gebhart/patrepeval huggingface dataset:
N‐Heterocyclic Carbenes: Generation under Mild Conditions and Formation of Group 8–10 Transition Metal Complexes Relevant to Catalysis (1996)

Abstract Stable mono‐ and dicarbene adducts of late transition metals are readily accessible either by reaction of imidazolium salts with metal complexes bearing basic ligands, or by the cleavage of chloro‐ and acetato‐bridged dinuclear metal complexes with the free carbenes (e.g., 1,3‐dimethylimidazoline‐2‐ylidene). A general novel method for the deprotonation of N‐substituted azolium salts in liquid ammonia–the liquid ammonia route–is described. This method yields not only the known free monimeric 1,3‐dimethylimidazoline‐2‐ylidene in quantitative yield, but also otherwise hardly accessible derivatives. For example, imidazoline‐2‐ylidenes with linear, branched, cyclic, heteroatom‐substituted and even chiral hydrocarbon residues can be obtained. The nucleophilic behaviour of 1,3‐dimethyl‐imidazoline‐2‐ylidene is reported and compared with that of other donor ligands. Novel carbene complexes of Ru II , Rh I Pd II , Os II and Ir I are presented. Reaction of the potentially chelating ligand 1,1′‐(1,2‐ethylene)‐3,3′‐dimethyldiimidazoline‐2,2′‐diylidene with [(COD)‐RhCl] 2 yields a dinuclear complex, in which two rhodium centres are linked by the dicarbene bridge. Four single‐crystal X‐ray diffraction structures of new metalcarbene complexes (Rh, Os) are reported. N‐Heterocyclic carbene complexes of Group 8–10 transition metals are both thermally and chemically very stable. They do not show the typical reactivity of metal–carbon double bonds. For a number of reasons, these complexes must be regarded as donor adducts of the Lewis‐ basic imidazoline‐2‐ylidene ligand and the Lewis‐ acidic organometallic fragment.
The Paramyxoviruses Simian Virus 5 and Mumps Virus Recruit Host Cell CD46 To Evade Complement-Mediated Neutralization (2009)

The complement system is a critical component of the innate immune response that all animal viruses must face during natural infections. Our previous results have shown that treatment of the paramyxovirus simian virus 5 (SV5) with human serum results in deposition of complement C3-derived polypeptides on virion particles. Here, we show that the virion-associated C3 component includes the inactive form iC3b, suggesting that SV5 may have mechanisms to evade the host complement system. Electron microscopy, gradient centrifugation, and Western blot analysis indicated that purified SV5 virions derived from human A549 cells contained CD46, a plasma membrane-expressed regulator of complement that acts as a cofactor for cleavage and inactivation of C3b into iC3b. In vitro cleavage assays with purified complement components showed that SV5 virions had C3b cofactor activity, resulting in specific factor I-mediated cleavage of C3b into inactive iC3b. SV5 particles generated in CHO cells, which do not express CD46, did not have cofactor activity. Conversely, virions derived from a CHO cell line that was engineered to overexpress human CD46 contained elevated levels of virion-associated CD46 and displayed enhanced C3b cofactor activity. In comparison with C3b, purified SV5 virions had very low cofactor activity against C4b, consistent with the known preference of CD46 for C3b versus C4b. Similar results were obtained for the closely related mumps virus (MuV), except that MuV particles derived from CHO-CD46 cells had higher C4b cofactor activity than SV5 virions. In neutralization assays with human serum, SV5 and MuV containing CD46 showed slower kinetics and more resistance to neutralization than SV5 and MuV that lacked CD46. Our results support a model in which the rubulaviruses SV5 and MuV incorporate cell surface complement inhibitors into progeny virions as a mechanism to limit complement-mediated neutralization.
Management of listeriosis (1997)

