gebhart/patrepeval huggingface dataset:
An endosperm‐specific DOF protein from barley, highly conserved in wheat, binds to and activates transcription from the prolamin‐box of a native B‐hordein promoter in barley endosperm (1998)

A cDNA encoding a DNA-binding protein of the DOF class of transcription factors was isolated from a barley endosperm library. The deduced amino acid sequence for the corresponding protein is 94% identical through the DOF domain to the prolamin-box (P-box) binding factor PBF from maize. The gene encoding the barley PBF (BPBF) maps to chromosome 7H, and its expression is restricted to the endosperm where it precedes that of the hordein genes. The BPBF expressed in bacteria as a GST-fusion binds a P-box 5'-TGTAAAG-3' containing oligonucleotide derived from the promoter region of an Hor2 gene. Binding was prevented when the P-box motif was mutated to 5'-TGTAgAc-3'. A P-box binding activity, present in barley and wheat endosperm nuclei, interacted similarly to BPBF with this synthetic oligonucleotide, and the binding was abolished by 1,10-phenanthroline. Transient expression experiments in developing barley endosperms demonstrate that BPBF transactivates transcription from the P-box element of a native Hor2 promoter and that direct binding of BPBF to its target site is essential for transactivation since mutations in the DOF DNA-binding domain or in the P-box motif of this promoter abolished both binding and transactivation. Evidence was also obtained for the presence in wheat of a Pbf homologue having similar DNA-binding properties to that of BPBF. These results strongly implicate this endosperm-specific DOF protein from barley as an important activator of hordein gene expression and suggest the evolutionary conservation of the Pbf gene function among small grain cereals.
Molecular Recognition of Carbohydrates by Artificial Polypyridine and Polypyrimidine Receptors (2000)

Despite their acyclic structure, the simple host molecules 1 and 2 can effectively hydrogen bond to monosaccharides. They show marked binding affinities to glucopyranosides in chloroform, and they are able to participate in three-dimensional recognition of monosaccharides.
Papules and plaques, on face and scalp, in an otherwise normal newborn (2006)

A newborn girl with skin eruption involving the face and scalp, and no adenopathy or organomegaly
Advances in the Development of Novel Cobalt Fischer−Tropsch Catalysts for Synthesis of Long-Chain Hydrocarbons and Clean Fuels (2007)

International audience
Abstract 2435: Validation of Cynomolgus monkeys as relevant species for safety assessment of a novel human BiTE antibody platform for cancer therapy (2010)

Abstract Nonclinical safety assessment of biopharmaceuticals for human use relies on their cross-reactivity with the respective target in other species, the absence of which precludes testing in commonly used animal models. This is the case for a first-generation of T cell-engaging BiTE antibodies, which solely cross-react with T cells of chimpanzee. BiTE antibodies are designed to transiently connect the CD3 subunit of T cell receptors on T cells with an antigen on target cells. This can very effectively activate T cells, leading to a potent redirected lysis of target cells. Here, we have generated a series of novel human anti-CD3 antibodies that cross-react with non-human primate species, including Cynomolgus monkeys (Macaca fascicularis) and marmoset (Callithrix jacchus). The variable domains of a selected anti-CD3 antibody were used to generate next-generation BiTE antibodies specific for (1) CD33, a target antigen for treatment of acute myelogenous leukemia, (2) melanoma-associated chondroitin sulfate proteoglycan (MCSP), a potential target for treatment of melanoma, and (3) epidermal growth factor receptor 1 (EGFR), a validated target for treatment of colorectal cancer. In vitro, CD33-, MCSP- and EGFR-specific BiTE antibodies showed comparable binding to CD3 on human and macaque T cells, and to CHO cells expressing CD33, MCSP and EGFR of human or macaque origin. In human and macaque cell-based assays, bispecific binding triggered redirected target cell lysis as well as conditional T cell activation, as previously described for first-generation BiTE antibodies. When continuously infused for one week to Cynomolgus monkeys, the CD33-specific BiTE antibody caused depletion of CD33-expressing peripheral blood cells at tolerated doses, and reached a maximum tolerated dose (MTD) at 120 µg/m2/day. The EGFR-specific BiTE antibody reached an MTD at 150 µg/m2/kg. In contrast, the MCSP-specific BiTE antibody was well-tolerated up to a dose of 5,000 µg/m2/day. Our primate data suggest that the tolerability and toxicity of CD33-, MCSP- and EGFR-specific BiTE antibodies were apparently determined by target cell-dependent bispecific binding, and not by monovalent binding to CD3 on macaque T cells. Our data validate the Cynomolgus monkey as a relevant species for assessing the safety and tolerability of next-generation BiTE antibodies that use a more broadly cross-reactive anti-CD3 human single-chain antibody. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2435.
Physical, structural, and shielding properties of cadmium bismuth borate-based glasses (2020)

