gebhart/patrepeval huggingface dataset:
Entwicklungstheorien der Religiosität als Determinanten des Religionsunterrichts: Exemplifiziert an der Parabel von den Arbeitern im Weinberg (Mt 20, 1–16) (1992)

Wenn ein Religionsoder Bibellehrer die Parabel von den Arbeitern im Weinberg (Mt 20, 1-16) behandeln und dabei den Anforderungen der didakti schen Analyse von Klafki und Schulz/Heimann einigermasen genugen will (vgl. die bundige Darstellung bei Fox 1986, 154f.), wird er sich an erster Stelle uberlegen mussen, welche Ziele er erreichen will. Mit ziemlicher Wahrschein lichkeit wohl auch dieses: „Der Schuler lernt, das Gott unendlich mehr schenkt als gerechten Lohn, wie es stellvertretend fur andere Lothar Knecht (1980, 89) formulierte. Damit hat er eine weitere Frage bereits beantwortet, die von der didaktischen Analyse aufgegeben wird: Inwieweit ist der Unterrichtsinhalt exemplarisch? Bereits Julicher (1910, II, 471) hatte in seinem zweibandigen Klassiker „Die Gleichnisreden Jesu formuliert, Mt 20, 1-16 sei ein „evange lium in nuce, das „blos von der Geberfreudigkeit Gottes handelt. In Entspre chung dazu wird der Religionslehrer auch die Strukturanalyse des Unterrichts inhalts durchfuhren. Sofern er das geschilderte Lernziel erreichen will, kann er die Parabel nicht im Sinne des Evangelisten Matthaus auslegen, wonach sie in erster Linie eine Warnung an die Junger bzw. Mitarbeiter in den urchristlichen Gemeinden sei, nicht die ersten sein zu wollen, sondern in erster Linie zu dienen (Schweitzer 1986, 257f.). Vielmehr wird er etwa im Anschlus an den bekann ten Gleichnishermeneuten Wolfgang Harnisch (1985,177-200) die Parabel als „Erscheinen der Liebe interpretieren. Mit genau diesen Uberlegungen und Zielsetzungen versuchte der Autor vor Jahren, mit Sechstklaslern Mt 20, 1-16 zu behandeln. Trotz methodischer Orchestrierung (Rollenspiel, Gruppenund schlieslich Klassendiskussion) en dete die Stunde in einem Fiasko. Der Lehrer verlies die Schuler im Wissen darum, das sie die Parabel dahingehend auslegten, sie sei ein Beispiel nicht da fur, wie Gott handle, sondern vielmehr dafur, wie er nicht handle. In der Retrospektive entpuppte sich dieses Debakel aber als ein heilsames Schlusselerlebnis. In drastischer Anschaulichkeit zeigte es, das ein hauptsachli cher Mangel der didaktischen Analyse darin gesehen werden mus, nicht hinrei chend in Rechnung zu stellen, das es die Struktur eines Inhalts nicht gibt. Zwar fordert sie, bezuglich der Inhalte zu fragen: „Gibt es verschiedene Sinnund
The molecular determinants of CD8 co‐receptor function (2012)

CD8(+) T cells respond to signals mediated through a specific interaction between the T-cell receptor (TCR) and a composite antigen in the form of an epitopic peptide bound between the polymorphic α1 and α2 helices of an MHC class I (MHCI) molecule. The CD8 glycoprotein 'co-receives' antigen by binding to an invariant region of the MHCI molecule and can enhance ligand recognition by up to 1 million-fold. In recent years, a number of structural and biophysical investigations have shed light on the role of the CD8 co-receptor during T-cell antigen recognition. Here, we provide a collated resource for these data, and discuss how the structural and biophysical parameters governing CD8 co-receptor function further our understanding of T-cell cross-reactivity and the productive engagement of low-affinity antigenic ligands.
Herpesvirus Entry Mediator, a Member of the Tumor Necrosis Factor Receptor (TNFR) Family, Interacts with Members of the TNFR-associated Factor Family and Activates the Transcription Factors NF-κB and AP-1 (1997)

