gebhart/patrepeval huggingface dataset:
Laminin promotes neuritic regeneration from cultured peripheral and central neurons. (1983)

The ability of axons to grow through tissue in vivo during development or regeneration may be regulated by the availability of specific neurite-promoting macromolecules located within the extracellular matrix. We have used tissue culture methods to examine the relative ability of various extracellular matrix components to elicit neurite outgrowth from dissociated chick embryo parasympathetic (ciliary ganglion) neurons in serum-free monolayer culture. Purified laminin from both mouse and rat sources, as well as a partially purified polyornithine-binding neurite promoting factor (PNPF-1) from rat Schwannoma cells all stimulate neurite production from these neurons. Laminin and PNPF-1 are also potent stimulators of neurite growth from cultured neurons obtained from other peripheral as well as central neural tissues, specifically avian sympathetic and sensory ganglia and spinal cord, optic tectum, neural retina, and telencephalon, as well as from sensory ganglia of the neonatal mouse and hippocampal, septal, and striatal tissues of the fetal rat. A quantitative in vitro bioassay method using ciliary neurons was used to (a) measure and compare the specific neurite-promoting activities of these agents, (b) confirm that during the purification of laminin, the neurite-promoting activity co-purifies with the laminin protein, and (c) compare the influences of antilaminin antibodies on the neurite-promoting activity of laminin and PNPF-1. We conclude that laminin and PNPF-1 are distinct macromolecules capable of expressing their neurite-promoting activities even when presented in nanogram amounts. This neurite-promoting bioassay currently represents the most sensitive test for the biological activity of laminin.
Overcoming Resistance to BRAF and MEK Inhibitors by Simultaneous Suppression of CDK4 (2013)

CDK4 is an effective strategy to overcome resistance to BRAF and MEK inhibitors. BRAF mutation assays have been used to guide treatment with BRAF and MEK inhibitors, development of sensitive and specific INK4A/p16 assays may serve as predictive biomarkers for treatment with CDK4 inhibitors.
PRECLINICAL STUDY: Effects of venlafaxine and desipramine on heroin‐induced conditioned place preference in the rat (2006)

Venlafaxine, an antidepressant with serotonin and noradrenaline reuptake inhibiting properties, has been reported to reduce acquisition (but not maintenance) of heroin intravenous self-administration (IVSA) in rats. The present study investigated whether this phase-dependent effect is due to an antidepressant-induced attenuation of the rewarding effect of heroin, as assessed in the conditioned place preference (CPP) paradigm. In order to study the effects of venlafaxine and the tricyclic antidepressant desipramine on acquisition and expression of heroin CPP, both compounds were administered prior to the conditioning sessions (together with heroin), or prior to the expression test after conditioning, respectively. As clinical evidence indicates that antidepressants require repeated administration for full efficacy, additional experiments were performed in which both antidepressants were administered for 2 weeks prior to conditioning, or for 1 week prior to the expression test, respectively. When tested alone, heroin [0.05-3.16 mg/kg intraperitoneally (i.p.)] produced a dose-dependent CPP, whereas the antidepressants (1-21.5 mg/kg i.p.) produced neither a CPP nor a conditioned place aversion (CPA). For both antidepressants (10 mg/kg i.p.), neither acute nor repeated pretreatment affected acquisition or expression of heroin (0.5 mg/kg) CPP. Thus, the present study does not support the hypothesis that the previously observed attenuation of acquisition of heroin IVSA by venlafaxine is due to an antidepressant-induced attenuation of the rewarding effect of heroin. It is conceivable, however, that the rewarding effect of the 0.5 mg/kg dose of heroin was too pronounced to be susceptible to modulation by antidepressants. Alternatively, the modulation of acquisition of heroin IVSA in the previous study may be related to mechanisms that cannot be modelled with the CPP paradigm.
Visualization of Chemokine Receptor Activation in Transgenic Mice Reveals Peripheral Activation of CCR2 Receptors in States of Neuropathic Pain (2009)