We explore a new glassy material for radiation shielding applications. Novel transparent and non-toxic Bi2O3–B2O3 glasses including different concentrations of CdO were prepared by the conventional melt quenching method. The prepared samples were characterized and analyzed by using various analytical tools (XRD, FTIR, Raman, DSC, and UV-Vis-NIR). Ab initio molecular dynamics simulations were carried out to create structural models of the materials, and these were compared to our measurements. To the best of our knowledge, this is the first study to compare the vibrations obtained experimentally with the vibrational density of states obtained from an ab initio computer model for these materials. The radiation shielding properties were measured for the photon energy range (10−3–105 MeV): both mass attenuation coefficient (μ/p) and effective atomic number (Zeff) showed a gradual increase with an increase in the CdO content. The mean-free-path, tenth value layer, half-value layer, and electron density for all prepared glasses were estimated. Promising results were achieved with the new glasses for radiation shielding purposes such as nuclear reactor and medical applications. The structural, electronic, and vibrational properties of the computer models revealed a topologically disordered, but chemically ordered network, and our vibrational computations provide direct insight into several Raman peaks observed for the materials.
Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations (2014)

The leukocyte adhesion cascade is important in chronic lymphocytic leukemia (CLL), as it controls migration of malignant cells into the pro-survival lymph node microenvironment. Circulating trisomy 12 CLL cells have increased expression of the integrins CD11a and CD49d, as well as CD38, but the tissue expression of these and other molecules, and the functional and clinical sequelae of these changes have not been described. Here, we demonstrate that circulating trisomy 12 CLL cells also have increased expression of the integrins CD11b, CD18, CD29, and ITGB7, and the adhesion molecule CD323. Notably, there was reduced expression of CD11a, CD11b, and CD18 in trisomy 12 cases with NOTCH1 mutations compared with wild type. Trisomy 12 cells also exhibit upregulation of intracellular integrin signaling molecules CALDAG-GEFI, RAP1B, and Ras-related protein ligand, resulting in enhanced very late antigen-4 [VLA-4] directed adhesion and motility. CD38 expression in CLL has prognostic significance, but the increased CD38 expression in trisomy 12 CLL cells must be taken into account in this subgroup, and the threshold of CD38 positivity should be raised to 40% for this marker to retain its prognostic value. In conclusion, trisomy 12 CLL cells exhibit functional upregulation of integrin signaling, with β2-integrin expression being modulated by NOTCH1 mutation status.
Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Implications for treatment (1992)

Hypertriglyceridemia is commonly found in patients with coronary heart disease. The reason for this connection, however, is not well understood, and two different views have been put forth to explain the link. First, triglyceriderich lipoproteins, particularly very-low-density lipoproteins, may be directly atherogenic. Or second, the metabolic consequences of hypertriglyceridemia may account for the triglyceride-coronary heart disease relationship. These consequences include an increase in postprandial lipoproteins, large very-low-density lipoprotein particles, small, dense low-density lipoprotein particles, low levels of high-density lipoprotein cholesterol, and possibly a procoagulant state. The appropriate treatment of hypertriglyceridemia depends on which of these views is nearer the truth. If triglyceride-rich lipoproteins are directly atherogenic, then the preferred therapy would be hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors, which lower both very-low-density lipoprotein and low-density lipoprotein levels. On the other hand, if the link to atherogenesis is through the metabolic consequences of hypertriglyceridemia, the appropriate therapy would be to directly lower serum triglyceride levels, as with niacin or a fibric acid. Thus, discovery of the mechanism of the connection between triglycerides and coronary heart disease is crucial for developing a rational therapy. (<i>Arch Intern Med.</i>1992;152:28-34)
Trust online (2000)

