gebhart/patrepeval huggingface dataset:
DNA-based immunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating antibody (1993)

The possibility of inducing an immune response to a protein expressed directly from an introduced gene represents an alternative to classic vaccination. We evaluated the ability of plasmid-based eukaryotic expression vectors to produce the Hepatitis B surface antigen (HBsAg) after injection of pure DNA into mouse tibialis anterior muscles. DNA was injected into either normal mature muscle, or regenerating muscle following cardiotoxin-induced degeneration. The sera obtained from these animals contained significant levels of HBsAg as early as 10 days after gene transfer, at which time low levels of antibodies to HBsAg (anti-HBsAg) were already present. Between 15-60 d after DNA transfer, serum levels of anti-HBsAg steadily increased whereas those for HbsAg fell, most likely due to the neutralizing effect of the antibodies. Analysis of proportions of HBs-seropositive mice showed that within 2 wk of injection of 100 micrograms pCMV-HBs in regenerating muscle, 91% of the mice were seropositive [defined as having more than 1 milli-International Unit/ml (mIU/ml) of anti-HBsAg]. Even at that early time, 68% had titers of anti-HBsAg greater than 10 mlU/ml, a level that is recognized as being sufficient in humans to confer protection against natural Hepatitis B virus infection. The proportion of seropositive animals rose to 95% by 4 wk, and 100% by 8 wk, at which time all mice had greater than 100 mIU anti-HBsAg in their sera. We have thus demonstrated that direct intramuscular injection of a plasmid vector encoding the HBsAg will give rise to secretion of the viral surface protein into the circulation which leads to an appropriate antibody response.(ABSTRACT TRUNCATED AT 250 WORDS)
Integrative analysis of environmental sequences using MEGAN4 (2011)

A major challenge in the analysis of environmental sequences is data integration. The question is how to analyze different types of data in a unified approach, addressing both the taxonomic and functional aspects. To facilitate such analyses, we have substantially extended MEGAN, a widely used taxonomic analysis program. The new program, MEGAN4, provides an integrated approach to the taxonomic and functional analysis of metagenomic, metatranscriptomic, metaproteomic, and rRNA data. While taxonomic analysis is performed based on the NCBI taxonomy, functional analysis is performed using the SEED classification of subsystems and functional roles or the KEGG classification of pathways and enzymes. A number of examples illustrate how such analyses can be performed, and show that one can also import and compare classification results obtained using others' tools. MEGAN4 is freely available for academic purposes, and installers for all three major operating systems can be downloaded from www-ab.informatik.uni-tuebingen.de/software/megan.
The synthesis of benzofuroquinolines. X. Some benzofuro[3,2‐c]isoquinoline derivatives (1995)

Abstract Condensation of salicylonitrile with ethyl α‐bromo‐α‐( o ‐ethoxycarbonylphenyl)acetate (4) effectively gave 5 (6 H )‐benzofuro[3,2‐ c ]isoquinolinone (2) , which was converted to some 5‐substituted benzofuro‐[3,2‐ c ]isoquinoline derivatives 1a‐g.
Complementary roles of neurotrophin 3 and a N- methyl- d -aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity (2000)

Recent progress has been made regarding the prevention of hearing loss. However, the complete protection of both hair cells and spiral ganglion neurons, with restored function, has not yet been achieved. It has been shown that spiral ganglion neuronal loss can be prevented by neurotrophin 3 (NT3) and hair cell damage by N-methyl-D-aspartate (NMDA) receptor antagonists. Here we demonstrate that the combined treatment with MK801, a NMDA antagonist, and NT3 protect both cochlear morphology and physiology from injury. Pretreatment with MK801 prevented hearing loss and the dendrites of the spiral ganglion neurons from swelling after noise-induced damage. The acute phase of insult with the aminoglycoside antibiotic amikacin resulted in swollen afferent dendrites beneath the inner hair cells. The chronic phase resulted in complete hair cell loss and near-complete loss of spiral ganglion neurons. This damage caused a near-complete loss of hearing sensitivity as displayed by elevated (>90-dB sound pressure levels) auditory brainstem response thresholds. The treatment of amikacin-exposed animals with MK801 gave only a partial protection of hearing. However, the combined treatment with NT3 and MK801 in the amikacin-comprised ear resulted in improved mean hearing within 20 dB of normal. Furthermore, hair cell loss was prevented in these animals and spiral ganglion neurons were completely protected. These results suggest that the NMDA antagonist MK801 protects against noise-induced excitotoxicity in the cochlea whereas the combined treatment of NT3 and MK801 has a potent effect on preserving both auditory physiology and morphology against aminoglycoside toxicity.
Planning and evaluation are crucial to multilateral wells (1996)

