gebhart/patrepeval huggingface dataset:
CNS Neurotransmitters and Neuromodulators: Acetylcholine (1994)

The Localization of Cholinergic Neurons and Markers in the CNS, R. Martinez-Murillo and J. Rodrigo. Subtypes of Neuronal Muscarinic Receptors: Pharmacological Criteria, E. Monferini. Subtypes of Muscarinic Receptors: Receptor Structure and Molecular Biology, E.E. El-Fakahany. Distribution of Muscarinic Acetylcholine Receptors in the CNS, R. Schliebs and S. Rossner. Distribution of Nicotinic Receptors in the CNS, J.A. Court and E.K. Perry. Function of Nicotinic Receptors in the CNS, L. Wecker, F. Cardozo, and Z. Jian Yu. Electrophysiological Effects of Acetylcholine on Central Neurons (Whole Cells and Interactions), J. H. Pirch. Acetylcholine-Operated Ionic Conductances in Neurons, H.C. Moises and M.D. Womble. Neurochemical Transduction Processes Associated with Neuronal Muscarinic Receptors, J. Baumgold. Compartmentalization and Release from Neurons in the CNS, V. Adam-Vizi. Muscarinic Acetylcholine Receptors and Long-Term Potentiation of Synaptic Transmission, H.W.G.M. Boddeke and P.H. Boeijinga. Nicotinic Receptors and Information Processing, J.M. Rusted and D.M. Warburton. Cholinergic Neurons and Memory: An Historical Perspective and an Overview of Current Research, R. Grette Lydon. Nerve Growth Factor: Influence on Cholinergic Neurons in the CNS, C. Eva.
Haemoglobin A1c separation by micro-column chromatography: a new rapid method of assay. (1979)

Since at present chromatographic methods for the separation of the glycosylated haemoglobins and determination of haemoglobin A1c are time-consuming and require continuous monitoring, a new micro-column method is reported that is cheap, rapid, easy to perform and permits anything up to 30 columns to be run simultaneously. The haemoglobin A1c leve in fifty normal subjects was measured and found to have a mean of 5.3 +/- 0.5% (m +/- S.D.).
Adenosine Kinase Inhibitors. 1. Synthesis, Enzyme Inhibition, and Antiseizure Activity of 5-Iodotubercidin Analogues (2000)

Adenosine receptor agonists produce a wide variety of therapeutically useful pharmacologies. However, to date they have failed to undergo successful clinical development due to dose-limiting side effects. Adenosine kinase inhibitors (AKIs) represent an alternative strategy, since AKIs may raise local adenosine levels in a more site- and event-specific manner and thereby elicit the desired pharmacology with a greater therapeutic window. Starting with 5-iodotubercidin (IC50 = 0.026 microM) and 5'-amino-5'-deoxyadenosine (IC50 = 0.17 microM) as lead inhibitors of the isolated human AK, a variety of pyrrolo[2,3-d]pyrimidine nucleoside analogues were designed and prepared by coupling 5-substituted-4-chloropyrrolo[2,3-d]pyrimidine bases with ribose analogues using the sodium salt-mediated glycosylation procedure. 5'-Amino-5'-deoxy analogues of 5-bromo- and 5-iodotubercidins were found to be the most potent AKIs reported to date (IC50S < 0.001 microM). Several potent AKIs were shown to exhibit anticonvulsant activity in the rat maximal electric shock (MES) induced seizure assay.
Potential Environmental Impact of Imidazolium Ionic Liquids (2007)

Excellent, non-volatile solvents for a wide range of applications, and claimed to be environmentally benign, room temperature ionic liquids are generating increasing interest for their potential in different chemical processes. However, the production, application and waste management of ionic liquids will inevitably lead to their accidental discharge into the environment. Therefore, responsible product design should always take into consideration not only technological demands but also the possible health and environmental hazards. This chapter includes data on the photodegradation rates of ionic liquids as well as their sorption to different types of soil and marine sediment. It outlines the toxicological screening of ionic liquids using algae, which takes environmental parameters such as salinity into account, and discusses the theoretical prediction and experimental determination of lipophilicity and possible metabolic pathways. The data presented here provide a preliminary insight into the prospective presence of ionic liquids in the environment.
Structural Basis of Mitochondrial Tethering by Mitofusin Complexes (2004)