The mammalian tumor necrosis factor receptor (TNFR) family consists of 10 cell-surface proteins that regulate development and homeostasis of the immune system. Based on an expressed sequence tag, we have cloned a cDNA encoding a novel member of the human TNFR family. A closely related protein, designated HVEM (for herpesvirus entry mediator), was identified independently by another group as a mediator of herpesvirus entry into mammalian cells (Montgomery, R., Warner, M., Lum, B., and Spear, P. (1996) Cell 87, 427-436). HVEM differed from our clone by two amino acid residues, suggesting that the two proteins represent polymorphism of a single HVEM gene. We detected HVEM mRNA expression in several human fetal and adult tissues, although the predominant sites of expression were lymphocyte-rich tissues such as adult spleen and peripheral blood leukocytes. The cytoplasmic region of HVEM bound to several members of the TNFR-associated factor (TRAF) family, namely TRAF1, TRAF2, TRAF3, and TRAF5, but not to TRAF6. Transient transfection of HVEM into human 293 cells caused marked activation of nuclear factor-kappaB (NF-kappaB), a transcriptional regulator of multiple immunomodulatory and inflammatory genes. HVEM transfection induced also marked activation of Jun N-terminal kinase, and of the Jun-containing transcription factor AP-1, a regulator of cellular stress-response genes. These results suggest that HVEM is linked via TRAFs to signal transduction pathways that activate the immune response.
Cloning of Two Novel Mammalian Paralogs of Relaxin/Insulin Family Proteins and Their Expression in Testis and Kidney (1999)

Based on sequence homology to insulin and relaxin, we have isolated two novel genes of the insulin superfamily from mouse tissues. Because these proteins show a high similarity to relaxin and relaxin-like factor (RLF or Ley I-L), they were named as RIF1 (relaxin/insulin-like factor 1) and RIF2 (relaxin/insulin-like factor 2). After RT-PCR, full-length cDNAs of RIF1 and RIF2 were obtained from mouse testis and ovary, respectively. In addition, a putative human ortholog of RIF1 was isolated from human testis. The deduced coding regions of mRIF1, mRIF2, and hRIF1 were 191, 145, and 213 amino acids, respectively, and all three proteins contain a typical signal sequence for secretion at their amino terminus. Sequence comparison indicated that RIFs encode proteins consisting of B and A subunits connected by a long C domain peptide, and the deduced mature proteins of these putative ligands are most closely related to relaxin, RLF, and insulin from different species. Northern blot analysis showed that RIF1 transcripts are approximately 1.2 kb in size and are expressed mainly in testis of mouse and human. In contrast, RIF2 message of 2.0 and 1.2 kb are preferentially expressed in mouse kidney and are lower in testis, heart, and brain. In addition, immunohistochemical analysis showed that testis expression of RIF1 is restricted to interstitial cells surrounding seminiferous tubules. In kidney, the RIF2 message is localized to selected epithelial cells of loop of Henle. The exclusive expression pattern of RIF1 and related RLF in testis interstitial cells suggested potential physiological roles of these two distinct insulin/relaxin family ligands in testis function. Additionally, the spatial expression pattern of RIF2 suggests a novel role of RIF2 in nephrophysiology. Identification of RIF polypeptides expands the family of relaxin- and insulin-like hormones and allows future elucidation of the physiological role and hormonal mechanisms for these tissue-specific factors.
Protein–protein interactions as targets for small molecule drug discovery (2006)

Protein-protein interactions represent a highly populated class of targets for drug discovery. However, such systems present a number of unique challenges. This review presents an analysis of individual protein-protein interaction systems which have recently yielded success in discovering drug-like inhibitors. The structural characteristics of the protein binding sites and the attributes of the small molecule ligands are focused upon, in an attempt to derive commonly shared principles that may be of general usefulness in future drug discovery efforts within this target class.
Peptide-Catalyzed Conversion of Racemic Oxazol-5(4H)-ones into Enantiomerically Enriched α-Amino Acid Derivatives (2014)

