gebhart/patrepeval huggingface dataset:
Coordination-Driven Self-Assembly:  Solids with Bidirectional Porosity (2002)

Coordination-driven self-assembly reactions have been used in the preparation of a variety of discrete supramolecular species, some of which have shown promise as synthetic receptors. Many highly ordered coordination polymers and porous networks have been prepared in a similar fashion. While a few of these solids are capable of the uptake of small organic molecules in the resultant molecular channels, the formation of truly porous structures has frequently been thwarted by lattice interpenetration. A strategy for the formation of porous solids that may circumvent this problem is based on the covalent construction of nanoscale macrocycles which, when eclipsed in the solid state, may lead to porous, tubular assemblies. We have incorporated these concepts toward the realization of a bidirectionally porous solid. The metal-directed, self-assembly of a conjugated, macrocyclic ligand provides a discrete, supramolecular entity in solution and the solid state. X-ray crystallographic analysis establishes that this assembly packs such that bidirectional channels are realized, and the incorporation of only ClCH2CH2Cl into the crystal lattice demonstrates that these channels are potentially suitable for the selective uptake of small organic guests.
Das „Ambulante Gruppenprogramm zum kontrollierten Trinken (AkT)” (2002)

Das Ambulante Gruppenprogramm zum kontrollierten Trinken (AkT) ist ein seit 1999 erprobtes, manualisiertes verhaltenstherapeutisches und lsungsorientiertes Programm zur Vermittlung von Kompetenzen zur Selbstkontrolle des Trinkverhaltens. Es richtet sich an Menschen mit akuten Alkoholproblemen unterschiedlichen Schweregrades und (zumindest anfnglicher) Ablehnung des Abstinenzziels. Das Akt umfasst 1 2 diagnostische Einzelsitzungen und 10 wchentliche, inhaltlich und didaktisch standardisierte Gruppentermine (max. 14 Teilnehmer) a 2 1 / 4 Stunden, geleitet von ein bis zwei im AkT fortgebildeten Suchtfachkrften. Die Ergebnisse fr die ersten N = 58 AkT-Teilnehmer (Durchschnitt 48 Jahre, 33 % Frauen, 67 % alkoholabhngig [ICD-10]) zeigen eine hohe Zufriedenheit mit den 10 Gruppensitzungen und eine durchschnittliche wchentliche Trinkmengenreduktion von mehr als 50 % (signifikant mehr als in einer Wartekontrollgruppe, p <.001), die auch nach einem Jahr noch nachweisbar ist. Etwa 10 % der Teilnehmer leben abstinent, 47 % befinden sich in Weiterbehandlung (mit dem Ziel der Abstinenz oder des kontrollierten Trinkens). Weitere Programmentwick-
ChemInform Abstract: AGENTS ACTING ON THE CENTRAL NERVOUS SYSTEM‐ PART XXVI. SYNTHESIS OF SOME DIPHENYLPROPYLAMINE AND DIBENZOCYCLOHEPTENYLETHYLAMINE DERIVATIVES (1977)

Abstract Die Hydrierung der ungesättigten Aldehyde (I) bzw. (IV) an Raney‐Ni in Gegenwart der prim. Amine (II) ergibt die Propylamine (III) bzw. die Dibenzocycloheptenylidenäthylamine (V).
Transient up-regulation of P2Y2nucleotide receptor mRNA expression is an immediate early gene response in activated thymocytes (1997)

In studies designed to understand the roles of P2 nucleotide receptors in differentiation of T lymphocytes, we observed a transient and protein synthesis-independent enhancement of mRNA expression for the G protein-coupled P2Y2 receptor in mouse thymocytes after the addition of steroid hormone or T cell receptor (TCR) crosslinking by anti-TCR mAb. Conversely, dexamethasone-induced increases in mRNA expression for the ligand-gated ion channel P2X1 receptor was detected in rat, but not mouse, thymocytes, raising questions about the previously suggested role of P2X1 receptors in thymocyte apoptosis. Flow cytometry analysis of thymocyte subsets excluded the possibility that the observed increases in P2Y2 receptor mRNA expression were due to the enrichment of steroid-treated cells with an P2Y2 mRNA-rich thymocyte subset. Triggering of TCR-mediated intracellular signaling pathways through crosslinking of TCR or by addition of phorbol ester and Ca2+ ionophore also resulted in the up-regulation of P2Y2, but not P2X1, receptor mRNA. It is proposed that the rapid increase of P2Y2 receptor mRNA expression could be a common early event in responses of T cells to different activating stimuli. Taken together with the recently discovered ability of nucleotide receptor-initiated signaling to antagonize or enhance the effects of TCR crosslinking or steroids on thymocytes, the observed rapid up-regulation of P2Y2 receptor mRNA expression may reflect an immediate early gene response where newly expressed cell surface nucleotide receptors provide regulatory feedback signaling from extracellular ATP in the T cell differentiation process.
Error-related potentials during continuous feedback: using EEG to detect errors of different type and severity (2015)