article Free Access Share on Trust online Authors: Batya Friedman Univ. of Washington, Seattle Univ. of Washington, SeattleView Profile , Peter H. Khan Univ. of Washington, Seattle Univ. of Washington, SeattleView Profile , Daniel C. Howe Univ. of Washington, Seattle Univ. of Washington, SeattleView Profile Authors Info & Claims Communications of the ACMVolume 43Issue 12Dec. 2000pp 34–40https://doi.org/10.1145/355112.355120Published:01 December 2000Publication History 441citation12,816DownloadsMetricsTotal Citations441Total Downloads12,816Last 12 Months1,533Last 6 weeks264 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteView all FormatsPDF
Ligand Selectivity of the Peroxisome Proliferator-Activated Receptor α (1998)

Peroxisome proliferator-activated receptors (PPAR alpha, beta, and gamma) are nuclear hormone receptors that play critical roles in regulating lipid metabolism. It is well established that PPARs are the targets for the hypolipidemic synthetic compounds known as peroxisome proliferators, and it has been proposed that various long-chain fatty acids and metabolites of arachidonic acid serve as the physiological ligands that activate these receptors in vivo. However, a persistent problem is that reported values of the equilibrium dissociation constants (Kds) of complexes of PPARs with these ligands are in the micromolar range, at least an order of magnitude higher than the physiological concentrations of the ligands. Thus, the identity of the endogenous ligands for PPAR remains unclear. Here we report on a fluorescence-based method for investigating the interactions of PPAR with ligands. It is shown that the synthetic fluorescent long-chain fatty acid trans-parinaric acid binds to PPARalpha with high affinity and can be used as a probe to monitor protein-ligand interactions by the receptor. Measurements of Kds characterizing the interactions of PPARalpha with various ligands revealed that PPARalpha interacts with unsaturated C:18 fatty acids, with arachidonic acid, and with the leukotriene LTB4 with affinities in the nanomolar range. These data demonstrate the utility of the optical method in examining the ligand-selectivity of PPARs, and resolve a long-standing uncertainty in understanding how the activities of these receptors are regulated in vivo.
Structural and Kinetic Evidence for an Extended Hydrogen-bonding Network in Catalysis of Methyl Group Transfer (2006)

The methyltetrahydrofolate (CH(3)-H(4)folate) corrinoid-iron-sulfur protein (CFeSP) methyltransferase (MeTr) catalyzes transfer of the methyl group of CH(3)-H(4)folate to cob(I)amide. This key step in anaerobic CO and CO(2) fixation is similar to the first half-reaction in the mechanisms of other cobalamin-dependent methyltransferases. Methyl transfer requires electrophilic activation of the methyl group of CH(3)-H(4)folate, which includes proton transfer to the N5 group of the pterin ring and poises the methyl group for reaction with the Co(I) nucleophile. The structure of the binary CH(3)-H(4)folate/MeTr complex (revealed here) lacks any obvious proton donor near the N5 group. Instead, an Asn residue and water molecules are found within H-bonding distance of N5. Structural and kinetic experiments described here are consistent with the involvement of an extended H-bonding network in proton transfer to N5 of the folate that includes an Asn (Asn-199 in MeTr), a conserved Asp (Asp-160), and a water molecule. This situation is reminiscent of purine nucleoside phosphorylase, which involves protonation of the purine N7 in the transition state and is accomplished by an extended H-bond network that includes water molecules, a Glu residue, and an Asn residue (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Shi, W., Fedorov, A., Lewandowicz, A., Cahill, S. M., Almo, S. C., and Schramm, V. L. (2002) Biochemistry 41, 14489-14498). In MeTr, the Asn residue swings from a distant position to within H-bonding distance of the N5 atom upon CH(3)-H(4)folate binding. An N199A variant exhibits only approximately 20-fold weakened affinity for CH(3)-H(4)folate but a much more marked 20,000-40,000-fold effect on catalysis, suggesting that Asn-199 plays an important role in stabilizing a transition state or high energy intermediate for methyl transfer.
The Role of Rho in G Protein-Coupled Receptor Signal Transduction (2000)

