gebhart/patrepeval huggingface dataset:
Interleukin‐6 and α‐2‐macroglobulin indicate an acute‐phase state in Alzheimer's disease cortices (1991)

Recent studies indicated that the formation of a major constituent of Alzheimer's disease (AD) senile plaques, called beta A4-peptide, does not result from normal processing of its precursor, amyloid precursor protein (APP). Since proteolytic cleavage of APP inside its beta A4 sequence was found to be part of APP processing the formation of the beta A4-peptide seems to be prevented under normal conditions. We considered whether in AD one of the endogenous proteinase inhibitors might interfere with APP processing. After we had recently found that cultured human neuronal cells synthesize the most potent of the known human proteinase inhibitors, alpha-2-macroglobulin (alpha 2M), upon stimulation with the inflammatory mediator interleukin-6 (IL-6) we now investigated whether alpha 2M and IL-6 could be detected in AD brains. Here we report that AD cortical senile plaques display strong alpha 2M and IL-6 immunoreactivity while no such immunoreactivity was found in age-matched control brains. Strong perinuclear alpha 2M immunoreactivity in hippocampal CA1 neurons of Alzheimer's disease brains indicates that neuronal cells are the site of alpha 2M synthesis in AD brains. We did not detect elevated IL-6 or alpha 2M levels in the cerebrospinal fluid of AD patients. Our data indicate that a sequence of immunological events which seem to be restricted to the local cortical environment is part of AD pathology.
Small Molecule Toxins Targeting Tumor Receptors (2004)

Targeting toxic therapeutics to tumors through receptors over expressed on the surface of cancer cells can reduce systemic toxicity and increase the effectiveness of the targeted compounds. Small molecule targeted therapeutics have a number of advantages over toxic immunoconjugates including better tumor penetration, lack of neutralizing host immune response and superior flexibility in selection of drug components with optimal specificity, potency and stability in circulation. Three major components of the targeted drug, the toxic warhead, tumor-specific ligand and the linker can influence the properties of each other and thus have to be optimized for each system. All receptor-targeted drugs are delivered inside the cells through endocytosis and undergo processing liberating the toxins in endosomes and lysosomes. Common delivery route defines a number of general requirements for each drug component. The review addresses currently known possible receptor targets and their ligands along with toxins that have been used and that have a potential to be successfully applied in tumor targeting. Linkers that are stable in circulation, but efficiently cleaved in lysosomes constitute an essential component of receptor-targeted drugs and are evaluated in greater detail.
The link between obesity and oncology (2003)

A number of factors are now known increase a person’s chance of developing cancer. For example, cancer is related to tobacco use; to what people eat and drink; to exposure to ultraviolet radiation from the sun; and exposure to cancer causing agents (carcinogens) in the environment and the workplace. In addition, epidemiological evidence gathered in recent years shows that certain types of cancer are also associated with excess body weight.
Crystal Structures of a Multifunctional Triterpene/Flavonoid Glycosyltransferase from Medicago truncatula (2005)

Glycosylation is a ubiquitous reaction controlling the bioactivity and storage of plant natural products. Glycosylation of small molecules is catalyzed by a superfamily of glycosyltransferases (GTs) in most plant species studied to date. We present crystal structures of the UDP flavonoid/triterpene GT UGT71G1 from Medicago truncatula bound to UDP or UDP-glucose. The structures reveal the key residues involved in the recognition of donor substrate and, by comparison with other GT structures, suggest His-22 as the catalytic base and Asp-121 as a key residue that may assist deprotonation of the acceptor by forming an electron transfer chain with the catalytic base. Mutagenesis confirmed the roles of these key residues in donor substrate binding and enzyme activity. Our results provide an initial structural basis for understanding the complex substrate specificity and regiospecificity underlying the glycosylation of plant natural products and other small molecules. This information will direct future attempts to engineer bioactive compounds in crop plants to improve plant, animal, and human health and to facilitate the rational design of GTs to improve the storage and stability of novel engineered bioactive compounds.
Differential Effect of Saturated and Unsaturated Free Fatty Acids on the Generation of Monocyte Adhesion and Chemotactic Factors by Adipocytes (2009)