Vesicle fusion involves vesicle tethering, docking, and membrane merger. We show that mitofusin, an integral mitochondrial membrane protein, is required on adjacent mitochondria to mediate fusion, which indicates that mitofusin complexes act in trans (that is, between adjacent mitochondria). A heptad repeat region (HR2) mediates mitofusin oligomerization by assembling a dimeric, antiparallel coiled coil. The transmembrane segments are located at opposite ends of the 95 angstrom coiled coil and provide a mechanism for organelle tethering. Consistent with this proposal, truncated mitofusin, in an HR2-dependent manner, causes mitochondria to become apposed with a uniform gap. Our results suggest that HR2 functions as a mitochondrial tether before fusion.
Down-regulation of Vascular Endothelial Growth Factor and Up-regulation of Pigment Epithelium-derived Factor (2002)

We have previously shown that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits ischemia-induced retinal neovascularization in a rat model. Here we report that K5 down-regulates an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF) and up-regulates an angiogenic inhibitor, pigment epithelium-derived factor (PEDF) in a dose-dependent manner in vascular cells and in the retina. The regulation of VEGF and PEDF by K5 in the retina correlates with its anti-angiogenic effect in a rat model of ischemia-induced retinopathy. Retinal RNA levels of VEGF and PEDF are also changed by K5. K5 inhibits the p42/p44 MAP kinase activation and nuclear translocation of hypoxia-inducible factor-1alpha, which may be responsible for the down-regulation of VEGF. Down-regulation of endogenous angiogenic stimulators and up-regulation of endogenous angiogenic inhibitors, thus leading toward restoration of the balance in angiogenic control, may represent a mechanism for the anti-angiogenic activity of K5.
Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas. (1999)

Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen-activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR-specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand-mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation.
Stereotactic Surgery for Temporal Lobe Epilepsy (2000)

In light of the recent resurgence of interest in stereotactic functional procedures, the authors have reviewed the role of stereotactic ablative surgery in the treatment of temporal lobe epilepsy. Literature pertaining to stereotactic amygdalotomy, hippocampotomy and fornicotomy is reviewed and summarized. However, the results presented in those early studies are difficult to interpret given the surgical techniques and outcome assessment used. Modern stereotactic ablative surgery using current image-guided technology offers the opportunity to revisit some of these techniques. In recent studies of stereotactic amygdalohippocampotomy, outcomes are not as favorable as those obtained with standard temporal resections. However, these relatively discrete ablative techniques may shed light on the anatomical substrate underlying temporal lobe epilepsy.
Antibody Covalent Immobilization on Carbon Nanotubes and Assessment of Antigen Binding (2011)

Controlling the covalent bonding of antibodies onto functionalized carbon nanotubes is a key step in the design and preparation of nanotube-based conjugates for targeting cancer cells. For this purpose, an anti-MUC1 antibody (Ab) is linked to both multi-walled (MWCNTs) and double-walled carbon nanotubes (DWCNTs) using different synthetic strategies. The presence of the Ab attached to the nanotubes is confirmed by gel electrophoresis and thermogravimetric analysis. Most importantly, molecular recognition of the antigen by surface plasmon resonance is able to determine similar Ab binding capacities for both Ab-DWCNTs and Ab-MWCNTs. These results are very relevant for the design of future receptor-targeting strategies using chemically functionalized carbon nanotubes.
Multifunctional Surface Modification of Gold-Stabilized Nanoparticles by Bioorthogonal Reactions (2011)

