gebhart/patrepeval huggingface dataset:
Formulation Optimization and In Vivo Proof-of-Concept Study of Thermosensitive Liposomes Balanced by Phospholipid, Elastin-Like Polypeptide, and Cholesterol (2014)

One application of nanotechnology in medicine that is presently being developed involves a drug delivery system (DDS) employing nanoparticles to deliver drugs to diseased sites in the body avoiding damage of healthy tissue. Recently, the mild hyperthermia-triggered drug delivery combined with anticancer agent-loaded thermosensitive liposomes was widely investigated. In this study, thermosensitive liposomes (TSLs), composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP), were developed and optimized for triggered drug release, controlled by external heat stimuli. We introduced modified ELP, tunable for various biomedical purposes, to our thermosensitive liposome (e-TSL) to convey a high thermoresponsive property. We modulated thermosensitivity and stability by varying the ratios of e-TSL components, such as phospholipid, ELP, and cholesterol. Experimental data obtained in this study corresponded to results from a simulation study that demonstrated, through the calculation of the lateral diffusion coefficient, increased permeation of the lipid bilayer with higher ELP concentrations, and decreased permeation in the presence of cholesterol. Finally, we identified effective drug accumulation in tumor tissues and antitumor efficacy with our optimized e-TSL, while adjusting lag-times for systemic accumulation.
Variational Learning of Inducing Variables in Sparse Gaussian Processes (2009)

Sparse Gaussian process methods that use inducing variables require the selection of the inducing inputs and the kernel hyperparameters. We introduce a variational formulation for sparse approximations that jointly infers the inducing inputs and the kernel hyperparameters by maximizing a lower bound of the true log marginal likelihood. The key property of this formulation is that the inducing inputs are defined to be variational parameters which are selected by minimizing the Kullback-Leibler divergence between the variational distribution and the exact posterior distribution over the latent function values. We apply this technique to regression and we compare it with other approaches in the literature. 1
Upstream CpG island methylation of the PAX3 gene in human rhabdomyosarcomas (2004)

PAX3 CpG island methylation appears to distinguish embryonal subtype of rhabdomyosarcoma from alveolar, and methylation at certain sites within this CpG island is inversely correlated with PAX3 expression. In addition to exemplifying developmental dysregulation, methylation of PAX3 has potential in the development of an epigenetic profile for the diagnosis of rhabdomyosarcoma.
Interleukin-12 synthesis is a required step in trehalose dimycolate-induced activation of mouse peritoneal macrophages (1997)

Trehalose dimycolate (TDM), a glycolipid present in the cell wall of Mycobacterium spp., is a powerful immunostimulant. TDM primes murine macrophages (Mphi) to produce nitric oxide (NO) and to develop antitumoral activity upon activation with low doses of lipopolysaccharide (LPS). In this study, we investigated the ability of TDM to induce interleukin 12 (IL-12) and the role of this cytokine in TDM-induced activation of murine Mphi. RNA isolated from peritoneal exudate cells (PEC) collected at different times after TDM injection was used to determine IL-12 (p35 and p40 subunits) and gamma interferon (IFN-gamma) mRNA levels by semiquantitative reverse transcriptase-PCR. Constitutive expression of IL-12p35 was observed in PEC from untreated as well as from TDM-injected mice. In contrast, expression of the IL-12p40 subunit was almost undetectable in control PEC but was dramatically upregulated in PEC from TDM-injected mice. IL-12p40 expression peaked at 8 h and subsided to baseline levels at 39 h postinjection. TDM was also able to induce IFN-gamma expression; however, kinetics of induction of IFN-gamma was different from that of IL-12p40. Maximal levels of IFN-gamma mRNA were reached by 24 h and did not return to baseline by 4 days. In addition, pretreatment of mice with neutralizing monoclonal antibodies directed against IL-12 (C15.6.7 and C15.1.2) blocked IFN-gamma mRNA induction in PEC from TDM-treated mice. We further determined if the induction of IL-12 and/or IFN-gamma contributes to the in vivo priming effect of TDM on peritoneal Mphi. TDM-injected mice were treated in vivo with anti-IL-12 or anti-IFN-gamma (XMG.1.6) monoclonal antibodies. TDM-primed Mphi were then activated in vitro with LPS and tested for their ability to produce NO and to develop cytostatic activity toward cocultivated L1210 tumor cells. Priming of Mphi by TDM was completely blocked by in vivo neutralization of either IL-12 or IFN-gamma as demonstrated by an absence of tumoricidal activity and NO production by TDM-elicited Mphi in the presence of LPS. Taken together our results show that TDM, a defined molecule from M. tuberculosis, induces in vivo production of IL-12. Moreover, synthesis of IL-12 mediates TDM priming of mouse peritoneal Mphi through IFN-gamma induction.
Chemokine network in multiple sclerosis: role in pathogenesis and targeting for future treatments (2004)

