gebhart/patrepeval huggingface dataset:
In Vitro and In Vivo Pharmacology of trans‐ and cis‐(±)‐1‐Amino‐1,3‐Cyclopentanedicarboxylic Acid: Dissociation of Metabotropic and Ionotropic Excitatory Amino Acid Receptor Effects (1991)

This study explored further the function of the metabotropic excitatory amino acid receptor in the rat brain. The trans and cis isomers of (+-)-1-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were characterized for relative affinities at ionotropic and metabotropic excitatory amino acid receptors in vitro, as well as ability to produce in vivo excitatory or excitotoxic effects in rats. trans-ACPD was about 12 times more potent in vitro as an agonist for metabotropic excitatory amino acid receptors when compared to its ability to displace N-methyl-D-aspartate (NMDA) ([3H]CGS-19755) receptor binding, cis-ACPD was about 30 times more potent as a displacer of [3H]CGS-19755 binding than as a stimulant of phosphoinositide hydrolysis. When administered intraperitoneally to neonatal rats, both cis- and trans-ACPD produced convulsions that were prevented by the competitive NMDA receptor antagonists, LY233053 and LY274614. cis-ACPD was six times more potent as a convulsant when compared to trans-ACPD. Both compounds were examined for excitotoxic effects in vivo following stereotaxic injection into the mature or neonatal rat striatum. Doses of trans-ACPD of up to 5,000 or 1,200 nmol produced few signs of striatal neuronal degeneration in the mature or neonatal brain, respectively. However, cis-ACPD produced extensive dose-related neuronal degeneration at doses of 100-1,000 nmol in the mature brain and 50-200 nmol in the neonatal brain. These studies suggest that, unlike the ionotropic excitatory amino acid receptors, activation of the metabotropic excitatory amino acid receptor does not result directly in excitatory effects, such as excitotoxicity.
Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells. (1995)

Growth factors have been used experimentally to accelerate wound healing by increasing scar tissue formation at a wound site. These studies suggest that stimulation of fibroblastic differentiation and proliferation are essential components of adult tissue repair. Recent studies report the presence of mesenchymal stem cells within granulation tissue and as connective tissue-resident stem cells. This suggests that mesenchymal stem cells as well as fibroblasts may contribute to wound healing and repair. To determine the potential for mesenchymal stem cells to contribute to nonfibrogenic tissue repair, a clonal population of murine mesenchymal stem cells was examined with dexamethasone, a general differentiation agent, and muscle morphogenetic protein, a specific differentiation-inducing agent. Dexamethasone induced the expression of phenotypic markers for fat, cartilage, and bone in the stem cells. Muscle morphogenetic protein induced the expression of mRNAs for the muscle specific regulatory genes MyoD1 and myogenin in these cells. These results suggest that pluripotent mesenchymal stem cells within connective tissue compartments and granulation tissue have the potential to contribute to functional tissue restoration, rather than contributing solely to fibrogenic scar tissue formation during tissue repair.
2×2 wavelength-selective cross connect capable of switching 128 channels in sets of 8 (2001)

We present an efficient 2×2 wavelength selective cross connect that is serviceable without interrupting traffic. It can handle over a hundred channels in a compact fashion by operating on them in sets. The 50-GHz-spaced passbands are flat topped with no gaps between them.
Reciprocal mesenchymal-epithelial interaction affecting prostate tumour growth and hormonal responsiveness. (1991)

A novel cell-cell recombination model was established to test the reciprocal mesenchymal (fibroblast)-epithelial interaction in the prostate gland. Both growth factors and ECM pathways were found to be actively engaged during cellular communications. The application of this cell-cell recombination concept to prostate cancer established a new human prostate cancer animal model in which the tumours actively secrete prostate specific antigen, a known human prostate cancer marker. This review explores the significance of mesenchymal-epithelial interaction in determining prostate hormonal responsiveness and prostate cell transformation and speculates on the potential roles of mesenchymal-epithelial interaction in prostate cancer growth and progression.
Denoising MR Spectroscopic Imaging Data With Low-Rank Approximations (2012)