Nanocarriers that combine multiple properties in an all-in-one system hold great promise for drug delivery. The absence of technology to assemble highly functionalized devices has, however, hindered progress in nanomedicine. To address this deficiency, we have chemically synthesized poly(ethylene oxide)-β-poly(ε-caprolactone) (PEO-b-PCL) block polymers modified at the apolar PCL terminus with thioctic acid and at the polar PEO terminus with an acylhydrazide, amine, or azide moiety. The resulting block polymers were employed to prepare nanoparticles that have a gold core, an apolar polyester layer for drug loading, a polar PEO corona to provide biocompatibility, and three different types of surface reactive groups for surface functionalization. The acylhydrazide, amine, or azide moieties of the resulting nanoparticles could be reacted with high efficiencies with modules having a ketone, isocyanate, or active ester and alkyne function, respectively. To demonstrate proof of principle of the potential of multisurface functionalization, we prepared nanoparticles that have various combinations of an oligo-arginine peptide to facilitate cellular uptake, a histidine-rich peptide to escape from lysosomes, and an Alexa Fluor 488 tag for imaging purposes. It has been shown that uptake and subcellular localization of the nanoparticles can be controlled by multisurface modification. It is to be expected that the modular synthetic methodology provides unique opportunities to establish optimal configurations of nanocarriers for disease-specific drug delivery.
The Endomembrane System and the Problem of Protein Sorting (2001)

Yes there are two paths you can go by But in the long run, There's still time to change the road you're on."
Fluid saturation from well logs using committee neural networks (2002)

Neural computing has made a major step forward by the introduction of multi-net systems in practical applications. In this study we developed and tested a modular artificial neural network system for predicting underground fluids, water, oil and gas, and their partial saturations, directly from well logs, without explicit knowledge of the fluid and rock properties as required by conventional methods. Based on laboratory data on relative permeability for alternative fluid systems –oil–water or gas–oil – respectively, relative permeability logs may also be provided for input to reservoir simulation while drilling. Simple three-layer back-propagation artificial neural networks (ANN) constitute the building blocks of a modular system, where the input logs are sonic, density, neutron porosity and resistivity. By numerical experiments using synthetic logs we have determined the optimal architecture of the ANN. We find that the overtraining strategy is a suitable technique for bias reduction and an unconstrained optimal linear combination is the best method of combining outputs in the committee neural net. The accuracy of the net is restricted only by accuracy of data. Comparison between ANN predictions of fluid saturation with those of conventional petrophysical analysis, in wells unknown to the network, indicates a standard error of less than 0.03.
New and future drug therapies for rheumatoid arthritis (2000)

Several new drugs have recently been introduced for the treatment of rheumatoid arthritis (RA). These include the cyclooxygenase-2 inhibitor, celecoxib, the anti-tumour necrosis factor agents, etanercept and infliximab, and the new disease-modifying anti-rheumatic drug (DMARD), leflunomide. In clinical trials, celecoxib has been shown to be effective for palliation of the signs and symptoms of RA and to have fewer gastrointestinal side-effects than conventional non-steroidal anti-inflammatory drugs. Etanercept and infliximab are indicated for reduction of the signs and symptoms of RA in patients who have failed to respond adequately to previous DMARDs. The clinical success rate in etanercept-treated patients is significantly better than in placebo-treated patients for up to 18 months. Leflunomide is a DMARD with a novel mechanism of action that has been approved as a first-line treatment for RA. Treatment with leflunomide results in significantly greater improvement of the signs and symptoms of RA than placebo for up to 2 yr and slows radiographically assessed disease progression. Agents are currently in development that will be targeted against components of the immune activation and co-stimulatory pathways. These include antibodies directed against the interleukin-2 receptor and blockers of the CD28 and CD40 co-stimulatory pathways. Continuing research into the pathogenesis of RA will undoubtedly identify even more effective therapeutic approaches for the management of this disease in the future.
High-quality motion deblurring from a single image (2008)

