gebhart/patrepeval huggingface dataset:
Adenosine, an endogenous anti-inflammatory agent (1994)

Adenosine receptors are present on most cells and organs, yet, although the physiological effects of adenosine were first described over 60 years ago, the potential therapeutic uses of adenosine have only been recognized and realized recently. A decade ago the potent anti-inflammatory effects of adenosine were first described; adenosine, acting at specific A2 receptors, inhibits some, but not all, neutrophil functions. Adenosine inhibits phagocytosis, generation of toxic oxygen metabolites, and adhesion (to some surfaces and to endothelial cells) but does not inhibit degranulation or chemotaxis. Occupancy of adenosine A2 receptors modulates leukocyte function by a novel mechanism. Although adenosine A2 receptors are classically linked to heterotrimeric GS signaling proteins and stimulation of adenylate cyclase, adenosine 3',5'-cyclic monophosphate does not act as the second messenger for inhibition of leukocyte function. By a mechanism that still remains obscure, occupancy of adenosine A2 receptors on neutrophils "uncouples" chemoattractant receptors from their stimulus-transduction proteins. The concentrations of adenosine that inhibit inflammatory cell function are similar to those observed in vivo and suggest a role for adenosine in the modulation of inflammation in vivo. Indeed, recent studies indicate that nonmetabolized adenosine receptor agonists are potent anti-inflammatory agents, and other studies indicate that methotrexate, a commonly used anti-inflammatory agent, diminishes inflammation by increasing adenosine release at inflamed sites. The observations reviewed here suggest that adenosine and agents that act through adenosine are excellent candidates for development as anti-inflammatory agents.
Interleukin 1 induces new protein formation in isolated rat islets of Langerhans (1989)

It is hypothesized that interleukin 1 induces toxic free radical formation in pancreatic beta-cells leading to beta-cell degeneration and destruction. Therefore, isolated rat pancreatic islets were examined for interleukin 1 and heat shock induced proteins. Afer exposure to human interleukin 1 beta (0.015 to 10 micrograms/1) or heat (40 degrees C) for up to 24 h, islets were labelled with 35S-methionine and solubilized. Islets proteins were analysed by SDS-polyacrylamide gel electrophoresis. By autoradiography it was shown that both interleukin 1 and heat exposure induced the formation of a 70 kD protein. Further, interleukin 1 induced the formation of two proteins of 32 and 80 kD, respectively, which was not seen after heat exposure. Possibly, the 70 kD protein is a member of the heat shock protein 76 family, participating in unspecific cellular defence and maybe free radical scavenging. Other candidates are the superoxide radical scavenging enzyme manganous superoxidedismutase, MHC class II molecules, and heme oxygenase.
Synthesis and Insecticidal Activity of Acyclic Nitroethene Compounds Containing a Heteroarylmethylamino Group (1993)

1-メチルアミノ-1-[N-メチル-N-(3-ピリジルメチル)]アミノ-2-ニトロエテンがトビイロウンカ, ツマグロヨコバイ, ヒメトビウンカに対して強い活性を示すことを前報で報告した. 本報では3-ピリジル基を他の芳香族複素環に変換し, トビイロウンカに対する活性を検討した. その結果6-クロロ-3-ピリジル, 6-プロモ-3-ピリジル, 6-フルオロ-3-ピリジル, 2-クロロ-5-チアゾリル基を有する化合物は0.5または0.8ppmで100%の死虫率を示したので, 芳香族複素環を6-ハロゲノ-3-ピリジル, 2-クロロ(またはプロモ)-5-チアゾリル基に固定して構造-活性相関を検討した. アミノ基としてはメチルアミノ, ジメチルアミノ, N-ホルミル-N-メチルアミノ基が, 芳香族複素環メチル基が結合した窒素原子の置換基としては水素, メチル, エチル, ホルミル, シクロプロピル基が好ましいことが判明し, 0.5または0.8ppmで100%の死虫率を示す化合物および低濃度での試験を実施しなかった化合物5b-1はさらに評価を行なった. その結果1-[N-(6-クロロ-3-ピリジルメチル)-N-エチル]アミノ-1-メチルアミノ-2-ニトロエテン (5b-8, TI-304, ニテンピラム) が候補化合物として選ばれた.
Spinal Cord Demyelination Associated with Biotinidase Deficiency in 3 Chinese Patients (2007)