This paper addresses the denoising problem associated with magnetic resonance spectroscopic imaging (MRSI), where signal-to-noise ratio (SNR) has been a critical problem. A new scheme is proposed, which exploits two low-rank structures that exist in MRSI data, one due to partial separability and the other due to linear predictability. Denoising is performed by arranging the measured data in appropriate matrix forms (i.e., Casorati and Hankel) and applying low-rank approximations by singular value decomposition (SVD). The proposed method has been validated using simulated and experimental data, producing encouraging results. Specifically, the method can effectively denoise MRSI data in a wide range of SNR values while preserving spatial-spectral features. The method could prove useful for denoising MRSI data and other spatial-spectral and spatial-temporal imaging data as well.
The somatotrophic axis in young steers: influence of nutritional status and oestradiol-17β on hepatic high-and low-affinity somatotrophic binding sites (1988)

The binding of bovine GH (bGH) to hepatic membranes obtained from steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an oestradiol-17 beta implant was studied (n = 5 per group). Binding studies were performed on both crude membrane homogenates and on 100,000 g microsomal membrane fractions; identical results were obtained using both preparations. In all four groups of animals, linear Scatchard plots were obtained, but following pretreatment of the membranes with MgCl2 to remove endogenously bound hormone, curvilinear plots were obtained in the groups on the high plane of nutrition. Analysis of these curves suggested the presence of a high- and low-affinity binding site, the high-affinity site being fully occupied in the absence of MgCl2 pretreatment. The specific binding of bGH in MgCl2-pretreated crude membranes was greater (P less than 0.01) in well-fed steers (14.8 +/- 1.6%) than in poorly fed steers (9.8 +/- 0.9%). Scatchard analysis showed this to be due to the presence of a high-affinity site (dissociation constant (Kd) = 11.6 +/- 3.3 pmol/l) in the well-fed animals only. In addition, there was an increase (P less than 0.01) in the affinity, but not in the capacity, of the low-affinity site (Kd = 106.4 +/- 22.8 pmol/l in well-fed steers and 197.0 +/- 23.8 pmol/l in poorly fed steers).(ABSTRACT TRUNCATED AT 250 WORDS)
Gd-DOTA, A Potential MRI Contrast Agent Current Status of Physicochemical Knowledge (1988)

The complex (Gd-DOTA) meglumine has recently been used as an MRI contrast agent in humans. Due to its particularly interesting physicochemical properties, the risk of in vivo dissociation of the complex is reduced. Indeed, as a result of the macrocyclic nature of the DOTA ligand, Gd-DOTA appears very stable, demonstrating a calculated conditional stability constant of 10(22.19) at pH = 7. Other characteristics making Gd-DOTA a positively attractive compound include slow dissociation kinetics inherent in the rigidity of the macrocycle and marked specific affinity of DOTA for gadolinium in comparison with other endogenous ions. Finally, although the relaxivity R1 of Gd-DOTA at 20 MHz appears similar to that of Gd-DTPA, Gd-DOTA demonstrates higher paramagnetic efficacy at low field strength due to greater symmetry of the complex. Such promising properties open up wide prospects for the use of Gd-DOTA in MRI.
STATL: An attack language for state-based intrusion detection (2002)

STATL is an extensible state/transition-based attack description language designed to support intrusion detection. The language allows one to describe computer penetrations as sequences of actions that an attacker performs to compromise a computer system. A STATL description of an attack scenario c an be used by an intrusion detection system to analyze a stream of events and detect possible ongoing intrusions. Since intrusion detection is performed in different domains (i.e., the network or the hosts) and in different operating environments (e.g., Linux, Solaris, or Windows NT), it is useful to have an extensible language that can be easily tailored to different target environments. STATL defines domain-independent features of attack scenarios and provides constructs for extending the language to describe attacks in particular domains and environments. The STATL language has been successfully used in describing both network-based and host-based attacks, and it has been tailored to very different environments, e.g., Sun Microsystems' Solaris and Microsoft's Windows NT. An implementation of the runtime support for the STATL language has been developed and a toolset of intrusion detection systems based on STATL has been implemented. The toolset was used in a recent intrusion detection evaluation effort, delivering very favorable results. This paper presents the details of the STATL syntax and its semantics. Real examples from both the host and network-based extensions of the language are also presented.
GABAAReceptor Pharmacology and Subtype mRNA Expression in Human Neuronal NT2-N Cells (1998)

