gebhart/patrepeval huggingface dataset:
Novel Effects of the Acyl-Coenzyme A:Cholesterol Acyltransferase Inhibitor 58-035 on Foam Cell Development in Primary Human Monocyte–Derived Macrophages (1999)

We examined the effect of acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors on intracellular cholesterol stores in primary human monocyte-derived macrophages (HMMs) during foam cell formation. HMMs were exposed to acetylated low density lipoprotein (acLDL, 500 microg protein per mL) with or without 58-035 (1 to 10 microg/mL) or CI-976 (2 microg/mL) for 2 to 48 hours. Total cholesterol (TC) and esterified cholesterol (EC) mass was significantly lower while unesterified cholesterol (UC) increased slightly in cells incubated with acLDL plus ACAT inhibitors. Sterol mass was also measured in cells coincubated with acLDL (500 microg protein per mL) with or without 58-035 (2 microg/mL), high density lipoprotein (HDL, 400 microg protein per mL), or HDL+58-035 for 48 hours. TC and EC were 23% and 55% lower, respectively (P<0.0004), while UC was 11% higher (P<0.04) in cells incubated with acLDL plus 58-035. In contrast, coincubation with HDL alone did not significantly affect TC, EC, or UC mass compared with acLDL alone. The effect of 58-035 could not be explained by cytotoxicity, because adenine release, secreted lactate dehydrogenase, glucose utilization, and cell protein were similar in cells exposed to acLDL regardless of the presence of 58-035. We investigated several potential mechanisms for the decreased TC mass, including increased UC efflux and decreased acLDL binding and uptake. Efflux was measured in cells exposed to [1,2-(3)H]cholesteryl oleate-labeled acLDL, unlabeled control acLDL, and native untreated acLDL (500 microg protein per mL) with or without 58-035 (5 microg/mL) for 24 or 48 hours. UC efflux increased in a time-dependent manner from cells exposed to acLDL plus 58-035 compared with cells exposed to acLDL alone (P<0. 04). High-affinity binding was measured in cells exposed to (125)I-acLDL (5 microg protein per mL) with or without excess unlabeled acLDL (100 or 500 microg protein per mL) for 4 hours at 4 degrees C. Specific acLDL binding, uptake, and total degradation were significantly lower when 58-035 was present during cholesterol enrichment compared with cells exposed to acLDL alone (P<0.001). Unlike the effects of ACAT inhibitors on foam cell formation in rodent macrophages, these compounds lowered TC accumulation in HMMs during foam cell formation by limiting the uptake of acLDL and enhancing UC efflux. They may offer promise as drug therapies for atherosclerosis.
Structure–Activity and Structure–Conformation Relationships of Aryl Propionic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1/Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1/NRF2) Protein–Protein Interaction (2019)

The KEAP1-NRF2-mediated cytoprotective response plays a key role in cellular homoeostasis. Insufficient NRF2 signaling during chronic oxidative stress may be associated with the pathophysiology of several diseases with an inflammatory component, and pathway activation through direct modulation of the KEAP1-NRF2 protein-protein interaction is being increasingly explored as a potential therapeutic strategy. Nevertheless, the physicochemical nature of the KEAP1-NRF2 interface suggests that achieving high affinity for a cell-penetrant druglike inhibitor might be challenging. We recently reported the discovery of a highly potent tool compound which was used to probe the biology associated with directly disrupting the interaction of NRF2 with the KEAP1 Kelch domain. We now present a detailed account of the medicinal chemistry campaign leading to this molecule, which included exploration and optimization of protein-ligand interactions in three energetic "hot spots" identified by fragment screening. In particular, we also discuss how consideration of ligand conformational stabilization was important to its development and present evidence for preorganization of the lead compound which may contribute to its high affinity and cellular activity.
Confluent focal nodular hyperplasia mimicking liver cancer: Value of liver-specific contrast-enhanced MRI for diagnosis (2012)

Focal nodular hyperplasia is the second most common benign hepatic tumor. Unlike adenoma as well as the malignant neoplasms, focal nodular hyperplasia can often be managed successfully without surgery. Use of liver-specific contrast-enhanced magnetic resonance imaging allows clinicians to confirm the diagnosis noninvasively in some patients, allowing select patients to avoid surgery. We report a case of a patient who presented with the rare profile of multiple, confluent lesions that were diagnosed, using magnetic resonance imaging with gadolinium-dimeglumine, as focal nodular hyperplasia. This complicated case was managed successfully and noninvasively based on algorithm found in the recent literature that allows patients to avoid unnecessary surgery.
Visibility of halftone dot textures (1984)