CCR2 chemokine receptor signaling has been implicated in the generation of diverse types of neuropathology, including neuropathic pain. For example, ccr2 knock-out mice are resistant to the establishment of neuropathic pain, and mice overexpressing its ligand, monocyte chemoattractant protein-1 (MCP1; also known as CCL2), show enhanced pain sensitivity. However, whether CCR2 receptor activation occurs in the central or peripheral nervous system in states of neuropathic pain has not been clear. We developed a novel method for visualizing CCR2 receptor activation in vivo by generating bitransgenic reporter mice in which the chemokine receptor CCR2 and its ligand MCP1 were labeled by the fluorescent proteins enhanced green fluorescent protein and monomeric red fluorescent protein-1, respectively. CCR2 receptor activation under conditions such as acute inflammation and experimental autoimmune encephalomyelitis could be faithfully visualized by using these mice. We examined the status of CCR2 receptor activation in a demyelination injury model of neuropathic pain and found that MCP1-induced CCR2 receptor activation mainly occurred in the peripheral nervous system, including the injured peripheral nerve and dorsal root ganglia. These data explain the rapid antinociceptive effects of peripherally administered CCR2 antagonists under these circumstances, suggesting that CCR2 antagonists may ameliorate pain by inhibiting CCR2 receptor activation in the periphery. The method developed here for visualizing CCR2 receptor activation in vivo may be extended to G-protein-coupled receptors (GPCRs) in general and will be valuable for studying intercellular GPCR-mediated communication in vivo.
GeneWise and Genomewise (2004)

We present two algorithms in this paper: GeneWise, which predicts gene structure using similar protein sequences, and Genomewise, which provides a gene structure final parse across cDNA- and EST-defined spliced structure. Both algorithms are heavily used by the Ensembl annotation system. The GeneWise algorithm was developed from a principled combination of hidden Markov models (HMMs). Both algorithms are highly accurate and can provide both accurate and complete gene structures when used with the correct evidence.
Genetic approach to insight into the immunobiology of human dendritic cells and identification of CD84-H1, a novel CD84 homologue. (2001)

To better understand the immunobiology of dendritic cells (DCs), we took the expressed sequence tag (EST) approach to describe their transcript profile and discovered novel genes. ESTs (n = 25,668) were generated from monocyte-derived DCs, and 15,863 ESTs (61.8%) represented unique genes in GenBank. Integration of ESTs allowed for the generation of a profile of 4,367 known genes and identification of > 100 novel genes. HLA-DR invariant chain p33, cathepsin D, HLA-DR alpha chain, beta2-microglobulin, HLA-DP beta chain, CD11a, and mannose receptor were in the top 30 transcripts, and 451 known genes were potentially associated with the immunobiology of DCs. This transcript profile was consistent with the unique antigen-presenting capacity of DCs and provided invaluable information to better understand the immunobiology of DCs. On the basis of the EST database, a full-length novel gene was identified that exhibited close homology with CD84; it was designated CD84-H1. The full-length cDNA of CD84-H1 contained an open reading frame of 870 bp encoding a type I transmembrane protein of 289 amino acids. Consistent with the structural feature of the CD2 family, the predicted 270-amino acid mature protein of CD84-H1 contained two extracellular immunoglobulin-like domains that shared homology with CD2 family members, e.g., CD84, Ly-9, CD48, and signaling lymphocyte activation molecule. Its intracellular domain was short and contained no putative signaling structure. Northern blot analysis revealed that CD84-H1 expression was predominantly restricted in hematopoietic tissues. Reverse transcription-PCR analysis showed that it was widely expressed in the immune cells, including monocytes, DCs, B cells, and T cells. These data indicate that CD84-H1 may be relevant to immune responses.
Integral membrane protein biosynthesis: why topology is hard to predict (2002)

Integral membrane protein biogenesis requires the coordination of several events: accurate targeting of the nascent chain to the membrane; recognition, orientation and integration of transmembrane (TM) domains; and proper formation of tertiary and quaternary structure. Initially unanticipated inter- and intra-protein interactions probably mediate each stage of biogenesis for single spanning, polytopic and C-terminally anchored membrane proteins. The importance of these regulated interactions is illustrated by analysis of topology prediction algorithm failures. Misassigned or misoriented TM domains occur because the primary sequence and overall hydrophobicity of a single TM domain are not the only determinants of membrane integration.
A Fully-Implicit Thermal Reservoir Simulator (1997)

