gebhart/patrepeval huggingface dataset:
Control of Angiogenesis in Fibroblasts by p53 Regulation of Thrombospondin-1 (1994)

As normal cells progress toward malignancy, they must switch to an angiogenic phenotype to attract the nourishing vasculature that they depend on for their growth. In cultured fibroblasts from Li-Fraumeni patients, this switch was found to coincide with loss of the wild-type allele of the p53 tumor suppressor gene and to be the result of reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. Transfection assays revealed that p53 can stimulate the endogenous TSP-1 gene and positively regulate TSP-1 promoter sequences. These data indicate that, in fibroblasts, wild-type p53 inhibits angiogenesis through regulation of TSP-1 synthesis.
Chemical Modification of a Bridging Ligand Inside a Metal–Organic Framework while Maintaining the 3D Structure (Eur. J. Inorg. Chem. 10/2008) (2008)

Abstract The cover picture shows the post‐synthetic functional group modification of a Metal–Organic Framework without destroying the original 3D architecture. Details are discussed in the Short Communication by P. Gamez et al. on p. 1551 ff. The authors are indebted to the Chemical Research Council of the Netherlands and the Graduate Research School Combination “NRSC Catalysis” for financial support.
Immune responses to inactivated vaccine in people naturally infected with hantaviruses (1996)

An inactivated Hantaan virus vaccine for hemorrhagic fever with renal syndrome (HFRS) was given by injection to 15 people who were naturally infected with either Hantaan or Seoul viruses. Immunofluorescent antibody (IFA), reversed passive hemagglutination inhibition (RPHI), hemagglutination inhibition (HI), and neutralization antibody (NA) assays were used to measure the antibody titers of the vaccinated people before and after three doses of vaccine. The results indicated that IFA and RPHI antibody titers were boosted significantly (P < 0.05) after the vaccination. Either Hantaan or Seoul virus could induce two-way cross-reactive neutralization antibody responses in humans. After HTNV vaccine immunization, the NA titers of people with natural infection increased significantly (P < 0.05) to both Hantaan and Seoul viruses, while the relative dominance between these two type responses was still similar to that of natural infection. It is worthwhile to studying the procedure further to inoculate two different virus vaccines for improving the cross-protective effect. © 1996 Wiley-Liss, Inc.
Circulating Epstein-Barr virus DNA in the serum of patients with gastric carcinoma. (2001)

Our data indicate that serum EBV DNA reflects tumoral EBER status and opens up the possibility that circulating EBV DNA may be used as a tumor marker for the EBER-positive gastric carcinomas. The biological and clinical significance of the presence of low levels of circulating EBV DNA in the minority of gastritis patients and healthy individuals remains to be elucidated.
Gene Expression along the Cerebral-Spinal Axis after Regional Gene Delivery (1999)

We demonstrate here that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or cationic liposome: DNA complexes (CLDCs) produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Gene expression was identified both within the spinal cord and the brain after intracerebroventricular or intrathecal injection of either CLDCs or plasmid DNA alone. Intracerebroventricular or intrathecal injection of CLDCs containing the beta-galactosidase (beta-Gal) gene produced patchy, widely scattered areas of beta-Gal expression. The chloramphenicol acetyltransferase (CAT) reporter gene product reached peak levels between 24 hr and 1 week postinjection, and was still present at significant levels 3 weeks after a single intracerebroventricular or intrathecal injection. Intrathecal injection of the human granulocyte colony-stimulating factor (G-CSF) gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine nerve growth factor (NGF) gene increased mNGF levels in the hippocampus, a target region for cholinergic neurons in the medial septum, and increased cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) activity within the brain, a well-characterized effect of both purified and recombinant NGF protein. These findings indicate that intracerebroventricular or intrathecal injection of CLDCs can produce significant levels of expression of biologically and therapeutically relevant genes within the CNS. Efficient gene transfer into the CNS will facilitate the evaluation of gene function and regulation within the brain and spinal cord. We attempted to transfer and express genes within the brain and spinal cord by direct CNS injection of either DNA alone or CLDCs into the intraventricular and subarachnoid compartments. We show that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or CLDCs produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Intrathecal injection of the hG-CSF gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine NGF gene increased mNGF levels in the hippocampus, and increased cholinergic neurotransmitter synthetic enzyme ChAT activity within the brain. Locoregional diffusion of gene products expressed by transfected meningeal lining cells into brain and spinal cord parenchyma could potentially target secreted proteins within brain and spinal cord regions relevant to neuropathological states while limiting peripheral side effects.
Acid hydrolase activity during the growth, necrosis, and regression of the Jensen sarcoma. (1968)