Human NT2 teratocarcinoma cells differentiate into neuron-like NT2-N cells when treated with retinoic acid. GABA evoked concentration-dependent whole-cell currents in NT2-N cells with an EC50 of 21.8 microM and a Hill slope of 1.2. GABAA receptor (GABAR) currents reversed at ECl- and did not display voltage-dependent rectification. GABAR single channels opened in bursts to a 23 pS main conductance level and a 19 pS subconductance level, with infrequent openings to a 27 pS conductance level. Kinetic properties of the main conductance level were similar to other native and recombinant GABAR channels. Diazepam and zolpidem enhanced GABAR currents with moderate affinity, whereas methyl-6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate inhibited GABAR currents. Loreclezole enhanced GABAR currents with high affinity, but furosemide antagonized GABAR currents with low affinity. The neurosteroids alphaxalone and pregnenolone sulfate appropriately modulated GABAR currents. Zinc blocked GABAR currents with low affinity, but lanthanum did not significantly alter NT2-N GABAR currents. Reverse transcription PCR (RT-PCR) performed on RNA from NT2-N cells clearly detected transcripts encoding human alpha2, alpha3, alpha5, beta3, gamma3, and pi subtypes. The combined pharmacological and RT-PCR results are most consistent with a single or predominant GABAR isoform composed of an alpha2 and/or alpha3 subtype combined with the beta3 and gamma3 subtypes. The data do not rule out receptors containing combinations of alpha2 and/or alpha3 subtypes with the alpha5 subtype or receptors with both beta1 and beta3 subtypes. The presence or absence or the pi subunit in functionally expressed receptors could not be determined.
Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of type 2 diabetes (2008)

Exenatide, sitagliptin and vildagliptin are useful add-on therapy for type 2 diabetes that is suboptimally controlled on oral agents, particularly when there is concern about weight gain and hypoglycemia, or when postprandial hyperglycemia is the major cause of inadequate glycemic control. Sitagliptin and vildagliptin may be used as monotherapy in patients who cannot tolerate metformin or SU, and sitagliptin may be used as alternative to metformin in renal insufficiency.
Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF‐α (2008)

An unbiased cDNA expression phage library derived from bone-marrow endothelial cells was used to identify novel surface adhesion molecules that might participate in metastasis. Herein we report that reticulocalbin 1 (RCN1) is a cell surface-associated protein on both endothelial (EC) and prostate cancer (PCa) cell lines. RCN1 is an H/KDEL protein with six EF-hand, calcium-binding motifs, found in the endoplasmic reticulum. Our data indicate that RCN1 also is expressed on the cell surface of several endothelial cell lines, including human dermal microvascular endothelial cells (HDMVECs), bone marrow endothelial cells (BMEC), and transformed human bone marrow endothelial cells (TrHBMEC). While RCN1 protein levels were highest in lysates from HDMVEC, this difference was not statistically significant compared BMEC and TrHBMEC. Given preferential adhesion of PCa to bone-marrow EC, these data suggest that RCN1 is unlikely to account for the preferential metastasis of PCa to bone. In addition, there was not a statistically significant difference in total RCN1 protein expression among the PCa cell lines. RCN1 also was expressed on the surface of several PCa cell lines, including those of the LNCaP human PCa progression model and the highly metastatic PC-3 cell line. Interestingly, RCN1 expression on the cell surface was upregulated by tumor necrosis factor alpha treatment of bone-marrow endothelial cells. Taken together, we show cell surface localization of RCN1 that has not been described previously for either PCa or BMEC and that the surface expression on BMEC is regulated by pro-inflammatory TNF-alpha.
The Utility of Serum C-Reactive Protein in Differentiating Bacterial from Nonbacterial Pneumonia in Children (2008)

In children with pneumonia, serum CRP concentrations exceeding 40-60 mg/L weakly predict a bacterial etiology.
Sequence and genome organization of Borna disease virus (1994)

