gebhart/patrepeval huggingface dataset:
Anti–Tumor Necrosis Factor Therapy Inhibits Pancreatic Tumor Growth and Metastasis (2008)

Chronic inflammation has been implicated in the pathogenesis of many severe autoimmune disorders, as well as in diabetes, pulmonary diseases, and cancer. Inflammation accompanies most solid cancers including pancreatic ductal adenocarcinoma (PDAC), one of the most fatal cancers with surgery being the only curative therapeutic approach currently available. In the present work, we investigated the role of the major proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) in the malignancy of PDAC cells in vitro and in vivo. In vitro, TNFalpha strongly increased invasiveness of Colo357, BxPc3, and PancTuI cells and showed only moderate antiproliferative effect. TNFalpha treatment of mice bearing orthotopically growing PDAC tumors led to dramatically enhanced tumor growth and metastasis. Notably, we found that PDAC cells themselves secrete TNFalpha. Although inhibition of TNFalpha with infliximab or etanercept only marginally affected proliferation and invasiveness of PDAC cells in vitro, both reagents exerted strong antitumoral effects in vivo. In severe combined immunodeficient mice with orthotopically growing Colo357, BxPc3, or PancTuI tumors, human-specific anti-TNF antibody infliximab reduced tumor growth and metastasis by about 30% and 50%, respectively. Importantly, in a PDAC resection model performed with PancTuI cells, we found an even stronger therapeutic effect for both anti-TNF compounds. Infliximab and etanercept reduced the number of liver metastases by 69% and 42%, respectively, as well as volumes of recurrent tumors by 73% and 51%. Thus, tumor cell-derived TNFalpha plays a profound role in malignancy of PDAC, and inhibition of TNFalpha represents a promising therapeutic option particularly in adjuvant therapy after subtotal pancreatectomy.
Role of the Maillard Reaction in Aging of Tissue Proteins (1998)

Dicarbonyl compounds such as glyoxal and methylglyoxal are reactive dicarbonyl intermediates in the nonenzymatic browning and cross-linking of proteins during the Maillard reaction. We describe here the quantification of glyoxal and methylglyoxal-derived imidazolium cross-links in tissue proteins. The imidazolium salt cross-links, glyoxal-lysine dimer (GOLD) and methylglyoxal-lysine dimer (MOLD), were measured by liquid chromatography/mass spectrometry and were present in lens protein at concentrations of 0. 02-0.2 and 0.1-0.8 mmol/mol of lysine, respectively. The lens concentrations of GOLD and MOLD correlated significantly with one another and also increased with lens age. GOLD and MOLD were present at significantly higher concentrations than the fluorescent cross-links pentosidine and dityrosine, identifying them as major Maillard reaction cross-links in lens proteins. Like the N-carboxy-alkyllysines Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine, these cross-links were also detected at lower concentrations in human skin collagen and increased with age in collagen. The presence of GOLD and MOLD in tissue proteins implicates methylglyoxal and glyoxal, either free or protein-bound, as important precursors of protein cross-links formed during Maillard reactions in vivo during aging and in disease.
Enzymic Synthesis and Biochemical Activity of Various Indazole Adenine Dinucleotides (1985)

Abstract Each of 5- or 6-amino-, acetamido-, hydroxy-, methoxy-, and chloroindazoles (including an unsubstituted one) and β NAD were subjected to an NADase-catalyzed base-exchange reaction to produce a corresponding title compound with a 41–76% yield. A difficulty, due to the poor solubility in water of indazole bases, was overcome by the addition of DMSO (∼20%) without a remarkable decrease in NADase activity. In most cases, the obtained dinucleotides were ascertained to be N2-ribosylated compounds. From 5- and 6-aminoindazoles, however, N1-ribosylated dinucleotide was also obtained as a minor product. In some of the N2-ribosylated dinucleotides, an unusual tautomerism was suggested to occur on the benzene ring of an indazole moiety. Finally, the synthesized title compounds were examined for inhibition activity against NAD-linked inosine monophosphate dehydrogenase. Four compounds among them were markedly effective at a 10−3 M concentration.
Accurate detection of aneuploidies in array CGH and gene expression microarray data (2004)