Summary The subcutaneously transplanted Jensen sarcoma grew to a weight of 50–60 gm in 16–18 days and then regressed. During the period of growth the tissue could be divided into a region of necrotic dead cells and a region of live cells by the lissamine green exclusion test. The activity of 4 acid hydrolases (cathepsin, aryl sulfatase, β-galactosidase, and acid phosphatase) were determined in both tumor regions during growth and the beginning of regression. Measurements were made of the total enzymatic activity and the free activity or that not bound to large cellular particles under the uniform set of conditions employed. A high percentage of the activity of the 4 enzymes was free in the inner necrotic region of the tumor. The total activity of cathepsin and acid phosphatase declined in the necrotic portion with tumor age. There was a marked increase in both the free and total activities of cathepsin, aryl sulfatase, and β-galactosidase in the outer portion of the tumor during the early periods of regression. Total acid phosphatase activity declined in the outer portion of the tumor during regression. The data suggest that acid hydrolases are involved in the degradation of tumor cells during both necrosis and regression of the tumor.
High temporal and inter‐individual variation detected in the human ileal microbiota (2010)

The diversity and temporal stability of the predominant bacteria in the human ileum was studied with the use of ileal effluent samples of seven individuals with Brooke ileostomies. The total number of bacteria within the ileal effluent was in the range of 10⁷ -10⁸ bacteria per gram (wet weight). The diversity of the bacteria in the ileal effluent showed marked differences compared with that in faecal samples from age-matched healthy adults. The ileal effluent had a higher relative abundance of species within the orders Lactobacillales and Clostridiales, mainly Streptococcus bovis-related species, and the Veillonella group, and a lower proportion of species related to Ruminococcus gnavus, R. obeum and Bacteroides plebeius. In addition, inter-individual differences were found, indicative of a highly personal ileal microbiota profile. Furthermore, temporal profiles showed large fluctuations per individual over a period of 9-28 days (average similarity over a period of 9 days was as low as 44%), and differences between morning and afternoon profiles were observed. Parallel cloning and sequencing efforts revealed several phylotypes that were not identified in previous studies (12 out of 65 phylotypes showed less than 97% sequence similarity with previously reported sequences). Achaea were found to be below detection limit by quantitative PCR. Overall, the results indicate that the microbiota of the human ileum is relatively unstable, less complex and consisting of different dominating phylotypes when compared with the colonic microbiota.
An Efficient Robotic Tendon for Gait Assistance (2006)

A robotic tendon is a spring based, linear actuator in which the stiffness of the spring is crucial for its successful use in a lightweight, energy efficient, powered ankle orthosis. Like its human analog, the robotic tendon uses its inherent elastic nature to reduce both peak power and energy requirements for its motor. In the ideal example, peak power required of the motor for ankle gait is reduced from 250 W to just 77 W. In addition, ideal energy requirements are reduced from nearly 36 J to just 21 J. Using this approach, an initial prototype has provided 100% of the power and energy necessary for ankle gait in a compact 0.95 kg package, seven times less than an equivalent motor/gearbox system.
Protein denaturation. C. Theoretical models for the mechanism of denaturation. (1970)