We have previously demonstrated that Borna disease virus (BDV) has a negative nonsegmented single-stranded (NNS) RNA genome that replicates in the nucleus of infected cells. Here we report for the first time the cloning and complete sequence of the BDV genome. Our results revealed that BDV has a genomic organization similar to that of other members of the Mononegavirales order. We have identified five main open reading frames (ORFs). The largest ORF, V, is located closest to the 5' end in the BDV genome and, on the basis of strong homology with other NNS-RNA virus polymerases, is a member of the L-protein family. The intercistronic regions vary in length and nucleotide composition and contain putative transcriptional start and stop signals. BDV untranslated 3' and 5' RNA sequences resemble those of other NNS-RNA viruses. Using a set of overlapping probes across the BDV genome, we identified nine in vivo synthesized species of polyadenylated subgenomic RNAs complementary to the negative-strand RNA genome, including monocistronic transcripts corresponding to ORFs I, II, and IV, as well as six polycistronic polyadenylated BDV RNAs. Interestingly, although ORFs III and V were detected within polycistronic transcripts, their corresponding monocistronic transcripts were not detected. Our data indicate that BDV is a member of the Mononegavirales, specially related to the family Rhabdoviridae. However, in contrast to the rest of the NNS-RNA animal viruses, BDV replication and transcription occur in the nucleus of infected cells. These findings suggest a possible relationship between BDV and the plant rhabdoviruses, which also replicate and transcribe in the nucleus.
Enzyme catalyzed synthesis of structured phospholipids with conjugated linoleic acid and plant sterols (2006)

Structured phospholipids with functional ingredients like conjugated linoleic acid\n(CLA) and plant sterols to deliver their physiological effects in different food\nformulations were synthesized. The lipase and phospholipase A2 catalyzed enzymatic\nacidolysis reaction between phospholipids (PLs) and CLA was used for fatty acid\nmodification, while the phospholipase D catalyzed transphosphatidylation reaction\nbetween PLs and sterol was used for head group modification. Enzymatic processes\nwere an effective way to produce structured phospholipids. Screening of four lipases and\nimmobilized phospholipase A2 and combination of lipase and phospholipase showed that\nonly Lipozyme RM IM and Lipozyme TL IM were effective in incorporation of CLA\ninto PLs. The maximum incorporation achieved by the latter enzyme was 16% with soy\nPLs in 72 h. The class of phospholipids had a significant effect on the rate of\nincorporation of CLA compare to source of PLs. A method capable of predicting the rate\nof incorporation of CLA into phospholipids was developed using response surface\nmethodology. A three-level four-factor Central Composite Rotatable Design (CCRD)\nwas used. The four factors selected were lipase dosage (Ed, wt.% of substrate), substrate\nratio (Sr,mol%), reaction time (ti, h) and reaction temperature (Te,oC). The enzyme load\nand substrate ratio had a greater effect on the rate of incorporation than did reaction time\nand temperature. A polynomial regression equation was developed to predict the\nreaction rate. The new phosphatidyl derivative, phosphatidyl-sitosterol, was found to be\nsynthesized by the transfer reaction of phosphatidyl residue from phosphatidylcholine to\n&amp;#946;-sitosterol by phospholipase D from Streptomyces sp. in biphasic medium. The novel\nphosphatidyl .sitosterol derivative was identified by MALDI-TOF mass spectrometry.\nPlant sterols were modified to a more polar lipid class by synthesizing phospholipid\nderivatives of them. When these structured phospholipids were added to a whey protein\nbased oil-in-water emulsion, the CLA incorporated structured phospholipids (CLA-PL)\nhad higher heat stability and oxidative stability compared to the controls.
IL6 Receptor Blockade Enhances Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma (2017)