A method for estimating the visibility of halftone dot textures is presented. The estimates can be used in the design of dither signals. The method is based on the properties of human visual contrast sensitivity. The accuracy of the estimates was tested experimentally with dot textures produced by four different kinds of dither signals. The visibility predictions agreed very well with the results of psychophysical measurements.
Fatty acid activation of the reconstituted brown adipose tissue mitochondria uncoupling protein. (1985)

The effect of fatty acids, palmitoyl-CoA, and N',N-dicyclohexylcarbodiimide on the ion conductance of the reconstituted brown adipose tissue mitochondria uncoupling protein was investigated. 1, 5, and 10 microM palmitic acid induced a specific, GDP inhibited, increase in proton conductance in proteoliposomes containing the uncoupling protein but not in proteoliposomes prepared with purified protein extracts of liver mitochondria. 10 microM oleic acid, like palmitic acid, increased proton conductance in proteoliposomes prepared with the uncoupling protein. Palmitoyl-CoA and caprylic acid had no effect on increasing proton conductance. Similar to the observation in mitochondria, there was no effect of palmitic acid on Cl-conductance, but unlike mitochondria its activation by palmitoyl-CoA or inhibition by N',N-dicyclohexylcarbodiimide was lost. The results, obtained in an isolated system, provide support for the contention that long chain fatty acids act as an acute physiological activator of the uncoupling protein.
The AC Stark, Stern-Gerlach, and Quantum Zeno Effects in Interferometric Qubit Readout (1996)

This article describes the AC Stark, Stern-Gerlach, and Quantum Zeno effects as they are manifested during continuous interferometric measurement of a two-state quantum system (qubit). A simple yet realistic model of the interferometric measurement process is presented, and solved to all orders of perturbation theory in the absence of thermal noise. The statistical properties of the interferometric Stern-Gerlach effect are described in terms of a Fokker-Plank equation, and a closed-form expression for the Green's function of this equation is obtained. Thermal noise is added in the form of a externally-applied Langevin force, and the combined effects of thermal noise and measurement are considered. Optical Bloch equations are obtained which describe the AC Stark and Quantum Zeno effects. Spontaneous qubit transitions are shown to be observationally equivalent to transitions induced by external Langevin forces. The effects of delayed choice are discussed. Practical experiments involving trapped ions are suggested. The results are relevant to the design of qubit readout systems in quantum computing, and to single-spin detection in magnetic resonance force microscopy.
Low‐dose brimonidine for relief of ocular redness: integrated analysis of four clinical trials (2018)

In this integrated analysis, low-dose brimonidine significantly reduced ocular redness with no tachyphylaxis, and minimal rebound redness, and was generally safe and well tolerated.
New features of the temperature dependence of photoconductivity in plasma-deposited hydrogenated amorphous silicon alloys (1981)

The temperature and flux dependences of photoconductivity have been investigated for plasma-deposited hydrogenated amorphous silicon alloys produced under a variety of processing conditions. In undoped films, new features such as thermal quenching and supralinearity are observed. Such behavior is critically dependent on the position of the Fermi level, and is not observed in alloys doped by the addition to the plasma of PH3, B2H6, O2+N2 mixtures, or air. Interpretation of the data is based on a model of competing recombination centers.
Preparation and characterization of cubic boron nitride and metal boron nitride films* (1994)

