gebhart/patrepeval huggingface dataset:
Prognostic Values of CD38+CD101+PD1+CD8+ T Cells in Pancreatic Cancer (2019)

Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1<sup>+</sup> T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy. However, whether this subpopulation of PD-1 expressing CD8<sup>+</sup> T cells could be useful in predicting PDAC stage or prognosing survival is unknown. In this study, we used flow cytometry and immunofluorescence assay to analyze the expression of CD38 and CD101 in 183 clinical PDAC samples, including 84 of peripheral blood and 99 of surgical tissues. High coexpression of CD38/CD101 on peripheral PD-1<sup>+</sup>CD8<sup>+</sup> T cells or tumor-infiltrating lymphocytes (TILs) was found to be most significantly correlated with Tumor/Node/Metastasis (T/N/M) classification and clinical stage, in contrast PD-1<sup>+</sup>CD8<sup>+</sup> T cells could not correlate with T classification. CD38/CD101 co-repression on TILs also correlated with the poor survival in these PDAC patient samples. Our data suggest that CD38/CD101 might represent a more helpful biomarker than PD-1 alone for diagnosis and prognosis of PDAC.
NGF induces neonatal rat sensory neurons to extend dendrites in culture after removal of satellite cells (1993)

Vertebrate sensory neurons have a pseudo-unipolar morphology; their somata are covered by satellite cells and lack dendrites or synaptic contacts. However, when neonatal rat sensory neurons from the nodose ganglia develop in culture in absence of satellite cells and with NGF, they form synapses among themselves. In this study, we investigated whether neonatal rat nodose neurons express dendrites under the same culture conditions. We show by Lucifer yellow injection that nodose neurons remain typically unipolar when cocultured with their ganglionic satellite cells. However, when these neurons are cultured without satellite cells, virtually all neurons acquire a multipolar morphology. Moreover, when NGF is added to satellite cell-free cultures, several neurons extend dendrites; these processes stain positively for microtubule-associated protein-2. NGF induces a 17-fold increase in dendritic outgrowth after 3 weeks but has little effect on axon number. In addition, we find that the ability of nodose neurons to extend dendrites is developmentally regulated. Furthermore, in a combined morphological and electrophysiological study, using whole-cell voltage-clamp technique with Lucifer yellow in the recording solution, we demonstrate a positive correlation between the extent of dendritic outgrowth and the density of ACh currents, suggesting that these dendrites have ACh receptors. Our results indicate that neonatal rat nodose neurons are capable of extending dendrites and that extrinsic factors can induce or suppress their extension. In addition, the results suggest that these dendrites may act as principal post-synaptic structures for synapse formation that occurs in these cultures.
Heparanase-1 Gene Expression and Regulation by High Glucose in Renal Epithelial Cells (2005)

The molecular mechanisms of heparan sulfate proteoglycan downregulation in the glomerular basement membrane (GBM) of the kidneys with diabetic nephropathy remain controversial. In the present study, we showed that the expression of heparanase-1 (HPR1), a heparan sulfate-degrading endoglycosidase, was upregulated in the renal epithelial cells in the kidney with diabetic nephropathy. Urinary HPR1 levels were elevated in patients with diabetic nephropathy. In vitro cell culture studies revealed that HPR1 promoter-driven luciferase reporter gene expression, HPR1 mRNA, and protein were upregulated in renal epithelial cells under high glucose conditions. Induction of HPR1 expression by high glucose led to decreased cell surface heparan sulfate expression. HPR1 inhibitors were able to restore cell surface heparan sulfate expression. Functional analysis revealed that renal epithelial cells grown under high glucose conditions resulted in an increase of basement membrane permeability to albumin. Our studies suggest that loss of heparan sulfate in the GBM with diabetic nephropathy is attributable to accelerated heparan sulfate degradation by increased HPR1 expression.
Roles of HGF as a pleiotropic factor in organ regeneration. (1993)

