gebhart/patrepeval huggingface dataset:
Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/syndecan-1/TGF-β autocrine loop (2016)

Sphingosine-1-phosphate (S1P) induces epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC). However, its underlying mechanism remains largely unknown. In the present study, we investigated the correlation between S1P and syndecan-1 in HCC, the molecular mechanism involved, as well as their roles in EMT of HCC. Results revealed a high serum S1P level presents in patients with HCC, which positively correlated with the serum syndecan-1 level. A significant inverse correlation existed between S1P1 and syndecan-1 in HCC tissues. S1P elicits activation of the PI3K/AKT signaling pathways via S1P1, which triggers HPSE, leading to increases in expression and activity of MMP-7 and leading to shedding and suppression of syndecan-1. The loss of syndecan-1 causes an increase in TGF-β1 production. The limited chronic increase in TGF-β1 can convert HCC cells into a mesenchymal phenotype via establishing an MMP-7/Syndecan-1/TGF-β autocrine loop. Finally, TGF-β1 and syndecan-1 are essential for S1P-induced epithelial to mesenchymal transition. Taken together, our study demonstrates that S1P induces advanced tumor phenotypes of HCC via establishing an MMP-7/syndecan-1/TGF-β1 autocrine loop, and implicates targetable S1P1-PI3K/AKT-HPSE-MMP-7 signaling axe in HCC metastasis.
Cell-Lysate Conversion of Prion Protein into Its Protease-Resistant Isoform Suggests the Participation of a Cellular Chaperone (1999)

A conformational transition between the normal cellular prion protein (PrPC) and the beta-sheet-rich pathological isoform (PrPSc) is a central event in the pathogenesis of spongiform encephalopathies. The prion infectious agent seems to contain mainly, if not exclusively, PrPSc, which has the ability to propagate its abnormal conformation by transforming the host PrPC into the pathological isoform. We have developed an in vitro system to induce the PrPC --> PrPSc conversion by incubating a cell-lysate containing mouse PrPC with partially purified mouse PrPSc. After 48 h of incubation with a 10-fold molar excess of PrPSc, the cellular protein acquired PK-resistance resembling a PrPSc-like state. Time course experiments suggest that the conversion follows a stepwise mechanism involving kinetic intermediates. The conversion was induced by PrPSc extracted from mice infected with two different prion strains, each propagating its characteristic Western blot profile. The latter results and the fact that all the cellular components are present in the conversion reaction suggest that PrPC-PrPSc interaction is highly specific and required for the conversion. No transformation was observed under the same conditions using purified proteins without cell-lysate. However, when PrPC-depleted cell-lysate was added to the purified proteins the conversion was recovered. These findings provide direct evidence for the participation of a chaperone-like activity involved in catalyzing the conversion of PrPC into PrPSc.
Role of Negative Pressure Wound Therapy in Treating Peripheral Vascular Graft Infections (2008)

Wound complications involving large subcutaneous vessels can cause significant challenges for surgeons. Negative pressure wound therapy (NPWT) has been increasingly used for treating complex wounds in vascular surgery, including groin infections, either as a bridge to surgical closure or as a primary wound treatment modality. Although a growing body of evidence exists for managing various problematic wounds, such as diabetic foot ulcers and open abdominal wounds, the role of NPWT in wounds involving large blood vessels or wounds complicating infected vascular grafts has not been well defined. A multidisciplinary advisory panel reviewed the literature relevant to wounds related to vascular surgical procedures and complications, focusing on large subcutaneous or infected vascular conduits. The results supported by the literature and the clinical practice of the consensus panel suggested that NPWT can be a useful adjunct to the management of vascular groin infections and dehiscences but must be used with caution.
Renewable hydrogen by aqueous-phase reforming of glucoseElectronic Supplementary Information (ESI) available: catalyst preparation and characterization; reaction kinetics studies; acknowledgements. See http://www.rsc.org/suppdata/cc/b3/b310152e/ (2003)