Inflammation mediated by activation of JAK/STAT signaling is a major cause of chemotherapy resistance in cancer. We studied the impact of selectively blocking the IL6 receptor (IL6R) as a strategy to inhibit IL6-induced STAT activation and to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). To do this, STAT activation was investigated in tumors arising spontaneously in <i>LSL-Kras<sup>G12D/+</sup>;LSL-Trp53<sup>R172H/+</sup>;Pdx-1Cre</i> (KPC) mice. Plasma from patients with PDAC was assessed for its ability to activate STAT3/SOCS3 in human monocytes using immunofluorescence microscopy and quantitative gene expression assays. KPC mice and syngeneic mice (wild type and IL6<sup>-/-</sup>) implanted with KPC-derived cell lines were treated with an IL6R-blocking antibody (anti-IL6R). The impact of treatment on tumor growth in KPC mice and mice with KPC-derived tumor implants was monitored using ultrasonography and calipers, respectively. Tumors were analyzed by IHC to detect changes in STAT activation, tumor viability, and proliferation. We found that STAT3 was the most activated STAT protein in PDAC tumors from KPC mice. Plasma from patients with advanced PDAC stimulated STAT3/SOCS3 activation in human monocytes. In mice, anti-IL6R antibodies targeted Ly6C<sup>hi</sup> monocytes, inhibited STAT3 activation in tumor cells, and decreased tumor cell proliferation <i>in vivo</i> IL6R blockade in combination with chemotherapy induced tumor cell apoptosis, tumor regressions, and improved overall survival. Overall, we show that IL6 signaling drives STAT3 activation in tumor cells and mediates chemoresistance in PDAC. Thus, disrupting IL6 signaling using anti-IL6R antibodies holds promise for improving chemotherapy efficacy in PDAC. <i>Mol Cancer Ther; 16(9); 1898-908. ©2017 AACR</i>.
Ca2+-Handling Proteins and Heart Failure: Novel Molecular Targets? (2003)

Calcium (Ca(2+)) ions are the currency of heart muscle activity. During excitation-contraction coupling Ca(2+) is rapidly cycled between the cytosol (where it activates the myofilaments) and the sarcoplasmic reticulum (SR), the Ca(2+) store. These fluxes occur by the transient activity of Ca(2+)-pumps and -channels. In the failing human heart, changes in activity and expression profile of Ca(2+)-handling proteins, in particular the SR Ca(2+)-ATPase (SERCA2a), are thought to cause an overall reduction in the amount of SR-Ca(2+) available for contraction. In the steady state, the Ca(2+)-content of the SR is essentially a balance between Ca(2+)-uptake via SERCA2a pump and Ca(2+)-release via the cardiac SR Ca(2+)-release channel complex (Ryanodine receptor, RyR2). This review discusses current pharmacological options available to enhance cardiac SR Ca(2+) content and the implications of this approach as an inotropic therapy in heart failure. Two options are considered: (i) activation of the SERCA2a pump to increase SR Ca(2+)-uptake, and (ii) reduction of SR Ca(2+)-leakage through RyR2. RyR2 forms a macromolecular complex with a number of regulatory proteins that either remain permanently bound or that interact in a time- and/or Ca(2+)-dependant manner. These regulatory proteins can dramatically affect RyR2 function, e.g. over-expression of the accessory protein FK 506-binding protein 12.6 (FKBP12.6) has recently been shown to reduce SR Ca(2+)-leak. Recent attempts to design positive inotropes for chronic administrations have focussed on the use of phosphodiesterase III inhibitors (PDE III inhibitors). These compounds, which increase intracellular cAMP-levels, have failed in clinical trials. Therefore medical researchers are seeking new drugs that act through alternative pathways. Novel cardiac inotropes targeting SR Ca(2+)-cycling proteins may have the potential to fill this gap.
Phospholipid meets all-trans-retinal: the making of RPE bisretinoids (2009)

The lipid phase of the photoreceptor outer segment membrane is essential to the photon capturing and signaling functions of rhodopsin. Rearrangement of phospholipids in the bilayer accompanies the formation of the active intermediates of rhodopsin following photon absorption. Furthermore, evidence for the formation of a condensation product between the photolyzed chromophore all-trans-retinal and phosphatidylethanolamine indicates that phospholipid may also participate in the movement of the retinoid in the membrane. The downside of these interactions is the formation of bisretinoid-phosphatidylethanolamine compounds that accumulate in retinal pigment epithelial cells with age and that are particularly abundant in some retinal disorders. The propensity of these compounds to negatively impact on the cells has been linked to the pathogenesis of some retinal disorders including juvenile onset recessive Stargardt disease and age-related macular degeneration.