Low molecular weight G proteins of the Rho subfamily are regulators of actin cytoskeletal organization. In contrast to the heterotrimeric G proteins, the small GTPases are not directly activated through ligand binding to G protein-coupled receptors (GPCRs). However, a subset of GPCRs, including those for lysophosphatidic acid and thrombin, induce stress fibers, focal adhesions, and cell rounding through Rho-dependent pathways. C3 exoenzyme has been a useful tool for demonstrating Rho involvement in these and other responses, including Ca2+ sensitization of smooth muscle contraction, cell migration, transformation, and serum response element-mediated gene expression. Most of the GPCRs that induce Rho-dependent responses can activate Gq, but this is not a sufficient signal. Recent data demonstrate that G alpha 12/13 can induce Rho-dependent responses. Furthermore, G alpha 12/13 can bind and activate Rho-specific guanine nucleotide exchange factors, providing a mechanism by which GPCRs that couple to G alpha 12/13 could activate Rho and its downstream responses.
The significance of sociolinguistic backgrounds of teachers of IELTS Test preparation courses in selected Malaysian institutions (2008)

This research investigated the teaching of IELTS Test preparation classes in Malaysia. Malaysia has been ranked 7th in a list of top 25 IELTS Test locations worldwide (IELTS Review 2002). This ethnographic study focused on the linguistic, social and cultural values which different teachers bring to the IELTS Test practice classroom and to washback into the curriculum according to the requirements of IELTS Test preparation and associated academic and social language skills. We visited six institutions which held IELTS Test practice classes. These were both public and private, located in and around the Kuala Lumpur area and in the state of Pahang. Within these institutions, 92 students completed questionnaires and we interviewed nine teachers. As the student questionnaires were researcher-administered in all centres but one, the return was high (90%). Of these 92 students, 47 claimed Bahasa Malaysia as the first language (with most having English as another language), 30 claimed Chinese, Mandarin or Cantonese as the first language (with most having English as another language), the remainder claimed a mixture of Tamil, Punjabi, Indonesian, Burmese, Persian, English (one student) and Malaysian ethnic languages. Within this context, the relevance of the term 'non-native speaker teacher' was revisited alongside the suggestion that the richness of multilingual speech communities should be better appreciated by centre-based researchers than is currently the case. We found that the teachers' varied linguistic and cultural backgrounds enabled them to understand the relevance of the IELTS Test in their programs, institutions and in their country, and hence to teach its skills appropriately. Furthermore, despite not being familiar with the term 'washback', both teachers and students commented in detail on the positive effects they perceived the Test to have on the Malaysian teaching/learning environment. Finally, we discovered that teachers working in this region had a strong desire for more specific information about the IELTS Test and candidate assessment; they felt that such information would enable them to provide better guidance for their students.
Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. (1990)

The lutropin-choriogonadotropin (LH/CG) receptor is a cell surface receptor comprised of two domains of roughly equivalent size. The amino-terminal half of the receptor is relatively hydrophilic and is located extracellularly, whereas the carboxyl-terminal half of the receptor shares amino acid homology with other receptors that couple to G proteins and is similarly thought to span the plasma membrane seven times, ending with a relatively short carboxyl-terminal tail. In order to test the role of the extracellular domain in binding hormone, we constructed a mutated rat luteal LH/CG receptor cDNA (termed pCLHR-D2), which encodes for only the extracellular domain, and used it to transiently transfect human kidney 293 cells. Here we report that the expressed extracellular domain of the LH/CG receptor is capable of binding human CG with a high affinity, comparable with that of the full-length receptor. Thus, not only is the extracellular domain of the glycoprotein hormone receptors involved in binding hormone, but it alone is capable of conferring high affinity binding. Unexpectedly, it was also found that this truncated receptor is not secreted into the culture media but remains trapped within the cells.
Intratumoral Administration of Adenoviral Interleukin 7 Gene-Modified Dendritic Cells Augments Specific Antitumor Immunity and Achieves Tumor Eradication (2000)