This chapter reviews theoretical models that may be constructed and equations that may be derived from them to understand the process of protein denaturation. Given that the native state is stable under physiological conditions, the question arises whether the effects of environmental changes on the equilibrium between native and denatured states can be predicted, so as to account for the loss of stability of the native state and the appearance of different denatured states under specified conditions. This question involves not the absolute values for the free energies and other thermodynamic parameters for denaturation processes, but the changes in these parameters, along with changes in environmental variables. These changes can be predicted semiquantitatively. Furthermore, one can account both for the products formed under different conditions and for the character of the transitions from native to denatured state, at least for the simple proteins that have been studied in detail.
Pharmacology of Adenosine Receptors: The State of the Art (2018)

Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A<sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub>, and A<sub>3</sub>. Due to the rapid generation of adenosine from cellular metabolism, and the widespread distribution of its receptor subtypes in almost all organs and tissues, this nucleoside induces a multitude of physiopathological effects, regulating central nervous, cardiovascular, peripheral, and immune systems. It is becoming clear that the expression patterns of adenosine receptors vary among cell types, lending weight to the idea that they may be both markers of pathologies and useful targets for novel drugs. This review offers an overview of current knowledge on adenosine receptors, including their characteristic structural features, molecular interactions and cellular functions, as well as their essential roles in pain, cancer, and neurodegenerative, inflammatory, and autoimmune diseases. Finally, we highlight the latest findings on molecules capable of targeting adenosine receptors and report which stage of drug development they have reached.
Enhancing the Photon- and Gas-Sensing Properties of a Single SnO2Nanowire Based Nanodevice by Nanoparticle Surface Functionalization (2008)

Field-effect transistors based on a single SnO 2 nanowire were successfully fabricated, and their photon- and gas-sensing properties were investigated. It is found that the sensitivity of single SnO 2 nanowire based devices was remarkably improved by surface functionalization with ZnO or NiO nanoparticles. The heterojunction between the surface coating layers and SnO 2 and the corresponding coupling effect of the two sensing materials play a critical role in controlling device sensitivity.
Development of Capture Assays for Different Modifications of Human Low-Density Lipoprotein (2005)

Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), Nepsilon(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and also with oxLDL. CML-LDL antibodies reacted strongly with CML-LDL and also AGE-LDL. oxLDL antibodies reacted with oxLDL but not with MDA-LDL, and AGE-LDL antibodies reacted with AGE-LDL but not with CML-LDL. Capture assays were set with each antiserum, and we tested their ability to capture ApoB-containing lipoproteins isolated from precipitated immune complexes (IC) and from the supernatants remaining after IC precipitation (free lipoproteins). All antibodies captured lipoproteins contained in IC more effectively than free lipoproteins. Analysis of lipoproteins in IC by gas chromatography-mass spectrometry showed that they contained MDA-LDL and CML-LDL in significantly higher concentrations than free lipoproteins. A significant correlation (r=0.706, P<0.019) was obtained between the MDA concentrations determined by chemical analysis and by the capture assay of lipoproteins present in IC. In conclusion, we have developed capture assays for different LDL modifications in human ApoB/E lipoprotein-rich fractions isolated from precipitated IC. This approach obviates the interference of IC in previously reported modified LDL assays and allows determination of the degree of modification of LDL with greater accuracy.
Bioactivation of Metal Oxide Surfaces. 1. Surface Characterization and Cell Response (1999)