We present a new algorithm for removing motion blur from a single image. Our method computes a deblurred image using a unified probabilistic model of both blur kernel estimation and unblurred image restoration. We present an analysis of the causes of common artifacts found in current deblurring methods, and then introduce several novel terms within this probabilistic model that are inspired by our analysis. These terms include a model of the spatial randomness of noise in the blurred image, as well a new local smoothness prior that reduces ringing artifacts by constraining contrast in the unblurred image wherever the blurred image exhibits low contrast. Finally, we describe an effficient optimization scheme that alternates between blur kernel estimation and unblurred image restoration until convergence. As a result of these steps, we are able to produce high quality deblurred results in low computation time. We are even able to produce results of comparable quality to techniques that require additional input images beyond a single blurry photograph, and to methods that require additional hardware.
Chromatin decondensation and DNA synthesis in human sperm activated in vitro by using Xenopus laevis egg extracts (1987)

An in vitro sperm activation system was used to study nuclear swelling-chromatin decondensation and DNA synthesis; processes that occur in vivo following fertilization. Lysolecithin-permeabilized human sperm were incubated in Xenopus laevis egg extract and examined by using phase-contrast light microscopy, electron microscopy, and autoradiography. During a 3-hour incubation, the activated sperm nuclear chromatin underwent a decondensation-recondensation cycle during which DNA was synthesized. This also occurred when egg extract was given a 3-hour preincubation before the addition of the sperm, suggesting that the factor(s) required for initiating the decondensation-recondensation cycle is associated with the sperm. Because both nuclear swelling and DNA synthesis were found to be reproducible and quantifiable, we studied the effect of various agents on the two processes, characterizing the critical component(s) in the egg extract that induces these events. EGTA was found to have no effect on the induced nuclear swelling or DNA synthesis that occurs in the activated sperm. Freezing and thawing the extract or treating the extract with aphidicolin also had no effect on subsequent nuclear swelling; however, the DNA synthesis activity was blocked. Sperm incubated in extract treated with alkaline phosphatase (AP) had both nuclear swelling and DNA synthesis blocked. However, if the sperm were pretreated with DTT, and then incubated with the AP-treated extract, only the DNA synthesis activity of the extract was blocked. When the extract was treated with serine protease inhibitors (PMSF, soybean trypsin inhibitor, or alpha-2-macroglobulin), nuclear swelling occurred; however, DNA synthesis was blocked. These data suggest that phosphoproteins are involved in one or more of the activation events and that a serine protease(s) is involved in the synthesis of DNA.
Bacterial Separation and Concentration from Complex Sample Matrices: A Review (2004)

The use of many rapid detection technologies could be expanded if the bacteria were separated, concentrated, and purified from the sample matrix before detection. Specific advantages of bacterial concentration might include facilitating the detection of multiple bacterial strains; removal of matrix-associated assay inhibitors; and provision of adequate sample size reduction to allow for the use of representative food sample sizes and/or small media volumes. Furthermore, bacterial concentration could aid in improving sampling techniques needed to detect low levels of pathogens or sporadic contamination, which may perhaps reduce or even eliminate the need for cultural enrichment prior to detection. Although bacterial concentration methods such as centrifugation, filtration, and immunomagnetic separation have been reported for food systems, none of these is ideal and in many cases a technique optimized for one food system or microorganism is not readily adaptable to others. Indeed, the separation and subsequent concentration of bacterial cells from a food sample during sample preparation continues to be a stumbling block in the advancement of molecular methods for the detection of foodborne pathogens. The purpose of this review is to provide a detailed understanding of the science, possibilities, and limitations of separating and concentrating bacterial cells from the food matrix in an effort to further improve our ability to harness molecular methods for the rapid detection of foodborne pathogens.
Polyglycylation of Tubulin: a Posttranslational Modification in Axonemal Microtubules (1994)