Hepatocyte growth factor (HGF) has been discovered, purified, and molecularly cloned as a potent mitogen for mature hepatocytes. HGF is produced by mesenchymal cells and predominantly acts on a wide variety of epithelial cells, as a mitogen (stimulation of cell growth), a motogen (stimulation of cell motility), and a morphogen (induction of multicellular architecture). HGF mRNA and HGF protein are rapidly and markedly increased in the liver and plasma of rats with various types of liver injuries, and HGF receptors on plasma membranes of the liver were almost completely down-regulated due to HGF-binding and subsequent internalization. Thus HGF acts as a hepatotrophic factor for regeneration; intravenously injected recombinant HGF remarkably enhances liver regeneration. HGF mRNA, HGF protein, and HGF receptors in the kidney are also rapidly altered prior to the onset of renal tubular cell replication after various renal insults, thus HGF also acts as a renotropic factor in renal regeneration. HGF mRNA is rapidly induced not only in the injured organ but also in non-injured organs such as the lung and spleen following hepatic or renal injury. Because "injurin", a protenous factor which induces HGF mRNA expression, was detected in the plasma of rats with various organ injuries, it seems to increase HGF mRNA expression in non-injured organs and HGF produced in non-injured organs may also participate in the regeneration of the liver or kidney through an endocrine mechanism. Based on these results and its uniquely suited ability to act as mitogen, motogen and morphogen, HGF is considered to be a key molecule for construction of normal tissue structure during embryogenesis, organogenesis, and organ regeneration.
DNA Variation in the Basic Chitinase Locus (ChiB) Region of the Wild Plant Arabidopsis thaliana (1999)

Nucleotide variation in a 2.2-kbp region of basic chitinase (ChiB) locus in 17 ecotypes of Arabidopsis thaliana was compared with previously investigated regions to investigate genetic mechanisms acting on DNA polymorphism. In the ChiB region, dimorphic DNA variation was detected, as in the Adh and ChiA regions. Nucleotide diversity (pi) of the entire region was 0.0091, which was similar to those of the two other regions. About half of polymorphic sites (37/87) in the ChiB region were observed in only two ecotypes. Tajima's D was negative but not significantly, while Fu and Li's D* was positive. Neither McDonald-Kreitman nor Hudson, Kreitman, Aguadé tests showed a significant result, indicating that these loci were under similar evolutionary mechanisms before and after speciation. Linkage disequilibria were observed within the three regions because of dimorphic polymorphisms. Interlocus linkage disequilibrium was not detected between the Adh and the two chitinase regions, but was observed between the ChiA and ChiB regions. This could be due to epistatic interaction between the two chitinase loci, which are located on different chromosomes.
CpG-DNA Activates In Vivo T Cell Epitope Presenting Dendritic Cells to Trigger Protective Antiviral Cytotoxic T Cell Responses (2000)

MHC class I-restricted T cell epitopes lack immunogenicity unless aided by IFA or CFA. In an attempt to circumvent the known inflammatory side effects of IFA and CFA, we analyzed the ability of immunostimulatory CpG-DNA to act as an adjuvant for MHC class I-restricted peptide epitopes. Using the immunodominant CD8 T cell epitopes, SIINFEKL from OVA or KAVYNFATM (gp33) from lymphocytic choriomeningitis virus glycoprotein, we observed that CpG-DNA conveyed immunogenicity to these epitopes leading to primary induction of peptide-specific CTL. Furthermore, vaccination with the lymphocytic choriomeningitis virus gp33 peptide triggered not only CTL but also protective antiviral defense. We also showed that MHC class I-restricted peptides are constitutively presented by immature dendritic cells (DC) within the draining lymph nodes but failed to induce CTL responses. The use of CpG-DNA as an adjuvant, however, initiated peptide presenting immature DC progression to professional licensed APC. Activated DC induced cytolytic CD8 T cells in wild-type mice and also mice deficient of Th cells or CD40 ligand. CpG-DNA thus incites CTL responses toward MHC class I-restricted T cell epitopes in a Th cell-independent manner. Overall, these results provide new insights into CpG-DNA-mediated adjuvanticity and may influence future vaccination strategies for infectious and perhaps tumor diseases.
A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene (1997)