Hydrogen can be produced from aqueous solutions containing 10 wt% glucose with high selectivities through the combined use of a hydrogenation reactor for conversion of glucose to sorbitol, followed by a reforming reactor for conversion of sorbitol to H(2) and CO(2) and then a gas-liquid separator for the removal of high-pressure H(2)-rich reformate gas, ready for use in a fuel cell.
Optimization of Codon Usage of Plasmid DNA Vaccine Is Required for the Effective MHC Class I-Restricted T Cell Responses Against an Intracellular Bacterium (1998)

In an attempt to study codon usage effects of DNA vaccines on the induction of MHC class I-restricted T cell responses against an intracellular bacterium, Listeria monocytogenes, we designed two plasmid DNA vaccines encoding an H-2Kd-restricted epitope of listeriolysin O (LLO) of L. monocytogenes, LLO 91-99. One DNA vaccine, p91wt, carries the wild-type DNA sequence encoding LLO 91-99, and the other one, p91mam, possesses the altered DNA sequence in which the codon usage was optimized for murine system. Our read-through analyses with LLO 91-99/luciferase fusion genes confirmed that the optimized 91mam DNA sequence showed extremely higher translation efficiency than the wild-type sequence in murine cells. Consistent with this, i.m. injections of p91mam, but not of p91wt, into BALB/c mice were capable of inducing specific CTL- and IFN-gamma-producing CD8+ T cells able to confer partial protection against listerial challenge. Taken together, these observations suggest that optimization of codon should be taken into consideration in the construction of DNA vaccines against nonviral pathogens.
Metal‐Catalyzed Etching of Vertically Aligned Polysilicon and Amorphous Silicon Nanowire Arrays by Etching Direction Confinement (2010)

Abstract A systematic study of metal‐catalyzed etching of (100), (110), and (111) silicon substrates using gold catalysts with three varying geometrical characteristics: isolated nanoparticles, metal meshes with small hole spacings, and metal meshes with large hole spacings is carried out. It is shown that for both isolated metal catalyst nanoparticles and meshes with small hole spacings, etching proceeds in the crystallographically preferred &lt;100&gt; direction. However, the etching is confined to the single direction normal to the substrate surface when a catalyst meshes with large hole spacings is used. We have also demonstrated that the metal catalyzed etching method when used with metal mesh with large hole spacings can be extended to create arrays of polycrystalline and amorphous vertically aligned silicon nanowire by confining the etching to proceed in the normal direction to the substrate surface. The ability to pattern wires from polycrystalline and amorphous silicon thin films opens the possibility of making silicon nanowire array‐based devices on a much wider range of substrates.
Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents (2009)

First-time second-generation antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotic medications.
Getting our head in the clouds (2007)

Tagclouds are visual presentations of a set of words, typically a set of "tags" selected by some rationale, in which attributes of the text such as size, weight, or color are used to represent features, such as frequency, of the associated terms. This note describes two studies to evaluate the effectiveness of differently constructed tagclouds for the various tasks they can be used to support, including searching, browsing, impression formation and recognition. Based on these studies, we propose a paradigm for evaluating tagclouds and ultimately guidelines for tagcloud construction.
Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern (2022)

We assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir and its parent nucleoside EIDD-1931 and the viral protease inhibitor nirmatrelvir against the ancestral SARS-CoV2 strain and the five variants of concern including Omicron. VeroE6-GFP cells were pre-treated overnight with serial dilutions of the compounds before infection. The GFP signal was determined by high-content imaging on day 4 post-infection. All molecules have equipotent antiviral activity against the ancestral virus and the VOCs Alpha, Beta, Gamma, Delta and Omicron. These findings are in line with the observation that the target proteins of these antivirals (respectively the viral RNA dependent RNA polymerase and the viral main protease Mpro) are highly conserved.
Full Functionalization of the Imidazole Scaffold by Selective Metalation and Sulfoxide/Magnesium Exchange (2013)

Abstract A simple, flexible, and straightforward method for the functionalization of all the positions of the imidazole heterocycle through regioselective arylations, allylations, acylations, and additions to aldehydes is disclosed. Starting from the readily available key imidazole 1 , highly functionalized imidazole derivatives have been synthesized in a regioselective manner from directed metalations and a sulfoxide/magnesium exchange. Moreover, the selective N3‐alkylation followed by deprotection of N1 (trans‐N‐alkylation) allows the regioselective N‐alkylation of complex imidazoles.
Mechanical chest stimulation as a physiotherapy aid (1994)