Code available by request from the authors and on Web supplement at http://function.cs.princeton.edu/ChARM/
Enhanced Transepithelial Transport of Peptides by Conjugation to Cholic Acid (1997)

The potential of the intestinal bile acid transporter to serve as a shuttle for small peptide molecules was investigated. Eleven peptides with a 2-6 amino acid backbone were conjugated to the 24-position of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oic acid (cholic acid) via an amide bond using an automated peptide synthesizer. In a human intestinal cell line (CaCo-2), cholic acid-peptide conjugates were able to inhibit the transepithelial transport of [3H]taurocholic acid, a natural substrate for the bile acid carrier, at a 100:1 conjugate/substrate ratio. Affinity for the carrier decreased significantly when the conjugate in the 24-position increased from 1 to 2 amino acids. Further increase in the amino acid chain length caused only minor decrease in affinity. A tetrapeptide-bile acid conjugate, [3H]-ChEAAA (Ch = cholic acid), was transported by the bile acid transporter, showing markedly higher apical (AP)-to-basolateral (BL) compared to BL-to-AP transport and inhibition by a 100-fold excess taurocholic acid. Another conjugate with 6 amino acids (ChEASASA) was transported by a passive diffusion pathway but still showed higher transport rates than the passive permeability marker mannitol, suggesting the possibility that the cholic acid moiety aids the passive membrane transfer of peptide molecules by increasing its lipophilicity. Metabolism of bile acid-peptide conjugates in CaCo-2 cells was 3% over 3 h. In conclusion, these studies show that the coupling of peptides to the 24-position of the sterol nucleus in cholic acid results in a combination of decreased metabolism and increased intestinal absorption, either by a carrier-mediated pathway or by accelerated passive diffusion.
Use of Antibiotic-Loaded Polymethyl Methacrylate Beads in the Management of Musculoskeletal Sepsis — A Retrospective Study (2003)

In chronic infections, especially those following osteosynthesis, antibiotic beads are a valuable adjuvant. The most valuable advantage is that the wound can be closed primarily, thereby reducing the incidence of nosocomial infections and requirement of nursing care.
A long-period grating refractometer: measurements of refractive index sensitivity (2004)

We report the development and demonstration of a long-period grating refractometer. The principle of operation is based on in the use of a long-period grating that is structurally induced by a CO/sub 2/ laser, and where the resonance wavelengths are shifted by the refractive index of the medium surrounding the cladding of the long-period grating. The different concentrations for three types of solutions (ethylene glycol, salt, and sugar) were experimentally measured, and results show that, as a refractometer, this fiber-based device can not only differentiate chemicals based on their refractive index, but it can also become a concentration indicator of a particular chemical solution, and applied in the oil and petroleum industry.
Progress with Proteome Projects: Why all Proteins Expressed by a Genome Should be Identified and How To Do It (1996)

(1996). Progress with Proteome Projects: Why all Proteins Expressed by a Genome Should be Identified and How To Do It. Biotechnology and Genetic Engineering Reviews: Vol. 13, No. 1, pp. 19-50.
Extension of yeast artificial chromosomes by cosmid multimers (1993)

Journal Article Extension of yeast artificial chromosomes by cosmid multimers Get access Nicholas P. Davies, Nicholas P. Davies AFRC, Institute of Animal Physiology and Genetics ResearchBabraham, Cambridge CB2 4AT, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Marianne Brüggemann Marianne Brüggemann * AFRC, Institute of Animal Physiology and Genetics ResearchBabraham, Cambridge CB2 4AT, UK * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 21, Issue 3, 11 February 1993, Pages 767–768, https://doi.org/10.1093/nar/21.3.767 Published: 11 February 1993 Article history Received: 12 November 1992 Revision received: 10 January 1993 Accepted: 10 January 1993 Published: 11 February 1993
Prevention ofPorphyromonas gingivalis-Induced Oral Bone Loss following Immunization with Gingipain R1 (2001)

