gebhart/patrepeval huggingface dataset:
Overexpression of Autophagy-Related Genes Inhibits Yeast Filamentous Growth (2007)

Under conditions of nitrogen stress, the budding yeast S. cerevisiae initiates a cellular response involving the activation of autophagy, an intracellular catabolic process for the degradation and recycling of proteins and organelles. In certain strains of yeast, nitrogen stress also drives a striking developmental transition to a filamentous form of growth, in which cells remain physically connected after cytokinesis. We recently identified an interrelationship between these processes, with the inhibition of autophagy resulting in exaggerated filamentous growth. Our results suggest a model wherein autophagy mitigates nutrient stress, and filamentous growth is responsive to the degree of this stress. Here, we extended these studies to encompass a phenotypic analysis of filamentous growth upon overexpression of autophagy-related (ATG) genes. Specifically, overexpression of ATG1, ATG3, ATG7, ATG17, ATG19, ATG23, ATG24 and ATG29 inhibited filamentous growth. From our understanding of autophagy in yeast, overexpression of these genes does not markedly affect the activity of the pathway; thus, we do not expect that this filamentous growth phenotype is due strictly to diminished nitrogen stress in ATG overexpression mutants. Rather, these results highlight an additional undefined regulatory mechanism linking autophagy and filamentous growth, possibly independent of the upstream nitrogen-sensing machinery feeding into both processes.
Evolving conceptualizations of cocaine dependence. (1988)

Cocaine was considered incapable of producing dependence in 1980 but was proclaimed the "drug of greatest national public health concern" by 1984. Clinical consensus in 1980 held that cocaine did not produce a withdrawal syndrome, but recent clinical investigations demonstrate that cocaine produces unique abuse and withdrawal patterns that differ from other major abused drugs. Evolving pre-clinical research over the past two decades now suggests that chronic cocaine abuse produces neurophysiological alterations in specific central nervous system systems that regulate the capacity to experience pleasure. These evolving clinical and pre-clinical constructs have led to applications of promising experimental pharmacological treatments for cocaine abuse.
Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate (2003)

Hepatocyte growth factor (HGF)/scatter factor (SF) is a unique growth factor, in that it binds both heparan sulphate (HS) and dermatan sulphate (DS). The sequences in HS and DS that specifically interact with and modulate HGF/SF activity have not yet been fully identified. Ascidian DS, which uniquely possesses O-sulphation at C-6 (and not C-4) of its N -acetylgalactosamine unit, was analysed for HGF/SF-binding activity in the biosensor. The kinetic analysis revealed a strong, biologically relevant interaction with an equilibrium dissociation constant ( K (d)) of approx. 1 nM. An Erk activation assay also demonstrated stimulation of the MAP kinase pathway downstream of the Met receptor following addition of both HGF/SF and ascidian DS to the glycosaminoglycan-deficient CHO-745 mutant cell line. Furthermore, the activation of Met and the MAP kinase pathway by HGF/SF and ascidian DS leads to a cellular response in the form of migration.
Selective N-Type Calcium Channel Antagonist Omega Conotoxin MVIIA Is Neuroprotective Against Hypoxic Neurodegeneration in Organotypic Hippocampal-Slice Cultures (1996)

These studies present clear evidence that neuroprotection by selective N-type calcium channel antagonists is mediated directly through neuronal calcium channels. In contrast, the neuroprotective effects of dihydropyridines may be mediated through vascular calcium channels or indirectly through actions in other brain regions.
Folate-Chitosan Nanoparticles Loaded with Ursolic Acid Confer Anti-Breast Cancer Activities in vitro and in vivo (2016)

Ursolic acid (UA) has proved to have broad-spectrum anti-tumor effects, but its poor water solubility and incompetent targeting property largely limit its clinical application and efficiency. Here, we synthesized a nanoparticle-based drug carrier composed of chitosan, UA and folate (FA-CS-UA-NPs) and demonstrated that FA-CS-UA-NPs could effectively diminish off-target effects and increase local drug concentrations of UA. Using MCF-7 cells as in vitro model for anti-cancer mechanistic studies, we found that FA-CS-UA-NPs could be easily internalized by cancer cells through a folate receptor-mediated endocytic pathway. FA-CS-UA-NPs entered into lysosome, destructed the permeability of lysosomal membrane, and then got released from lysosomes. Subsequently, FA-CS-UA-NPs localized into mitochondria but not nuclei. The prolonged retention of FA-CS-UA-NPs in mitochondria induced overproduction of ROS and destruction of mitochondrial membrane potential, and resulted in the irreversible apoptosis in cancer cells. In vivo experiments showed that FA-CS-UA-NPs could significantly reduce breast cancer burden in MCF-7 xenograft mouse model. These results suggested that FA-CS-UA-NPs could further be explored as an anti-cancer drug candidate and that our approach might provide a platform to develop novel anti-cancer drug delivery system.
Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996)