Abstract Boron nitride has generated much scientific interest due to the outstanding material properties of its cubic modification (c‐BN) which can be compared with those of diamond, and to its metal (M) boron nitride compounds (MBN) which have extraordinary mechanical properties such as high hardness and high elasticity. This paper compares and discusses both of these thin film materials, concentrating in particular on their preparation and their mechanical properties in view of future applications as wear‐resistant coatings. There is a strong indication that the mechanism of c‐BN film formation by commonly used physical vapour deposition (PVD) methods is based on recoil implantation of surface atoms into deeper layers. This process creates considerable compressive stress compromising the production of technologically valuable coatings of c‐BN composition. On the other hand BN‐based transition metal films can be made as hard as or even harder than c‐BN films if suitable preparation methods are applied which promote nanometric grain sizes and a mixed phase composition. This paper discusses: (1) Ti implantation into hexagonal BN layers; and (2) co‐sputter deposition from a Ti and Hf target, respectively, and from a BN target; and (3) Ti/BN multilayer interdiffusion. MBN films show good adhesion to metallic substrates such as HSS steels, and preliminary wear tests with a pin‐on‐disk tribometer indicate promising characteristics. Bonding and chemical composition of the films were investigated by electron spectroscopy for chemical analysis (ESCA)‐Auger spectroscopy, the structure and crystallite size by glancing angle x‐ray diffractometry, and the hardness and elasticity by the nanoindentation technique.
Direct Small Molecule Activation of Mitofusins (2018)

Summary Mitochondrial fusion is a physiological process that is regulated by mitofusins on the outer mitochondrial membrane. Conformational plasticity between anti- and pro-tethering conformations of mitofusins permits mitochondrial tethering and subsequent fusion. Here we developed a pharmacophore-based model to rationally manipulate the conformational plasticity of mitofusin 2 and perfomed an in silico small-molecule screen. This enabled the discovery of a direct activator of mitofusins, MASM7, capable of potently promoting mitochondrial fusion. The specificity of the MASM7-mitofusin 2 interaction is highlighted by structure-activity relationships of MASM7 analogues, FRET, NMR and mitochondrial fusion studies using mitofusin mutants. Our study identified the first-in-class direct activator of mitofusins, demonstrating a new paradigm for chemical modulation of mitochondrial fusion and downstream processes.
Biodistribution of monoclonal IgG1, F(ab')2, and Fab' in mice after intravenous injection. Comparison between anti-B cell (anti-Lyb8.2) and irrelevant (MOPC-21) antibodies. (1987)

Quantitative pharmacokinetic measurements of uptake and metabolism for two murine immunoglobulin G1 (IgG1) monoclonal antibodies (anti-Lyb8.2, MOPC-21) and their F(ab')2 and Fab' fragments were obtained following i.v. administration into C57BL/6 mice. Anti-Lyb8.2 antibody, reactive with the allelic Lyb8.2 murine B cell antigen, was labeled with 125I, and MOPC-21, an antibody with no known target antigen, was labeled with 131I. The two IgG or their fragments were co-injected, and all major organs were analyzed. Specific uptake of anti-Lyb8.2 IgG, F(ab')2, and Fab' was observed in the spleen with maximum peak values occurring at 1 to 2 hr. For MOPC-21, blood and organ kinetics was indicative of a nontargeted IgG molecule. The kidneys showed significant and rapid uptake of anti-Lyb8.2 and MOPC-21 Fab' fragments. This uptake by kidneys attenuated the maximum peak values of anti-Lyb8.2 Fab' in spleen. Multiexponential data fitting provided mean residence times (MRT) for each organ. The MRT for anti-Lyb8.2 in all organs were greater than those for its F(ab')2 and Fab' fragments. Only the kidneys showed greater MRT for Fab' than for F(ab')2. Blood, spleen, kidneys, and carcass exhibited substantial differences across fragments. When total body MRT for each fragment was compared with that of the respective parent IgG molecule, a progressive decline was observed. For MOPC-21, the decrease in total body MRT for F(ab')2 demonstrates the influence of the Fc portion of the molecule on IgG1 metabolism. This organ-by-organ data set may be pertinent to other monoclonal antibodies and their fragments and should help in optimizing delivery of these molecules to specific sites in vivo for immunologic and clinical purposes.
Microcrystal delivery by pulsed liquid droplet for serial femtosecond crystallography (2016)

A liquid-droplet injector has been developed that delivers pristine microcrystals to an X-ray irradiation area for conducting serial femtosecond crystallography (SFX) with an X-ray free-electron laser (XFEL). By finely tuning the pulsed liquid droplets in time and space, a high hit rate of the XFEL pulses to microcrystals in the droplets was achieved for measurements using 5 µm tetragonal lysozyme crystals, which produced 4265 indexable diffraction images in about 30 min. The structure was determined at a resolution of 2.3 Å from <0.3 mg of protein. With further improvements such as reduction of the droplet size, liquid droplets have considerable potential as a crystal carrier for SFX with low sample consumption.
A promoter that acquired p53 responsiveness during primate evolution. (2003)

