gebhart/patrepeval huggingface dataset:
Mutual Dependence of MDM2 and MDMX in Their Functional Inactivation of p53 (2002)

MDMX, an MDM2-related protein, has emerged as yet another essential negative regulator of p53 tumor suppressor, since loss of MDMX expression results in p53-dependent embryonic lethality in mice. However, it remains unknown why neither homologue can compensate for the loss of the other. In addition, results of biochemical studies have suggested that MDMX inhibits MDM2-mediated p53 degradation, thus contradicting its role as defined in gene knockout experiments. Using cells deficient in either MDM2 or MDMX, we demonstrated that these two p53 inhibitors are in fact functionally dependent on each other. In the absence of MDMX, MDM2 is largely ineffective in down-regulating p53 because of its extremely short half-life. MDMX renders MDM2 protein sufficiently stable to function at its full potential for p53 degradation. On the other hand, MDMX, which is a cytoplasmic protein, depends on MDM2 to redistribute into the nucleus and be able to inactivate p53. We also showed that MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding. Our findings therefore provide a molecular basis for the nonoverlapping activities of these two p53 inhibitors previously revealed in genetic studies.
The β-Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential (2009)

The beta-amyloid (Abeta) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. The beta-secretase, beta-site amyloid precursor protein cleaving enzyme (BACE1; also called Asp2, memapsin 2), is the enzyme responsible for initiating Abeta generation. Thus, BACE is a prime drug target for the therapeutic inhibition of Abeta production in AD. Since its discovery 10 years ago, much has been learned about BACE. This review summarizes BACE properties, describes BACE translation dysregulation in AD, and discusses BACE physiological functions in sodium current, synaptic transmission, myelination, and schizophrenia. The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE.
Interstitial transport of rabbit and sheep antibodies in normal and neoplastic tissues. (1990)

Interstitial transport of fluorescein isothiocyanate-conjugated nonspecific polyclonal rabbit and sheep IgG was studied in normal (mature granulation) and neoplastic (VX2 carcinoma) tissues grown in a rabbit ear chamber. The interstitial concentration gradients after i.v. injection were analyzed to yield effective interstitial diffusion coefficients, Deff. The one-dimensional diffusion model underestimated Deff by a factor of up to 3 when compared with a two-dimensional model. Despite marked heterogeneities in Deff, the average values of Deff were higher in tumors than in normal tissue. Rabbit IgG moved faster in tumors than the sheep IgG by a factor of 2. When compared with the dextran of same molecular weight, the ratio of Deff between neoplastic and normal tissue decreased from 33 (dextran) to between 2 and 5 (sheep IgG and rabbit IgG, respectively). When compared with dextran of the same Stokes-Einstein radius, IgGs had a lower Deff in both tissue types. These results are consistent with the size, charge, and configuration of antibodies and the structure and charge of the interstitial matrix and suggest that the delivery of antibodies to tumors may be improved by modulating their charge, hydrophilicity, and antigenicity. The molecular weight dependence of Deff also provides a rational basis for the use of bifunctional antibodies and antibody-enzyme conjugates to increase the delivery of low molecular weight anticancer agents to solid tumors.
Low-Temperature Crystallization of Hydrogenated Amorphous Silicon Induced by Nickel Silicide Formation (1990)