Excess glucose and SFAs regulate chemotactic factor expression by a mechanism that involves ROS generation, NFkappaB, and PPARgamma, and which is repressed by PUFAs. Certain SFAs, but not excess glucose, trigger chemotactic factor expression via a TLR4-dependent pathway.
Design and Utilization of Natriuretic Peptide Antagonists (1997)

Natriuretic peptides play an important role in the hormonal regulation of blood pressure and sodium balance (for review, see refs. 1–3). Recently, the actions of these hormones have extended beyond vasodepressor and natriuretic functions to embrace antiproliferative effects and a role in vascular remodeling (3). The naturally occurring members of the natriuretic peptide family include atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) (1–3). Their tissue distribution differs substantially. Although the intracellular mechanisms through which natriuretic peptides elicit their diverse biological effects are not known, their biological effects are mediated by binding to specific membrane-associated receptors in the target tissues (4,5).
Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles (2010)

Inorganic colloidal nanoparticles are very small, nanoscale objects with inorganic cores that are dispersed in a solvent. Depending on the material they consist of, nanoparticles can possess a number of different properties such as high electron density and strong optical absorption (e.g. metal particles, in particular Au), photoluminescence in the form of fluorescence (semiconductor quantum dots, e.g. CdSe or CdTe) or phosphorescence (doped oxide materials, e.g. Y(2)O(3)), or magnetic moment (e.g. iron oxide or cobalt nanoparticles). Prerequisite for every possible application is the proper surface functionalization of such nanoparticles, which determines their interaction with the environment. These interactions ultimately affect the colloidal stability of the particles, and may yield to a controlled assembly or to the delivery of nanoparticles to a target, e.g. by appropriate functional molecules on the particle surface. This work aims to review different strategies of surface modification and functionalization of inorganic colloidal nanoparticles with a special focus on the material systems gold and semiconductor nanoparticles, such as CdSe/ZnS. However, the discussed strategies are often of general nature and apply in the same way to nanoparticles of other materials.
Folding and characterization of the amino‐terminal domain of human tissue inhibitor of metalloproteinases‐1 (TIMP‐1) expressed at high yield in E. coli (1996)

Methods are described for producing an active amino-terminal domain of tissue inhibitor of metalloproteinases-1 (N-TIMP-1) from inactive protein expressed as inclusion bodies in E. coli. Yields exceed 20 mg per litre of bacterial culture. Activity measurements, CD spectroscopy and NMR spectroscopy of the 15N-labeled protein show that it is fully active, homogeneous in conformation and suitable for high-resolution structural analysis. The affinity of N-TIMP-1 for matrix metalloproteinases 1, 2 and 3 is 6-8-fold less than that of the recombinant full-length protein, indicating that deletion of the C-terminal domain reduces the free energy of interaction by < 10%.
Zero voltage switching series resonant based DC-AC converter (2002)

This paper describes and analyses an isolated single-phase bidirectional DC-to-AC converter for uninterruptible power supply systems. The main achievements of the proposed converter are: (i) operation with zero voltage switching at all load conditions; (ii) inherent protection against short circuits in the load; (iii) high quality output waveform; (iv) isolation between the DC and AC sides using high frequency transformer; and (v) the leakage induction of the transformer is used as part of the series resonant inductor. The operating principles of the DC-to-AC converter are described and the relation among the power circuit variables are derived. Experimental results, which substantiate the analysis and demonstrate the feasibility of the DC-to-AC converter, are given.
Towards a molecular understanding of polycythemia rubra vera (2000)

Polycythemia rubra vera (PV) is one of four diseases collectively called the myeloproliferative disorders (MPDs). Each disorder leads to an increased production of one or several hematopoietic cell lineages. MPDs arise from acquired mutations in a pluripotent hematopoietic stem cell. However, the molecular mechanisms leading to the development of these diseases are poorly understood. This review will summarize and evaluate recent advances in our understanding of one particular MPD, PV.
Further purification and characterization of high-molecular-weight polysaccharide from Pseudomonas aeruginosa (1983)

