gebhart/patrepeval huggingface dataset:
Inhibition of p53 DNA binding by human papillomavirus E6 proteins (1994)

Transformation by the human papillomavirus (HPV) early gene products, E6 and E7, involves their interaction with cellular proteins p53 and Rb. Using glutathione S-transferase (GST) fusion proteins, we found that HPV E6 bound human p53 and that the relative efficiency of binding varied such that the GST-HPV type 16 E6 (16E6) protein bound p53 with highest affinity, followed by GST-31E6, GST-18E6, and GST-11E6. The GST-E6 fusion proteins were sufficient for binding p53 purified from a baculovirus expression system as well as in vitro translation sources, while no association was observed with GST-18E7 or a GST-16E6 mutant bearing a five-amino-acid deletion in E6. When the site-specific DNA binding activity of p53 was examined in the presence of GST-E6 proteins, an inhibition of DNA binding was observed. The degree of inhibition correlated with the relative affinity of different E6 proteins for p53; thus, GST-16E6 was the most potent inhibitor of p53 DNA binding activity, and GST-11E6 was the least effective. Prevention of p53 DNA binding is likely to play a role in the abrogation of the transcriptional activity of p53 by HPV E6 and provides a further mechanism for E6 disruption of p53 growth suppressor function in addition to its role in directing specific degradation of p53 through the ubiquitin-mediated pathway. The variation in inhibition of DNA binding seen with the various E6 proteins may thus contribute to the differences in oncogenic potential seen among the HPV types.
Bright red light-emitting electroluminescence devices based on a functionalized europium complex (2003)

The complex tris(dibenzoylmethanato)(1-ethyl-2-(4′-carbazole-9-yl)phenyl imidazo[4,5-f]1,10- phenanthroline) europium (III), Eu(DBM)3(CPIP), was newly synthesized. Devices using this complex as emitter showed greatly enhanced performance benefiting from the improved hole-transporting properties of the complex and good stability. A double-layer device with the configuration of ITO/TPD(50 nm)/Eu(DBM)3(CPIP)(60 nm)/Mg0.9Ag0.1(200 nm)/Ag(80 nm) exhibited Eu3+ based pure red emission with a brightness of 537 cd m−2 at 13 V and the power efficiency of 0.089 lm W−1 at 6 V, 33 cd m−2. A triple-layer device with the configuration of ITO/TPD(40 nm)/Eu(DBM)3(CPIP)(30 nm)/Eu(DBM)3 Bath(50 nm)/Mg0.9Ag0.1 (200 nm)/Ag (80 nm) also emitted pure red light with a highest brightness of 1050 cd m−2 at 16 V and the highest power efficiency of 0.50 lm W−1 at 8 V, 8 cd m−2. The highest brightness 1460 cd m−2 at 14 V was obtained from a four-layer device with the configuration of ITO/TPD(40 nm)/Eu(DBM)3(CPIP)(40 nm)/BCP(20 nm)/AlQ(10 nm)/Mg0.9Ag0.1(200 nm)/Ag(80 nm) and the highest power efficiency of 0.54 lm W−1 at 7 V, 56 cd m−2.
Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats (2013)

Use of protease inhibitors (PI) in HIV patients is associated with hyperlipidemia and increased risk of coronary heart disease. Chronic systemic and cardiac effects of ritonavir (RTV), a universal PI booster, and Mg supplementation were examined. RTV was administered (75 mg·kg(-1)·day(-1) po) to Lewis × Brown-Norway hybrid (LBNF1) rats for up to 8 wk; significant increases in plasma triglyceride and cholesterol occurred from 8 days to 8 wk. At 5 wk, the expression of selected hepatic genes (CYP7A1, CITED2, G6PC, and ME-1), which are key to lipid catabolism/synthesis, were altered toward lipogenesis. Dietary Mg supplementation (six-fold higher) completely reversed the altered expression of these genes and attenuated both hypertriglyceridemia and hypercholesterolemia. Neutrophils isolated from the RTV-treated rats displayed a three-fold higher basal and a twofold higher stimulated superoxide production; plasma isoprostane and red blood cell (RBC) GSSG levels were elevated two- to three-fold. All oxidative indices were normalized by Mg supplementation. After 5 wk, RTV caused significant decreases in cardiac left ventricular (LV) shortening fraction and LV ejection fraction; mitral valve early/late atrial ventricular filling (E/A) ratio was reduced accompanied by LV posterior wall thinning. Immunohistochemical staining revealed significant white blood cell (WBC) infiltration (5 wk) and prominent fibrosis (8 wk) in the RTV hearts. Mg supplementation attenuated RTV-induced declines in systolic and diastolic (improved mitral valve E/A ratio) function (>70%), lessened LV posterior wall thinning (by 75%), and substantially decreased the pathological markers. The known clinical hyperlipidemia effects of RTV can be mimicked in the LBNF1 rats; in association, systemic oxidative stress and progressive cardiac dysfunction occurred. Remarkably, Mg supplementation alone suppressed RTV-mediated hyperlipidemia, oxidative stress, and cardiac dysfunction.
Copolymer of star poly(epsilon‐caprolactone) and polyglycidols as potential carriers for hydrophobic drugs (2011)