Determination of the MIC in vitro is often used as the basis for predicting the clinical efficacy of antibiotics. Listeriae are uniformly susceptible in vitro to most common antibiotics except cephalosporins and fosfomycin. However, the clinical outcome is poor. This is partially because listeriae are refractory to the bactericidal mechanisms of many antibiotics, especially to ampicillin-amoxicillin, which still is regarded as the drug of choice. A true synergism can be achieved by adding gentamicin. Another point is that listeriae are able to reside and multiply within host cells, e.g., macrophages, hepatocytes, and neurons, where they are protected from antibiotics in the extracellular fluid. Only a few agents penetrate, accumulate, and reach the cytosol of host cells, where the listeriae are found. Furthermore, certain host cells may exclude antibiotics from any intracellular compartment. Thus, determination of the antibacterial efficacy of a drug against listeriae in cell cultures may be a better approximation of potential therapeutic value. Certain host cells may have acquired the property of excluding certain antibiotics, for example macrolides, from intracellular spaces, which might explain therapeutic failures of antibiotic therapy in spite of low MICs. Animal models do not completely imitate human listeriosis, which is characterized by meningitis, encephalitis, soft tissue and parenchymal infections, and bacteremia. Meningitis produced in rabbits is a hyperacute disease, whereby most listeriae lie extracellularly, fairly accessible to antibiotics that can cross the blood-cerebrospinal fluid barrier. In the murine model of systemic infection, Listeria monocytogenes is located mainly within macrophages and parenchymal cells of the spleen and liver, hardly accessible to certain drugs, such as ampicillin and gentimicin. The therapeutic efficacy of drugs clearly depends on the model used. Thus, for example, the combination of ampicillin with gentamicin acts synergistically in the rabbit meningitis model but not in the mouse model. Since conventional antimicrobial therapy with antibiotics is not satisfactory, particularly in the immunocompromised host (about 30% of patients with listeriosis die in spite of a rational choice of antibiotics), other possibilities must be considered for therapy as well as prevention. Indeed, listeriae are highly susceptible to several endogenous antibiotics, such as defensins. Bacteriocins produced by related bacterial species, e.g., lactobacilli and enterococci, are rapidly bactericidal. However, unfortunately, the use of such alternative measures along with immunization and immunmodulation is not yet feasible.
Biomolecular Recognition Based on Single Gold Nanoparticle Light Scattering (2003)

A method for biomolecular recognition is reported using light scattering of a single gold nanoparticle functionalized with biotin. Addition of streptavidin and subsequent specific binding events alter the dielectric environment of the nanoparticle, resulting in a spectral shift of the particle plasmon resonance. As we use single nanoparticles showing a homogeneous scattering spectrum, spectral shifts as small as 2 meV can be detected.
Directed Evolution of Nucleic Acids by Independent Replication and Selection (1990)

Specific interactions between nucleic acid and protein mediate the control of gene expression. The understanding of these interactions has been facilitated by the construction of sequence variants of both nucleic acid and protein. An exciting new experimental procedure is described by Tuerk and Gold. In their method, called SELEX for the systematic evolution of ligands by exponential enrichment, a random collection of RNA molecules is enriched for those that can bind to a particular protein. Those RNA molecules that bind are converted to complementary DNA and are replicated by the polymerase chain reaction. Continued cycles of enrichment and amplification lead to a collection of sequences that bind whith the highest affinity
Performance of a 10 kW power electronic interface for combined wind/PV isolated generating systems (2002)

The hoped exploitation of pollution-free, low cost, renewable energy resources has always stirred up interest and inventiveness. The double-input single-output DC/DC power converter discussed in this paper, developed for combined wind-photovoltaic generating systems, aims to mitigate the output power fluctuations due to the intermittent nature of both solar and wind energy. Digital control of the whole apparatus also contributes to optimise the converter modes of operation, running both the energy input circuits at their maximum power level. The paper reports an overall description of the power interface characteristics and experimental results recorded in extensive laboratory tests of a 10 kW rated prototype.
A D-Q Frame Controller for a Full-Bridge Single Phase Inverter Used in Small Distributed Power Generation Systems (2007)

This paper presents a Direct-Quadrature (DQ) rotating frame control method for single phase full-bridge inverters used in small hybrid power systems. A secondary orthogonal imaginary circuit is created to provide the second phase required for the transformation; thus a DQ model of the inverter is obtained and its controller designed emulating the controls of three-phase power converters. The proposed controller attains infinite loop gain in the rotating coordinate, thus providing zero steady-state error at the fundamental frequency of the converter. The proposed controller is designed and validated through simulations using a DQ-frame average model in Matlab and a detailed switching model in Saber, as well as experimental results obtained with a 2.5 kW single phase full-bridge inverter prototype using a DSP/FPGA based digital control system where the proposed DQ-frame controller is fully implemented.
1.3-Dioxolohetarene, 3 [1]. Darstellung und Reaktionen von Pyrido[2.3-d]- und Pyrido[3.4-d] [1.3]dioxolen / 1,3-Dioxolohetarenes, 3 [1]. Preparation and Reactions of Pyrido[2,3-d]-and Pyrido[3,4-d][1,3]dioxoles (1979)