The ability to drill and produce multilateral wells provides tremendous opportunity for profit from previously uneconomic projects. Where it may not be economical to drill to small pockets of deposits with a number of vertical or horizontal well bores, the economics may be very good with multilateral drilling and completion technology. Multilateral drilling and completion systems have been successfully run in several producing areas worldwide. Significant advances in drilling, casing and completions technology make it possible to drill and complete complex architecture multilateral wells. Whether a project involves a single well re-entry project or full field development, the flexibility and cost savings involved in a multilateral well versus multiple wells can be significant. This paper reviews the various design considerations in developing multivariant well systems.
Artificial Neural Networks for Misuse Detection (1998)

Misuse detection is the process of attempting to identify instances of network attacks by comparing current activity against the expected actions of an intruder. Most current approaches to misuse detection involve the use of rule-based expert systems to identify indications of known attacks. However, these techniques are less successful in identifying attacks which vary from expected patterns. Artificial neural networks provide the potential to identify and classify network activity based on limited, incomplete, and nonlinear data sources. We present an approach to the process of misuse detection that utilizes the analytical strengths of neural networks, and we provide the results from our preliminary analysis of this approach. Keywords: Intrusion detection, misuse detection, neural networks, computer security.
Nonlinear acoustic echo cancellation with 2nd order adaptive Volterra filters (1999)

Acoustic echo cancellers in today's speakerphones or video conferencing systems rely on the assumption of a linear echo path. Low-cost audio equipment or constraints of portable communication systems cause nonlinear distortions, which limit the echo return loss enhancement achievable by linear adaptation schemes. These distortions are a super-position of different effects, which can be modelled either as memoryless nonlinearities or as nonlinear systems with memory. Proper adaptation schemes for both cases of nonlinearities are discussed. An echo canceller for nonlinear systems with memory based on an adaptive second order Volterra filter is presented. Its performance is demonstrated by measurements with small loudspeakers. The results show an improvement in the echo return loss enhancement of 7 dB over a conventional linear adaptive filter. The additional computational requirement for the presented Volterra filter is comparable to that of existing acoustic echo cancellers.
Sertindole, a Potent Antagonist at Dopamine D<sub>2</sub> Receptors, Induces Autophagy by Increasing Reactive Oxygen Species in SH-SY5Y Neuroblastoma Cells (2012)

Autophagy is associated with cell survival and cell death. Autophagy is implicated in the pathophysiology of various human diseases. In order to identify autophagy regulatory molecules, we screened a chemical drug library in SH-SY5Y cells and selected Sertindole as a potent autophagy inducer. Sertindole was developed as an antipsychotic drug for Schizophrenia. Sertindole treatment highly induced the formation of autophagosomes as well as LC3 conversion. Subsequently, Sertindole-induced autophagy was efficiently suppressed by down regulation of ATG5. Sertindole also increased reactive oxygen species (ROS) production, which contributes to autophagy-associated cell death in neuroblastoma cells. ROS scavengers such as N-acetylcysteine and Trolox suppressed not only ROS generation but also autophagy activation by Sertindole. These results suggest Sertindole induces autophagy and autophagy-associated cell death by ROS production in neuroblastoma cells.
Transmission of Chlamydia pneumoniae (1993)