When a person recognizes an error during a task, an error-related potential (ErrP) can be measured as response. It has been shown that ErrPs can be automatically detected in tasks with time-discrete feedback, which is widely applied in the field of Brain-Computer Interfaces (BCIs) for error correction or adaptation. However, there are only a few studies that concentrate on ErrPs during continuous feedback. With this study, we wanted to answer three different questions: (i) Can ErrPs be measured in electroencephalography (EEG) recordings during a task with continuous cursor control? (ii) Can ErrPs be classified using machine learning methods and is it possible to discriminate errors of different origins? (iii) Can we use EEG to detect the severity of an error? To answer these questions, we recorded EEG data from 10 subjects during a video game task and investigated two different types of error (execution error, due to inaccurate feedback; outcome error, due to not achieving the goal of an action). We analyzed the recorded data to show that during the same task, different kinds of error produce different ErrP waveforms and have a different spectral response. This allows us to detect and discriminate errors of different origin in an event-locked manner. By utilizing the error-related spectral response, we show that also a continuous, asynchronous detection of errors is possible. Although the detection of error severity based on EEG was one goal of this study, we did not find any significant influence of the severity on the EEG.
RGD-CAP (βig-h3) Exerts a Negative Regulatory Function on Mineralization in the Human Periodontal Ligament (2002)

In our previous studies, RGD-CAP/betaig-h3 was isolated from a fiber-rich fraction of cartilage and was found to have a negative function on mineralization of hypertrophic chondrocytes. However, the expression and biological function of RGD-CAP in the periodontal ligament (PDL) are not known. We hypothesized that RGD-CAP could be expressed in the PDL and regulate its mineralization. To test this, we investigated the expression of RGD-CAP in human PDL and the effects of RGD-CAP on mineralization of cultured PDL cells. RGD-CAP was detected in the human PDL as multimeric proteins greater than 200 kDa. The RGD-CAP mRNA level decreased in cultured PDL cells exposed to 10(-8) M dexamethasone or 10(-8) M 1alpha,25-dihydroxyvitamin D(3) when these steroids increased alkaline phosphatase (ALP) activity. Furthermore, exogenous RGD-CAP suppressed the ALP activity and bone nodule formation of cultured PDL cells. These findings suggest that RGD-CAP in the PDL modulates the mineralization which affects adjacent alveolar bone metabolism.
Laboratory-based evaluation of a compression-bandaging system. (2003)

Graduate external compression is a key factor in the successful treatment of venous leg ulcers, but can be damaging if used inappropriately. A new type of bandage has been designed to minimise the risk of tissue damage by controlling the amount of tension within the bandage during application. This laboratory study suggests that the bandage meets its design criteria, and highlights the importance of correct application to avoid excessive sub-bandage pressure.
Mannose-Binding Lectin (MBL) Facilitates Opsonophagocytosis of Yeasts but Not of Bacteria despite MBL Binding (2008)