The tumor suppressor p53 activates the transcription of human PIG3 through direct interaction with a polymorphic microsatellite sequence, (TGYCC)(n). Here, the evolution of this p53-responsive element was recapitulated. Comparison between primate species revealed that the PIG3 promoter acquired this sequence element in its full length only in Hominoidea (apes and humans), whereas the number of TGYCC repeats is far lower in monkeys. Accordingly, only the PIG3 promoters from Hominoidea respond efficiently to p53, whereas those from monkeys respond poorly or not at all. In parallel, the PIG3 gene was strongly induced by p53 in human and chimpanzee cells but was unaffected by p53 in cells derived from a common marmoset monkey. Thus, a novel p53 target gene appeared as recently as during the evolution of primates. This suggests that mechanisms of tumor suppression are subject to ongoing evolution in humans and their closest relatives.
Relationship between the Tissue Distribution and Antitumor Activity of Highly Branched (1.RAR.3)-.BETA.-D-Glucan, SSG. (1994)

Distribution of 3H-labeled (1-->3)-beta-D-glucan([3H]SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, in various tissues in tumor-bearing mice was examined. [3H]SSG administered intra-peritoneally was mainly detected in liver, spleen, kidney and tumor masses. In contrast to i.p. administration, intra-lesionally administered [3H]SSG was not released from the tumor. Similarly, in a double grafted tumor system, [3H]SSG was located in the administered tumor and not distributed in the distant site tumor, in spite of the fact that significant antitumor effect was shown in both tumor sites in this system. Winn assay confirmed the activation of the systemic antitumor immunity. These results suggested that the distribution of glucans would be one important factor in determining their antitumor effects. However, this would not always be necessary if systemic immunity could be induced.
Altering Genotype and Phenotype by DNA-Mediated Gene Transfer (1980)

Transformation, or DNA-mediated gene transfer, permits the introduction of new genetic information into a cell and frequently results in a change in phenotype. The transforming DNA is ultimately integrated into a recipient cell chromosome. No unique chromosomal locations are apparent, different lines contain the transforming DNA on different chromosomes. Expression of transformed genes frequently results in the synthesis of new polypeptide products which restore appropriate mutant cells to the wild-type phenotype. Thus transformation provides an in vivo assay for the functional role of DNA sequence organization about specific genes. Transforming genes coding for selectable functions, such as adenine phosphoribosyltransferase or thymidine kinase, have now been isolated by utilizing transformation in concert with molecular cloning. Finally, transformation may provide a general approach to the analysis of complex heritable phenotypes by permitting the distinction between phenotypic changes without concomitant changes in DNA and functional genetic rearrangements.
Computer modeling of the effect of perfusion on heating patterns in radiofrequency tumor ablation (2007)

Computer modeling demonstrates that perfusion reduces both RF coagulation and the time to achieve thermal equilibrium. These results further show the importance of considering not only tumor perfusion, but also size (in addition to background tissue perfusion) when attempting to predict the effect of perfusion on RF heating and ablation times.
Torque density improvements for high performance machines (2013)

In this paper, the main aim is to propose and investigate possible methods for extending and improving the torque density capabilities of high performance, electrical machines. This is achieved by combining performance enhancing strategies such as the use of an outer rotor, the use of cobalt iron laminations and the adoption of high performance winding arrangements into a structured methodology that details the potential improvements step by step. A main point of interest of this paper is the permanent magnet demagnetisation analysis, resulting in the adoption of an optimum arrangement of a five stage, full-Halbach array. The above is presented in terms of an electrical machine used as an in-wheel motor in an aircraft traction application.
Histologic evaluation of rat mammary tumor necrosis by interstitial Nd:YAG laser hyperthermia (1992)