Abstract Amphiphilic star shape poly(ε‐caprolactone)‐b‐hyperbranched polyglycidol (sPCL‐HPG) were synthesized and used to investigate micell formation and to encapsulate hydrophobic drugs. The synthesis of sPCL‐HPG copolymers was carried out by using sPCL as macroinitiator for the ensuing of hypergrafting reaction with glycidols. 1 H‐NMR and FTIR were used to characterize sPCL‐b‐HPG structures. The self‐assembled structure of the sPCL‐HPG was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The size and size dispersities of micelles were measured by dynamic light scattering DLS. Critical micelle concentration (CMC) was determined using pyrene as fluorescent probe. Hydrophobic methyl red was encapsulated in sPCL‐HPG micelles to illustrate hydrophobic drug loading. The copolymer micelles were used to enhance paclitaxel solubility. The results showed that hydrophobic drugs could be encapsulated in the sPCL‐HPG micelles. The paclitaxel solubility in the micelles of 5 wt% of sPCL23‐HPG170 got to 168 µg/ml. sPCL‐HPG, which have biodegrability and hydrophobicity at PCL part and smaller size of HPG fragments while maintaining the total repeating units of glycidols, provide an alternative choice of carriers for poorly soluble drugs. Copyright © 2011 John Wiley &amp; Sons, Ltd.
The heat-shock-regulated grpE gene of Escherichia coli is required for bacterial growth at all temperatures but is dispensable in certain mutant backgrounds (1989)

Previous work has established that the grpE+ gene product is a heat shock protein that is essential for bacteriophage lambda growth at all temperatures and for Escherichia coli growth at temperatures above 43 degrees C. Here it is shown that the grpE+ gene product is essential for bacterial viability at all temperatures. The strategy required constructing a grpE deletion derivative carrying a selectable chloramphenicol drug resistance marker provided by an omega insertion and showing that this deletion construct can be crossed into the bacterial chromosome if and only if a functional grpE+ gene is present elsewhere in the same cell. As a control, the same omega insertion could be placed immediately downstream of the grpE+ coding sequence without any observable effects on host growth. This result demonstrates that the inability to construct a grpE-deleted E. coli strain is not simply due to a lethal polar effect on neighboring gene expression. Unexpectedly, it was found that the grpE deletion derivative could be crossed into the bacterial chromosome in a strain that was defective in DnaK function. Further analysis showed that it was not the lack of DnaK function per se that allowed E. coli to tolerate a deletion in the grpE+ gene. Rather, it was the presence of unknown extragenic suppressors of a dnaK mutation that somehow compensated for the deficiency in both DnaK and GrpE function.
Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials (2017)

Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial design.
How to make a functional β-cell (2013)

Insulin-secreting pancreatic β-cells are essential regulators of mammalian metabolism. The absence of functional β-cells leads to hyperglycemia and diabetes, making patients dependent on exogenously supplied insulin. Recent insights into β-cell development, combined with the discovery of pluripotent stem cells, have led to an unprecedented opportunity to generate new β-cells for transplantation therapy and drug screening. Progress has also been made in converting terminally differentiated cell types into β-cells using transcriptional regulators identified as key players in normal development, and in identifying conditions that induce β-cell replication in vivo and in vitro. Here, we summarize what is currently known about how these strategies could be utilized to generate new β-cells and highlight how further study into the mechanisms governing later stages of differentiation and the acquisition of functional capabilities could inform this effort.
C-Reactive Protein in the Arterial Intima (2000)