Biotinidase deficiency is a treatable cause of severe neurological disorders and skin problems. Spinal cord impairment is a rare complication of this disease and is commonly unrecognized. The authors encountered 3 Chinese patients with progressive spinal cord demyelination associated with biotinidase deficiency. Case 1 exhibited fatigue, proximal muscular weakness, and hypotonic paraplegia from the age of 7 years 4 months. Demyelination of cervical and thoracic cord was evident on magnetic resonance imaging (MRI). Case 2 developed visual impairment, blepharoconjunctivitis, and optic nerve atrophy from 5 years of age, which combined with progressive hypertonic paralysis, ataxia, and alopecia from the age of 7 years. His spinal MRI T2-weighted sequence revealed an extensive hyperintense lesion involving the cervical spinal cord C(2) to C(4). Bilateral optic nerves were significantly thick. In case 3, intercurrent wheezing, tachypnea, dyspnea, and lethargy occurred from the age of 1 year. Medulla and upper cervical spine edema and demyelination were found on MRI. Markedly elevated urine organic acids and decreased blood biotinidase activities were observed in the 3 patients. Biotin supplementation led to a dramatic improvement of clinical symptoms in 3 patients. The findings indicate that biotinidase deficiency should be considered in the differential diagnosis of unexplained spinal cord demyelination because prompt diagnosis and treatment with biotin may enable an excellent recovery.
Independent guidance of retinal axons in the developing visual system of Drosophila (1993)

The development of the adult visual system of Drosophila requires the establishment of precise retinotopic connections between retinal photoreceptor cell axons and their synaptic partners in the optic lobe of the brain. To assess the role of axon-axon interactions in retinal axon guidance, we used genetic methods to disrupt the normal spatiotemporal order of retinal axon ingrowth. We examined retinal axon projections to the developing first optic ganglion, the lamina, in two mutants in which reduced numbers of ommatidia develop in the eye imaginal disk. We find that in the developing lamina of these mutants, sine oculis and Ellipse, retinal axons project to proper dorsoventral positions despite the absence of the usual array of neighboring retinal axons. In a second approach, we examined animals that were somatic mosaics for the mutation, glass. In glass- animals, retinal axons project aberrantly and the larval optic nerve is absent. We find that in the developing lamina of glass mosaic animals, wild-type retinal axons project to proper dorsoventral positions despite the misrouted projections of neighboring glass- retinal axons. In addition, wild-type retinal axons project normally in the absence of the larval optic nerve, indicating that the latter is not an essential pioneer for retinal axon navigation. Our observations support the proposal that axon fascicles can make at least some pathfinding decisions independently of other retinal axon fascicles. We suggest that positional guidance cues that might label axon pathways and target destinations contribute to retinotopic pattern formation in the Drosophila visual system.
Double-shell target designs for the Los Alamos Scientific Laboratory eight-beam laser system (1978)

We investigate two double-pusher laser fusion targets, one that incorporates an outer exploding pusher shell and another that uses velocity multiplication. Specific designs are presented for the Los Alamos Scientific Laboratory Eight-Beam Laser System.
Microtubule Network Facilitates Nuclear Targeting of Human Cytomegalovirus Capsid (2003)

We assessed the requirement of the host cytoskeleton for the intracytosolic transport of incoming human cytomegalovirus (HCMV) capsids. Treatments with microtubule (MT)-depolymerizing drugs nocodazole and colchicine led to a drastic decrease in levels of IE1 antigen, whereas cytochalasin B had no effect on the level of IE1 as determined by Western blot analyses. Sequential treatment including nocodazole washout and removal of cell surface virion revealed that HCMV entry into the cells occurred normally in the absence of the MT network. This finding was also supported by data obtained by monitoring pUL83 signals with an immunofluorescent assay (IFA). Furthermore, we demonstrated a close association of incoming HCMV capsids with MTs by IFA and ultrastructural analyses. In the absence of the MT network, the capsids which had entered the cytoplasm did not move to close proximity of the nucleus. These data suggest that HCMV capsids associate with the MT network to facilitate their own movement to the nucleus before the onset of immediate-early (IE) gene expression and that this association is required to start efficient IE gene expression.
Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells. (2002)