In patients with lung disorders there is often a build up of mucus inside the lungs which in healthy people is normally removed by the action of cilia on the lung tissue surfaces. In the diseased lung, however, this clearance mechanism may be ineffective and so patients are offered physiotherapy in order to assist the mucus removal process. The consequences of not properly removing the mucus are impaired lung function and a much higher risk of contracting lung infections and suffering consequent permanent scarring of the lung tissues. If unchecked the latter leads ultimately to failure of the lungs and to the patient's death. The most common forms of chest physiotherapy used are percussion coupled with postural drainage and an active cycle of breathing. This requires the patient to lie head downwards on an inclined surface, so that gravity might assist the mucus removal process, whilst the physiotherapist strikes the patient's chest with the hands. The procedure is interspaced by periods of 'huffing and coughing' by the patient to remove the loosened sputum from the body. An alternative to the manual percussion described above is to use machinery to provide the stimulus to the chest. If such a procedure were found to be satisfactory then it would enable more patients to manage their own physiotherapy, may make the required duration of the physiotherapy sessions shorter, and would free much of the professional physiotherapists' time to enable them to assume more of a physiotherapy management role.(ABSTRACT TRUNCATED AT 250 WORDS)
Novel anti‐fatty acid synthase compounds with anti‐cancer activity in HER2+ breast cancer (2010)

Fatty acid synthase (FASN) expression and activity has emerged as a common phenotype in most human carcinomas, including breast cancer, and its expression is tightly linked to HER2 signaling pathways. The development of inhibitors of FASN activity has consequently appeared as a novel antitarget modality for treating cancer. However, the clinical use of FASN inhibitors, such as cerulenin, C75, and epigallocatechin 3-gallate (EGCG), is limited by anorexia and induced body weight loss or by its low in vivo potency and stability. Here, we summarize the design and development of G28UCM, the lead-compound of a novel family of synthetic FASN inhibitors, with both in vitro and in vivo activity in a human breast cancer model of FASN(+) and HER2(+) .
Magnesium homeostasis and aging (2009)

Aging is very often associated with magnesium (Mg) deficit. Total plasma magnesium concentrations are remarkably constant in healthy subjects throughout life, while total body Mg and Mg in the intracellular compartment tend to decrease with age. Dietary Mg deficiencies are common in the elderly population. Other frequent causes of Mg deficits in the elderly include reduced Mg intestinal absorption, reduced Mg bone stores, and excess urinary loss. Secondary Mg deficit in aging may result from different conditions and diseases often observed in the elderly (i.e. insulin resistance and/or type 2 diabetes mellitus) and drugs (i.e. use of hypermagnesuric diuretics). Chronic Mg deficits have been linked to an increased risk of numerous preclinical and clinical outcomes, mostly observed in the elderly population, including hypertension, stroke, atherosclerosis, ischemic heart disease, cardiac arrhythmias, glucose intolerance, insulin resistance, type 2 diabetes mellitus, endothelial dysfunction, vascular remodeling, alterations in lipid metabolism, platelet aggregation/thrombosis, inflammation, oxidative stress, cardiovascular mortality, asthma, chronic fatigue, as well as depression and other neuropsychiatric disorders. Both aging and Mg deficiency have been associated to excessive production of oxygen-derived free radicals and low-grade inflammation. Chronic inflammation and oxidative stress are also present in several age-related diseases, such as many vascular and metabolic conditions, as well as frailty, muscle loss and sarcopenia, and altered immune responses, among others. Mg deficit associated to aging may be at least one of the pathophysiological links that may help to explain the interactions between inflammation and oxidative stress with the aging process and many age-related diseases.
Human leukemia inhibitory factor inhibits development of experimental atherosclerosis. (1994)