Infiltration of monocytes into the arterial wall is an early cellular event in atherogenesis. Recent evidence shows that C-reactive protein (CRP) is deposited in the arterial intima at sites of atherogenesis. In this study, we demonstrate that CRP deposition precedes the appearance of monocytes in early atherosclerotic lesions. CRP is chemotactic for freshly isolated human blood monocytes. A specific CRP receptor is demonstrated on monocytes in vitro as well as in vivo, and blockage of the receptor by use of a monoclonal anti-receptor antibody completely abolishes CRP-induced chemotaxis. CRP may play a major role in the recruitment of monocytes during atherogenesis.
Hydrazide Derivatives of Poly(ethylene glycol) and Their Bioconjugates (1997)

Hydrazide derivatives of poly(ethylene glycol) (PEG-Hz) have a number of attributes making them useful for preparation of conjugates, particularly of polypeptides and glycoproteins. They form conjugates in mildly acidic aqueous solutions via two modes of reactivity. The first one involves hydrazone formation with reactive carbonyls generated on the substrate molecule by several different methods. These include oxidation of oligosaccharide residues of glycoproteins, glyoxylate / Cu2+ -mediated transamination of the N-terminal residue of polypeptides, periodate oxidation of N-terminal Ser or Thr residues. The second mode involves coupling with carbodiimide-activated carboxyl groups forming diacylhydrazide linkages with PEG. Synthesis of PEG-Hz is straightforward by hydrazinolysis of esters of either carboxymethylated PEG or urethane-linked amino acid. Having an unusual amino acid, e.g. β-Ala, as part of the linker offers a convenient way for composition determination of protein conjugates, particularly those containing multiple chains of mPEG-O(C=O)-β-Ala-Hz, by amino acid analysis. Our work involving PEG-Hz conjugation, including examples of preparation of N-terminally modified polypeptides, oligosaccharide-linked glycoproteins, polypeptides modified on their carboxyl groups, and immunoconjugates of enzymes and liposomes is discussed in this review.
Facile DNA Immobilization on Surfaces through a Catecholamine Polymer (2010)

Simple immersion of noble metals, oxides, semiconductors, and synthetic polymer substrates in a mussel-mimetic catecholamine polymer solution p(DOMA-AEMA) leads to formation of a thin film on the substrate. The resulting coated substrates can bind DNA without further surface treatment. This approach provides a new entrance to DNA microarray fabrication. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. 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.
X-ray Crystal Structures of 70 S Ribosome Functional Complexes (1999)

Structures of 70S ribosome complexes containing messenger RNA and transfer RNA (tRNA), or tRNA analogs, have been solved by x-ray crystallography at up to 7.8 angstrom resolution. Many details of the interactions between tRNA and the ribosome, and of the packing arrangements of ribosomal RNA (rRNA) helices in and between the ribosomal subunits, can be seen. Numerous contacts are made between the 30S subunit and the P-tRNA anticodon stem-loop; in contrast, the anticodon region of A-tRNA is much more exposed. A complex network of molecular interactions suggestive of a functional relay is centered around the long penultimate stem of 16S rRNA at the subunit interface, including interactions involving the "switch" helix and decoding site of 16S rRNA, and RNA bridges from the 50S subunit.
Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design (2012)

Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family of proteins, is overexpressed and amplified in various cancers and promotes the aberrant survival of tumor cells that otherwise would undergo apoptosis. Here we describe the discovery of potent and selective Mcl-1 inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified two chemically distinct hit series that bind to different sites on Mcl-1. Members of the two fragment classes were merged together to produce lead compounds that bind to Mcl-1 with a dissociation constant of <100 nM with selectivity for Mcl-1 over Bcl-xL and Bcl-2. Structures of merged compounds when complexed to Mcl-1 were obtained by X-ray crystallography and provide detailed information about the molecular recognition of small-molecule ligands binding Mcl-1. The compounds represent starting points for the discovery of clinically useful Mcl-1 inhibitors for the treatment of a wide variety of cancers.
Disposal of blood [1-13C]lactate in humans during rest and exercise (1986)