A posttranslational modification was detected in the carboxyl-terminal region of axonemal tubulin from Paramecium. Tubulin carboxyl-terminal peptides were isolated and analyzed by Edman degradation sequencing, mass spectrometry, and amino acid analysis. All of the peptides, derived from both alpha and beta tubulin subunits, were modified by polyglycylation, containing up to 34 glycyl units covalently bound to the gamma carboxyl group of glutamyl residues. This modification, present in one of the most stable microtubular systems, may influence microtubule stability or axoneme function, or both.
Self-phase-modulated Kerr-lens mode-locked Cr:forsterite laser source for optical coherence tomography (1996)

An all-solid-state Kerr-lens mode-locked Cr:forsterite laser operating at 1.28 microm is demonstrated as a shortcoherence-length, high-average-power source for optical coherence tomographic (OCT) imaging. We achieve ultrahigh resolution by spectrally broadening the laser pulses, using self-phase modulation in a dispersionshifted single-mode fiber. OCT imaging with a resolution of 6 microm and a dynamic range of 115 dB is achieved.
Asymmetric twin-waveguide 1.55-μm wavelength laser with a distributed Bragg reflector (2000)

We demonstrate a single frequency, 1.55 μm wavelength laser based on an asymmetric twin-waveguide structure using a single growth step and a simple fabrication process. The external Bragg grating is formed on the passive ridge waveguide, optically coupled to the twin-guide gain section using a low loss, tapered mode transformer. The grating is produced by near-field holographic printing using a phase mask. Output powers >11 mW in a small-spot waveguide with a side-mode suppression ratio >40 dB and a slope efficiency of 0.11 W/A are obtained under pulsed operation. These performance characteristics are comparable to conventional, nonintegrated, conventional discrete DBR lasers, although the twin-waveguide design is compatible with photonic integrated circuits such as monolithic transmitters and WDM coherent receivers.
Developing a Dynamic Pharmacophore Model for HIV-1 Integrase (2000)

We present the first receptor-based pharmacophore model for HIV-1 integrase. The development of "dynamic" pharmacophore models is a new method that accounts for the inherent flexibility of the active site and aims to reduce the entropic penalties associated with binding a ligand. Furthermore, this new drug discovery method overcomes the limitation of an incomplete crystal structure of the target protein. A molecular dynamics (MD) simulation describes the flexibility of the uncomplexed protein. Many conformational models of the protein are saved from the MD simulations and used in a series of multi-unit search for interacting conformers (MUSIC) simulations. MUSIC is a multiple-copy minimization method, available in the BOSS program; it is used to determine binding regions for probe molecules containing functional groups that complement the active site. All protein conformations from the MD are overlaid, and conserved binding regions for the probe molecules are identified. Those conserved binding regions define the dynamic pharmacophore model. Here, the dynamic model is compared to known inhibitors of the integrase as well as a three-point, ligand-based pharmacophore model from the literature. Also, a "static" pharmacophore model was determined in the standard fashion, using a single crystal structure. Inhibitors thought to bind in the active site of HIV-1 integrase fit the dynamic model but not the static model. Finally, we have identified a set of compounds from the Available Chemicals Directory that fit the dynamic pharmacophore model, and experimental testing of the compounds has confirmed several new inhibitors.
Monoamine Receptors in the Regulation of Feeding Behaviour and Energy Balance (2006)

We evaluate the likely utility of drugs that interact, either directly or indirectly, with monoamine binding receptors for the treatment of obesity. We discuss ligands at dopaminergic, adrenergic, serotoninergic and histaminergic receptors and also drugs that either release or inhibit the reuptake of monoamine neurotransmitters. We review evidence from preclinical studies of receptor distribution and function, together with the consequences of gene deletion in transgenic mouse strains and the results from human studies where these are available. In addition we consider the side effect profiles that would be expected of these potential anti-obesity treatments. We conclude that compounds interacting with 5- HT2C, 5-HT6 and histamine H3 receptors may be of particular interest as specific drug development targets for the treatment of appetite disturbance in obesity.