The extent of coagulative necrosis caused by interstitial laser hyperthermia was measured for different quantities of laser energy in a rat mammary tumor model. Continuous wave Nd:YAG laser at a power level of 5 W was focused onto a 600 mu diameter bare tip quartz fiber and placed inside a 19-gauge needle, which allowed the para-axial flow of normal saline at 1 cc/min. A microthermocouple soldered to the outside of the probe continuously provided the interstitial temperature. After the probe was inserted into the tumor, it was withdrawn as laser energy was administered at a rate sufficient to maintain the temperature within 42-45 degrees C. Tumors were excised after 48 hours, fixed in formalin, cut in 3 mm slices, and the coagulated surfaces measured microscopically. Laser fiber transmission loss was 1% per 1,000 J of laser energy and the average time required to coagulate 1 cc of tumor was 2 minutes. There was a statistically significant correlation between the volume of tumor necrosis and the level of laser irradiation (r = 0.71, P less than 0.001). It is concluded that the described technique is an efficient method of tumor coagulation by interstitial laser hyperthermia and proportionally larger volumes of necrosis are created with greater amounts of laser energy.
Unique Molecular Characteristics of Radiation-Induced Glioblastoma (2007)

Radiation-induced glioblastomas (RIGs) represent a significant proportion of glioblastomas (GBMs) seen in children and young adults and manifest poor prognosis. Little is known about their underlying biology, although limited studies have suggested no unique histologic or cytogenetic characteristics to distinguish them from de novo GBMs. In this study, we confirmed that a series of 5 RIGs showed no unique histologic or cytogenetic features compared with de novo pediatric GBMs, prompting us to further investigate RIGs using gene expression microarray profiling and Western blot analysis. Despite the inability of histologic and molecular genetic studies to identify distinguishing features between RIGs and pediatric GBMs, gene microarrays suggested significant differences between these 2 tumor types, at least those occurring in pediatric patients. Pediatric RIGs show greater homogeneity of gene expression than do de novo pediatric GBMs. Greater overlap was detected in gene expression patterns between RIGs and pilocytic astrocytomas than between RIGs and GBMs, medulloblastomas, ependymomas, atypical teratoid rhabdoid tumors, or rhabdomyosarcomas, suggesting a common precursor cell for RIG and pilocytic astrocytoma. Western blot analyses confirmed that ErbB3, Sox10, and platelet-derived growth factor receptor-alpha proteins were consistently expressed in RIGs but rarely in pediatric GBMs.
Macrophages as accessory cells for class I MHC-restricted immune responses (1991)

Ag do not elicit T lymphocyte responses unless they are presented in conjunction with MHC molecules on the surface of an appropriate APC. In the case of CD4+ T lymphocytes dendritic cells can deliver all signals required for complete induction as can macrophages and (activated) B cells. The function of CTL also depends on the presence of specialized accessory cells. Here we show that these accessory cells can behave like scavenger cells. They use foreign Ag in the form of cellular debris as immunogen. They are also crucial for CTL induction because in vivo depletion of phagocytotic cells completely inhibits CTL responses. In these animals CTL activity could be restored by transfer of macrophages. All of the reappearing CTL used MHC restriction elements expressed by the infused macrophages. These experiments suggest that a cognate interaction between macrophages and CTL precursors initiates class I MHC-restricted immune responses.
203 SAFETY AND EFFICACY OF THE MONOCLONAL ANTI-TNF ANTIBODY-FRAGMENT MAK 195F IN PATIENTS WITH SEPSIS AND SEPTIC SHOCK (1995)

Reinhart, K. MD.; Wieqand-Löhnert, C. MD.; Grimminqer, F. MD.; Kaul, M. MD. Author Information
A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. (1987)

Supernatants from a subset of helper T cell clones can enhance IgA, IgE, and IgG1 production in cultures of lipopolysaccharide-stimulated, T cell-depleted spleen cells. The lymphokine interleukin (IL)-4 has been shown to cause the IgE and IgG1 enhancement produced by these supernatants. IgA enhancement, however, is mediated by a factor distinct from IL-4, although IL-4 can potentiate the effect of the IgA-enhancing factor. IgA-enhancing factor is also distinct from IL-1, IL-2, IL-3, granulocyte-macrophage colony-stimulating factor, and interferon-gamma and acts directly on B cells. Purified IgA-enhancing factor enhances IgA production three- to sixfold yet causes less than a twofold increase in other isotypes. The IgA enhancing activity is not inhibited by concentrations of interferon-gamma that inhibit IL-4 activities. In the accompanying article, we show that this IgA enhancing activity is a novel property of the lymphokine IL-5.
Deep Lamellar Keratoplasty (DLKP) in Keratoconus Patients Using Viscoadaptive Viscoelastics (2005)

Healon V is a valuable tool for performing DLKP in difficult cases such as keratoconus.