The effect of human leukemia inhibitory factor (hLIF) on the development of atherosclerosis was investigated in an experimental animal model. Two conditions were examined: one in which lesions could arise because of the influence of both "injury" (cuffed vessel) and diet and one in which only the effect of diet could be significant in other areas of the vasculature (aorta). At time zero, the right carotid artery of rabbits (n = 32) was ensheathed in a soft Silastic cuff, and an osmotic minipump (2-mL capacity; 2.5 microL/h; 28 days) containing either hLIF or saline was inserted into the peritoneal cavity. Rabbits were divided into four groups (n = 8): group 1 received normal diet/saline; group 2, normal diet/LIF (30 micrograms.kg-1.d-1); group 3, 1% cholesterol diet/saline; and group 4, 1% cholesterol diet/LIF (30 micrograms.kg-1.d-1). After 28 days, the cholesterol diet (group 3) resulted in a sixfold increase in plasma cholesterol level compared with group 1 rabbits on a normal diet (3.80 +/- 0.50 versus 0.55 +/- 0.01 mmol/L). This was significantly lower (P = .01) with hLIF treatment in group 4 rabbits (2.80 +/- 0.44 mmol/L). Group 2 rabbits had higher aortic tissue cholesterol levels (1.40 +/- 0.35 mg/g) compared with group 1 rabbits on a normal diet (0.10 +/- 0.06 mg/g) (P = .01), whereas hLIF treatment decreased tissue cholesterol levels by 60% in group 4 rabbits (0.60 +/- 0.05 mg/g) (P = .01). Group 3 rabbits developed lipid-filled lesions covering 63.25 +/- 17.66% of the thoracic aorta surface, whereas lesions were significantly reduced (9.88 +/- 8.79%) (P = .01) with LIF treatment (group 4).(ABSTRACT TRUNCATED AT 250 WORDS)
THE ACTION OF SODIUM CROMOGLYCATE ON ‘C’ FIBRE ENDINGS IN THE DOG LUNG (1980)

The effect has been studied of sodium cromoglycate (SCG) on the activity of 'C' fibre sensory nerve endings in the canine lung. Pretreatment with SCG (100 microgram/kg i.v.) reduced the excitation of these endings by capsaicin (10 microgram/kg i.v.) for approximately 45 min. This property of SCG may explain its ability to suppress certain types of bronchoconstrictor responses in man.
Structure of polymerizable lipid bilayers. 6. Bilayer structure of three polymerizable diacetylenic glutamate lipids (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of polymerizable lipid bilayers. 6. Bilayer structure of three polymerizable diacetylenic glutamate lipidsDavid G. Rhodes, David A. Frankel, Thauming Kuo, and David F. O'BrienCite this: Langmuir 1994, 10, 1, 267–275Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/la00013a040https://doi.org/10.1021/la00013a040research-articleACS PublicationsRequest reuse permissionsArticle Views114Altmetric-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
Spinal cord injury‐induced lesional expression of the repulsive guidance molecule (RGM) (2005)

The repulsive guidance molecule (RGM) is involved in the formation of the central nervous system (CNS) during development by modulating guidance of growing axons. However, a role of RGM in CNS injury remains to be established. We studied the expression of RGM in the spinal cord of rats with spinal cord injury (SCI). After SCI, RGM+ cells accumulated in lesions and peri-lesional areas. During the first days after SCI, RGM expression was confined to neurons, ballooned neurite fibers/retraction bulbs, smooth muscle/endothelial cells, and to leucocytes infiltrating the lesion. Lesional RGM expression was frequently confined to hypertrophic beta-APP+ and RhoA+ neurites/retraction bulbs. With maturation of the lesion, we observed RGM expression by components of the developing scar tissue (cicatrix), such as fibroblastoid cells, reactive astrocytes and in addition a pronounced extracellular RGM deposition resembling neo-laminae. Frequent RGM+, RhoA+ coexpression by lesional retraction bulbs represent first preliminary evidence of RGM to exert growth inhibitory effects by the second messenger system RhoA. To date, RGM is one of the most potent axonal growth inhibitors identified and present in axonal growth impediments (i) oligodendrocytes; (ii) the plexus choroideus and (iii) components of the developing scar.
Identification of two flavivirus-like genomes in the GB hepatitis agent. (1995)