Multiple sclerosis is the most common inflammatory disorder of the CNS. Evidence suggests that an immunomediated mechanism plays a crucial role during the development of the disease. Currently, two classes of immunomodulatory agents -- interferon-beta and glatiramer acetate (Copaxone, Teva Pharmaceutical Industries), have been approved for the long-term treatment of multiple sclerosis. New drugs which effectively target the immunological processes occurring in multiple sclerosis have been proposed. This review summarizes the immunological background that occurs during the pathogenesis of multiple sclerosis focusing on chemokines and related receptors. The effects of standard treatments on the immune system are analyzed along with the current knowledge of potential new immunomodulatory molecules, such as antiadhesion molecules, statins, estriol, cannabinoids, neurotrophic factors and chemokine antagonists.
Factors Influencing the Quality of Carbon Coatings on LiFePO[sub 4] (2007)

Several composites were prepared and characterized electrochemically in lithium half-cells. Pressed-pellet conductivities correlated well with the electrochemical performance in lithium half-cells. It was found that carbon structural factors such as and disordered/graphene (D/G), as determined by Raman spectroscopy, and ratios determined from elemental analysis influenced the conductivity and rate behavior strongly. The structure of the residual carbon could be manipulated through the use of additives during synthesis. Increasing the pyromellitic acid (PA) content in the precursor mix prior to calcination resulted in a significant lowering of the D/G ratio and a concomitant rise in the ratio of the carbon. Addition of both iron nitrate and PA resulted in higher ratios without further lowering the D/G ratios or increasing carbon contents. The best electrochemical results were obtained for processed with both ferrocene and PA. The improvement is attributed to better decomposition of the carbon sources, as evidenced by lower ratios, a slight increase of the carbon content (still below ), and more homogeneous coverage. A discussion of the influence of carbon content vs structural factors on the composite conductivities and, by inference, the electrochemical performance is included.
DEVELOPMENT OF CRYOGENIC LOOP HEAT PIPE (2008)

The design of a cryogenic loop heat pipe (CLHP) is presented in the paper. As the wick is required only in the evaporator section, very small pore size wicks can be used in applications with high thermal transport requirements and/or where the heat must be transported over a long distance against gravity. A FORTRAN program to solve the mathematical model and to determine the parameters for various boundary conditions has been developed. The CLHP is designed to transfer 5W heat at 70K using nitrogen or oxygen as working fluid. It will be a self priming type device which can operate against gravity with evaporator above the condenser as well as under microgravity condition. A G-M type single stage double inlet pulse tube refrigerator is coupled to the CLHP to test its performance. The mathematical model, design, fabrication integration of the heat pipe with the pulse tube system and testing with stainless steel wick at the evaporator will be described in the paper.
Circulating Nonesterified Fatty Acid Level as a Predictive Risk Factor for Sudden Death in the Population (2001)

Circulating NEFA concentration is an independent risk factor for sudden death in middle-aged men. Some form of primary prevention could be envisaged in subjects at high risk of sudden death.
Adhesion of human breast carcinoma to extracellular matrix proteins is modulated by galectin-3. (1997)