The arginine gingipains RgpA and RgpB of Porphyromonas gingivalis are well-documented virulence factors of this organism. Structurally, RgpA and RgpB have nearly identical catalytic domains, while RgpA possesses an additional hemagglutinin domain. In this study, we examined the abilities of these proteins to elicit protection against P. gingivalis-mediated oral bone loss in a murine oral challenge model. Mice immunized subcutaneously with heat-killed P. gingivalis or purified RgpA or RgpB possessed elevated levels of P. gingivalis-specific immunoglobulin G; however, only the animals immunized with P. gingivalis whole cells or RgpA were protected from maxillary bone loss. These data suggest that immunization with RgpA stimulates the production of hemagglutinin domain-specific antibodies, which contribute to the prevention of P. gingivalis-mediated periodontal disease.
A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. (2000)

The microbially derived antiproliferative agent rapamycin inhibits cell growth by interfering with the signaling functions of the mammalian target of rapamycin (mTOR). In this study, we demonstrate that interleukin-3 stimulation induces a wortmannin-sensitive increase in mTOR kinase activity in a myeloid progenitor cell line. The involvement of phosphoinositide 3'-kinase (PI3K) in the regulation of mTOR activity was further suggested by findings that mTOR was phosphorylated in vitro and in vivo by the PI3K-regulated protein kinase, AKT/PKB. Although AKT phosphorylated mTOR at two COOH-terminal sites (Thr2446 and Ser2448) in vitro, Ser2448 was the major phosphorylation site in insulin-stimulated or -activated AKT-expressing human embryonic kidney cells. Transient transfection assays with mTOR mutants bearing Ala substitutions at Ser2448 and/or Thr2446 indicated that AKT-dependent mTOR phosphorylation was not essential for either PHAS-I phosphorylation or p70S6K activation in HEK cells. However, a deletion of amino acids 2430-2450 in mTOR, which includes the potential AKT phosphorylation sites, significantly increased both the basal protein kinase activity and in vivo signaling functions of mTOR. These results demonstrate that mTOR is a direct target of the PI3K-AKT signaling pathway in mitogen-stimulated cells, and that the identified AKT phosphorylation sites are nested within a "repressor domain" that negatively regulates the catalytic activity of mTOR. Furthermore, the activation status of the PI3K-AKT pathway in cancer cells may be an important determinant of cellular sensitivity to the cytostatic effect of rapamycin.
Binding and activation of the promoter for the neural cell adhesion molecule by Pax-8. (1994)

The neural cell adhesion molecule (N-CAM), is expressed in definite spatiotemporal patterns during development. To identify factors that may influence place-dependent n-cam gene expression, we have studied the binding and activation of the n-cam promoter by Pax-8, a member of the Pax family of transcription factors. Pax-8 increased n-cam promoter activity 13.4-fold in cellular co-transfection experiments, and a short segment of the promoter (-143 to -15) mediated the response. This region of the n-cam promoter produced a DNA-protein complex when incubated with either extracts from COS-7 cells transfected with the Pax-8 expression vector or a Pax-8/GST fusion protein. Pax-8 bound to the n-cam promoter through two TGCTCC motifs (designated PBS-1 and PBS-2) that resemble paired domain binding sites. Mutation of PBS-1 and PBS-2 eliminated Pax-8 activation of the n-cam promoter. Transfection of N2A neuroblastoma cells with the Pax-8 expression vector resulted in a 5-fold increase in the transcription of the endogenous n-cam gene. The combined results suggest that Pax-8 activates transcription of the n-cam gene through binding of sequences resembling paired domain binding sites in the n-cam promoter. The data raise the possibility that the n-cam promoter may be regulated by other members of the Pax gene family.
Three‐Dimensional Catheter Positioning During Radiofrequency Ablation in Patients: First Application of a Real‐Time Position Management System (2000)