The methylester of 3,4-dihydroxy-pyridine-6-carboxylic acid (1) reacts with bromochloromethane/potassjumcarbonate leading to the methylester of pyrido[3,4-d][1,3]-dioxole-6-onrhoxylic apid (2a). 2,3-Dihydroxy-pyridine (3a), 6-methyl- (3b), 5-chloro- (3c), and 5-bromo-2,3-dihydroxy-pyridine (3d) lead under the same conditions to the pyrido-[2,3-d][1,3]dioxole derivatives 4a, 4b, 4c, and 4d. The ester of 2,3-dihydroxy-pyridine-5-carboxylic acid (3e) and 4,6-dibromo-2,3-dihydroxy-pyridine (3f) also can be subjected to methylenation yielding the pyrido[2,3-d][1,3]dioxole compounds 4e and 4f. Treatment of 6-bromo-pyrido[2,3-d][1,3]dioxole (4d) with n-butyllithium gives 6- lithium-pyrido[2,3-d][1,3]dioxole (5a) allowing reaction with carbondioxide, N,N-di- methylformamide, N,N-dimethylacetamide, and sulphur/iodine to obtain the carboxylic acid 5b, the aldehyde of, the ketone 5g, and the disulfide 5n. The structures of compound 5b, 5f, and 5g were proofed by synthesis of derivatives.
Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes. (2001)

The antipsychotic agent risperidone, is metabolized by different cytochrome P-450 (CYP) enzymes, including CYP2D6, to the active 9-hydroxyrisperidone, which is the major metabolite in plasma. Two enantiomers, (+)- and (-)-9-hydroxyrisperidone might be formed, and the aim of this study was to evaluate the importance of CYP2D6 and CYP3A4/CYP3A5 in the formation of these two enantiomers in human liver microsomes and in recombinantly expressed enzymes. The enantiomers of 9-hydroxyrisperidone were analyzed with high pressure liquid chromatography using a chiral alpha-1 acid glycoprotein column. A much higher formation rate was observed for (+)-9-hydroxyrisperidone than for (-)-9-hydroxyrisperidone in microsomes prepared from six individual livers. The formation of (+)-9-hydroxyrisperidone was strongly inhibited by quinidine, a potent CYP2D6 inhibitor, whereas ketoconazole, a CYP3A4 inhibitor, strongly inhibited the formation of (-)-9-hydroxyrisperidone. Recombinant human CYP2D6 produced only (+)-9-hydroxyrisperidone, whereas a lower formation rate of both enantiomers was detected with expressed CYP3A4 and CYP3A5. In vivo data from 18 patients during treatment with risperidone indicate that the plasma concentration of the (+)-enantiomer is higher than that of the (-)-enantiomer in extensive metabolizers of CYP2D6. These findings clearly suggest that CYP2D6 plays a predominant role in (+)-9-hydroxylation of risperidone, the major metabolic pathway in clinical conditions, whereas CYP3A catalyzes the formation of the (-)-9-hydroxymetabolite. Further studies are required to evaluate the pharmacological/toxic activity of both enantiomers.
Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress (2018)

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960-2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (<i>n</i> = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (<i>n</i> = 104), mostly with psilocybin treatment (<i>n</i> = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.
Securing Name Servers on UNIX (1999)

Because the DNS plays such a vital role in the Internet, it is important that this service be protected and secured
Magnitude and Diversity of Cytotoxic-T-Lymphocyte Responses Elicited by Multiepitope DNA Vaccination in Rhesus Monkeys (2003)

In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an immunogenic simian immunodeficiency virus gag DNA vaccine elicited high-frequency CTL responses specific for all of the epitopes included in the vaccine. Both multiepitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant modified vaccinia virus Ankara vaccines expressing complete viral proteins. The natural hierarchy of immunodominance for these epitopes was clearly evident in the boosted monkeys. These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance.
Teichoic acid and lipoteichoic acid of Streptococcus pneumoniae possess identical chain structures (1993)

Teichoic acid (C polysaccharide) was extracted and purified from Streptococcus pneumoniae R6 with standard procedures except that lipoteichoic acid was extracted first. The dephosphorylated repeating unit was isolated after hydrolysis with 48% (by mass) HF, the bis(phosphocholine)-containing repeating unit was isolated by alkali hydrolysis, anion-exchange chromatography and phosphomonoester cleavage. On the basis of compositional analysis, fast-atom-bombardment mass spectrometry and NMR spectroscopy the following structure is proposed: [formula: see text] where AATGal is 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose. The repeating units are linked to each other by phosphodiester bonds between O5 of the ribitol and O6 of the glucopyranosyl residue of adjacent units. This chain structure is identical with that previously established for pneumococcal lipoteichoic acid [Behr, T., Fischer, W., Peter-Katalinić, J. & Egge, H. (1992) Eur. J. Biochem. 207, 1063-1075]. This represents a unique situation because in other Gram-positive bacteria teichoic and lipoteichoic acids are structurally unrelated.
Antifreeze Solution Improves DNA Recovery by Preserving the Integrity of Pathogen-Infected Blood and Other Tissues (2000)