Silicon and titanium oxide surfaces (SiO2/Si and TiO2/Ti) were covalently modified with bioactive molecules (e.g., peptides) in a simple three-step procedure. Bioactive surfaces were synthesized by first immobilizing N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS) to either polished quartz disks, polished silicon wafers, or sputter-deposited titanium films. Subsequently, a maleimide-activated surface amenable to tethering molecules with a free thiol (e.g., cysteine) was created by coupling sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) to the terminal amine on EDS. In particular, Cys-Gly-Gly-Asn-Gly-Glu-Pro-Arg-Gly-Asp-Thr-Tyr-Arg-Ala-Tyr (-RGD-) and Cys-Gly-Gly-Phe-His-Arg-Arg-Ile-Lys-Ala (-FHRRIKA-) peptides with terminal cysteine residues were immobilized on maleimide-activated oxides. X-ray photoelectron spectroscopy (XPS) and spectroscopic ellipsometry were used to assess the chemistry, thickness, and surface density of the grafted layers. EDS deposited from anhydrous methanol produced reaction site-limited monolayers (∼0.28 nmol/cm2). Coupling of the sulfo-SMCC cross-linker (∼0.03 nmol/cm2) and peptides (∼0.004 nmol/cm2) resulted in an order of magnitude drop in surface density for each stage of the reaction scheme. Peptide-modified surfaces with densities varying over 2 orders (0.01−4 pmol/cm2) of magnitude were synthesized to study the effect of the peptides on mammalian cell function. The adhesion and spreading of cells derived from mammalian bone, in contact with the peptide-modified surfaces, was dependent on the specific peptide sequence grafted in a concentration-dependent manner. The grafting scheme presented has generality in coupling thiol-specific molecules to silicon or titanium surfaces.
A Preliminary Study of the Osteogenic Potential of a Biodegradable Alloplastic-Osteoinductive Alloimplant (1988)

A biodegradable copolymer of polylactide-polyglycolide was combined with allogeneic demineralized freeze-dried bone (DFDB) and implanted into 15-mm diameter defects in the calvaria of 26 New Zealand White rabbits. Similar defects were created in the calvaria of another 26 rabbits. These animals served as controls and did not receive copolymer implants. Upon sacrifice, both the implants and the controls were evaluated clinically, roentgenographically, and histomorphometrically using a Zeiss Image Analysis System (Videoplan, version 4.1). Both controls and implants were evaluated in groups at four, eight, 12, 16, 20, and 24 weeks. When compared with the control defects, the copolymer-DFDB implants displayed a significantly greater volume of trabecular bone. Three of the 15-mm diameter defects displayed evidence of complete osseous bridging at eight weeks. No adverse host-tissue responses were observed histologically in any of the implant specimens.
Footprinting of Chlorella Virus DNA Ligase Bound at a Nick in Duplex DNA (1999)

The 298-amino acid ATP-dependent DNA ligase of Chlorella virus PBCV-1 is the smallest eukaryotic DNA ligase known. The enzyme has intrinsic specificity for binding to nicked duplex DNA. To delineate the ligase-DNA interface, we have footprinted the enzyme binding site on DNA and the DNA binding site on ligase. The size of the exonuclease III footprint of ligase bound a single nick in duplex DNA is 19-21 nucleotides. The footprint is asymmetric, extending 8-9 nucleotides on the 3'-OH side of the nick and 11-12 nucleotides on the 5'-phosphate side. The 5'-phosphate moiety is essential for the binding of Chlorella virus ligase to nicked DNA. Here we show that the 3'-OH moiety is not required for nick recognition. The Chlorella virus ligase binds to a nicked ligand containing 2',3'-dideoxy and 5'-phosphate termini, but cannot catalyze adenylation of the 5'-end. Hence, the 3'-OH is important for step 2 chemistry even though it is not itself chemically transformed during DNA-adenylate formation. A 2'-OH cannot substitute for the essential 3'-OH in adenylation at a nick or even in strand closure at a preadenylated nick. The protein side of the ligase-DNA interface was probed by limited proteolysis of ligase with trypsin and chymotrypsin in the presence and absence of nicked DNA. Protease accessible sites are clustered within a short segment from amino acids 210-225 located distal to conserved motif V. The ligase is protected from proteolysis by nicked DNA. Protease cleavage of the native enzyme prior to DNA addition results in loss of DNA binding. These results suggest a bipartite domain structure in which the interdomain segment either comprises part of the DNA binding site or undergoes a conformational change upon DNA binding. The domain structure of Chlorella virus ligase inferred from the solution experiments is consistent with the structure of T7 DNA ligase determined by x-ray crystallography.
Tuberculin skin testing and the HIV epidemic (1992)