Previously published reports on high-molecular-weight polysaccharides from immunotype 1 and 2 of Pseudomonas aeruginosa indicated the presence of high levels of mannose in these preparations. This mannose has been found to be due to the presence of a yeastlike mannan in high-molecular-weight polysaccharide preparations. The source of the mannan was found to be the tryptic soy broth used to grow the bacteria. Mannan could be removed from the polysaccharide preparations by chromatography over columns of concanavalin A-Sepharose. The resulting polysaccharides had the same serological reactivity against rabbit antisera and the same immunogenic properties in mice as did the mannan-containing polysaccharides. Comparison of mannan-depleted polysaccharide with preparations of high-molecular-weight polysaccharide obtained from either ultrafiltered tryptic soy broth or a chemically defined medium showed that these polysaccharides were immunologically and chemically similar. Human immune responses to mannan-depleted polysaccharide from the immunotype 1 strain of P. aeruginosa were comparable with those previously seen in humans receiving mannan-containing polysaccharides. Thus, we found that P. aeruginosa high-molecular-weight polysaccharides prepared in either tryptic soy broth and then subjected to concanavalin A-Sepharose chromatography, ultrafiltered tryptic soy broth, or a chemically defined medium were immunologically and chemically comparable.
Aflibercept (VEGF Trap-eye): the newest anti-VEGF drug (2012)

The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology over the past 7 years has revolutionised the treatment of exudative age-related macular degeneration (AMD) and holds great promise for diabetic macular oedema, branch and central retinal vein occlusions, and retinopathy of prematurity. Each of the three available drugs (pegaptanib, bevacizumab and ranibizumab) was eagerly embraced by surgeons, but the subsequent clinical results have been mixed, and the regulatory hurdles, particularly those regarding off-label use of bevacizumab, have been challenging.

Into this mix enters aflibercept (VEGF Trap-eye (VTE); Eylea, Regeneron, Tarrytown, New York, USA), for which the US Food and Drug Administration granted approval for the treatment of subfoveal choroidal neovascularisation due to AMD on 18 November 2011. In contrast to the antibody-based VEGF binding strategy used by ranibizumab and bevacizumab, the VTE incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the VEGFR-2 receptor.1 By fusing these extracellular protein sequences to the Fc segment of a human IgG backbone, in a manner similar to the rheumatoid arthritis drug etanercept, developers have created a chimeric protein with a very high VEGF binding affinity (Kd≈1 pM).2 Like ranibizumab and bevacizumab, the VTE binds all isomers of the VEGF-A family, and although the clinical significance of this is not yet known, it also binds VEGF-B and placental growth factor.

The approval application draws on the strengths of two concurrent AMD trials: the VIEW 1 trial, which enrolled 1217 patients in North American centres, and the VIEW 2 trial, which enrolled 1240 patients in South American, European, Asian and Australian centres. Each trial randomised patients among four treatment arms: monthly 0.5 mg VTE, monthly or bimonthly 2 mg VTE, and monthly …
Context-dependent splicing regulation (2011)

Splicing is a crucial process in gene expression in higher organisms because: 1) most vertebrate genes contain introns; and 2) alternative splicing is primarily responsible for increasing proteomic complexity and functional diversity. Intron definition, the coordination across an intron, is a mandatory step in the splicing process. However, exon definition, the coordination across an exon, is also thought to be required for the splicing of most vertebrate exons. Recent investigations of exon definition complexes provide insights into splicing dynamics. That splicing regulators act in a context-dependent mode is supported by a large collection of evidence. Splicing contexts generally can be classified as cis-element and trans-element contexts. A widespread cis-element context is defined by co-occurring motif pairs to which splicing regulatory factors bind to direct specific molecular interactions. Splicing regulation is also coordinated by trans-element contexts as exemplified by tissue specific splicing, where alternative exons can be coordinately regulated by a few splicing factors, the expression and/or activity of which are concertedly higher or lower in the corresponding tissues.
Application of Centrifugal Partition Chromatography for Bioactivity-Guided Purification of Antioxidant-Response-Element-Inducing Constituents from Atractylodis Rhizoma Alba (2018)