We have investigated the silicidation process of the Ni/a-Si:H system on a fused silica substrate mainly by in situ electric resistance measurement. A rise of the resistance is observed in the temperature range of 480–510°C of the resistance curve at a heating rate of 2 K/min. The results of the RBS measurements and the XRD measurements show that the rise of the resistance originates from the diffusion of Ni from the NiSi 2 layer to a-Si:H film, and that the a-Si:H crystallizes during the diffusion. Noting that the crystallization temperature of a-Si:H film is higher than 700°C, the present crystallization occurs at a much lower temperature. It is suggested that this low-temperature crystallization is induced by heterogeneous nucleation, where the NiSi 2 becomes the nucleus for Si crystallization.
Selective Oxidation with N-Bromosuccinimide. I. Cholic Acid (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective Oxidation with N-Bromosuccinimide. I. Cholic AcidLouis F. Fieser and Srinivasa. RajagopalanCite this: J. Am. Chem. Soc. 1949, 71, 12, 3935–3938Publication Date (Print):December 1, 1949Publication History Published online1 May 2002Published inissue 1 December 1949https://pubs.acs.org/doi/10.1021/ja01180a015https://doi.org/10.1021/ja01180a015research-articleACS PublicationsRequest reuse permissionsArticle Views1225Altmetric-Citations108LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Activation of the AT2 Receptor of Angiotensin II Induces Neurite Outgrowth and Cell Migration in Microexplant Cultures of the Cerebellum (1999)

Microexplant cultures from three-day-old rats were used to investigate whether angiotensin II (Ang II), through its AT(1) and AT(2) receptors, could be involved in the morphological differentiation of cerebellar cells. Specific activation of the AT(2) receptor during 4-day treatment induced two major morphological changes. The first was characterized by increased elongation of neurites. The second change was cell migration from the edge of the microexplant toward the periphery. Western blot analyses and indirect immunofluorescence studies revealed an increase in the expression of neuron-specific betaIII-tubulin, as well as an increase in expression of the microtubule-associated proteins tau and MAP2. These effects were demonstrated by co-incubation of Ang II with 1 microM DUP 753 (AT(1) receptor antagonist) or with 10 nM CGP 42112 (AT(2) receptor agonist) but abolished when Ang II was co-incubated with 1 microM PD 123319 (AT(2) receptor antagonist), indicating that differentiation occurs through AT(2) receptor activation and that the AT(1) receptor inhibits the AT(2) effect. Taken together, these results demonstrate that Ang II is involved in cerebellum development for both neurite outgrowth and cell migration, two important processes in the organization of the various layers of the cerebellum.
Atlas of breast imaging (1999)

Mammography Screening Calcifications on Mammograms Masses and Architectural Distortion on Mammograms Unusual Lesions Ultrasound Atlas Magnetic Resonance Imaging Atlas Inde
Efficient retroviral mediated transfer of the glucocerebrosidase gene in CD34+ enriched umbilical cord blood human hematopoietic progenitors. (1995)

Obtaining efficient transfer of a normal gene and its sustained expression in self-renewing hematopoietic stem cell populations is a central concern for gene therapy initiatives. Potentially, 10(8) to 10(9) CD34+ enriched cells per patient will be required for transduction and subsequent reimplantation. These studies present an efficient method for the transduction of human CD34+ cells that can be used in a clinical study of gene transfer. The method uses a centrifugation-enhanced technique for the retroviral-mediated transfer of the normal human glucocerebrosidase (GC) gene to human CD34+ enriched umbilical cord blood cells (CB). Previous studies had described high expression of GC in CD34+ enriched cells but had not reported transduction efficiency in the progenitor population specifically. The data demonstrate an average transduction efficiency in the progenitor cell population of 50% as measured by polymerase chain reaction (PCR) for the integrated GC-cDNA in clonogenic cells. Measurements of enzyme activity comparing transduced and nontransduced fractions at 6 days posttransduction indicate an average enzyme increase of six-fold over normal background levels. PCR of colony forming units-granulocyte/macrophage (CFU-GM) plated at 6 weeks from long-term culture-initiating cell (LTC-IC) cultures also indicates transfer of the transgene to early progenitor cells. Finally, experiments were carried out with the human erythroleukemia cell line, TF-1, to estimate the durable expression of the transgene. Enzymatic activities in transduced TF-1 cultures remained at 30-fold above the activity of nontransduced controls. The expression persisted for 6 weeks in culture. These studies demonstrate efficient transduction of early progenitor cells and sustained expression of the transgene in cell cultures.
Resistive fibre-meshed transducers (2004)

