gebhart/patrepeval huggingface dataset:
Angiotensin-Converting Enzyme 2 Overexpression in the Subfornical Organ Prevents the Angiotensin II–Mediated Pressor and Drinking Responses and Is Associated With Angiotensin II Type 1 Receptor Downregulation (2008)

We recently reported the presence of angiotensin-converting enzyme (ACE)2 in brain regions controlling cardiovascular function; however, the role of ACE2 in blood pressure regulation remains unclear because of the lack of specific tools to investigate its function. We hypothesized that ACE2 could play a pivotal role in the central regulation of cardiovascular function by regulating other renin-angiotensin system components. To test this hypothesis, we generated an adenovirus expressing the human ACE2 cDNA upstream of an enhanced green fluorescent protein (eGFP) reporter gene (Ad-hACE2-eGFP). In vitro characterization shows that neuronal cells infected with Ad-hACE2-eGFP (10 to 100 multiplicities of infection), but not Ad-eGFP (100 multiplicities of infection), exhibit dose-dependent ACE2 expression and activity. In addition, an active secreted form was detected in the conditioned medium. In vivo, Ad-hACE2-eGFP infection (2x10(6) plaque-forming units intracerebroventricularly) produced time-dependent expression and activity (with a peak at 7 days) in the mouse subfornical organ. More importantly, 7 days after virus infection, the pressor response to angiotensin (Ang) II (200 pmol intracerebroventricularly) was significantly reduced in Ad-hACE2-eGFP-treated mice compared with controls. Furthermore, subfornical organ-targeted ACE2 overexpression dramatically reduced the Ang II-mediated drinking response. Interestingly, ACE2 overexpression was associated with downregulation of the Ang II type 1 receptor expression both in vitro and in vivo. These data suggest that ACE2 overexpression in the subfornical organ impairs Ang II-mediated pressor and drinking responses at least by inhibiting the Ang II type 1 receptor expression. Taken together, our results show that ACE2 plays a pivotal role in the central regulation of blood pressure and volume homeostasis, offering a new target for the treatment of hypertension and other cardiovascular diseases.
Optomechanically Induced Transparency (2010)

Electromagnetically induced transparency is a quantum interference effect observed in atoms and molecules, in which the optical response of an atomic medium is controlled by an electromagnetic field. We demonstrated a form of induced transparency enabled by radiation-pressure coupling of an optical and a mechanical mode. A control optical beam tuned to a sideband transition of a micro-optomechanical system leads to destructive interference for the excitation of an intracavity probe field, inducing a tunable transparency window for the probe beam. Optomechanically induced transparency may be used for slowing and on-chip storage of light pulses via microfabricated optomechanical arrays.
Transgenic Mouse Model for Rapid Pharmacodynamic Evaluation of Antiandrogens (2006)

Persistent androgen receptor signaling has been implicated as a critical factor in prostate cancer progression even at the hormone-refractory stage and provides strong rationale for developing novel androgen receptor antagonists. Traditional models for in vivo evaluation of antiandrogens are cumbersome because they rely on physiologic end points, such as the size of androgen-dependent tissues. Here, we describe a transgenic mouse (ARR2 Pb-Lux) that expresses luciferase specifically in the prostate in an androgen-dependent fashion. This signal is reduced by castration or by treatment with bicalutamide and can be quantified through noninvasive bioluminescent imaging. ARR2 Pb-Lux mice provide a novel method for rapid pharmacodynamic evaluation of novel pharmacologic compounds designed to inhibit androgen receptor signaling.
Na+/K+-ATPase α1 subunit, a novel therapeutic target for hepatocellular carcinoma (2015)

We aimed to identify the expression patterns of Na+/K+-ATPase (NKA) α subunits in human hepatocellular carcinoma (HCC) samples and evaluate these subunits as potential targets for HCC treatment. The mRNA expression profiles of NKA α subunits in human HCC samples were analyzed. We found that the mRNA expression for NKA α1 subunit (ATP1A1) was higher than that for other NKA α subunits. Also, ATP1A1 gene expression was markedly higher in HCC samples than in adjacent nontumor tissue samples. Western blotting data suggested that 6 of 14 (43%) HCC samples had elevated ATP1A1 protein expression. Furthermore, knockdown of ATP1A1 expression in human HCC HepG2 and MHCC97H cells markedly reduced their proliferation in vitro and suppressed the tumorigenicity of MHCC97H cells in vivo. Downregulation of ATP1A1 expression resulted in cell-cycle arrest at G2/M phase and apoptosis in HepG2 cells as well as decreased migration in Hep3B cells. We further validated that ATP1A1 downregulation caused intracellular accumulation of reactive oxygen species. Pretreatment with N-acetyl cysteine blocked cell-growth inhibition induced by ATP1A1 downregulation. Collectively, these data suggested that targeting ATP1A1 is a novel approach to the treatment of HCC.
Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth (1989)