We report the development and optimization of a tetrapeptide that catalyzes the methanolytic dynamic kinetic resolution of oxazol-5(4H)-ones (azlactones) with high levels of enantioinduction. Oxazolones possessing benzylic-type substituents were found to perform better than others, providing methyl ester products in 88:12 to 98:2 er. The mechanism of this peptide-catalyzed process was investigated through truncation studies and competition experiments. High-field NOESY analysis was performed to elucidate the solution-phase structure of the peptide, and we present a plausible model for catalysis.
A Mitogen-activated Protein Kinase Pathway Is Required for μ-Opioid Receptor Desensitization (1998)

The mu-opioid receptor mediates not only the beneficial painkilling effects of opiates like morphine but also the detrimental effects of chronic exposure such as tolerance and dependence. Different studies have linked tolerance to opioid receptor desensitization. Agonist activation of the mu-opioid receptor stimulates a mitogen-activated protein kinase (MAPK) activity, but the functional significance of this pathway remains unclear. We have focused on the MAPK signaling cascade to study mu-opioid receptor desensitization. We report that inhibition of the MAPK pathway blocks desensitization of mu-opioid receptor signaling as well as the loss of receptor density due to internalization. Our results suggest that a feedback signal emanating from the MAPK cascade is required for mu-opioid receptor desensitization.
p27Kip1 links cell proliferation to morphogenesis in the developing organ of Corti (1999)

Strict control of cellular proliferation is required to shape the complex structures of the developing embryo. The organ of Corti, the auditory neuroepithelium of the inner ear in mammals, consists of two types of terminally differentiated mechanosensory hair cells and at least four types of supporting cells arrayed precisely along the length of the spiral cochlea. In mice, the progenitors of greater than 80% of both hair cells and supporting cells undergo their terminal division between embryonic day 13 (E13) and E14. As in humans, these cells persist in a non-proliferative state throughout the adult life of the animal. Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. p27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells. In wild-type animals, p27(Kip1) expression is downregulated during subsequent hair cell differentiation, but it persists at high levels in differentiated supporting cells of the mature organ of Corti. In mice with a targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell progenitors continues after E14, leading to the appearance of supernumerary hair cells and supporting cells. In the absence of p27(Kip1), mitotically active cells are still observed in the organ of Corti of postnatal day 6 animals, suggesting that the persistence of p27(Kip1) expression in mature supporting cells may contribute to the maintenance of quiescence in this tissue and, possibly, to its inability to regenerate. Homozygous mutant mice are severely hearing impaired. Thus, p27(Kip1) provides a link between developmental control of cell proliferation and the morphological development of the inner ear.
Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside—a Comprehensive Review (2015)

Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.
Enantioselective Copper‐Catalyzed Propargylic Etherification of Propargylic Esters with Phenols Promoted by Inorganic Base Additives (2016)

Abstract An enantioselective copper‐catalyzed propargylic etherification of both aromatic and aliphatic propargylic esters with phenols has been developed, in which the employment of inorganic base additives, in particular cesium carbonate (Cs 2 CO 3 ), was found to significantly promote not only the reactivity but also the enantioselectivity of the reaction. By using a structurally hindered chiral ketimine P,N,N‐ligand, a wide range of optically active propargylic ethers were prepared in high yields and with excellent enantioselectivities (up to 98% ee ). magnified image
Integrin alpha IIb beta 3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. (1993)

Lyme disease is a chronic, multisystemic infection caused by the tick-borne spirochete Borrelia burgdorferi. Attachment of the spirochete to host cells via specific receptors is likely to be important in the establishment of infection. B. burgdorferi have previously been shown to bind to a variety of mammalian cells in vitro. Here we demonstrate that binding of B. burgdorferi to human platelets is mediated by the integrin alpha IIb beta 3 (glycoprotein IIb-IIIa), a critical receptor in thrombosis and hemostasis. Functional expression of this receptor requires platelet activation, and binding of the spirochete was observed only to activated platelets. Binding was inhibited by a synthetic Arg-Gly-Asp peptide that blocks ligand interaction with many integrins and by a synthetic peptide based on the gamma chain of fibrinogen that blocks binding to alpha IIb beta 3. In addition, attachment of the spirochete to platelets was inhibited by monoclonal antibodies directed against alpha IIb beta 3 that are known to block ligand-receptor interaction. No inhibition was seen with control peptides or with antibodies directed against other platelet receptors. B. burgdorferi bound efficiently to purified alpha IIb beta 3 but did not bind to platelets deficient in this integrin. Efficient platelet binding was displayed by a cloned, infectious B. burgdorferi strain, whereas a cloned noninfectious strain did not bind to platelets. Binding to integrins may be important for the ability of B. burgdorferi to establish infection in the diverse tissues affected by Lyme disease.
Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat) (1998)