Preserving blood samples for shipping and later DNA extraction has been performed by cooling, freezing, drying, freeze-drying, and protease treatment, among other methods. Most methods to preserve field samples for further DNA extraction do not prevent cellular and DNA damage or are useful only in preserving them for short periods. This report introduces a novel method for blood and tissue that allows preservation in freezing temperatures for a prolonged period of time. The solution reported here (20% ethylene glycol-propylene glycol) preserves cells and tissues integrity, as judged by microscopic analysis, and improves DNA yield and quality.
Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. (1993)

The cellular mechanism underlying the generation of beta-amyloid in Alzheimer disease and its relationship to the normal metabolism of the amyloid precursor protein are unknown. In this report, we show that 3- and 4-kDa peptides derived from amyloid precursor protein are normally secreted. Epitope mapping and radiolabel sequence analysis suggest that the 4-kDa peptide is closely related to full-length beta-amyloid and the 3-kDa species is a heterogeneous set of peptides truncated at the beta-amyloid N terminus. The beta-amyloid peptides are secreted in parallel with amyloid precursor protein. Inhibitors of Golgi processing inhibit secretion of beta-amyloid peptides, whereas lysosomal inhibitors have no effect. The secretion of beta-amyloid-related peptides occurs in a wide variety of cell types, but which peptides are produced and their absolute levels are dependent on cell type. Human astrocytes generated higher levels of beta-amyloid than any other cell type examined. These results suggest that beta-amyloid is generated in the secretory pathway and provide evidence that glial cells are a major source of beta-amyloid production in the brain.
HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling (2007)

Ischemic tissues require mechanisms to alert the immune system of impending cell damage. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. We elucidate the mechanism by which HMGB1, one of the key alarm molecules released during liver ischemia/reperfusion (I/R), is mobilized in response to hypoxia. HMGB1 release from cultured hepatocytes was found to be an active process regulated by reactive oxygen species (ROS). Optimal production of ROS and subsequent HMGB1 release by hypoxic hepatocytes required intact Toll-like receptor (TLR) 4 signaling. To elucidate the downstream signaling pathways involved in hypoxia-induced HMGB1 release from hepatocytes, we examined the role of calcium signaling in this process. HMGB1 release induced by oxidative stress was markedly reduced by inhibition of calcium/calmodulin-dependent kinases (CaMKs), a family of proteins involved in a wide range of calcium-linked signaling events. In addition, CaMK inhibition substantially decreased liver damage after I/R and resulted in accumulation of HMGB1 in the cytoplasm of hepatocytes. Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling.
Metabolic phenotypes of retinoic acid and the risk of lung cancer. (1996)

The metabolic activity of cytochrome P-450 enzymes has been associated with an increased risk of developing lung cancer. We found previously that all-trans retinoic acid is catabolized by these oxidative enzymes, and that an inhibitor of this system discriminated between two populations of lung cancer patients. We examined the association between this metabolic phenotype and the risk of lung cancer in 85 subjects. The area under the plasma concentration x time curve (AUC) was calculated after a single oral dose of all-trans retinoic acid (45 mg/m2). The mean AUC for patients who had either squamous or large cell carcinomas was significantly lower than that of patients with adenocarcinomas (P = 0.0001) or control subjects (P = 0.01). Individuals with an AUC < 250 ng x h/ml had a greater likelihood of having squamous or large cell carcinoma (odds ratio = 5.93). This study suggests that the "rapid" catabolism of all-trans retinoic acid is linked to an increased risk of squamous or large cell cancers of the lung.
Synthesis, Characterization, and Receptor Interaction Profiles of Enantiomeric Bile Acids (2007)

Bile acids are endogenous steroid detergents with receptor-mediated physiologic actions including activation of the G-protein coupled receptor TGR5 and gene regulation mediated by nuclear receptors. In this study, we report the first synthesis of enantiomeric lithocholic acid (ent-LCA, ent-1) and chenodeoxycholic acid (ent-CDCA, ent-2) via ent-testosterone (3). ent-1 was synthesized in 21 total steps in 4.2% yield, whereas ent-2 was obtained in 23 total steps in 0.8% yield. Critical micelle concentrations of the enantiomeric bile acids were found to be identical to their natural counterparts. Furthermore, enantiomeric bile acids were also tested for their ability to modulate bile acid activated proteins: farnesoid X receptor, vitamin D receptor, pregnane X receptor, and TGR5. Interestingly, ent-1 and ent-2 showed differential interactions with these proteins as compared to their corresponding natural bile acids. These data highlight the potential for using enantioselectivity as a way to distinguish between receptor and nonreceptor-mediated functions of natural bile acids.