Sympathetic neurons release both urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA). A number of inhibitors of serine proteases have been tested to determine their effects on neurite outgrowth from rat sympathetic neurons. Some inhibitors increase neurite outgrowth while others have little or no effect on outgrowth. Inhibition of plasminogen activator (PA) activity but not other serine protease activity correlates with the increase in neurite outgrowth (uPA, r = 0.89; tPA, r = 0.86; plasmin, r = 0.015; thrombin, r = 0.025). Antibodies that inhibit uPA activity increase neurite outgrowth, while antibodies that bind to uPA but do not inhibit activity do not alter outgrowth. Time-lapse videomicroscopy of neurite outgrowth indicates that about 85% of the neurites increase their rate of outgrowth following exposure to inhibitors of PA. Routinely, 1-2 min after exposure of a growth cone to an inhibitor, there is an increase in lamellipodial activity at the leading edge of the growth cone and a decrease in lamellipodial activity on the sides and base of the growth cone. The increase in the rate of outgrowth combined with the decrease in lamellipodial activity on the sides of the growth cones results in neurites being very long and straight in the presence of inhibitors (persistence time P = 3.7 and 15.3 hr for controls and in the presence of inhibitors of PA, respectively). PAs released from sympathetic neurons and PC12 cells interact with 3 different binding sites on the cell surface: (1) an inhibitor of serine proteases (including uPA and tPA) is bound to the surface via a heparinase-sensitive site; (2) a uPA-selective binding site is present in patches on the bottom surface of PC12 cells; and (3) a tPA-selective binding site with high affinity (KD = 23 +/- 10 nM) and high capacity (340,000 +/- 130,000 sites/neuron) for 125I-tPA is homogeneously distributed over the entire surface. Data in the present study are consistent with PA being involved in neurite outgrowth and open the possibility of other PA-dependent functions occurring when tPA and/or uPA interacts with cell surface binding sites.
Demonstration of Distortion Suppression in Photonic Time-Stretch ADC using Back Propagation Method (2007)

We experimentally demonstrate the performance of the recently proposed "OBP" algorithm based on optical phase retrieval by numerical back-propagation. Using this technique, distortion due to the modulator transfer function as well as the group velocity dispersion in a photonic time-stretch ADC (TS-ADC) can be suppressed, and frequency fading eliminated thanks to the use of a dual output "phase diverse" modulator. The algorithm was tested with a swept input signal frequency from 10 to 50 GHz. as well as with a two-tone signal, and is shown to recover the signal even in the presence of fading with a distortion suppression of up to 26 dB. These results also constitute the first experimental demonstration of channel combining in a phase diverse TS-ADC.
Comparative Biodistribution of PAMAM Dendrimers and HPMA Copolymers in Ovarian-Tumor-Bearing Mice (2010)

The biodistribution profile of a series of linear N-(2-hydroxylpropyl)methacrylamide (HPMA) copolymers was compared with that of branched poly(amido amine) dendrimers containing surface hydroxyl groups (PAMAM-OH) in orthotopic ovarian-tumor-bearing mice. Below an average molecular weight (MW) of 29 kDa, the HPMA copolymers were smaller than the PAMAM-OH dendrimers of comparable molecular weight. In addition to molecular weight, hydrodynamic size and polymer architecture affected the biodistribution of these constructs. Biodistribution studies were performed by dosing mice with (125)iodine-labeled polymers and collecting all major organ systems, carcass, and excreta at defined time points. Radiolabeled polymers were detected in organ systems by measuring gamma emission of the (125)iodine radiolabel. The hyperbranched PAMAM dendrimer, hydroxyl-terminated, generation 5 (G5.0-OH), was retained in the kidney over 1 week, whereas the linear HPMA copolymer of comparable molecular weight was excreted into the urine and did not show persistent renal accumulation. PAMAM dendrimer, hydroxyl-terminated, generation 6.0 (G6.0-OH), was taken up by the liver to a higher extent, whereas the HPMA copolymer of comparable molecular weight was observed to have a plasma exposure three times that of this dendrimer. Tumor accumulation and plasma exposure were correlated with the hydrodynamic sizes of the polymers. PAMAM dendrimer, hydroxyl-terminated, generation 7.0 (G7.0-OH), showed extended plasma circulation, enhanced tumor accumulation, and prolonged retention with the highest tumor/blood ratio for the polymers under study. Head-to-head comparative study of HPMA copolymers and PAMAM dendrimers can guide the rational design and development of carriers based on these systems for the delivery of bioactive and imaging agents.
Crown polyether chemistry. Potassium permanganate oxidations in benzene (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrown polyether chemistry. Potassium permanganate oxidations in benzeneDonnie J. Sam and Howard E. SimmonsCite this: J. Am. Chem. Soc. 1972, 94, 11, 4024–4025Publication Date (Print):May 1, 1972Publication History Published online1 May 2002Published inissue 1 May 1972https://doi.org/10.1021/ja00766a069RIGHTS & PERMISSIONSArticle Views1946Altmetric-Citations256LEARN 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 InReddit PDF (261 KB) Get e-Alerts Get e-Alerts
Transduction of cytotoxic signals in natural killer cells: a general model of fine tuning between activatory and inhibitory pathways in lymphocytes (1997)