Alteration in cytoskeletal organization appears to underlie mechanisms of gravity sensitivity in space-flown cells. Human T lymphoblastoid cells (Jurkat) were flown on the Space Shuttle to test the hypothesis that growth responsiveness is associated with microtubule anomalies and mediated by apoptosis. Cell growth was stimulated in microgravity by increasing serum concentration. After 4 and 48 h, cells filtered from medium were fixed with formalin. Post-flight, confocal microscopy revealed diffuse, shortened microtubules extending from poorly defined microtubule organizing centers (MTOCs). In comparable ground controls, discrete microtubule filaments radiated from organized MTOCs and branched toward the cell membrane. At 4 h, 30% of flown, compared to 17% of ground, cells showed DNA condensation characteristic of apoptosis. Time-dependent increase of the apoptosis-associated Fas/ APO-1 protein in static flown, but not the in-flight 1 g centrifuged or ground controls, confirmed microgravity-associated apoptosis. By 48 h, ground cultures had increased by 40%. Flown populations did not increase, though some cells were cycling and actively metabolizing glucose. We conclude that cytoskeletal alteration, growth retardation, and metabolic changes in space-flown lymphocytes are concomitant with increased apoptosis and time-dependent elevation of Fas/APO-1 protein. We suggest that reduced growth response in lymphocytes during spaceflight is linked to apoptosis.
γ‐Purothionins: amino acid sequence of two polypeptides of a new family of thionins from wheat endosperm (1990)

Two homologous sulfur-rich basic polypeptides form wheat endosperm, so-called gamma 1-purothionin and gamma 2-purothionin, are described. Purification involves extraction with volatile solvents and ammonium bicarbonate fractionation followed by reversed-phase high-performance liquid chromatography. The complete primary structure of these two polypeptides has been determined by automatic degradation of the intact, S-carboxymethylated gamma-purothionins and peptides obtained by enzymatic cleavage. gamma 1-Purothionin and gamma 2-purothionnin consist of 47 amino acids with an molecular weight of 5239 and 5151 Da, respectively and 8 cysteines organized in 4 disulfide bridges. They present a high degree of homology among themselves (89% of identity) and are the first two thionin-like polypeptides, so-called gamma-thionins, described from wheat endosperm.
Liver-Specific igf-1 Gene Deletion Leads to Muscle Insulin Insensitivity (2001)

Insulin and insulin-like growth factors (IGFs) mediate a variety of signals involved in mammalian development and metabolism. To study the metabolic consequences of IGF-I deficiency, we used the liver IGF-I-deficient (LID) mouse model. The LID mice show a marked reduction (approximately 75%) in circulating IGF-I and elevated growth hormone (GH) levels. Interestingly, LID mice show a fourfold increase in serum insulin levels (2.2 vs. 0.6 ng/ml in control mice) and abnormal glucose clearance after insulin injection. Fasting blood glucose levels and those after a glucose tolerance test were similar between the LID mice and their control littermates. Thus, the high levels of circulating insulin enable the LID mice to maintain normoglycemia in the presence of apparent insulin insensitivity. Insulin-induced autophosphorylation of the insulin receptor and tyrosine phosphorylation of insulin receptor substrate (IRS)-1 were absent in muscle, but were normal in liver and white adipose tissue of the LID mice. In contrast, IGF-I-induced autophosphorylation of its cognate receptor and phosphorylation of IRS-1 were normal in muscle of LID mice. Thus, the insulin insensitivity seen in the LID mice is muscle specific. Recombinant human IGF-I treatment of the LID mice caused a reduction in insulin levels and an increase in insulin sensitivity. Treatment of the LID mice with GH-releasing hormone antagonist, which reduces GH levels, also increased insulin sensitivity. These data provide evidence of the role of circulating IGF-I as an important component of overall insulin action in peripheral tissues.
Frequent p53 mutations in chemically induced murine fibrosarcoma. (1991)