In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease. These findings provide preclinical evidence that the presence of the epsilon 4 allele is a risk factor for Alzheimer's disease. PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease.
Materialized Views in Oracle (1998)

Oracle Materialized Views (MVs) are designed for data warehousing and replication. For data warehousing, MVs based on inner/outer equijoins with optional aggregation, can be refreshed on transaction boundaries, on demand, or periodically. Refreshes are optimized for bulk loads and can use a multi-MV scheduler. MVs based on subqueries on remote tables support bidirectional replication. Optimization with MVs includes transparent query rewrite based on costbased selection method. The ability to rewrite a large class of queries based on a small set of MVs is supported by using Dimensions (new Oracle object), losslessness of joins, functional dependency, column equivalence, join derivability, joinback and aggregate rollup.
Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes. (1997)

The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.
Novel Fatty Acid Acylation of Lens Integral Membrane Protein Aquaporin-0 (2010)

Fatty acid acylation of proteins is a well-studied co- or posttranslational modification typically conferring membrane trafficking signals or membrane anchoring properties to proteins. Commonly observed examples of protein acylation include N-terminal myristoylation and palmitoylation of cysteine residues. In the present study, direct tissue profiling mass spectrometry of bovine and human lens sections revealed an abundant signal tentatively assigned as a lipid-modified form of aquaporin-0. LC/MS/MS proteomic analysis of hydrophobic tryptic peptides from lens membrane proteins revealed both N-terminal and C-terminal peptides modified by 238 and 264 Da which were subsequently assigned by accurate mass measurement as palmitoylation and oleoylation, respectively. Specific sites of modification were the N-terminal methionine residue and lysine 238 revealing, for the first time, an oleic acid modification via an amide linkage to a lysine residue. The specific fatty acids involved reflect their abundance in the lens fiber cell plasma membrane. Imaging mass spectrometry indicated abundant acylated AQP0 in the inner cortical region of both bovine and human lenses and acylated truncation products in the lens nucleus. Additional analyses revealed that the lipid-modified forms partitioned exclusively to a detergent-resistant membrane fraction, suggesting a role in membrane domain targeting.
Molecular Targets of Cancer Imaging and Therapy Application (2000)

Improvement of scintigraphic tumor imaging is extensively determined by development of more tumor specific radiopharmaceuticals. Radionuclide imaging modalities(positron emission tomography, PET; single photon emission computed tomography, SPECT)are diagnostic cross-sectional imaging techniques that map the location and concentration of radionuclide-labeled radiotracers. Although CT and MRI provide considerable anatomic information about the location and the extent of tumors, these imaging modalities cannot adequately differentiate invasive lesions from edema, radiation necrosis or grading. PET and SPECT can be used to localize and characterize tumors by measuring metabolic activity. Due to favorable physical characteristics and low price,99mTc radionuclide has been the choice for labeling. To improve the diagnosis, prognosis, planning and monitoring of treatment of cancer using functional pharmaceuticals, we have developed a series of99mTc-labeled radiotracers. Application of molecular targets for cancer imaging and therapy are the major focus of this report.
Selective catalytic dehydrogenation of 1,4-cyclohexadiene to benzene. 1. Radical anions derived from transition-metal arene complexes as promoters (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective catalytic dehydrogenation of 1,4-cyclohexadiene to benzene. 1. Radical anions derived from transition-metal arene complexes as promotersGiovanni FochiCite this: Organometallics 1988, 7, 10, 2255–2256Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/om00100a037https://doi.org/10.1021/om00100a037research-articleACS PublicationsRequest reuse permissionsArticle Views268Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals. (2007)