NK-cells are large granular lymphocytes, which are capable of exerting two major types of effector function, cell cytotoxicity and lymphokine secretion. NK-cells can exert cell cytotoxicity in one of two ways. First, NK-cells are able to recognize and to induce the lysis of antibody-coated target cells during antibody-dependent cell cytotoxicity (ADCC). Second, during natural cytotoxicity NK-cells are also able to recognize and to induce the lysis of a variety of target cells, including primarily virus-infected cells as well as tumor cells. Recently, a novel mechanism has been elucidated which controls NK-cell-activation programs and which is based on the cell surface expression of killer-cell inhibitory receptors (KIR). We will review here the molecular dissection of this inhibitory signalling pathway which utilizes immunoreceptor tyrosine-based inhibition motifs (ITIM) expressed in KIR intracytoplasmic domain. We will also show that this strategy used by NK-cells to regulate their effector functions is a general decision mechanism which exists not only in T- and B-lymphocytes, but also in a variety of other hematopoietic cells.
Regulation of glut1 mRNA by Hypoxia-inducible Factor-1 (2001)

Oncogenic transformation and hypoxia both induce glut1 mRNA. We studied the interaction between the ras oncogene and hypoxia in up-regulating glut1 mRNA levels using Rat1 fibroblasts transformed with H-ras (Rat1-ras). Transformation with H-ras led to a substantial increase in glut1 mRNA levels under normoxic conditions and additively increased glut1 mRNA levels in concert with hypoxia. Using a luciferase reporter construct containing 6 kilobase pairs of the glut1 promoter, we showed that this effect was mediated at the transcriptional level. Promoter activity was much higher in Rat1-ras cells than in Rat1 cells and could be down-regulated by cotransfection with a dominant negative Ras construct (RasN17). A 480-base pair (bp) cobalt/hypoxia-responsive fragment of the promoter containing a HIF-1 binding site showed significantly higher activity in Rat1-ras cells than in Rat1 cells, suggesting that Ras might mediate its effect through HIF-1 even under normoxic conditions. Consistent with this, Rat1-ras cells displayed higher levels of HIF1-alpha protein under normoxic conditions. In addition, a promoter construct containing a 4-bp mutation in the HIF1 binding site showed lower activity in Rat1-ras cells than a construct with an intact HIF1 binding site. The activity of the latter construct but not the former could be down-regulated by RasN17, supporting the importance of the HIF1 binding site in regulation by Ras. The phosphatidylinositol 3-kinase inhibitor LY29004 down-regulated glut1 promoter activity and mRNA levels under normoxia and also decreased HIF1alpha protein levels in these cells. Collectively these results indicate that H-Ras up-regulates the glut1 promoter, at least in part, by increasing HIF-1alpha protein levels leading to transactivation of promoter through the HIF-1 binding site.
Guillain–Barré syndrome, CIDP and other chronic immune‐mediated neuropathies (1998)

aDepartments of Neurology, Karl Franzens University Graz, Austria, bErasmus University Rotterdam, The Netherlands and cInstitute of Clinical Neurosciences, University of Sydney, Australia Correspondence to Professor Hans-Peter Hartung, Department of Neurology Karl Franzens University, Auenbruggerplatz 22, A‐8036 Graz, Austria Tel: +43 316 385 2981; Fax: +43 316 325520; E-mail: [email protected] Abbreviations; AIDP: acute inflammatory demyelinating neuropathy; AMAN: acute motor axonal neuropathy; CIDP: chronic inflammatory demyelinating polyradiculoneuropathy; GBS: Guillan–Barré syndrome
A spherical-section ultrasound phased array applicator for deep localized hyperthermia (1991)