Abstract This paper describes a 3D thermal reservoir simulator that models the injection of steam into heavy oil. The variables are pressure, energy and molar densities, and the equations are volume balance and component and energy conservation. The use of energy and molar densities means that there is no variable-switching, and the formulation combines the advantages of volume balance with a fully-implicit code. A number of example problems are presented, including a large full-field fine-grid model run on parallel processors. Introduction We describe a full-featured thermal simulator that works in a number of coordinate systems: cartesian or radial, rectangular or corner-point geometry, and PEBI grids. It calculates non-neighbor connections, and will solve both single- and dual-porosity models. Local grid refinements can be defined, and these are treated simultaneously and fully coupled in the linear solver. A nine-point method can be used to reduce grid orientation effects. Computer memory requirements are minimized by only storing properties and derivatives for active cells. The new simulator is based on an existing simulator that runs in either compositional or black oil mode. A choice has been maintained and we can either model dead or live oil. We define live oil as having at least one volatile component and dead oil as having none. This paper will describe the general formulation then give examples for the dead oil case. In practice, the dead oil model can be applied to oils that have a small proportion of volatile components as long as these components do not have a significant effect on the simulation. To solve the thermal effects in the reservoir we choose energy rather than temperature as our new variable. The main advantage of an energy variable is that we avoid the problems of variable switching. In the dead-oil case, for instance, we can use energy to describe the boiling of water at a constant pressure and temperature. By adding an energy variable and an energy conservation equation to the existing formulation, we can simulate the injection of steam or hot or cold water (or hot or cold gas) into the reservoir. The formulation differs from many others in calculating energy bounds for each state in each grid block. The energy in the grid block then defines its state and a flash is performed within that state. We use a conventional fully-implicit discretization of the flow equations. Once the non-linear equations have been set up, they are iterated using Newton's method. The linear equations are solved using nested factorization. The simulator can be run either in scalar or parallel mode, and results are presented for both cases.
Androgen Receptor Drives Cellular Senescence (2012)

The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.
New Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy (2009)

Abstract Advances in nanotechnology have contributed to the development of novel nanoparticles that enable the tumor‐specific delivery of imaging probes and therapeutic agents in cancer imaging and therapy. Nanobiotechnology combines nanotechnology with molecular imaging, which has led to the generation of new multifunctional nanoparticles for cancer imaging and therapy. Multifunctional nanoparticles hold great promise for the future of cancer treatment because they can detect the early onset of cancer in each individual patient and deliver suitable therapeutic agents to enhance therapeutic efficacy. The combination of tumor‐targeted imaging and therapy in an all‐in‐one system provides a useful multimodal approach in the battle against cancer. Novel multifunctional nanoparticles thus offer a new avenue in the application of personalized medicine in the near future. Herein, new trends and the significance of novel multifunctional nanoparticles in cancer imaging and therapy are reviewed. magnified image
Adenovirus core protein VII displays a linear epitope conserved in a range of human adenoviruses. (1999)

A monoclonal antibody (MAb) which recognized a linear epitope on polypeptide VII of human adenovirus (Ad) serotype 4 also interacted with polypeptides VII of Ad serotypes 2, 5, 7 and 10, but not with 12 and 40, in Western blotting. Utilizing a hexapeptide phage display library, the MAb was found to recognize the consensus sequence RXYXPX. A peptide based on a similar sequence from Ad2, viz. VEEARNYTPTPPPV, was synthesized and shown to inhibit binding of the MAb to polypeptide VII. Direct sequencing of the Ad4 polypeptide VII gene validated these observations, the sequence RNYTPA being detected. Comparison with gene sequences from other Ads indicates that this sequence is preserved in polypeptide VII of types 2 and 5 but in types 12 and 40 insertion of another residue disrupts this motif.
Tuning Near-Infrared Absorbing Donor Materials: A Study of Electronic, Optical, and Charge-Transport Properties of aza-BODIPYs (2017)

The class of 4,4′-difluoro-4-bora-3a,4a,8-triaza-s-indacenes (aza-BODIPYs) are promising near-infrared absorber materials which are successfully used in organic solar cells to extend their absorption to the near-infrared regime. We computationally studied electronic properties, internal reorganization energies, and the optical properties of more than 100 promising candidates and derived design principles, including novel functionalization routes, to improve their performance as donor materials. We synthesized and characterized several of the promising molecules, confirming the predicted trends. The best charge transport properties and absorption characteristics are obtained for naphthalene-annulated molecular cores due to optimally delocalized frontier molecular orbitals. Further optimization can be achieved by α-functionalization with fluorinated groups, β-functionalization with accepting substituents, and modification of the borondifluoride group. For such molecules, we predict a bathochromic shift in the absorption, which should not significantly reduce the open-circuit voltage. Torsional restriction of α-substituents by carbon bridges can further improve both charge transport and absorption. The theoretically and experimentally observed independence of most of the functionalization strategies makes BODIPYs an ideal material class for tailor-made absorber materials that can cover a broad range of absorption, charge transport, and energetic regimes, calling for further exploration in organic solar cell applications, fluorescence microscopy, and photodynamic therapy.
Functional and Molecular Differences between Voltage-Gated K+Channels of Fast-Spiking Interneurons and Pyramidal Neurons of Rat Hippocampus (1998)