Lactate irreversible disposal (RiLa) and oxidation (RoxLa) rates were studied in six male subjects during rest (Re), easy exercise [EE, 140 min of cycling at 50% of maximum O2 consumption (VO2max)] and hard exercise (HE, 65 min at 75% VO2max). Twenty minutes into each condition, subjects received a Na+-L(+)-[1-13C]lactate intravenous bolus injection. Blood was sampled intermittently from the contralateral arm for metabolite levels, acid-base status, and enrichment of 13C in lactate. Expired air was monitored continuously for determination of respiratory parameters, and aliquots were collected for determination of 13C enrichment in CO2. Steady-rate values for O2 consumption (VO2) were 0.33 +/- 0.01, 2.11 +/- 0.03, and 3.10 +/- 0.03 l/min for Re, EE, and HE, respectively. Corresponding values of blood lactate levels were 0.84 +/- 0.01, 1.33 +/- 0.05, and 4.75 +/- 0.28 mM in the three conditions. Blood lactate disposal rates were significantly correlated to VO2 (r = 0.78), averaging 123.4 +/- 20.7, 245.5 +/- 40.3, and 316.2 +/- 53.7 mg X kg-1 X h-1 during Re, EE, and HE, respectively. Lactate oxidation rate was also linearly related to VO2 (r = 0.81), and the percentage of RiLa oxidized increased from 49.3% at rest to 87.0% during exercise. A curvilinear relationship was found between RiLa and blood lactate concentration. It was concluded that, in humans, 1) lactate disposal (turnover) rate is directly related to the metabolic rate, 2) oxidation is the major fate of lactate removal during exercise, and 3) blood lactate concentration is not an accurate indicator of lactate disposal and oxidation.
The Early Development of Articular Cartilage After Perichondrial Grafting (1983)

In an experimental series of 39 rabbits the articular cartilage of the femur condyles was resected and the defect covered by a perichondrial graft from rib cartilage. The graft was fixed to the bony surface by using Tisseal (Immuno AG) and the joint was immobilized for two weeks. Beginning 24 hours postoperatively the neochondrogenesis from the perichondrial graft was analyzed histologically, sacrificing the rabbits with 48 hours interval. The fibrin glue acted as a visible border line between the bony surface and the graft. No vascular proliferations penetrated the fibrin glue, indicating that the perichondrial graft must be nourished by the synovial fluid only. The neochondrogenesis was found to occur in the median and fibrous layer of the graft.
Removing Ruthenium Residues from Olefin Metathesis Reaction Products (2012)

Olefin metathesis has revolutionized the way chemists design and synthesize molecules, mostly due to the development of well-defined ruthenium catalysts with high oxygen-, moisture-, and functional-group tolerance. However, the complete removal of residual ruthenium after the end of a metathesis reaction often imposes significant challenges. This Minireview summarizes the strategies for the sequestration of ruthenium impurities from olefin metathesis post-reaction mixtures, thus comprising a practical guide for synthetic chemists employing ruthenium-catalyzed metathesis reactions in the synthesis of organic or polymeric materials.
PCR-based HLA class II typing. (1991)

The human leukocyte antigen (HLA) class II molecules are cell-surface glycoproteins involved in the regulation of immune responses. Allelic variation at the HLA class lI loci is an important consideration in major areas of medicine and biology. For instance, detailed knowledge of the allelic constitution at class lI loci is required for matching of suitable donors and recipients for bone marrow and other tissue transplantations. Susceptibility to a number of autoimmune diseases has also been found to be associated with specific residues, alleles, or haplotypes at class II loci, (9-17) and characterization of these loci provides an opportunity for early identification and initiation of immunotherapy for individuals at risk of developing these diseases. The class II polymorphism also provides an excellent marker system for paternity determinations and for purposes of individual identification in forensic medicine. 118,19) Finally, these loci are valuable tools in determining evolutionary relationships at the DNA level. In this review we discuss the pros and cons of the alternate methods available for genetic typing of the allelic variation at class II loci for these various applications, using the polymerase chain reaction (PCR).
Recent advances in the understanding of Langerhans cell histiocytosis (2011)