The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001), negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left and spontaneously beating right atrial muscle preparations, respectively. Moreover, PAE reduced or abolished, in a concentration-dependent manner, the positive inotropic and chronotropic responses of guinea pig isolated atrial muscle strips induced by noradrenaline (NA, 10(-10)-10(-5) M), and calcium (Ca(2+), 5-40 mM). PAE (50-800 mg/ml) also significantly reduced (p < 0.05-0.001) or abolished, in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from healthy normal Wistar rats. Like acetylcholine (ACh, 10(-8)-10(-5) M), the plant extract (25- 800 mg/ml) produced concentration-related relaxations of isolated endothelium-containing thoracic aortic rings pre-contracted with noradrenaline. The vasorelaxant effects of PAE in the isolated, endothelium-intact aortic rings were markedly inhibited or annulled by N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor. Furthermore, PAE (25-400 mg/kg iv) caused dose-related, transient but significant reductions (p < 0.05-0.001) in the systemic arterial blood pressure and heart rates of the anaesthetised normotensive and hypertensive rats used. The results of this laboratory animal study indicate that PAE caused bradycardia, vasorelaxation and hypotension in the mammalian experimental models used. The vasorelaxant action of PAE was endothelium dependent, and was, therefore, possibly dependent on the synthesis and release of nitric oxide (NO). The vasorelaxant effects of PAE appeared to contribute significantly to the hypotensive (antihypertensive) effects of the plant extract. However, the findings of this study tend to suggest that P americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.
Comparison and analysis of phase noise in ring oscillators (2002)

Voltage-controlled oscillators are widely used circuit blocks, particularly in phase-locked loops. As CMOS is the technology of choice for many applications, CMOS oscillators with low phase noise and timing jitter are highly desired. CMOS ring oscillators with five different delay cell topologies have been designed, fabricated and evaluated for phase noise performance. Our results show that ring oscillators with linear loads provide much better phase noise performance than oscillators with nonlinear loads. We also observe that well designed single-ended oscillators have phase noise that is on par or better than oscillators with fully differential delay stages. Both our analysis and measurement results suggest that large signal voltage swing and improved linearity of the delay cells help reduce oscillator phase noise.
Laser welding of titanium in dentistry (1988)

Unalloyed titanium of the quality used for osseointegrated implants by the method of Brånemark is also sometimes used for the metallic part of the prosthetic superstructure placed on the fixtures and for crowns and bridges of conventional type. Forty bars of titanium, 8 of ASTM B 348 grade-1 quality and 32 of ASTM B 348 grade-2 quality, were laser-welded, using dissimilar laser joint variables. Tensile strength, 0.2% proof stress, and percentage elongation of the welded bars were measured and compared with the corresponding values for the titanium bars as delivered and with those of brazed type-3 gold alloy bars of similar dimensions. The type of fracture was evaluated from fractographs. The results showed that the use of certain defined laser joint variables during welding produced values for the mechanical properties studied which were more favorable than those obtained from the brazed gold bars. The fracture of the titanium specimens was ductile, with dimples occurring at the fracture surfaces.
Expression of 5-lipoxygenase and leukotriene A 4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability (2006)

Leukotrienes (LT) are a group of proinflammatory lipid mediators that are implicated in the pathogenesis and progression of atherosclerosis. Here we report that mRNA levels for the three key proteins in LTB4 biosynthesis, namely 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTA4 hydrolase (LTA4H), are significantly increased in human atherosclerotic plaque (n = 72) as compared with healthy controls (n = 6). Neither LTC4 synthase nor any of the LT receptors exhibits significantly increased mRNA levels. Immunohistochemical staining revealed abundant expression of 5-LO, FLAP, and LTA4H protein, colocalizing in macrophages of intimal lesions. Human lesion tissue converts arachidonic acid into significant amounts of LTB4, and a selective, tight-binding LTA4H inhibitor can block this activity. Furthermore, expression of 5-LO and LTA4H, but not FLAP, is increased in patients with recent or ongoing symptoms of plaque instability, and medication with warfarin correlates with increased levels of FLAP mRNA. In contrast to human plaques, levels of 5-LO mRNA are not significantly increased in plaque tissues from two atherosclerosis-prone mouse strains, and mouse plaques exhibit segregated cellular expression of LTA4H and 5-LO as well as strong increases of CysLT1 and CysLT2 mRNA. These discrepancies indicate that phenotypic changes in the synthesis and action of LT in specific mouse models of atherosclerosis should be cautiously translated into human pathology. The abundant expression of LTA4H and correlation with plaque instability identify LTA4H as a potential target for pharmacological intervention in treatment of human atherosclerosis.
Safe and Complete Exclusion of the Left Atrial Appendage (2008)