These observations support the concept that simultaneously co-targeting tyrosine kinase receptors may be therapeutically useful, and provide a specific rationale for combining IGF-1R and HER2/erbB2 targeting strategies in anti-neoplastic approaches.
A Biomechanical Finite Element Study of Subsidence and Migration Tendencies in Stand-Alone Fusion Procedures – Comparison of an In Situ Expandable Device with a Rigid Device (2013)

Study Design: Biomechanical study using a finite element model of the lumbar functional spinal unit (FSU).
The inhibition the Tet(K) efflux pump of tetracycline resistant Staphylococcus epidermidis by essential oils from three Salvia species (2015)

Our data from molecular and functional analyses of inhibitory effect of Salvia's essential oils, namely from S. fruticosa, on Tet(K) pump of Staphylococcus epidermidis and from modulatory studies may be the starting point for consecutive study of pharmacokinetic and pharmacodynamic parameters and their perspective use in combination therapy. Combination of antibiotic with efflux pump inhibitor would be expected to re-establish susceptibility of the bacteria to antibiotics that became no longer effective due to bacterial resistance through the efflux pumps. The inhibition of an efflux pump can potentially improve the clinical efficacy of an antibiotic and simultaneously decrease the selection of resistant mutants.
PEG-Polypeptide Dual Brush Block Copolymers: Synthesis and Application in Nanoparticle Surface PEGylation (2013)

Amphiphilic polypeptide-containing hybrid dual brush block copolymers with controlled molecular weights and narrow molecular weight distributions were synthesized in one pot via ring-opening metathesis polymerization of sequentially added norbornyl-PEG and <i>N</i>-(2-((trimethylsilyl)amino)ethyl)-5-norbornene-endo-2,3-dicarboximide (M1) followed by ring-opening polymerization of amino acid <i>N</i>-carboxyanhydrides. Polylactide nanoparticles coated with these am phiphilic dual brush block copolymers showed significantly improved stability in PBS solution compared to those coated with amphiphilic linear block copolymers such as PEG-polylactide and PEG-polypeptides.
Inhibiting MEK in MAPK pathway-activated myeloma (2015)

Over the last decade, new drugs have significantly changed the paradigm for treating multiple myeloma (MM), resulting in improved outcomes and reduced toxicity. However, many patients with MM relapse, and those who are refractory to or relapse after therapy with an immune-modulatory drug and a proteasome inhibitor have a dismal prognosis.1 Improving the outcome of relapsed and refractory MM is a significant clinical challenge. Importantly, in this respect, recently published data have established the frequent mutation of the RAS/mitogen-activated protein kinase (MAPK) pathway,2, 3, 4, 5 with mutations in NRAS, KRAS or BRAF being present in up to 50% of newly diagnosed MM cases. We routinely perform comprehensive genomic profiling using the FoundationOne Heme assay (Supplementary Methods). Review of these data shows the majority of the NRAS, KRAS and BRAF mutations occur in hotspots causing constitutive activation of the corresponding proteins. This makes the MAPK pathway a significant therapeutic target in MM.
Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors. (1992)