Activity-guided separation of antioxidant response element (ARE)-inducing constituents from the rhizomes of Atractylodis Rhizoma Alba was performed by the combination of centrifugal partition chromatography (CPC) and an ARE luciferase reporter assay. From 3 g of the active <i>n</i>-hexane fraction, one polyacetylene, (6<i>E</i>,12<i>E</i>)-tetradeca-6,12-dien-8,10-diyne-1,3-diyl diacetate (47.3 mg), and two sesquiterpenes, atractylenolide I (40.9 mg), and selina-4(14),7(11)-dien-8-one (6.0 mg) were successfully isolated by CPC with <i>n</i>-hexane⁻ethyl acetate⁻methanol⁻water (8:2:8:2, <i>v</i>/<i>v</i>). The chemical structures of the isolated compounds were determined by ¹H- and <sup>13</sup>C-NMR and ESI-MS. Among the isolated compounds, (6<i>E</i>,12<i>E</i>)-tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate and selina-4(14),7(11)-dien-8-one increased ARE activity 32.9-fold and 16.6-fold, respectively, without significant cytotoxicity, when 5 µM sulforaphane enhanced ARE activity 27.1-fold. However, atractylenolide I did not increase ARE activity at 100 µM, and showed cytotoxicity at concentrations over 10 µM.
Endothelial Nitric Oxide Gene Knockout Mice (1999)

We tested the hypothesis that nitric oxide (NO) released by endothelial NO synthase (eNOS) is not only important in blood pressure regulation but also involved in cardiac function and remodeling and in the cardioprotective effect of angiotensin-converting enzyme inhibitors (ACEi). With the use of a 2D Doppler echocardiography system equipped with a 15-MHz linear transducer, we evaluated left ventricular (LV) morphology and function in conscious eNOS knockout mice (eNOS(-/-); n=15) and their wild-type littermates (eNOS(+/+); n=16). We also studied whether in eNOS(-/-) mice (1) myocardial ischemia/reperfusion injury is more severe and (2) the cardioprotective effect of ACEi is diminished or absent. In comparison with the wild type, eNOS(-/-) mice had significantly increased systolic blood pressure (128+/-3 versus 108+/-5 mm Hg; P<0.001) and decreased heart rate (531+/-22 versus 629+/-18 bpm; P<0.001) associated with increased LV posterior wall thickness (0.80+/-0.04 versus 0.64+/-0.02 mm; P<0.001) and LV mass (18.3+/-0.9 versus 13.1+/-0.5 mg/10 g body weight; P<0.01). Despite hypertension and LV hypertrophy, LV chamber dimension, shortening fraction and ejection fraction (indicators of LV contractility), and cardiac output did not differ between the 2 strains, which indicates that LV function in eNOS(-/-) mice is well compensated. We also found that in eNOS(+/+) mice, ACEi decreased the ratio of myocardial infarct size to area at risk from 62.7+/-3.9% to 36.3+/-1.6% (P<0. 001), whereas in eNOS(-/-) mice this effect of ACEi was almost abolished: the ratio of myocardial infarct size to area at risk was 67.2+/-2.9% in the vehicle-treated group and 62.7+/-3.9% in mice treated with ACEi. Moreover, infarct size in vehicle-treated eNOS(-/-) mice was not significantly different from eNOS(+/+) mice given the same treatment. We concluded that (1) endothelium-derived NO plays an important role in the regulation of blood pressure homeostasis; (2) NO released under basal conditions has no significant impact on cardiac function; and (3) ACEi protect the heart against ischemia/reperfusion injury in mice and that this effect is mediated in part by endothelium-derived NO.
In Vivo Methods for Screening and Preclinical Testing (1997)

The classic question in the field of drug discovery is: Which tumor model is a satis-factory predictor for cancer in humans? The classic answer is: None of them!
Modelling power consumption of a H.263 video encoder (2004)