In this report, we have analyzed the adhesive interactions of a breast carcinoma cell line, BT-549, and its galectin-3-transfected subclone 11-9-1-4 with laminin, collagen IV and fibronectin. We determined that 11-9-1-4 cells adhered much more rapidly (within 1 h of plating) to laminin- and collagen IV-coated wells than the galectin-3 null expressing BT-549 cells. However, after 24 h, both cell lines fully adhered to laminin and collagen IV. Both cell lines also achieved maximum adhesion to fibronectin within 30 min. Not only did 11-9-1-4 express galectin-3 in the usual punctate pattern on its cell surface, it demonstrated a higher surface expression of alpha 6 beta 1 integrin compared to BT-549. The 11-9-1-4 cells were able to invade through matrigel-coated polycarbonate filters at approximately 3 times the rate of BT-549 parental cells. Our data suggest that galectin-3 is essential for adhesion to laminin and collagen IV but not fibronectin by breast carcinoma cells. In addition, galectin-3 expression may modulate the surface expression of some of the integrins specific for laminin and collagen IV adhesion and invasion of basement membrane by breast carcinoma cells.
Motuporamines A−C, Cytotoxic Alkaloids Isolated from the Marine Sponge Xestospongia exigua (Kirkpatrick) (1998)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTMotuporamines A−C, Cytotoxic Alkaloids Isolated from the Marine Sponge Xestospongia exigua (Kirkpatrick)David E. Williams, Peter Lassota, and Raymond J. AndersenView Author Information Departments of Chemistry and Oceanography, Earth & Ocean Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada, and Oncology and Immunology Division, Wyeth Ayerst Research, 401 North Middletown Road, Pearl River, New York 10965 Cite this: J. Org. Chem. 1998, 63, 14, 4838–4841Publication Date (Web):June 18, 1998Publication History Received24 February 1998Published online18 June 1998Published inissue 1 July 1998https://pubs.acs.org/doi/10.1021/jo980355phttps://doi.org/10.1021/jo980355pbrief-reportACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views497Altmetric-Citations56LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbene compounds,Carbon,Mixtures,Organic compounds,Resonance structures Get e-Alerts
Lateral membrane LXA4 receptors mediate LXA4's anti-inflammatory actions on intestinal epithelium (2003)

Lipoxin A(4) (LXA(4)) and its stable analogs downregulate chemokine secretion in polarized epithelia. This anti-inflammatory effect has been suggested to be mediated by the LXA(4) receptor (LXA(4)R), a G protein-coupled receptor. To determine whether LXA(4)R is expressed on the apical, basolateral, or both poles of intestinal epithelia, an NH(2)-terminal c-myc epitope tag was added to the human LXA(4)R cDNA and recombinant retroviruses were used to transduce polarized epithelial cells. In polarized T84 intestinal epithelial cells, c-myc-LXA(4)R was preferentially expressed on the basolateral surface as indicated by cell surface-selective biotinylation and confocal microscopy. Furthermore, expression of c-myc-LXA(4)R and a truncation mutant lacking the cytoplasmic terminus was primarily confined to the lateral subdomain. We also observed that the expression of myc-LXA(4) conferred enhanced downregulation of IL-8 expression in response to LXA(4) analog and that blockade of the CysLT1 receptor by montelukast did not prevent this response to LXA(4) analog. Thus LXA(4) generated in or near the paracellular space via neutrophil-epithelial interactions can rapidly act on epithelial LXA(4)R to downregulate epithelial promotion of intestinal inflammation.
Detection of seizure foci by recurrent neural networks (2002)

Localization of epileptic foci is an important step in planning surgical treatment of medically intractable epilepsy. The solution to this problem depends on the detection of the earliest time of seizure onset in multiple channels of EEG data. We have been investigating a seizure-detection system based on recurrent neural networks to detect the onset of seizure activity in multi-channel subdural EEG (SEEG) data. The recurrent neural network used in this investigation is a fully-connected, three-layer, recurrent network, in which the output is given by: x(t+1)=f([/spl Sigma/(P1(t)*W12)+x(t)*W3]), where f(/spl middot/) is the activation function; P1 is the output of the input unit; W12 is the weight of the connection between the input and the hidden units; W3 is the weight value of the recurrent connection. Using an adaptive backpropagation gradient-descent algorithm, the network is trained on sets of pre-seizure data (target value of zero) and seizure data (target value of unity), specified over discrete time-intervals, from 76-electrode SEEG records from a patient with intractable seizures. The network's performance is measured by a linear-regression metric (R value) obtained from a fit between the target value and network output for each electrode and time-interval in the record. A metric with a value approaching unity in the pre-seizure component of the record suggests the onset of seizure activity. Ordering these metrics with respect to subdural electrode positions may provide useful information about the epileptogenic foci.
Identification of the Sites of Interaction between Lymphocyte Phosphatase-associated Phosphoprotein (LPAP) and CD45 (1995)