In two murine lung cancer models adenoviral interleukin 7-transduced dendritic cells (DC-AdIL-7) were administered intratumorally, resulting in complete tumor regression. Intratumoral DC-AdIL-7 therapy was as effective as DCs pulsed with specific tumor peptide antigens. Comparison with other intratumoral therapies including recombinant IL-7, AdIL-7 vector alone, unmodified DCs, IL-7-transduced fibroblasts, or DCs pulsed with tumor lysates revealed DC-AdIL-7 therapy to be superior in achieving antitumor responses and augmenting immunogenicity. Mice with complete tumor eradication as a result of either DC-AdIL-7 or AdIL-7 therapy were rechallenged with parental tumor cells 30 days or more after complete tumor eradication. All the DC-AdIL-7-treated mice completely rejected a secondary rechallenge, whereas the AdIL-7-treated mice had sustained antitumor effects in only 20-25% of the mice. DC-AdIL-7 therapy was more effective than AdIL-7 in achieving systemic antitumor responses and enhancing immunogenicity. After complete tumor eradication, those mice treated with DC-AdIL-7 evidenced significantly greater release of splenocyte GM-CSF and IFN-gamma than did controls or AdIL-7-treated mice. After intratumoral injection, gene-modified DCs trafficked from the tumor to lymph node sites and spleen. DCs were detected in nodal tissues for up to 7 days after intratumoral injection. We report that intratumoral DC-AdIL-7 leads to significant systemic immune responses and potent antitumor effects in murine lung cancer models.
Recombination and Gene Conversion in a 170-kb Genomic Region of Arabidopsis thaliana (2002)

Arabidopsis thaliana is a highly selfing plant that nevertheless appears to undergo substantial recombination. To reconcile its selfing habit with the observations of recombination, we have sampled the genetic diversity of A. thaliana at 14 loci of approximately 500 bp each, spread across 170 kb of genomic sequence centered on a QTL for resistance to herbivory. A total of 170 of the 6321 nucleotides surveyed were polymorphic, with 169 being biallelic. The mean silent genetic diversity (pi(s)) varied between 0.001 and 0.03. Pairwise linkage disequilibria between the polymorphisms were negatively correlated with distance, although this effect vanished when only pairs of polymorphisms with four haplotypes were included in the analysis. The absence of a consistent negative correlation between distance and linkage disequilibrium indicated that gene conversion might have played an important role in distributing genetic diversity throughout the region. We tested this by coalescent simulations and estimate that up to 90% of recombination is due to gene conversion.
[Comparative study of endogenous RNA-polymerase activity of the cell nuclei and chloroplasts of pea leaves]. (1976)

The endogenous RNApolymerase activity of isolated cell nuclei and chloroplasts from young pea plants (Pisum sativum) has been studied. The presence of all four nucleoside triphosphates and Mg2+ ions is necessary for the reaction. The missing of one of these nucleotides from the reaction mixture, especially ATP, sharply decreases the transcription. Chloroplasts synthesize RNA per DNA unit more intensively, than nuclei. In spring such predominance is especially pronounced. Maximal synthesis of RNA is observed at pH 8.3 both in nuclei and chloroplasts. Maximal transcription was observed at 25 degrees in chloroplasts and at 30--35 degrees in nuclei. Actinomycin D inhibited the process of transcription both in nuclei and some stimulation in chloroplasts were observed, when rifamicin B was added. It is suggested that there are differences in nuclear and chloroplast forms of RNA polymerase.