We have examined gating and pharmacological characteristics of somatic K+ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K+ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal inhibitory concentrations <0.1 mM) predominated, contributing an average of 58% to the total K+ current in these cells. By contrast, in pyramidal neurons of the CA1 region a rapidly inactivating A-type K+ current component that was TEA-resistant prevailed, contributing 61% to the total K+ current. Both types of neurons also showed small amounts of the K+ current component mainly found in the other type of neuron and, in addition, a slow delayed rectifier K+ current component with intermediate properties (slow inactivation, intermediate sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K+ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.
Use of Bronchoalveolar Lavage To Detect Galactomannan for Diagnosis of Pulmonary Aspergillosis among Nonimmunocompromised Hosts (2007)

Pulmonary aspergillosis in nonimmunocompromised hosts, although rare, is being increasingly recognized. The diagnosis of pulmonary aspergillosis is difficult, since the recovery of Aspergillus from respiratory samples cannot differentiate colonization from invasion. We assessed the role of bronchoalveolar lavage (BAL) in detecting galactomannan (GM) for diagnosing pulmonary aspergillosis in 73 nonimmunocompromised patients with pulmonary infiltrates for whom the test was ordered. Six patients had pulmonary aspergillosis, two each with acute invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and aspergilloma. All six patients had a BAL GM level of >/=1.18. The sensitivity, specificity, and negative predictive value (NPV) for a BAL GM level of >/=1.0 were 100%, 88.1%, and 100%, respectively. Notably, the positive predictive value (PPV) was only 42.9%, likely reflecting the low prevalence of pulmonary aspergillosis among nonimmunosuppressed patients. The combination of BAL microscopy and culture had a sensitivity and NPV similar to those of BAL GM detection but a higher specificity and PPV (92.5% and 54.6%, respectively). Moreover, a BAL GM test did not identify any cases that were not diagnosed by conventional methods like microscopy and culture. In conclusion, there was no conclusive benefit of determining BAL GM levels in the diagnosis of pulmonary aspergillosis among nonimmunocompromised hosts. Given the likelihood of false-positive results, a BAL GM test should not be ordered routinely in this population.
Recent trends in Cys- and Ser/Thr-based synthetic strategies for the elaboration of peptide constructs (2012)

Recent conceptual advances in the chemical synthesis of peptide constructs are described, encompassing native chemical ligation (i.e. the chemoselective covalent condensation of unprotected peptide segments) and O-, S-acyl isopeptide strategies (i.e. internal O,S-to-N acyl transfer within peptides).
Luminescent Properties of Ca-α-SiAlON:Eu[sup 2+] Phosphors Synthesized by Gas-Pressured Sintering (2008)

Rare-earth-doped oxynitride or nitride compounds have been reported to be photoluminescent and may then serve as new phosphors with good thermal and chemical stabilities. In this work, based yellow and orange oxynitride phosphors with compositions of and were prepared using the gas-pressured sintering method. The crystallinity and particle morphology of the prepared phosphors were characterized. The temperature dependence of photoluminescence properties was investigated from 25 to . The Stokes shift and zero-phonon line was calculated mathematically and estimated from the spectral data. The prepared phosphors showed superior thermal quenching properties compared to commercially used phosphors. In addition, the activation energies for thermal quenching of the prepared phosphors were determined by Arrhenius fitting.
Glycine-Binding Site Stimulants of NMDA Receptors Alleviate Extrapyramidal Motor Disorders by Activating the Nigrostriatal Dopaminergic Pathway (2017)

Dysfunction of the <i>N</i>-methyl-d-aspartate (NMDA) receptor has been implicated in the pathogenesis of schizophrenia. Although agonists for the glycine-binding sites of NMDA receptors have potential as new medication for schizophrenia, their modulation of antipsychotic-induced extrapyramidal side effects (EPS) has not yet been clarified. We herein evaluated the effects of glycine-binding site stimulants of NMDA receptors on antipsychotic-induced EPS in mice and rats. d-cycloserine (DCS) and d-serine significantly improved haloperidol (HAL)-induced bradykinesia in mice, whereas glycine showed no effects. Sodium benzoate, a d-amino acid oxidase inhibitor, also attenuated HAL-induced bradykinesia. Improvements in HAL-induced bradykinesia by DCS were antagonized by the NMDA antagonist dizocilpine or nitric oxide synthase inhibitor L-N<sup>G</sup>-Nitro-l-arginine methyl ester. In addition, DCS significantly reduced HAL-induced Fos expression in the dorsolateral striatum without affecting that in the nucleus accumbens. Furthermore, a microinjection of DCS into the substantia nigra pars compacta significantly inhibited HAL-induced EPS concomitant with elevations in dopamine release in the striatum. The present results demonstrated for the first time that stimulating the glycine-binding sites of NMDA receptors alleviates antipsychotic-induced EPS by activating the nigrostriatal dopaminergic pathway, suggesting that glycine-binding site stimulants are beneficial not only for efficacy, but also for side-effect management.
Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. (2002)

Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.