The paper demonstrates the preliminary researchcarried out on fibre meshed transducers for wearablecomputing applications, their constructions using electro-conductive fibres via the route of modern electronicflatbed knitting technology. The paper reports theconstruction of resistive strain and displacementtransducers using electroconductive polymeric fibres(resistivity of 104?cm-1) and metallic fibres (resistivity of10?cm-1) and the modelling of electrical equivalentcircuits of the fibre meshed transducers. The models arediscussed in order to demonstrate the variation ofelectrical parameters under static and dynamic planarloads. Two methods of transducer construction are alsodiscussed; in the first method the electroconductive fibresare stretched out in the base fibre meshed structure, andin the second method the electroconductive fibres areintermeshed as an integral section of the base fibremeshed structure.
A mutagenesis study of a catalytic antibody. (1991)

We have generated seven site-specific mutations in the genes encoding the variable region of the heavy chain domain (VH) of the phosphocholine-binding antibody S107. S107 is a member of a family of well-characterized highly homologous antibodies that bind phosphorylcholine mono- and diesters. Two of these antibodies, MOPC-167 and T15, have previously been shown to catalyze the hydrolysis of 4-nitrophenyl N-trimethylammonioethyl carbonate. Two conserved heavy-chain residues, Tyr-33 and Arg-52, were postulated to be involved in binding and hydrolysis of 4-nitrophenylcholine carbonate esters. To more precisely define the catalytic roles of these residues, three Arg-52 mutants (R52K, R52Q, R52C) and four Tyr-33 mutants (Y33H, Y33F, Y33E, Y33D) of antibody S107 were generated. The genes encoding the VH binding domain of S107 were inserted into plasmid pUC-fl, and in vitro mutagenesis was performed. The wild-type and mutant S107 antibodies were expressed in P-3X63-Ag8.653 (P-3) myeloma cells by using a modified SV2 shuttle vector. The catalytic properties of wild-type antibody S107 are similar to those of the phosphocholine-specific antibody T15, which has the same VH protein sequence. In general, mutations at Tyr-33 had little effect on catalytic activity, whereas mutations at Arg-52 that result in loss of the positively charged side chain significantly lower the catalytic activity of S107. One mutant, Y33H, catalyzed the hydrolysis of 4-nitrophenyl N-trimethylammonioethyl carbonate with a kcat of 5.7 min-1 and a Km of 1.6 mM at pH 7.5. These results not only demonstrate the importance of electrostatic interactions in catalysis by antibody S107 but also show that catalytic side chains can be introduced into antibodies to enhance their catalytic efficiency.
Hydrogen/Deuterium Exchange Mass Spectrometry for Investigating Protein-Ligand Interactions (2004)

Amide hydrogen/deuterium exchange mass spectrometry is rapidly becoming a powerful method for high-resolution analyses of protein dynamics, structure, and function. Hydrogen/deuterium exchange approaches can provide information that greatly augments and refines information derived from high-resolution structural studies, and can provide detailed information on native protein structure when structural information is unavailable. Application of this method for rapid analyses of protein-ligand complexes could prove useful for studies of important disease-related protein complexes. The following review covers fundamentals of hydrogen/deuterium exchange and its applications to the study of protein-ligand complexes. In addition, hydrogen/deuterium exchange mass spectrometry studies on a protein-inhibitor complex are presented.
Cellulose Pyrolysis Kinetics:  Revisited (1998)

In the same thermogravimetric analyzer (TGA) under identical conditions, samples of pure, ash-free cellulose (i.e., Avicel PH-105, Whatman CF-11, Millipore ash-free filter pulp, and Whatman #42) obtained from different manufacturers undergo pyrolysis at temperatures which differ by as much as 30 °C. Thus, the pyrolysis chemistry of a sample of pure cellulose is not governed by a universal rate law, as is the case with a pure hydrocarbon gas (for example). Nevertheless, the pyrolytic weight loss of all the samples studied in this work is well represented by a high activation energy (228 kJ/mol), first-order rate law at both low and high heating rates. These results do not corroborate the recent findings of Milosavljevic and Suuberg (Ind. Eng. Chem. Res. 1995, 34, 1081−1091). For a particular cellulose sample (for example, Avicel PH-105), variations in the preexponential constant determined at different heating rates reflect uncontrolled, systematic errors in the dynamic sample temperature measurement (thermal lag).
Modern Technologies for Creating Synthetic Antibodies for Clinical Application (2009)