A subtractive PCR methodology known as representational difference analysis was used to clone specific nucleotide sequences present in the infectious plasma from a tamarin infected with the GB hepatitis agent. Eleven unique clones were identified, seven of which were examined extensively. All seven clones appeared to be derived from sequences exogenous to the genomes of humans, tamarins, Saccharomyces cerevisiae, and Escherichia coli. In addition, sequences from these clones were not detected in plasma or liver tissue of tamarins prior to their inoculation with the GB agent. These sequences were detected by reverse transcription-PCR in acute-phase plasma of tamarins inoculated with the GB agent. Probes derived from two of the seven clones detected an RNA species of > or = 8.3 kb in the liver of a GB-agent-infected tamarin by Northern blot hybridization. Sequence analysis indicated that five of the seven clones encode polypeptides that possess limited amino acid identity with the nonstructural proteins of hepatitis C virus. Extension of the sequences found in the seven clones revealed that plasma from an infected tamarin contained two RNA molecules > 9 kb long. Limited sequence identity with various isolates of hepatitis C virus and the relative positions of putative RNA helicases and RNA-dependent RNA polymerases in the predicted protein products of these molecules suggested that the GB agent contains two unique flavivirus-like genomes.
Altered Pharmacokinetics of 1α,25-Dihydroxyvitamin D3and 25-Hydroxyvitamin D3in the Blood and Tissues of the 25-Hydroxyvitamin D-24-Hydroxylase (Cyp24a1) Null Mouse (2004)

The 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) plays an important role in regulating concentrations of both the precursor 25-hydroxyvitamin D3 [25(OH)D3] and the hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)(2)D3]. Previous studies suggest that Cyp24a1-null mice cannot clear exogenous 1alpha,25(OH)2D3 efficiently. Here, we examined the metabolic clearance in Cyp24a1-null mice in vivo and in vitro using a physiological dose of [1beta-3H]1alpha,25(OH)2D3 or [26,27-methyl-3H]25(OH)D3. Cyp24a1-null mice showed difficulty in eliminating [1beta-3H]1alpha,25(OH)2D3 from the bloodstream and tissues over a 96-h time course, whereas heterozygotic mice eliminated the hormone within 6-12 h, although there was clearance of labeled hormone into water-soluble products involving liver in both genotypes. RT-PCR showed that Cyp24a1-null mice have decreased expression of 25-hydroxyvitamin D-1alpha-hydroxylase that must play a role in their survival. After the administration of [26,27-methyl-3H]25(OH)D3, Cyp24a1-null mice showed higher [26,27-methyl-3H]25(OH)D3 levels and no [26,27-methyl-3H]24,25(OH)2D3 formation, whereas heterozygotic mice showed significant [26,27-methyl-3H]24,25(OH)2D3 production. Based upon in vitro experiments, keratinocytes from Cyp24a1-null mice fail to synthesize [1beta-3H]calcitroic acid from [1beta-3H]1alpha,25(OH2D3 or [26,27-methyl-3H]24,25(OH)2D3 from [26,27-methyl-3H]25(OH)D3 as do control mice, confirming the target cell catabolic role of CYP24A1 in these processes. Finally, the role of vitamin D receptor (VDR) in the vitamin D catabolic cascade was examined using VDR-null mice. Keratinocytes from VDR-null mice failed to metabolize [1beta-3H]1alpha,25(OH)2D3 confirming the importance of vitamin D-inducible, VDR-mediated, C24 oxidation pathway in target cells. These results suggest that the absence of CYP24A1 or VDR retards catabolism of 1alpha,25(OH)2D3 and 25(OH)D3, reinforcing the physiological importance of CYP24A1 in vitamin D homeostasis.
RBP1 Recruits Both Histone Deacetylase-Dependent and -Independent Repression Activities to Retinoblastoma Family Proteins (1999)

Retinoblastoma (RB) tumor suppressor family proteins block cell proliferation in part by repressing certain E2F-specific promoters. Both histone deacetylase (HDAC)-dependent and -independent repression activities are associated with the RB "pocket." The mechanism by which these two repression functions occupy the pocket is unknown. A known RB-binding protein, RBP1, was previously found by our group to be an active corepressor which, if overexpressed, represses E2F-mediated transcription via its association with the pocket. We show here that RBP1 contains two repression domains, one of which binds all three known HDACs and represses them in an HDAC-dependent manner while the other domain functions independently of the HDACs. Thus, RB family members repress transcription by recruiting RBP1 to the pocket. RBP1, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function.