Human lymphocyte phosphatase-associated phospho-protein (LPAP) is a phosphoprotein of unknown function that noncovalently associates with CD45 in lymphocytes. In CD45-deficient human T cells, LPAP protein is synthesized at normal levels but is more rapidly degraded than in wild-type cells. Expression of CD45 cDNA rescues LPAP protein expression. This strongly suggests that LPAP is protected from degradation through its interaction with CD45. We have mapped the sites of interaction between LPAP and CD45 employing chimeric CD45 molecules and LPAP deletion mutants. Our data demonstrate that the interaction between LPAP and CD45 is mediated via the transmembrane regions of both molecules. In addition, the intracytoplasmic amino acids adjacent to the transmembrane region of LPAP may influence its binding to CD45.
A Bipolar Membrane Combined with Ferric Iron Reduction as an Efficient Cathode System in Microbial Fuel Cells (2006)

There is a need for alternative catalysts for oxygen reduction in the cathodic compartment of a microbial fuel cell (MFC). In this study, we show that a bipolar membrane combined with ferric iron reduction on a graphite electrode is an efficient cathode system in MFCs. A flat plate MFC with graphite felt electrodes, a volume of 1.2 L and a projected surface area of 290 cm2 was operated in continuous mode. Ferric iron was reduced to ferrous iron in the cathodic compartment according to Fe(3+) + e(-) --> Fe2+ (E0 = +0.77 V vs NHE, normal hydrogen electrode). This reversible electron transfer reaction considerably reduced the cathode overpotential. The low catholyte pH required to keep ferric iron soluble was maintained by using a bipolar membrane instead of the commonly used cation exchange membrane. For the MFC with cathodic ferric iron reduction, the maximum power density was 0.86 W/m2 at a current density of 4.5 A/m2. The Coulombic efficiency and energy recovery were 80-95% and 18-29% respectively.
Coordinate Regulation of STAT Signaling and c-fosExpression by the Tyrosine Phosphatase SHP-2 (1998)

The src homology 2 (SH2) domain-containing protein-tyrosine phosphatase SHP-2 has been implicated as an important positive regulator of several mitogenic signaling pathways. SHP-2 has more recently been shown to be tyrosine phosphorylated and recruited to the gp130 component of the ciliary neurotrophic factor (CNTF) receptor complex upon stimulation with CNTF. CNTF does not, however, have a proliferative effect on responsive cells, but rather enhances the survival and differentiation of sympathetic, motor, and sensory neurons. In this study, expression of an interfering mutant of SHP-2 in the neuroblastoma cell line NBFL increased CNTF induction of a vasoactive intestinal peptide (VIP) reporter gene, and in cultures of sympathetic neurons, it resulted in an up-regulation of endogenous VIP and substance P (SP) gene expression. Members of the CNTF family of cytokines transmit their signal by activating signaling pathways involving both STAT and Fos-Jun transcription factors. In CNTF-stimulated NBFL cells that constitutively express the SHP-2 interfering mutant, there was increased and prolonged formation of STAT/DNA complexes, but decreased AP-1 binding activity, that mirrored a down-regulation of c-fos expression both at the mRNA and protein level. Taken together, these data indicate that SHP-2 has dual and opposing roles in a signaling cascade triggered by the same ligand, as illustrated by its ability to differentially regulate the levels of activity of both STAT and AP-1 transcription factors.
Role of thromboxane in retinal microvascular degeneration in oxygen-induced retinopathy (2001)