Computer simulation shows that a new ultrasound phased-array with nonplanar geometry has considerable potential as an applicator for deep localized hyperthermia. The array provides precise control over the heating pattern in three dimensions. The array elements form a rectangular lattice on a section of a sphere. Therefore, the array has a natural focus at its geometric center when all its elements are driven in phase. When compared to a planar array with similar dimensions, the spherical-section array provides higher focal intensity gain which is useful for deep penetration and heat localization. Furthermore, the relative grating-lobe level (with respect to the focus) is lower for scanned foci synthesized with this array (compared to a planar array with equal center-to-center spacing and number of elements). This could be the key to the realization of phased-array applicator systems with a realistic number of elements. The spherical-section array is simulated as a spot-scanning applicator and, using the pseudo-inverse pattern synthesis method, to directly synthesize heating patterns overlaying the tumor geometry. A combination of the above two methods can be used to achieve the desired heating pattern in the rapidly varying tumor environment.
Efficacy, immunogenicity and stability of a novel intranasal Nanoemulsion-adjuvanted influenza vaccine in a murine model (2010)

Mutations of influenza virus increase concerns of worldwide epidemics resulting from the newly emergent strains. Current influenza vaccines are inefficient and require annual vaccinations. W805EC adjuvant is an oil-in-water emulsion composed of nanodroplets with an average diameter of approximately 400 nm. The nanoemulsion adjuvant has been used successfully to stimulate the immune response when mixed with several other antigens in animal models. In this study, W805EC nanoemulsion adjuvant activity was evaluated using nasal influenza vaccination in a murine model. Five to twenty percent W805EC adjuvant was used to inactivate influenza A/Puerto Rico/8/34/05 (H1N1). Mice immunized with the nanoemulsion adjuvanted influenza virus intranasally showed a robust specific humoral immune response as demonstrated using ELISA and HAI assays. Serum HAI titers were more than 104 following two vaccinations. Vaccinated mice were also protected against challenge with an LD80 of live influenza virus. Splenocytes from vaccinated mice were assayed for cytokine production following virus stimulation. The cytokine profile demonstrated a robust cellular immune response with enhanced Th1 and Th17 immunity that provided balanced immunity against both intracellular and extracellular forms of the virus. Additionally, the vaccine preparations showed minimal protein degradation but remained potent when stored at 4°C for up to three months. This work demonstrates that W805EC nanoemulsion adjuvant can effectively enhance the immunogenicity of influenza hemagglutinin antigen. The nanoemulsion adjuvant can result in antigen sparing and cross-protection. The potential exists for a nasally administered influenza vaccine that may require little or no refrigerated storage.
Ranibizumab for Macular Edema Due to Retinal Vein Occlusions: Implication of VEGF as a Critical Stimulator (2008)

Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3 or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the 0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical coherence tomography (OCT) showed that compared to injections of 0.3 mg, injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of central retinal thickening that lasted longer between injections, but in 3 months, excess central retinal thickening which is a quantitative assessment of the macular edema, was reduced by approximately 90% in all four treatment groups. There was no correlation between the amount of improvement and duration of disease or patient age at baseline, but there was some correlation between the aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of improvement. These data indicate that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to macular edema and suggest that additional studies investigating the efficacy of intraocular injections of ranibizumab are needed.
Synergistic anticellular effect of a combination of beta-interferon and retinoic acid against U937 cells. (1985)

Both human beta-interferon (IFN-beta) and retinoic acid (RA) are able to induce the differentiation of the human histiocytic lymphoma cell line U937, but neither one alone can effectively eliminate the leukemic cells. When U937 cells are incubated with a combination of IFN-beta (200 units/ml) and RA (0.1-1.0 microM), extensive cell death can be observed as early as day 3 posttreatment, and IFN-beta alone at a concentration as high as 10(4) units/ml is ineffective. These data suggest that there is a strong synergistic cell killing effect between IFN-beta and RA against the U937 cells. This effect is so highly selective that similar enhancement has not been detected using a closely related cell line, HL-60, and RA enhances neither IFN-alpha nor IFN-gamma in the killing of U937 cells. The mechanism of such synergism is unknown in the present study, but it appears that cytostasis or promotion of differentiation alone cannot account for this phenomenon since neither activity is enhanced to any appreciable extent.
Water solubility enhancements of DDT and trichlorobenzene by some surfactants below and above the critical micelle concentration (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTWater solubility enhancements of DDT and trichlorobenzene by some surfactants below and above the critical micelle concentrationDaniel E. Kile and Cary T. ChiouCite this: Environ. Sci. Technol. 1989, 23, 7, 832–838Publication Date (Print):July 1, 1989Publication History Published online1 May 2002Published inissue 1 July 1989https://doi.org/10.1021/es00065a012RIGHTS & PERMISSIONSArticle Views2917Altmetric-Citations363LEARN 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 InReddit PDF (895 KB) Get e-Alerts Get e-Alerts
Elucidating the Landscape of Aberrant DNA Methylation in Hepatocellular Carcinoma (2013)

Substantial changes of DNA methylation at a genome-wide level were observed in HCC. Understanding epigenetic changes in HCC will help to elucidate the pathogenesis and may eventually lead to identification of molecular markers for liver cancer diagnosis, treatment and prognosis.