As video transmission is integrated into wireless communication systems, the theory of power control should also be expanded to consider both signal processing power and transmission power when designing new algorithms, since video coding consumes a significant portion of power. To better understand the interaction between signal processing and transmission, it helps to develop power consumption models for video coding. The goal of this work is to model the power consumption of an H.263 video encoder, in which motion estimation is the most computation intensive component. Different models for algorithms using 1) full search motion estimation; and 2) a fast algorithm using spiral order motion estimation are presented for a software H.263 encoder. We observe that one set of model parameters fits all test sequences for full search, whereas the model parameters are sequence specific for the fast algorithm.
Encouraging Improvement in Cytopenias of Patients With Myelodysplastic Syndromes With Thalidomide (2000)

Myelodysplastic syndrome patients present with variable cytopenias even though their bone marrows are generally hypercellular. Excessive cytokine-induced apoptosis of hematopoietic cells in the marrows has been proposed as a possible
Strategies forin vitroandin vivotranslation with non-natural amino acids (1996)

The use of site-directed mutagenesis (Smith, 1985) to replace amino acids at any chosen position in a protein, coupled with advances in analytical procedures, has greatly advanced our understanding of biological structure-function relationships in recent years. The only limitation of conventional site-directed mutagenesis is that substitutions are restricted to the 20 naturally occurring amino acids. However, the discovery of a 21st amino acid, selenocysteine, and the development of novel in vitro translation techniques have demonstrated that considerably more site-specific replacements are possible during protein engineering. These techniques have already found a wide range of applications and have shown that the translational machinery is able to accommodate an enormously divergent range of aminoacylated tRNAs. Although these techniques are mainly restricted to in vitro systems, recent progress in our understanding of aminoacyl-tRNA synthetase-catalyzed tRNA charging suggests that it may ultimately be possible to extend this technique to growing cells.
High-speed gated x-ray imaging for ICF target experiments (invited) (1992)

We describe the use of gated microchannel-plate detectors as high-speed framing cameras in laser-driven inertial-confinement-fusion experiments. Using an array of pinholes to image the target, detectors capable of generating up to 16 individual frames with ∼90 ps resolution on a single laser shot are now in routine use. The detectors have been used to study the development of intentionally applied perturbations in laser-driven targets. In off-line tests new detectors have demonstrated time resolutions better than 40 ps.
Typing of Human Adenoviruses in Specimens from Immunosuppressed Patients by PCR-Fragment Length Analysis and Real-Time Quantitative PCR (2006)

Currently, 51 human adenovirus (AdV) serotypes, which are divided into six species (A to F), are known. AdV infections are a major cause of morbidity and mortality in immunosuppressed individuals, particularly in allogeneic stem cell transplant (SCT) recipients. Any AdV species may cause life-threatening disease, but little information is available on the clinical relevance of individual serotypes. The use of serological testing for serotype identification is limited due to the impaired immune response during the posttransplant period. A new molecular approach to serotype identification is presented here that exploits variable regions within the hexon gene. All serotypes belonging to the species A, B, C, E, and F can be determined by fragment length analysis of a single PCR product. For species C, which is the most prevalent in many geographic regions, an alternative technique based on serotype-specific real-time quantitative PCR was established. Of 135 consecutive pediatric patients screened for AdV infections after allogeneic SCT, 40 tested positive. Detailed analysis revealed the presence of 10 different serotypes; serotypes 1 and 2 from species C (C01 and C02) showed the highest prevalence, accounting for 77% of the AdV-positive cases. Representatives of other species were observed less commonly: serotype A12 in 6.5%; serotype A31 in 4.5%; and B03, B16, C05, C06, D19, and F41 in 2%. The approach to rapid molecular serotype analysis presented here provides a basis for detailed studies on adenovirus epidemiology and on the transmission of nosocomial infections. Moreover, in view of the increasing importance of tailored therapy approaches, serotype identification may in the future have implications for the selection of the most appropriate antiviral treatment.
Semiconductor Quantum Dots in Bioanalysis: Crossing the Valley of Death (2011)

Colloidal semiconductor quantum dots (QDs) have evolved beyond scientific novelties and are transitioning into bona fide analytical tools. We describe the burgeoning role of QDs in many different fields of bioanalyses and highlight the advantages afforded by their unique physical and optical properties.