditis or ΔSE mutants. These experiments suggested that cell surface expression of fliC alone markedly increased the clearance rate of the vector at or before 21d postvaccination in all 3 experiments. In a fourth experiment, broilers were vaccinated with one of the vaccine constructs or the ΔSE empty vector and then challenged with wild-type Salmonella Typhimurium. At 19 d posthatch, 16 d postinfection, neither candidate protected against challenge significantly better than the ΔSE empty vector, although there was significantly less Salmonella recovered from vaccinated chickens as compared with nonvaccinated controls. These experiments indicate that these experimental vaccines did not protect against heterologous challenge or enhance clearance after Salmonella Typhimurium challenge; as such, their value as vaccines is limited. The increased clearance of the candidate vaccines, particularly the vector expressing fliC alone, may have value in that the fliC epitope may decrease the clearance time of other recombinant vectored Salmonella vaccines.
Specific expression of unusual GM2 ganglioside with Hanganutziu-Deicher antigen activity on human colon cancers. (1987)

This paper reports the presence of GM2 ganglioside containing N-glycolylneuraminic acid (NeuGc) in human colon cancer tissues. GM2(NeuGc) was detected by two-dimensional thin layer chromatography (2d-TLC)/enzyme-immunostaining using affinity-purified chicken antibody against GM3(NeuGc) and horseradish peroxidase-conjugated rabbit anti-chicken IgG antibody. Like usual GM2 ganglioside containing N-acetylneuraminic acid (NeuAc) isolated from Tay-Sachs brain, GM2(NeuGc) in colon cancer could be converted into GM3(NeuGc) by human kidney beta-N-acetylhexosaminidase A in the presence of a GM2-specific activator protein isolated from guinea pig kidney. Three of 7 specimens of Hanganutziu-Deicher (HD) antigen-positive human colon cancer tissues so far examined expressed this unique ganglioside. In order to detect and determine specifically GM2(NeuGc) on human colon cancers, specific antibody against GM2 (NeuGc) has been prepared by immunizing chickens. By a sensitive TLC/immunostaining method using the antibody, the amounts of the antigen were determined to be 0.3-3% of total lipid-bound sialic acid. NeuGc-containing gangliosides were also detected in meconium and fetal intestinal tissues. Three species of antigenic gangliosides in pooled meconium were tentatively identified as GM3(NeuGc), sialylparagloboside and sialylhexaosylceramide on the basis of their migration positions on 2d-TLC and the results of endo-beta-galactosidase treatment. GM3(NeuGc) was the sole HD-active ganglioside in fetal intestinal tissue from one of 3 individuals tested; the other two showed no HD-active ganglioside at all. GM2(NeuGc), however, could not be detected in either meconium or fetal tissues so far examined, suggesting that this unique ganglioside is a tumor-specific antigen, at least for human intestinal tissues.
Case 3-1964 (1964)

Presentation of Case First admission. A seventy-four-year-old man was admitted to the hospital because of hematuria.One week previously the patient entered another hospital because of prostatism and hematuria and underwent suprapubic prostatectomy, with removal of benign, hypertrophied tissue weighing 106 gm. Four days later bright-red blood was passed through the indwelling catheter; transfusions were given. On the day of admission hematuria recurred, and he was transferred to this hospital.There was no history of previous abnormal bleeding. Five years before admission a left pneumonectomy was performed because of squamous-cell carcinoma; 1 of 12 hilar lymph nodes contained a metastasis. . . .