The new 3D real-time position management system facilitated RFCA procedures as it allowed accurate and reproducible 3D tracking of the mapping and ablation catheter.
Isolation of cDNA clones encoding protein kinase C: evidence for a protein kinase C-related gene family. (1987)

We have isolated cDNA clones encoding protein kinase C by using a 53-base-pair synthetic oligonucleotide probe corresponding to a peptide that we obtained from the rat brain enzyme. We also have isolated several closely related clones using the same oligonucleotide probe. Nucleotide sequence analysis of one of the protein kinase C clones, RP41, identifies a 224-amino-acid carboxyl-terminal region with approximately equal to 40% homology to the carboxyl-terminal catalytic domains of both the cAMP-dependent and cGMP-dependent protein kinases. The levels of mRNA homologous to RP41 are very high in brain, whereas much lower levels are present in heart and liver. Nucleotide sequence analysis of a second cDNA clone, RP16, identifies a deduced amino acid sequence that shares 65% homology with the corresponding region of the protein kinase C clone RP41. The levels of mRNA corresponding to RP16 are also high in rat brain, but the transcript sizes and tissue-specific expression patterns differ from those of RP41. These and additional results provide evidence that the gene encoding protein kinase C is a member of a novel serine/threonine protein kinase multigene family.
A theory of locally low dimensional light transport (2007)

Blockwise or Clustered Principal Component Analysis (CPCA) is commonly used to achieve real-time rendering of shadows and glossy reflections with precomputed radiance transfer (PRT). The vertices or pixels are partitioned into smaller coherent regions, and light transport in each region is approximated by a locally low-dimensional subspace using PCA. Many earlier techniques such as surface light field and reflectance field compression use a similar paradigm. However, there has been no clear theoretical understanding of how light transport dimensionality increases with local patch size, nor of the optimal block size or number of clusters. In this paper, we develop a theory of locally low dimensional light transport, by using Szego's eigenvalue theorem to analytically derive the eigenvalues of the covariance matrix for canonical cases. We show mathematically that for symmetric patches of area A , the number of basis functions for glossy reflections increases linearly with A , while for simple cast shadows, it often increases as √ A . These results are confirmed numerically on a number of test scenes. Next, we carry out an analysis of the cost of rendering, trading off local dimensionality and the number of patches, deriving an optimal block size. Based on this analysis, we provide useful practical insights for setting parameters in CPCA and also derive a new adaptive subdivision algorithm. Moreover, we show that rendering time scales sub-linearly with the resolution of the image, allowing for interactive all-frequency relighting of 1024 x 1024 images.
OUTROS OLHARES GEOGRÁFICOS (UM ESTUDO COM APRENDIZAGENS GEOGRAFICAS DE ALUNOS PORTADORES DE DEFICIÊNCIAS VISUAIS) (2011)

Demonstra os variados tipos de deficiência visuais existentes, desde a baixa visão, até a cegueira, classificando cada uma delas. Propõe o uso de oficinas pedagógicas para o aprimoramento do processo de ensino-aprendizagem de alunos deficientes visuais, melhorando a prática pedagógica de professores com pouca experiência e dando acesso a educação de direito aos deficientes visuais. Diagnostica, através de entrevistas, os problemas enfrentados por instituições que dão suporte aos deficientes visuais, bem como as dificuldades enfrentadas pelos mesmos no ensino de Geografia. Desenvolve uma oficina pedagógica, baseada nas dificuldades diagnosticadas em entrevistas realizadas com deficientes visuais. Produz recursos didáticos – mapa e globo tátil – com materiais diferenciados (miçangas, tecidos, papéis importados), a fim de levar aos deficientes visuais a compreensão de localização, sendo esta, uma iniciação cartográfica de que eles tanto urgem. Conclui que as dificuldades enfrentadas pelos deficientes visuais nas escolas de ensino regular são muitas e que há falta de formação para os profissionais que se relacionam com esses indivíduos.
Polymer Vesicles (2002)