To investigate the transmission of Chlamydia pneumoniae via hands and environmental surfaces, its survival on various surfaces was studied. The organism remained viable on formica countertops for 30 h and in tissue paper for 12 h. Measurable quantities of chlamydiae were transferred from these environmental surfaces to hands. However, titers were low and survival time on hands was limited to 10–15 min. C. pneumoniae survived small particle aerosolization well and was infectious to mice by both direct inoculation and aerosolization. These observations suggest that several mechanisms of transmission of C. pneumoniae are possible, including the transfer of fomites from environmental surfaces with subsequent autoinoculation.
SCN1A‐related phenotypes: Epilepsy and beyond (2019)

SCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with several epilepsy syndromes and a range of other diseases. SCN1A represents the archetypal channelopathy associated with a wide phenotypic spectrum of epilepsies ranging from genetic epilepsy with febrile seizures plus (GEFS+), to developmental and epileptic encephalopathies (DEEs). SCN1A disorders also result in other diseases such as hemiplegic migraine and autism spectrum disorder (ASD). Dravet syndrome (DS) is the prototypic DEE with an early onset of febrile status epilepticus, hemiclonic or generalized tonic-clonic seizures, and later onset of additional seizure types. Electroencephalography (EEG) and magnetic resonance imaging (MRI) are normal at onset. Development is normal in the first year of life but plateaus rapidly, with most patients ultimately having intellectual disability. Epilepsy is drug-resistant and necessitates polytherapy. Most pathogenic variants occur de novo in the affected child, but they are inherited from mosaic affected or unaffected parents in rare cases. The molecular finding of haploinsufficiency is consistent with a loss-of-function defect in cells and animal models. Although seizures are the most commonly reported symptom in DS, many additional issues critically affect patients' cognitive and behavioral functioning. Hemiplegic migraine (HM) is a rare form of migraine with aura, characterized by the emergence of hemiparesis as part of the aura phase. All SCN1A mutations reported in sporadic/familial HM3 are missense mutations. Most of the experimental results show that they cause a gain of function of Na<sub>V</sub> 1.1 as opposed to the loss of function of the epileptogenic Na<sub>V</sub> 1.1 mutations. SCN1A and SCN2A pathogenic variants have been identified in genetic studies of cohorts of patients with ASD. In addition, ASD features are often reported in patients with Dravet syndrome and other DEEs.
Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis (2011)

These findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments.
Studies on the mechanism of inhibition of tumor growth by the enzyme glutaminase. (1966)

Summary The Gardner 6C3HED lymphosarcoma, Leukemia L-1210, and Leukemia L-1210/aza in ascites form were inhibited in in vivo experiments by a highly purified preparation of glutaminase-asparaginase from a pseudomonad. The glutamine content of tumors was measured by an enzymatic micromethod. The results showed that glutaminase-treated tumors were depleted of free glutamine. The glutamine-synthetase activity in tissues of normal mice has been compared with that of tumor cells. Tumor tissues showed lower activity of this enzyme than did normal tissues. Glycine-14C and adenine-14C incorporation studies in vivo indicated the impairment of both the de novo and the reutilization pathways of purine synthesis. Combination therapy with azaserine-enzyme and 8-azaguanine-enzyme produced an augmentation of tumor inhibition.
Regulation of Interferon Production by Human Monocytes: Requirements for Priming for Lipopolysaccharide-Induced Production (1991)