The modular structure and versatility of antibodies enables one to modify natural immunoglobulins in different ways for various clinical applications. Rational design and molecular engineering make it possible to directionally modify the molecular size, affinity, specificity, and immunogenicity and effector functions of an antibody, as well as to combine them with other functional agents. This review focuses on up-to-date methods of antibody engineering for diagnosing and treating various diseases, particularly on new technologies meant to refine the effector functions of therapeutic antibodies.
Immortalization of Neural Cells Via Retrovirus-Mediated Oncogene Transduction (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Protein phosphatase 1 interacts with p53BP2, a protein which binds to the tumour suppressor p53 (1995)

The p53 binding protein, termed p53BP2, was identified as a protein interacting with protein phosphatase 1 (PP1) in the yeast two hybrid system. The interaction was confirmed by co-immunoprecipitation of p53BP2 with epitope-tagged PP1 in vitro. The p53BP2-PP1 complex was stable to NaCl at concentrations which dissociate the p53-p53BP2 complex, and the binding of PP1 and p53 to p53BP2 was mutually exclusive. The region required for interaction with PP1 was shown to be contained within amino acids 297-431 of p53BP2, which includes two ankyrin repeats. The phosphorylase phosphatase activity of PP1 was inhibited by p53BP2 at nanomolar concentrations. These results suggest that PP1 may be involved in dephosphorylation and regulation of p53 through interaction with p53BP2.
Increased frequencies of CD11b+CD33+CD14+HLA‐DRlow myeloid‐derived suppressor cells are an early event in melanoma patients (2014)

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population characterized by immunosuppressive activity. Elevated levels of MDSC in peripheral blood are found in inflammatory diseases as well as in malignant tumors where they are supposed to be major contributors to mechanisms of tumor-associated tolerance. We investigated the frequency and function of MDSC in peripheral blood of melanoma patients and observed an accumulation of CD11b(+) CD33(+) CD14(+) HLA-DR(low) MDSC in all stages of disease (I-IV), including early stage I patients. Disease progression and enhanced tumor burden did not result in a further increase in frequencies or change in phenotype of MDSC. By investigation of specific MDSC-associated cytokines in patients' sera, we found an accumulation of IL-8 in all stages of disease. T-cell proliferation assays revealed that MDSC critically contribute to suppressed antigen-specific T-cell reactivity and thus might explain the frequently observed transient effects of immunotherapeutic strategies in melanoma patients.
Distance, dependencies, and delay in a global collaboration (2000)

Collaborations over distance must contend with the loss of the rich, subtle interactions that co-located teams use to coordinate their work. Previous research has suggested that one consequence of this loss is that cross-site work will take longer than comparable single-site work. We use both survey data and data from the change management system to measure the extent of delay in a multi-site software development organization. We also measure site interdependence, differences in same-site and cross-site communication patterns, and analyze the relationship of these variables to delay. Our results show a significant relationship between delay in cross-site work and the degree to which remote colleagues are perceived to help out when workloads are heavy. This result is particularly troubling in light of the finding that workers generally believed they were as helpful to their remote colleagues as to their local colleagues. We discuss implications of our findings for collaboration technology for distributed organizations.
Robust crop resistance to broadleaf and grass herbicides provided by aryloxyalkanoate dioxygenase transgenes (2010)