Langerhans cell histiocytosis (LCH) is a proliferative disease of cells that share phenotypic characteristics with the primary antigen presenting cells of the epidermis. Its clinical manifestations are highly variable, extending from very benign forms to a disseminated, aggressive disease that causes significant mortality. Although many of the fundamental pathogenetic features of LCH have been enigmatic, recent advances have led to a much clearer understanding of the disease. In particular, careful molecular analyses of mouse models and human LCH samples suggest that LCH's cell of origin may not be the epidermal LC itself but a myeloid-derived precursor. Advanced genomic technologies have revealed the presence of activating, somatic BRAF mutations in the majority of patient specimens. Together, these observations have produced a new picture of LCH as a myeloid neoplasm. These advances are likely to have profound implications for the use of targeted therapeutics in LCH.
Amplification of T cell blastogenic responses in healthy individuals and patients with acquired immunodeficiency syndrome. (1990)

Human immunodeficiency virus (HIV) infection is associated with a profound impairment of T cell function. Hence, enhancement of T cell reactivity to viral and bacterial antigens is important in the treatment of patients with AIDS. To develop tools for amplifying T cell reactivity, we have immunized mice with human helper T cell clones and selected monoclonal antibodies (MAbs) that enhance in vitro blastogenic responses. MAb NDA5, which recognizes the leukocyte common antigen CD45, amplifies human T cell responses to mitogens and soluble antigens including HIV-1 glycoprotein (gp)-120 and peptides derived from the HIV-1 gp-120 sequence. In the presence of MAb NDA5, peripheral blood mononuclear cells (PBMC) from healthy, HIV-1-seronegative individual displayed augmented blastogenic responses to HIV-1 gp-120 and to HIV-1 gp-120 synthetic peptides. In vitro memory responses to various vaccines and to alloantigens were also enhanced in cultures with MAb. Similarly, the response of PBMC from AIDS patients to pokeweed mitogen, HIV-1 gp-120, and tetanus toxoid was enhanced with MAb NDA5. The finding that the in vitro immune response of patients with AIDS can be amplified with MAb NDA5, suggests that the in vivo immune response of immunodeficient individuals can also be enhanced.
A Prostate-Specific Membrane Antigen-Targeted Monoclonal Antibody–Chemotherapeutic Conjugate Designed for the Treatment of Prostate Cancer (2004)

MLN2704 is an antibody-chemotherapeutic conjugate designed to target prostate-specific membrane antigen (PSMA). PSMA is a transmembrane receptor whose expression is largely restricted to prostatic epithelium and prostate cancer cells with its expression level increasing during the progression of malignancy. MLN2704 consists of a de-immunized, monoclonal antibody that is specific for PSMA conjugated to drug maytansinoid 1 (DM1), a microtubule-depolymerizing compound. After antibody binding to PSMA and the subsequent cellular internalization of this complex, DM1 is released leading to cell death. MLN2704 has an approximate half-life of 39 hours in scid mice bearing CWR22 tumor tissue, and the antibody effectively penetrates xenograft tumor tissue. Optimization of dosage and schedule of MLN2704 administration defined interdependency between these conditions that maximized efficacy with no apparent toxicity. Tumor growth delays of approximately 100 days could be achieved on the optimized schedule of one dose of 60 mg/kg MLN2704 every 14 days for five doses (q14dx5). The unconjugated antibody (MLN591) demonstrated essentially no antitumor activity and DM1 alone or a non-PSMA targeted antibody-DM1 conjugate was only weakly active. Furthermore, we show that MLN2704 is active in a novel model of osteoblastic prostate cancer metastasis.
A New Buffer Cache Design Exploiting Both Temporal and Content Localities (2010)

This paper presents a Least Popularly Used buffer cache algorithm to exploit both temporal locality and content locality of I/O requests. Popular data blocks are selected as reference blocks that are not only accessed frequently but also identical or similar in content to other blocks that are being accessed. Fast delta compression and decompression are used to satisfy as many I/O requests as possible using the popular reference blocks together with small deltas inside the buffer cache. The popularity of a reference block is calculated based on the statistical analysis of data contents and access frequency. A prototype LPU has been implemented as a new cache layer for Kernel Virtual Machine (KVM) on Linux system. Experimental results show LPU is effective for a variety of workloads with the maximum speed up of over 300% compared with LRU.