Mannose-binding lectin (MBL) is a serum protein of the innate immune system. After binding to a microorganism, MBL in complex with MBL-associated serine proteases activates the complement system, resulting in cleavage of complement factor C3. Cleaved C3 on the surface of the microorganism mediates opsonization for clearance, but the impact of MBL on subsequent phagocytosis has not been widely studied. We investigated the role of MBL in complement activation and phagocytosis of various bacteria and yeast species by flow cytometry. We measured both the C3 deposition during serum opsonization of fluorescent-labeled microorganisms as well as subsequent uptake of these microorganisms by human neutrophils. In MBL-deficient sera, a consistently decreased C3 deposition on both zymosan and Candida albicans was found and a reduced phagocytosis by neutrophils that was restored by exogenous MBL. This indicates that the lectin pathway of complement activation is important for the opsonophagocytosis of yeasts. In contrast, the C1q-dependent classical pathway dominated in the opsonization and phagocytosis of Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli, whereas no effect of MBL was found. Both the lectin and the classical pathway of complement activation were highly amplified by the alternative route for opsonophagocytosis by neutrophils of yeast as well as microbial species. In summary, our data demonstrate that yeast species are preferentially opsonized and subsequently phagocytosed via activation of the lectin pathway of complement, whereas the uptake of bacterial strains was found to be largely MBL independent.
Dilazep Hydrochloride, an Antiplatelet Drug, Inhibits Lipopolysaccharide-Induced Mouse Mesangial Cell IL-6 Secretion and Proliferation (2001)

It appears that these effects of dilazep may prevent progression of mesangial proliferative glomerulonephritis.
Electric‐Field‐Assisted Alignment of Supramolecular Fibers (2006)

Supramolecular fibers possessing an intrinsic large dipole moment can be manipulated with a DC electric field, triggering their alignment in preferred directions on a patterned surface made of Au electrodes supported on an insulating SiOx/Si substrate. The figure shows the electric-field stream lines over the electrodes used to align the nanofibers, calculated using finite element analysis. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2006/c0269_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer. (2003)

2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), the most abundant heterocyclic amine (HCA) in cooked food, is a mammary carcinogen in female rats. In humans, consumption of well-done meat and PhIP intake have been associated with an increased risk of breast cancer, but PhIP-DNA adducts have not been analyzed in breast tissues from women having unknown exposure to HCAs. Using an immunohistochemistry (IHC) method, we measured PhIP-DNA adducts in normal breast tissues of 106 women having newly diagnosed breast cancer in comparison with those of 49 women undergoing reduction mammoplasty. The IHC method was first validated in MCF-7 cells treated with different doses of N-hydroxy-PhIP. We detected significant dose-response relationship and correlation (r=0.94) between the levels of PhIP-DNA adducts detected by IHC and 32P-postlabeling. Using IHC, PhIP-DNA adducts were detected in 82 and 71% of the normal breast tissue sections from the cancer and control patients respectively. The median (range) absorbance was 0.18 (0-0.57) and 0.08 (0-0.38) in the cancer and control patients, respectively (P<0.001). Using the median in the controls as a cutoff point, 71% of the cancer patients and 47% of the controls were distributed in the higher range (chi2=8.17; P=0.004). Logistic regression analysis demonstrated an OR of 4.03 (95% CI, 1.41-11.53) after adjusting for age and ethnicity (P=0.009). Stratified analyses did not find any significant effect of age, ethnicity, smoking, well-done meat consumption, dietary intake of PhIP, or polymorphisms of CYP1A1, CYP1B1, NAT2, and GSTM1 genes on the level of PhIP-DNA adducts. However, a potential interactive effect of well-done meat consumption and NAT2 genotype on the level of PhIP-DNA adducts was observed (P=0.047). This is the first study of detection of PhIP-DNA adducts in breast tissue samples obtained from women having unknown exposure to HCAs. These data strongly support the hypothesis that HCA exposure contributes to human breast cancer among genetically susceptible individuals.
Probing Low Affinity and Multivalent Interactions with Surface Plasmon Resonance:  Ligands for Concanavalin A (1998)

The affinities of the carbohydrate-binding protein concanavalin A (Con A) for mono- and multivalent ligands were measured by surface plasmon resonance (SPR) detection. Assessing protein−carbohydrate affinities is typically difficult due to weak affinities observed and the complications that arise from the importance of multivalency in these interactions. We describe a convenient method to rapidly evaluate the inhibitory constants for a panel of different ligands, both monovalent and multivalent, for low-affinity receptors, such as the carbohydrate-binding protein Con A. A nonnatural, mannose-substituted glycolipid was synthesized, and self-assembled monolayers of varying carbohydrate density were generated. The synthetic surfaces bind Con A. Competition experiments that employed monovalent ligands in solution yielded Ki values similar to equilibrium binding constants obtained in titration microcalorimetry experiments. In addition, this assay could be used to examine various polymeric ligands of defined lengths, generated by ring-opening metathesis polymerization (ROMP). This study demonstrates the utility of this method for rapidly screening ligands that engage in low affinity interactions with their target receptors. Our results emphasize that those molecules that can simultaneously occupy two or more saccharide binding sites within a lectin oligomer are effective inhibitors of protein−carbohydrate interactions.
Molecular Cloning and Characterization of a Novel Human G-protein-coupled Receptor, EDG7, for Lysophosphatidic Acid (1999)