Strains of Escherichia coli with mutations in the ubiE gene are not able to catalyze the carbon methylation reaction in the biosynthesis of ubiquinone (coenzyme Q) and menaquinone (vitamin K2), essential isoprenoid quinone components of the respiratory electron transport chain. This gene has been mapped to 86 min on the chromosome, a region where the nucleic acid sequence has recently been determined. To identify the ubiE gene, we evaluated the amino acid sequences encoded by open reading frames located in this region for the presence of sequence motifs common to a wide variety of S-adenosyl-L-methionine-dependent methyltransferases. One open reading frame in this region (o251) was found to encode these motifs, and several lines of evidence that confirm the identity of the o251 product as UbiE are presented. The transformation of a strain harboring the ubiE401 mutation with o251 on an expression plasmid restored both the growth of this strain on succinate and its ability to synthesize both ubiquinone and menaquinone. Disruption of o251 in a wild-type parental strain produced a mutant with defects in growth on succinate and in both ubiquinone and menaquinone synthesis. DNA sequence analysis of the ubiE401 allele identified a missense mutation resulting in the amino acid substitution of Asp for Gly142. E. coli strains containing either the disruption or the point mutation in ubiE accumulated 2-octaprenyl-6-methoxy-1,4-benzoquinone and demethylmenaquinone as predominant intermediates. A search of the gene databases identified ubiE homologs in Saccharomyces cerevisiae, Caenorhabditis elegans, Leishmania donovani, Lactococcus lactis, and Bacillus subtilis. In B. subtilis the ubiE homolog is likely to be required for menaquinone biosynthesis and is located within the gerC gene cluster, known to be involved in spore germination and normal vegetative growth. The data presented identify the E. coli UbiE polypeptide and provide evidence that it is required for the C methylation reactions in both ubiquinone and menaquinone biosynthesis.
Gene therapy of rat 9L gliosarcoma tumors by transduction with selectable genes does not require drug selection. (1994)

9L rat glioma cells have been used as a model for brain tumor therapies. It has been reported that in vivo infection of 9L cells with a replication-defective retrovirus expressing the herpes simplex thymidine kinase gene resulted in decreased tumor formation following treatment with the antiviral drug ganciclovir. In the study reported here, rats were injected either intracerebrally or subcutaneously with 9L glioma cells expressing a chimeric hygromycin phosphotransferase-thymidine kinase fusion protein or with unmodified 9L cells. Tumor formation was decreased in the rats receiving modified cells, even in the absence of treatment with ganciclovir. Suppression of tumor growth was also observed with cells modified to express the intracellular selectable marker neomycin phosphotransferase. These results indicate that an intracellular selectable marker, in the absence of pharmacologic selection, can inhibit tumor growth of 9L cells. The demonstration that intracellular marker genes can negatively influence the survival of transplanted cells has important implications for in vivo studies that use genetically modified cells.
RNAi-based Therapies for Huntington‘s Disease: Delivery Challenges and Opportunities (2012)

Huntington's disease (HD) is a polyglutamine neurodegenerative disease caused by a mutation in the HTT gene coding for the Huntingtin protein (HTT). Unfortunately, there is no cure for HD and there is also no known way to modify the disease progression. RNAi approaches offer the promise of a certain degree of control over the disease. However, there are several challenges in potential use of RNAi in the treatment of HD. This article will discuss the details of RNAi technology as applied to the treatment of HD, and novel approaches to overcome the drug delivery challenges.
A Facile Synthesis of 3-Pyrrolines (1990)

Abstract N-substituted 3-pyrrolines were conveniently synthesized in high yield by the treatment of primary amines with cis-2-butene-l,4-diol dimesylate, which was generated from cis-1, 4-butenediol.
1-N-Glycyl .beta.-oligosaccharide derivatives as stable intermediates for the formation of glycoconjugate probes (1992)

Incubation of reducing sugars in ammonium bicarbonate was found to be a simple procedure for the formation of beta-D-glycosylamines of purified complex oligosaccharides in 70-80% yield. These provide valuable intermediates for the synthesis of a wide range of oligosaccharide probes and derivatives by acylation of the 1-amino function. The 1-amino function showed different rates of reactivity with different reagents. In general, interactions with large ring systems such as the fluorophores dansyl chloride and carboxyfluorescein gave 10-20% yields of products, which consisted of mixtures of both anomeric forms, whereas smaller acylating reagents gave near-quantitative yields of the desired beta-D-derivatives. Steric effects may explain differences in reactivity. N-Chloroacetamido derivatives could be obtained in high yield with retention of the beta-anomeric configuration. Subsequent ammonolysis of the chloroacetamido function afforded the corresponding N-glycyl beta-derivatives. The linker thereby introduced retains the amino function, possesses the useful properties of fixed anomeric configuration, improved stability, and uniform reactivity with a variety of reagents, and is structurally analogous to an asparagine side chain. The potential therefore exists for the generation of oligosaccharide derivatives tailored for different applications.
Dopamine: A Novel Antitumor Agent Active Against B-16 Melanoma In Vivo (1978)