Patterns of p53 expression were investigated in chemically induced fibrosarcoma tumors and cell lines. Most, if not all, cell lines were found to carry alterations at the protein level, reflected in the overproduction of greatly stabilized p53 proteins. In many cases, this was accompanied by formation of complexes with hsc70. Hence, all of these lines may be expressing one sort or another of mutant p53. The mutant nature of the p53 gene was directly verified, in a number of cases, by PCR-amplified cDNA cloning. In one line, no p53 protein was made at all; this turned out to be because of a mutation in a splice donor site, resulting in the production of an aberrant mRNA. In all other cases, mRNAs carrying mis-sense mutations were present, and were sometimes expressed along with wt p53 mRNA. When tested in an in vitro transformation assay, all cloned mutants possessed a discrete oncogenic activity, while having lost the ability to interfere with oncogene-mediated transformation. The system described here could potentially be very helpful in elucidating the significance of p53 mutations.
Self-Adjusted, Three-Dimensional Lattice-Matched Buffer Layer for Growing ZnO Epitaxial Film:  Homologous Series Layered Oxide, InGaO3(ZnO)5 (2006)

Effects of a lattice-matched buffer layer on growth, structure, and transport properties of ZnO thin films were examined using a homologous series layered compound, InGaO3(ZnO)5 (IGZO5). High-quality single-crystalline IGZO5 layers were fabricated on yttria-stabilized zirconia (YSZ) (111) substrates by reactive solid-phase epitaxy. ZnO layers deposited on the IGZO5 buffer layers showed smooth and uniform surface morphologies compared to those deposited on YSZ (111) without the IGZO5 buffer layer. Then postgrowth annealing was examined to convert the ZnO surface to an atomically flat surface. When the IGZO5 buffer layer was used, the annealing temperature was reduced from 1000 to 700 °C, which was attributable to the smooth surface morphology and good lattice matching of the buffer layer. The annealed films exhibited rather large Hall mobilities 73−82 cm2 (Vs)-1, which are larger than those reported for epitaxial ZnO films fabricated at similar temperatures with similar thicknesses. Cross-sectional high-resolution transmission electron microscopy revealed that the step height of the IGZO5 buffer layer is automatically adjusted to the c-axis period of the ZnO crystal lattice. The present findings demonstrate the IGZO5 layer works as a three-dimensional lattice-matching substrate for ZnO.
Synthesis and Evaluation of the β‐Turn Properties of 4‐Amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐ones and of Their Spirocyclic Derivative (2006)

Abstract A series of 4‐amino‐tetrahydro‐2‐benzazepin‐3‐one derivatives (Ac–Aba–Xxx–NHMe) were prepared as tetrapeptide mimetics. Considering the structural resemblance with the so‐called Freidinger lactams, their propensity to adopt a β‐turn conformation was investigated by NMR spectroscopy (solvent and temperature dependence) and molecular modeling. Interestingly, most of these lactams adopt extended conformations, only the spiro‐benzazepinone 9 has a strong preference for the formation of a β‐turn. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
Investigation of Deep UV Resists by NMR. Residual Casting Solvents, Chemistries, and PAG Decomposition in Film. (1999)

Inverse gated 1H-decoupled carbon-13 nuclear magnetic resonance (NMR) spectroscopy has been employed in the investigation of ESCAP-related deep UV resist films. The concentrations of residual casting solvents were determined as a function of the bake temperature and of storage conditions. In addition to quantification of deprotection, side reactions such as C- and O-alkylation of the phenol unit in the resist film were quantitatively analyzed while varying the exposure dose, bake temperature, resin structure, and acid generator. Furthermore, photochemical decomposition of several acid generators in the resist film was monitored in a quantitative fashion. This paper demonstrates that the 13C NMR technique can provide a wealth of quantitative and indispensable information about constituents and chemistries in resist films.