Lysophosphatidic acid (LPA), together with sphingosine 1-phosphate, is a bioactive lipid mediator that acts on G-protein-coupled receptors to evoke multiple cellular responses, including Ca 2 mobilization, modulation of adenylyl cyclase, and mitogen-activated protein (MAP) kinase activation. In this study, we isolated a human cDNA encoding a novel G-protein-coupled receptor, designated EDG7, and characterized it as a cellular receptor for LPA. The amino acid sequence of the EDG7 protein is 53.7 and 48.8% identical to those of the human functional LPA receptors EDG2 and EDG4, respectively, previously identified. LPA (oleoyl) but not other lysophospholipids induced an increase in the [Ca 2 ] i of EDG7-overexpressing Sf9 cells. Other LPA receptors, EDG4 but not EDG2, transduced the Ca 2 response by LPA when expressed in Sf9 cells. LPAs with an unsaturated fatty acid but not with a saturated fatty acid induced an increase in the [Ca 2 ] i of EDG7-expressing Sf9 cells, whereas LPAs with both saturated and unsaturated fatty acids elicited a Ca 2 response in Sf9 cells expressing EDG4. In EDG7-or EDG4-expressing Sf9 cells, LPA stimulated forskolin-induced increase in intracellular cAMP levels, which was not observed in EDG2-expressing cells. In PC12 cells, EDG4 but not EDG2 or EDG7 mediated the activation of MAP kinase by LPA. Neither the EDG7-nor EDG4-transduced Ca 2 response or cAMP accumulation was inhibited by pertussis toxin. In conclusion, the present study demonstrates that EDG7, a new member of the EDG family of G-protein-coupled receptors, is a specific LPA receptor that shows distinct properties from known cloned LPA receptors in ligand specificities, Ca 2 response, modulation of adenylyl cyclase, and MAP kinase activation.
Randomized phase II, three-arm trial of lenvatinib (LEN), everolimus (EVE), and LEN+EVE in patients (pts) with metastatic renal cell carcinoma (mRCC). (2015)

4506 Background: Lenvatinib (LEN), an oral tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, in combination with EVE had manageable toxicity and antitumor activity in a phase 1 mRCC trial (CCP 2013;73:181). This phase II, open-label, multicenter study compared LEN, EVE, and LEN+EVE in pts with mRCC. Methods: Pts with progressive clear cell mRCC following 1 VEGF-targeted therapy were randomized 1:1:1 to LEN (24 mg/d), EVE (10 mg/d), or LEN+EVE (18+5 mg/d) in 28d cycles. The primary objective was progression-free survival (PFS) of LEN+EVE or LEN vs EVE. Secondary objectives included overall survival (OS), objective response rate (ORR), and safety. Primary analysis data cutoff was June 13, 2014. Results: One hundred and fifty-three pts were enrolled: 99% had one prior VEGF-targeted therapy, 1% had two; 18% had prior immunotherapy. LEN+EVE prolonged PFS vs EVE (Table; hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.24–0.68; P < 0.001). LEN alone also prolonged PFS vs EVE (HR 0.61; 95% CI 0.38–0.98; P = 0.048). LEN+EVE and LEN improved ORR vs EVE (P < 0.001 and P = 0.007, respectively). Median duration of response (months) was longest in LEN+EVE, 13.1; LEN, 7.5; EVE, 8.5. OS analysis showed a trend favoring LEN+EVE vs EVE (HR 0.55; 95% CI 0.30–1.01; P = 0.062); this reached significance (HR 0.51; 95% CI 0.30–0.88; P = 0.024) in an updated analysis on Dec 10, 2014. For LEN+EVE, most common any-grade treatment-emergent adverse events (TEAEs) were diarrhea (84%), decreased appetite (51%), and fatigue (47%). Most common grade ≥ 3 TEAEs were diarrhea (20%), hypertension (14%), and fatigue (10%). Conclusions: LEN+EVE improved PFS and ORR versus EVE alone in this phase II trial of pts with mRCC following prior VEGF-targeted therapy. Updated OS also showed improvement with LEN+EVE. A phase III randomized trial of the combination in mRCC is planned. Clinical trial information: NCT01136733. Primary analysis LEN+EVE n = 51 LEN n = 52 EVE n = 50 Median survival, months (95% CI) PFS 14.6 (5.9–20.1) 7.4 (5.6–10.2) 5.5 (3.5–7.1) OS 25.5 (20.8–25.5) 18.4 (13.3–NE) 17.5 (11.8–NE) ORR, n (%) 22 (43) 14 (27) 3 (6) Median duration of response, months (95% CI) 13.1 (3.8–NE) 7.5 (3.8–NE) 8.5 (7.5–9.4) Median # of cycles, (range) 9.0 (1–25) 8.5 (1–25) 5.0 (1–22) NE, not evaluable
Effect of recombinant hematopoietic growth factors on proliferation of human marrow progenitor cells in serum-deprived liquid culture (1988)