Vesicles are microscopic sacs that enclose a volume with a molecularly thin membrane. The membranes are generally self-directed assemblies of amphiphilic molecules with a dual hydrophilic-hydrophobic character. Biological amphiphiles form vesicles central to cell function and are principally lipids of molecular weight less than 1 kilodalton. Block copolymers that mimic lipid amphiphilicity can also self-assemble into vesicles in dilute solution, but polymer molecular weights can be orders of magnitude greater than those of lipids. Structural features of vesicles, as well as properties including stability, fluidity, and intermembrane dynamics, are greatly influenced by characteristics of the polymers. Future applications of polymer vesicles will rely on exploiting unique property-performance relations, but results to date already underscore the fact that biologically derived vesicles are but a small subset of what is physically and chemically possible.
Differential Interactions of FGFs with Heparan Sulfate Control Gradient Formation and Branching Morphogenesis (2009)

The developmental activities of morphogens depend on the gradients that they form in the extracellular matrix. Here, we show that differences in the binding of fibroblast growth factor 7 (FGF7) and FGF10 to heparan sulfate (HS) underlie the formation of different gradients that dictate distinct activities during branching morphogenesis. Reducing the binding affinity of FGF10 for HS by mutating a single residue in its HS-binding pocket converted FGF10 into a functional mimic of FGF7 with respect to gradient formation and regulation of branching morphogenesis. In particular, the mutant form of FGF10 caused lacrimal and salivary gland epithelium buds to branch rather than to elongate. In contrast, mutations that reduced the affinity of the FGF10 for its receptor affected the extent, but not the nature, of the response. Our data may provide a general model for understanding how binding to HS regulates other morphogenetic gradients.
Eu5In2Sb6, Eu5In2–xZnxSb6: rare earth zintl phases with narrow band gaps (2002)

The new Zintl phase Eu5In2Sb6 was obtained from a direct element combination reaction in a sealed graphite tube at 870 °C and its structure was determined. It crystallizes in the orthorhombic space group Pbam(No. 55), with a unit cell of a = 12.510(3) Å, b = 14.584(3) Å, c = 4.6243(9) Å, and Z = 2. Eu5In2Sb6 shows the Ca5Ga2As6–type structure and has a one-dimensional structure with infinite anionic double chains [In2Sb6]10− separated by Eu2+ ions. Each single chain is made of corner sharing InSb4 tetrahedra. Two such tetrahedral chains are bridged by a Sb2 group to form double chains. The compound satisfies the classical Zintl concept and is a narrow band gap semiconductor. The substitution of Zn for In atoms in Eu5In2Sb6 resulted in an increase in hole concentration and the material is more metallic. Polycrystalline ingots of Eu5In2Sb6 and Eu5In2−xZnxSb6 showed electrical conductivity of ∼36 S cm−1, ∼146 S cm−1 and Seebeck coefficient of ∼76 µV K−1and ∼51 µV K−1 at room temperature, respectively.
Electric‐Field‐Responsive Handle for Large‐Area Orientation of Discotic Liquid‐Crystalline Molecules in Millimeter‐Thick Films (2011)

Unter Strom gesetzt: Eine auf elektrische Felder reagierende Steuereinheit (siehe Bild), die bei großflächiger und millimeterdicker unidirektionaler Orientierung columnar organisierter π-konjugierter flüssigkristalliner Moleküle funktioniert, wurde entwickelt. In den Säulen sind die Einheiten über Wasserstoffbrücken miteinander verbunden und ordnen sich entlang der Richtung des angelegten elektrischen Felds.
Fast Kinetic Studies by Fluorescence Correlation Spectroscopy of Pna-Dna Interactions (1997)

Abstract The kinetics of the hybridization of fluorescently labeled Peptide nucleic acid (PNA) with its complementary single strand DNA templates and strand displacement from the same DNA duplexed with its 18-nucleotide(nt) long sequencing primer was measured. We used M13mp18(+)ssDNA as template and the PNA molecule was 18-nt long with the identical sequence as to that of the sequencing primer of the DNA template. Kinetic studies show that hybridization was approximately 100-fold faster than the oligonucleotide-displacement at room temperature.