Agonist-regulated redistribution of human beta 2-adrenergic receptors was examined in 293 cells. A specific antiserum recognizing the carboxyl-terminal hydrophilic domain of the receptor was developed, characterized, and used for immunocytochemical localization of receptors in fixed cells by conventional fluorescence and confocal fluorescence microscopy. The beta-adrenergic agonist isoproterenol induced redistribution of receptors from the surface of cells into small (less than 1 micron diameter) punctuate accumulations which were detected in cells within 2 min of agonist addition. The time course of receptor redistribution paralleled that of receptor sequestration measured by ligand binding, and receptor redistribution was reversible in the presence of the beta-adrenergic antagonist alprenolol. Optical sections imaged through cells by confocal microscopy localized receptor accumulations within the cytoplasm. To address the question of receptor internalization further, a mutant receptor possessing an engineered antigenic epitope in the amino-terminal hydrophilic domain was constructed, transfected into cells, and localized using both a monoclonal antibody recognizing the epitope tag (receptor ectodomain) and an antiserum recognizing the carboxyl terminus (receptor endodomain). In untreated cells most receptor antigen was detected at the cell surface, as assessed by accessibility to ectodomain antibodies in unpermeabilized specimens. In isoproterenol-treated cells, however, little receptor antigen was detected at the cell surface. Punctate receptor accumulations present in isoproterenol-treated cells were labeled by antibodies only following permeabilization of cells, as expected if these receptor accumulations were intracellular. Finally, internalized beta-adrenergic receptors colocalized with transferrin receptors, which are markers of endosomal membranes. These data provide several lines of evidence establishing that beta-adrenergic receptors undergo ligand-regulated internalization, they suggest that internalized receptors may be recycled back to the cell surface, and they provide the first direct indication that these processes involve the same endosomal membrane system passaged by constitutively recycling receptors.
Invloed van vloeren op klauw koe (2004)

Kreupelheid en klauwgebreken vormen een van de voornaamste welzijnsproblemen in de huidige melkveehouderij. De stalvloer wordt hierbij gezien als een belangrijke oorzaak. In een onderzoek van de Faculteit Diergeneeskunde en Wageningen UR, blijkt dat koeien in een potstal veruit de gezondste klauwen hebben
Surrogate Splicing for Functional Analysis of Sesquiterpene Synthase Genes (2005)

A method for the recovery of full-length cDNAs from predicted terpene synthase genes containing introns is described. The approach utilizes Agrobacterium-mediated transient expression coupled with a reverse transcription-polydeoxyribonucleotide chain reaction assay to facilitate expression cloning of processed transcripts. Subsequent expression of intronless cDNAs in a suitable prokaryotic host provides for direct functional testing of the encoded gene product. The method was optimized by examining the expression of an intron-containing beta-glucuronidase gene agroinfiltrated into petunia (Petunia hybrida) leaves, and its utility was demonstrated by defining the function of two previously uncharacterized terpene synthases. A tobacco (Nicotiana tabacum) terpene synthase-like gene containing six predicted introns was characterized as having 5-epi-aristolochene synthase activity, while an Arabidopsis (Arabidopsis thaliana) gene previously annotated as a terpene synthase was shown to possess a novel sesquiterpene synthase activity for alpha-barbatene, thujopsene, and beta-chamigrene biosynthesis.
Therapy of noninfectious granulomatous skin diseases with fumaric acid esters (2005)

The data presented here indicate that FAE may be considered for the treatment of recalcitrant granulomatous skin disease.
Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies (2007)

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer-oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein-uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA-plasminogen activator inhibitor type 1-mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents.
Evidence that l -Glutamate Can Act as an Exogenous Signal to Modulate Root Growth and Branching in Arabidopsis thaliana (2006)

The roots of many plant species are known to use inorganic nitrogen, in the form of , as a cue to initiate localized root proliferation within nutrient-rich patches of soil. We report here that, at micromolar concentrations and in a genotype-dependent manner, exogenous l-glutamate is also able to elicit complex changes in Arabidopsis root development. l-Glutamate is perceived specifically at the primary root tip and inhibits mitotic activity in the root apical meristem, but does not interfere with lateral root initiation or outgrowth. Only some time after emergence do lateral roots acquire l-glutamate sensitivity, indicating that their ability to respond to l-glutamate is developmentally regulated. Comparisons between different Arabidopsis ecotypes revealed a remarkable degree of natural variation in l-glutamate sensitivity, with C24 being the most sensitive. The aux1-7 auxin transport mutant had reduced l-glutamate sensitivity, suggesting a possible interaction between l-glutamate and auxin signaling. Surprisingly, two loss-of-function mutants at the AXR1 locus (axr1-3 and axr1-12) were hypersensitive to l-glutamate. A pharmacological approach, using agonists and antagonists of mammalian ionotropic glutamate receptors, was unable to provide evidence of a role for their plant homologs in sensing exogenous glutamate. We discuss the mechanism of l-glutamate sensing and the possible ecological significance of the observed l-glutamate-elicited changes in root architecture.
Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-d-aspartate antagonist activity. (1990)