Engineered glyphosate resistance is the most widely adopted genetically modified trait in agriculture, gaining widespread acceptance by providing a simple robust weed control system. However, extensive and sustained use of glyphosate as a sole weed control mechanism has led to field selection for glyphosate-resistant weeds and has induced significant population shifts to weeds with inherent tolerance to glyphosate. Additional weed control mechanisms that can complement glyphosate-resistant crops are, therefore, urgently needed. 2,4-dichlorophenoxyacetic acid (2,4-D) is an effective low-cost, broad-spectrum herbicide that controls many of the weeds developing resistance to glyphosate. We investigated the substrate preferences of bacterial aryloxyalkanoate dioxygenase enzymes (AADs) that can effectively degrade 2,4-D and have found that some members of this class can act on other widely used herbicides in addition to their activity on 2,4-D. AAD-1 cleaves the aryloxyphenoxypropionate family of grass-active herbicides, and AAD-12 acts on pyridyloxyacetate auxin herbicides such as triclopyr and fluroxypyr. Maize plants transformed with an AAD-1 gene showed robust crop resistance to aryloxyphenoxypropionate herbicides over four generations and were also not injured by 2,4-D applications at any growth stage. Arabidopsis plants expressing AAD-12 were resistant to 2,4-D as well as triclopyr and fluroxypyr, and transgenic soybean plants expressing AAD-12 maintained field resistance to 2,4-D over five generations. These results show that single AAD transgenes can provide simultaneous resistance to a broad repertoire of agronomically important classes of herbicides, including 2,4-D, with utility in both monocot and dicot crops. These transgenes can help preserve the productivity and environmental benefits of herbicide-resistant crops.
Doped Silicon Oxide Deposition by Atmospheric Pressure and Low Temperature Chemical Vapor Deposition Using Tetraethoxysilane and Ozone (1991)

Doped silicon oxides, phosphosilicate glass (PSG), and borosilicate glass (BSG) films were deposited using organic doping sources, trimethylphosphate for PSG films, and trimethylborate (TMB) and SiOB for BSG films. Deposition rate, doping level, film stress, etching rate by an aqueous solution, IR spectra and leakage current of the films were studied. In PSG deposition, a content up to 6 mole percent (m/o), a deposition rate of as high as 150 nm/min and a film stress of less than were obtained at 400°C. IR spectra showed that the PSG films were very stable even after boiling in water. Step coverage on aluminum steps was conformal or slightly nonconformal, and base material dependence of deposition rate was not observed, which would indicate a partial gas‐phase reaction even in atmospheric pressure chemical vapor deposition. The extent of the nonconformality was much smaller than that of the silane‐base PSG films. In BSG deposition a 200 nm/min deposition rate, a film stress and a 14 m/o doping level were obtained at 400°C. The stress of films deposited at 400°C relaxed from tensile to compressive, . Leakage current of TMB/BSG films was very low, 15 nA/cm2, without annealing independent of doping level. Step coverage of both films was very conformal, however, base material dependence of deposition rate was observed. Both phenomena are the same as the USG case, but different from the PSG deposition. IR spectra of both films proved that the films were acceptably stable several days after deposition.
Age Synthesis and Estimation via Faces: A Survey (2010)

Human age, as an important personal trait, can be directly inferred by distinct patterns emerging from the facial appearance. Derived from rapid advances in computer graphics and machine vision, computer-based age synthesis and estimation via faces have become particularly prevalent topics recently because of their explosively emerging real-world applications, such as forensic art, electronic customer relationship management, security control and surveillance monitoring, biometrics, entertainment, and cosmetology. Age synthesis is defined to rerender a face image aesthetically with natural aging and rejuvenating effects on the individual face. Age estimation is defined to label a face image automatically with the exact age (year) or the age group (year range) of the individual face. Because of their particularity and complexity, both problems are attractive yet challenging to computer-based application system designers. Large efforts from both academia and industry have been devoted in the last a few decades. In this paper, we survey the complete state-of-the-art techniques in the face image-based age synthesis and estimation topics. Existing models, popular algorithms, system performances, technical difficulties, popular face aging databases, evaluation protocols, and promising future directions are also provided with systematic discussions.