We investigated the effects of recombinant interleukin-3 (IL-3), granulocyte-macrophage and granulocyte colony-stimulating factors (GM- CSF and G-CSF), and erythropoietin (Ep) on the number of human hematopoietic progenitors after two to ten days of incubation in liquid cultures deprived of fetal bovine serum (FBS). The source of progenitor cells was normal human marrow depleted of T lymphocytes and/or adherent cells. When adherent cell-depleted marrow was cultured without growth factors, the number of progenitor cells was relatively constant for periods up to eight days. In contrast, a progressive decline in the number of progenitor cells was detected in cultures of nonadherent, T- cell-depleted marrow cells. In both cases, the addition of IL-3 increased by two- to fourfold over input the number of erythroid burst- forming cells (BFU-E) per culture. The number of BFU-E peaked either at day 4 or 8. G-CSF had no effect on the number of progenitor cells per culture. GM-CSF and Ep had no effect in cultures of nonadherent marrow cells but maintained the number of BFU-E in cultures of nonadherent, T- cell-depleted marrow cells. The addition of a neutralizing anti-GM-CSF monoclonal antibody, but not anti-IL-3 neutralizing antiserum, decreased the number of BFU-E in cultures of nonadherent marrow cells. None of the growth factors investigated enhanced the number of GM progenitors to the same degree as the number of BFU-E. However, in cultures of nonadherent, T-cell-depleted marrow cells, IL-3 and GM-CSF maintained the number of GM progenitors up to eight days. These results indicate that IL-3 alone is capable of increasing the number of BFU-E and of maintaining the number of GM progenitors in liquid culture, whereas GM-CSF and Ep are capable of maintaining, but not increasing, BFU-E in this system.
Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis (2003)

In mammals, the continuous production of hematopoietic cells (HCs) is sustained by a small number of hematopoietic stem cells (HSCs) residing in the bone marrow. Early HSC activity arises in the aorta-gonad mesonephros region, within cells localized to the ventral floor of the major blood vessels, suggesting that the first HSCs may be derived from cells capable of giving rise to the hematopoietic system and to the endothelial cells of the vasculature. TIE1 (TIE) and TIE2 (TEK) are related receptor tyrosine kinases with an embryonic expression pattern in endothelial cells, their precursors, and HCs, suggestive of a role in the divergence and function of both lineages. Indeed, gene targeting approaches have shown that TIE1, TIE2, and ligands for TIE2, the angiopoietins, are essential for vascular development and maintenance. To explore possible roles for these receptors in HCs, we have examined the ability of embryonic cells lacking both TIE1 and TIE2 to contribute to developmental and adult hematopoiesis by generating chimeric animals between normal embryonic cells and cells lacking these receptors. We show here that TIE receptors are not required for differentiation and proliferation of definitive hematopoietic lineages in the embryo and fetus; surprisingly, however, these receptors are specifically required during postnatal bone marrow hematopoiesis.
Synthesis of Alcohols from m-Fluorophenylsulfones and Dialkylboranes: Application to the C14–C35 Building Block of E7389 (2012)

The reaction of m-fluorophenylsulfone anions with dialkylboranes, followed by alkaline hydroperoxide oxidation, yields alcohols in high yields. Optimization of the process, scope and limitation, and application to the synthesis of one of the C14-C35 building blocks of E7389, a right half analogue of halichondrin B, are reported.