A standardized technique to permanently exclude the left atrial appendage during cardiac surgical procedures to potentially prevent stroke has never been established. We describe a simplified technique using a combination of endoloop occlusion with direct purse-string suturing supported with multiple teflon pledgets placed epicardially at the base of the appendage. The left atrial appendage is subsequently opened and decompressed to facilitate contraction and scarring, reducing or eliminating the possibility of recannalization. The technique was used successfully in 195 off-pump coronary bypass grafting patients with long-term echocardiographic follow-up.
Molecular mechanism for the formation of the high-affinity complex of interleukin 2 and its receptor. (1988)

Interleukin 2 (IL-2) binds to its receptors with three distinct affinities, with Kd values of 10(-11) M (high), 10(-9) M (intermediate) and 10(-8) M (low). IL-2 responding cells express two proteins that bind IL-2, i.e. a 55 x 10(3) Mr protein (p55 or L chain), which has classically been known as the IL-2 receptor and a second 75 x 10(3) Mr chain (p75 or H chain) with intermediate affinity. Experiments were performed to clarify the mechanism of the high-affinity site formation. Crosslinking of human IL-2 with the high-affinity sites of human T lymphocytes yielded a 150 x 10(3) Mr ternary complex consisting of IL-2, L and H chains. The ternary complex with human IL-2 was formed on EL/Tac 3 cells expressing human L and murine H chains, although human IL-2 was unable to bind to the parental EL-4 cell, which does not express human L chain. The high-affinity ternary complex was stable during solubilization and fractionated by gel-filtration chromatography, and the numbers of these complexes were quantified by this method. The number of high-affinity sites on the CT/hR-1 cells, which express the human L, murine L and murine H chains, was almost constant even when either the human or murine L chain was blocked by specific antibodies in agreement with a previous observation. These results indicate that the L and H chains do not form a stable binary complex by themselves and that IL-2 binding induces the formation of the stable high-affinity ternary complex.
[Fluoxetin combined with cyclobenzaprine in the treatment of fibromyalgia]. (1994)

The aim of this study is to evaluate the effectiveness of fluoxetin associated with cyclobenzaprine vs cyclobenzaprine in the treatment of fibromyalgia. Twenty-one females with fibromyalgia were randomly assigned to 2 groups: group A (11 patients) was treated over 12 weeks with fluoxetin (20 mg/die) and cyclobenzaprine (10 mg/die), group B with cyclobenzaprine (10 mg/die). Basally and after 12 weeks patient self-assessment of pain, number of painful tender points, tender points index and morning stiffness were evaluated. The study has shown a significant improvement of the examined parameters in both treatment groups; however the comparison between the two groups showed a greater effectiveness, statistically significant, of the treatment with Fluoxetin associated with cyclobenzaprine.
Impaired tumor microenvironment in EphA2‐deficient mice inhibits tumor angiogenesis and metastatic progression (2005)

EphA2 belongs to a unique family of receptor tyrosine kinases that play critical roles in development and disease. Since EphA2 is required for ephrin-A1 ligand-induced vascular remodeling and is overexpressed in a variety of vascularized human adenocarcinomas, we assessed tumor angiogenesis and metastatic progression in EphA2-deficient host animals. 4T1 metastatic mammary adenocarcinoma cells transplanted subcutaneously and orthotopically into EphA2-deficient female mice displayed decreased tumor volume, tumor cell survival, microvascular density, and lung metastasis relative to tumor-bearing littermate controls. To determine if the phenotype in EphA2-deficient mice was endothelial cell intrinsic, we also analyzed endothelial cells isolated from EphA2-deficient animals for their ability to incorporate into tumor vessels in vivo, as well as to migrate in response to tumor-derived signals in vitro. EphA2-deficient endothelial cells displayed impaired survival and failed to incorporate into tumor microvessels in vivo, and displayed impaired tumor-mediated migration in vitro relative to controls. These data suggest that host EphA2 receptor tyrosine kinase function is required in the tumor microenvironment for tumor angiogenesis and metastatic progression.
Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial (2005)

Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.