Conantokin-T, a 21-amino acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa. The amino acid sequence of the peptide was determined and verified by chemical synthesis. The peptide has 4 residues of the modified amino acid, gamma-carboxyglutamate (Gla). The sequence of the peptide is: Gly-Glu-Gla-Gla-Tyr-Gln-Lys-Met-Leu-Gla-Asn-Leu-Arg-Gla-Ala-Glu-Val-Lys- Lys-Asn-Ala-NH2. Conantokin-T inhibits N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. This observation suggests that like conantokin-G (a homologous Conus peptide with recently identified NMDA antagonist activity) conantokin-T has NMDA antagonist activity. A sequence comparison of conantokins-T and -G identifies the 4 Gla residues and the N-terminal dipeptide sequence as potential key elements for the biological activity of this peptide.
Perspectives on percutaneous penetration: Silica nanoparticles (2014)

Nanotechnology is a rapidly expanding area of research involved in developing science-based solutions for innovative therapeutics. Silica nanoparticles (SNPs) have received wide attention in several industries and medicine and are being developed for biomedical and biotechnological applications such as drug delivery, DNA transfection, and targeted molecular imaging of cancer. Recently, they are emerging in the fields of cosmetics and dermal preparations. SNP may offer a revolutionized treatment of several skin diseases by controlled and sustained release of drugs to skin, as well as enhanced skin penetration of encapsulated drug ingredients. SNPs are candidates for transcutaneous vaccination and transdermal gene therapy, too. Yet there exist concerns that whilst the properties of SNPs have enabled numerous industrial and medical applications, their toxicological and environmental safety mandates evaluation. The knowledge of passage of SNPs through skin following skin exposure (intentionally or unintentionally) and subsequent effects is limited. This review surveys the key experiments on SNP-based formulations in the fields of dermatology and cosmetics with the goal of rationalizing data and informing public health concerns related to SNPs' toxicity among scientists and manufacturers handling them, while highlights the research gaps in dermal absorption of these compounds.
Alterations of CSF Cystatin C Levels and Their Correlations with CSF Αβ40 and Αβ42 Levels in Patients with Alzheimer's Disease, Dementia with Lewy Bodies and the Atrophic Form of General Paresis (2013)

Immunohistochemical studies have revealed that cystatin C (CysC) co-localizes with amyloid-β (Αβ) in amyloid-laden vascular walls and in the senile plaque cores of amyloid. In vitro and in vivo animal studies suggest that CysC protects against neurodegeneration by inhibition of cysteine proteases, inhibition of Αβ aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aβ levels in various types of dementia with characteristic amyloid deposits, such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and the atrophic form of general paresis (AF-GP). We assessed the serum and CSF levels of CysC and the CSF levels of Aβ40 and Aβ42 in patients with AD (n = 51), DLB (n = 26) and AF-GP (n = 43) and normal controls (n = 30). Using these samples, we explored the correlation between CSF CysC and CSF Aβ levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aβ42 levels were significantly lower in all three dementia groups (all p<0.001); serum CysC levels were the same in the AD and DLB groups, and were lower in the AF-GP group (p = 0.008). The CSF CysC levels were positively correlated with both the CSF Aβ40 and Aβ42 levels in the AD, AF-GP and normal control groups (r = 0.306∼0.657, all p<0.05). Lower CSF CysC levels might be a common feature in dementia with characteristic amyloid deposits. Our results provide evidence for the potential role of CysC involvement in Aβ metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.
Correlation feedback resource allocation RBF (2002)

A model validation test based on simple linear autocorrelation is proposed as an objective method to determine the optimal number of units in the hidden layer of a radial basis function network. The data to be fitted is assumed to consist of a signal with additive iid noise. A novel stopping criteria is introduced based on the statistics of the residuals rather than on ad hoc parameters. Consequently, this network is shown to neither overfit nor underfit the data. In addition, each new unit is adjusted to respond locally to the target data.