Microvascular degeneration is an important event in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity. Because oxidant stress abundantly generates thromboxane A2 (TxA2), we tested whether TxA2 plays a role in retinal vasoobliteration of OIR and contributes to such vascular degeneration by direct endothelial cytotoxicity. Hyperoxia-induced retinal vasoobliteration in rat pups (80% O2 exposure from postnatal days 5-14) was associated with increased TxB2 generation and was significantly prevented by TxA2 synthase inhibitor CGS-12970 (10 mg x kg(-1) x day(-1)) or TxA2-receptor antagonist CGS-22652 (10 mg x kg(-1) x day(-1)). TxA2 mimetics U-46619 (EC50 50 nM) and I-BOP (EC50 5 nM) caused a time- and concentration-dependent cell death of neuroretinovascular endothelial cells from rats as well as newborn pigs but not of smooth muscle and astroglial cells; other prostanoids did not cause cell death. The peroxidation product 8-iso-PGF2, which is generated in OIR, stimulated TxA2 formation by endothelial cells and triggered cell death; these effects were markedly diminished by CGS-12970. TxA2-dependent neuroretinovascular endothelial cell death was mostly by necrosis and to a lesser extent by apoptosis. The data identify an important role for TxA2 in vasoobliteration of OIR and unveil a so far unknown function for TxA2 in directly triggering neuroretinal microvascular endothelial cell death. These effects of TxA2 might participate in other ischemic neurovascular injuries.
Mammalian .beta.2-adrenergic receptor: reconstitution of functional interactions between pure receptor and pure stimulatory nucleotide binding protein of the adenylate cyclase system (1984)

Pure beta-adrenergic receptors (beta-AR) isolated from guinea pig lung and pure guanine nucleotide binding regulatory protein (NS) of adenylate cyclase isolated from human erythrocytes have been inserted into phospholipid vesicles, resulting in the functional coupling of these two components. The reconstitution of receptor and NS interactions results in the establishment of a guanine nucleotide sensitive state of the receptor that binds agonists with high affinity. Competition curves of isoproterenol for labeled antagonist binding to vesicles containing both beta-AR and NS are biphasic and reveal two affinity states, one of high (approximately 2 nM) and the other of low affinity (approximately 300 nM). In the presence of guanine nucleotides, the competition curves become monophasic and are shifted to a single low-affinity state for the agonist similar to the situation observed in membrane preparations. In addition, the interactions of the receptor and NS lead to the induction of a GTPase activity in NS. The GTPase activity can be stimulated by beta-adrenergic agonists such as isoproterenol (2-5-fold) and is completely blocked by antagonists such as alprenolol in a stereoselective manner. The established hormone responsive activity retains the beta 2-adrenergic specificity conferred by the pure receptor, and similar extents of stimulation (up to 4-fold) are observed with pure receptor from frog erythrocytes, indicating a similar efficiency of coupling between receptors from different species and NS.(ABSTRACT TRUNCATED AT 250 WORDS)
Defining epithelial cell dynamics and lineage relationships in the developing lacrimal gland (2017)

The tear-producing lacrimal gland is a tubular organ that protects and lubricates the ocular surface. The lacrimal gland possesses many features that make it an excellent model in which to investigate tubulogenesis, but the cell types and lineage relationships that drive lacrimal gland formation are unclear. Using single-cell sequencing and other molecular tools, we reveal novel cell identities and epithelial lineage dynamics that underlie lacrimal gland development. We show that the lacrimal gland from its earliest developmental stages is composed of multiple subpopulations of immune, epithelial and mesenchymal cell lineages. The epithelial lineage exhibits the most substantial cellular changes, transitioning through a series of unique transcriptional states to become terminally differentiated acinar, ductal and myoepithelial cells. Furthermore, lineage tracing in postnatal and adult glands provides the first direct evidence of unipotent KRT5<sup>+</sup> epithelial cells in the lacrimal gland. Finally, we show conservation of developmental markers between the developing mouse and human lacrimal gland, supporting the use of mice to understand human development. Together, our data reveal crucial features of lacrimal gland development that have broad implications for understanding epithelial organogenesis.