L-dopa methyl ester has been shown to be an effective antitumor agent against the B-16 melanoma in vivo. We have now examined the analog, dopamine, a major catabolite of L-dopa. Dopamine administration at a daily dose of 600 mg/kg resulted in a 48% (p less than .001) increase in survival of treated mice as compared to non-treated controls. In vitro, an effect similar to that observed with L-dopa methyl ester was noted, specifically, a rapid and profound inhibition of thymidine incorporation with little effect on uridine or leucine incorporation. We have postulated that the inhibition of a DNA polymerase might be the site of action of these novel antitumor agents.
Role of lysine 758 of Escherichia coli DNA polymerase I as assessed by site-directed mutagenesis. (1994)

Lys-758 of Escherichia coli DNA polymerase I has been implicated in the process of substrate dNTP binding (Basu, A., and Modak, M. J. (1987) Biochemistry 26, 1704-1709). To confirm and define the role of Lys-758 in the catalytic mechanism, we carried out site-directed mutagenesis of this residue. Catalytic activity of the purified mutant enzymes, K758A and K758R, showed severe reduction in the polymerase activity but little difference in the 3'-->5' exonuclease activity. Most interestingly, the catalytic ability of both mutant enzymes was maximally affected (300-1,000-fold decrease in kcat) with poly(dA).(dT)15 as template-primer (TP), whereas the ability to use poly(dC) templates decreased by only 20-fold in K758A and remained nearly unchanged with K758R. Kinetic characterization showed that Km(dNTP) increased moderately only with K758A, whereas Kd(TP) remained unchanged for both the mutants. However, binary complex formation between K758A and dNTP, but not between K758A and TP, was severely reduced. Analysis of the processive mode of DNA synthesis by K758A indicated that the mutant enzyme pauses at dA bases but does not dissociate from TP, suggesting a defect in its translocation ability. Thus, Lys-758 in polymerase I appears to participate in two distinct functions: (a) it facilitates the dNTP binding, and (b) it is required for the translocation along the template polynucleotide.
Grammatikerfragment περὶ πνευμάτων (1982)

Die drei Fragmente, von denen nur das größte einen zusammenhängenden Text bietet, sind mit einer sorgfältigen Schönschrift, die sich ins frühe 2. Jh. n. Chr. datieren läßt, parallel zum Faserverlauf beschrieben worden. Fr. a bildet den linken Teil einer Kolumne mit den Zeilenanfängen, wie die Reste von Paragraphoi zwischen Z. 13 und 14 sowie 18 und 19 zeigen. Zwischen Z. 18 und 19 ist der Zeilenabstand eine Spur größer als sonst. Die auf dem winzigen Fragment verhältnismäßig häufig verwendete Interpunktion ist der Hochpunkt (Z. 12, 13, 14, 16 [2], 18, 20 [2]), der vornehmlich dazu verwendet wird, die Glieder einer Aufzählung abzuteilen; nach diesen System fehlt ein Hochpunkt in Z. 7 und 20. Auch der Strich, der über die substantivierten Buchstabenbezeichnungen gesetzt ist, ist nicht konsequent verwendet worden; er steht Z. 14 u. 19 (τὸ ᾱ), Z. 19 (τοῦ ϰ), Fr. b 2 (τὸ ᾱ), fehlt aber, wenn die Ergänzung richtig ist, in Z. 8. Auf Fr. b ist ebenfalls eine Paragraphos erkennbar, wodurch auch dieses Stückchen dem Zeilenanfang zugewiesen werden kann. Fr. könnte ans Zeilenende gehören, doch kann dies nicht mit Sicherheit gesagt werden, da dort, wo die Schrift aufhört, auch die Papyrusschicht mit den Fasern der Rectoseite abgerieben ist. Weder Fr. b noch Fr. c läßt sich unmittelbar an Fr. a anfügen.
Comparative angiotensin II receptor blockade in healthy volunteers: The importance of dosing (2002)