Tuberculosis (TB) cases in the United States have steadily increased in number since 1985. Much of this increase appears attributable to the human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) epidemic, with TB occurring both in those HIV-infected persons with latent as well as recently acquired TB infection.<sup>1</sup>Infection with HIV now is recognized as the most important risk factor for progression from tuberculous infection to active disease. The annual risk of disease in persons dually infected with TB and HIV is 7% to 10%, considerably greater than the 10% lifetime risk in HIV-uninfected tuberculin reactors.<sup>1,2</sup> See also p 369. As a result of the increasing TB morbidity associated with HIV, screening for tuberculous infection now is recommended practice for all patients with HIV infection as well as patients in drug treatment centers, sexually transmitted disease clinics, and HIV/AIDS clinics.<sup>1</sup>Treatment of TB-infected persons with isoniazid can
Tyrosine Phosphorylation of p130 by Bombesin, Lysophosphatidic Acid, Phorbol Esters, and Platelet-derived Growth Factor (1997)

Treatment of Swiss 3T3 cells with bombesin rapidly induced tyrosine phosphorylation of the p130 Crk-associated substrate (p130(cas)). Vasopressin, endothelin, bradykinin, lysophosphatidic acid, sphingosylphosphorylcholine, and phorbol 12,13-dibutyrate also stimulated p130(cas) tyrosine phosphorylation. Bombesin-induced p130(cas) tyrosine phosphorylation could be dissociated from both protein kinase C activation and Ca2+ mobilization from intracellular stores. In contrast, cytochalasin D, which disrupts the network of actin microfilaments, completely prevented tyrosine phosphorylation of p130(cas) by bombesin. Platelet-derived growth factor, at low concentrations (1-5 ng/ml), also induced tyrosine phosphorylation of p130(cas) via a pathway that depended on the integrity of the actin cytoskeleton. The phosphatidylinositol 3'-kinase inhibitors wortmannin and LY294002 prevented tyrosine phosphorylation of p130(cas) in response to platelet-derived growth factor but not in response to neuropeptides, lysophosphatidic acid, sphingosylphosphorylcholine, or phorbol 12,13-dibutyrate. All agonists that induced p130(cas) tyrosine phosphorylation also promoted the formation of a p130(cas).Crk complex in intact Swiss 3T3 cells. Thus, our results identified distinct signal transduction pathways that lead to tyrosine phosphorylation of p130(cas) in the same cells and suggest that p130(cas) could play a role in mitogen-mediated signal transduction.
Improved in Vivo Stability of Actinium-225 Macrocyclic Complexes (1999)

The favorable nuclear properties of actinium-225 ((225)Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free (225)Ac, a series of ligands were evaluated for stability in vivo. Loss of (225)Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, PEPA, and HEHA were evaluated, and (225)Ac-HEHA showed exceptional stability in vivo. (225)Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the (225)Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.
Reliability Analysis of Ku-Band 5-bit Phase Shifters Using MEMS SP4T and SPDT Switches (2015)

This work presents a Ku-band microelectromechanical systems (MEMS) based 5-bit phase shifter using dc contact single-pole-four-throw (SP4T) and single-pole-double-throw switches. The design is implemented using a coplanar waveguide transmission line. Two individual 2-bit phase shifters and one 1-bit phase shifter are cascaded to develop the complete 5-bit phase shifter. The phase shifters are fabricated on 635- μm alumina substrate using a surface micromachining process. The 5-bit phase shifter demonstrates an average insertion loss of 2.65 dB in the 13-18-GHz band with a return loss better than 22 dB and average phase error less than 0.68 ° at 17 GHz. Total area of the fabricated 5-bit phase shifter is 4.7 × 2.8 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The reliability of the single-pole-single-throw and SP4T switches show more than 10 million cycles with an RF power of 0.1-2 W. Furthermore, reliability of the MEMS phase shifter is extensively investigated and presented with cold and hot switched conditions. To the best of our knowledge, this is the first reported MEMS 5-bit phase shifter in the literature that has undergone different reliability and qualification testing including 3-axis vibrations.