These results show that the differences in angiotensin II receptor blockade observed with the various AT(1) antagonists are explained mainly by differences in dosing. When 160-mg or 320-mg doses were investigated, the effects of valsartan hardly differed from those obtained with recommended doses of irbesartan and candesartan.
A Functionalizable Biomaterial Based on Dihydroxyacetone, an Intermediate of Glucose Metabolism (2006)

A biomaterial and its potential degradation products should be biocompatible, nontoxic, and removed by the body upon expiration of its functional lifetime. One historically successful approach is to create new materials from biomolecules that naturally occur in the human body. Herein, we report the synthesis and characterization of a polycarbonate based on dihydroxyacetone, a 3-carbon ketose, and an intermediate in the glucose metabolic pathway. The polymer was synthesized in a range of molecular weights ( approximately 8000 to approximately 37,500) by ring-opening polymerization. The C2 carbonyl of dihydroxyacetone is reactive to amines, and this reactivity was used to functionalize the polymer's surface in a one-step reaction by reductive amination. Additionally, contact angle measurements show the surface of poly(2-oxypropylene carbonate) is hydrophilic even though it is insoluble in water. Mechanical analysis of the polymer revealed it is exceptionally strong for an aliphatic polycarbonate. Specifically, poly(2-oxypropylene carbonate), M(w) 37 500, yielded a Young's modulus of 0.5 GPa and a compressive yield stress of 50 MPa. These values equal or exceed those of cancellous bone with similar dimensions.
THE SYNTHESIS AND CHLOROSULFONATION OF SOME DIARYLIDENE AND HETEROARYLIDENE KETONES WITH VARYING ALICYCLIC RING SIZE (1995)

Abstract A series of diarylidene and heteroarylidene ketones (1–20) was prepared using alicyclic ketones ((CH2)nC=O where n = 3 to 7). An improved synthesis of 2,4-dibenzylidenecyclobutanone (1) is described and the ease of preparation of the arylidene derivatives is considered in terms of the size of the alicyclic ring. Treatment of 2,5-dibenzylidenecyclopentanone (2) with chlorosulfonic acid (10 mole equivalents) afforded the 4,4′-bis-sulfonyl chloride (23), reducing the amount of chlorosulfonic acid (6 mole equivalents) produced the corresponding mono-sulfonyl chloride (24). Only the respective 4,4′-bis-sulfonyl chlorides (39, 45, 51) could be isolated from the diarylidene ketones derived from larger alicyclic rings. Attempted chlorosulfonation of 2,4-dibenzylidene cyclobutanone (1) gave a mixture of products which could not be clearly characterised. The sulfonyl chlorides were converted into stable sulfonamides (25–29, 35, 36, 38, 40–44, 46–48, 52, 54) by condensation with amines, and selected samples were screened for biological activity as potential insecticides, herbicides and fungicides. The orientation of sulfonation is discussed in relation to stereoelectronic factors and the relevant spectral data.
Ion Motion in Conjugated Polyelectrolyte Electron Transporting Layers (2007)

The time responses of polymer light-emitting diodes (PLEDs) incorporating conjugated polyelectrolyte electron transport layers (ETLs) are reported. Longer times are required with thicker ETL layers and with smaller applied voltages. These observations are consistent with a reduction of the electron injection barrier that depends on the ion motion in the ETL. The devices are a hybrid between PLEDs and light-emitting electrochemical cells.
Novel multimode J-pHEMT front-end architecture with power-control scheme for maximum efficiency (2005)

Based upon a unique junction pseudomorphic high electron-mobility transistor (J-pHEMT) device, a novel method of providing high-efficiency power amplifier (PA) power control for variable envelope modulation schemes is demonstrated for enhanced data rates for global system for mobile communications evolution and wide-band code division multiple access. This new technique, based upon the use of a linear PA, was extended to provide a simple, but highly effective method of PA efficiency enhancement based upon dynamic adaptive bias control. Together, the architecture allows for substantially higher efficiency levels compared with conventional linear solutions over the entire range of handset operating conditions, while avoiding the necessity for complex control loops and linearization schemes. Furthermore, it is shown that the characteristics of the J-pHEMT, when used with this architecture, can be exploited to facilitate an efficient and completely novel single-chip PA plus antenna switch to substantially reduce the RF complexity of a cellular handset.