Abstract Macrophages are uniquely responsive to bacterial lipopolysaccharide (LPS) for activation of a number of host defense functions and production of bioactive mediators. One potentially important mediator produced by LPS-stimulated macrophages is interferon (IFN-α/β). In contrast to murine observations, we have observed that freshly isolated human monocytes, purified by counter-current centrifugal elutriation, do not produce interferon in response to LPS. This is not due to a lack of response to LPS, as assessed by the induction of other monokines, or to an incapacity for IFN production, since IFN was inducible by poly-l,C treatment of monocytes in the absence of any other exogenous stimulus. However, human monocytes can be primed for the production of IFN in response to LPS if they are cultured in the presence of either granulocyte-macrophage colony stimulating factor (GM-CSF) or interferon-γ (IFN-γ). The IFN secreted is of the α subtype. Monocytes primed with GM-CSF or IFN-γ also maintained LPS responses for production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1). M-CSF did not prime monocytes for LPS-induced IFN production, although it did enhance production of TNF-α and promoted monocyte survival. Northern analysis indicated that the induction of IFN-α by LPS was regulated primarily at the mRNA level. The highly regulated production of IFN-α by monocytes/macrophages has important implications for autocrine action of interferons in the activation and differentiation of these cells.
Adjunctive Aripiprazole, Olanzapine, or Quetiapine for Major Depressive Disorder: An Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed (2010)

Number needed to treat and NNH can be used to quantify efficacy and tolerability outcomes and help place various therapeutic options into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and the patient the trade-offs between obtaining potential benefits versus harms. In the case of the adjunctive second-generation antipsychotics approved for treating major depressive disorder, these trade-offs vary greatly among the choices available and require careful, individualized, patient-centered clinical decision making.
New Assay Procedure for Thyroxine Analogs (1965)

The large increase in rat liver and kidney α-glycerophosphate dehydrogenase activity (GPD) which results from the administration of thyroxine (T4) has been developed into a simple assay procedure for thyromimetic substances. The dose-response curves obtained with T4 and other analogs were analyzed by 2 variations of the usual semilog plot as well as by a new hemisigmoid procedure. The results agreed well with previously reported calorigenic activities. Both weanling and adult rats produced endogenously the equivalent of about 1 μg T4/100 g body wt /day, but the adults were appreciably less sensitive to the hormone. The nature of the diet fed to rats during the assay period modified the response even when the T4 was administered subcutaneously; approximately 3 times as much T4 was required to produce a given response on a chow diet as on a purified diet. (Endocrinology77: 802, 1965)
Effects of Chronic Systemic Administration of Basic Fibroblast Growth Factor on Collateral Development in the Canine Heart (1995)

Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.
Formation of Polyphenylene Films on Metal Electrodes by Electrochemical Reduction of Benzenediazonium Salts (2006)

It is possible to form micrometer thick polyphenylene (PP) films by electrochemical reduction of benzenediazonium tetrafluoroborate on metals in acetonitrile. The electrochemical behavior of the PP film is characterized by different electrochemical transient methods and is surprisingly different from that observed with other diazonium salts. The films are analyzed by IR and time-of-flight secondary ion mass spectroscopies; their thickness and conductivity are also characterized. Because they are conductive, these micrometer thick films can be further derivatized by electrochemical reduction of other diazonium salts, for example, nitrophenyl or bromophenyl diazonium salts. Copper can also be deposited on the top of the PP film. The behavior of redox probes on PP films is discussed as well as the origin of this increased conductivity. A simple model for the reaction kinetics of electrografting is presented.
Differences in gut microbiota composition between obese and lean children: a cross-sectional study (2013)

An altered gut microbiota composition has recently been linked to obesity. The principal aim of this study is to investigate and compare the gut microbiota composition in obese and lean children. Secondly, associations between analysed gut bacterial species, dietary compounds, energy intake and biochemical blood parameters are evaluated. In this prospective cross-sectional study, 26 overweight/obese (mean BMI: 28.7 ± 6.5) and 27 lean (mean BMI: 16.5 ± 2.1) children aged 6 to 16 were included. Faecal samples were collected and subjected to selective plating and quantitative real-time PCR (qPCR) in order to determine the concentrations of bacterial species belonging to the genera: Bacteroides, Bifidobacterium, Clostridium, Staphylococcus and Lactobacillus. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for an in-depth identification of species of Bacteroides fragilis group. Differences in the concentrations of gut bacterial species between obese and lean children were statistically analysed using Mann Whitney U test. Subsequently, random forest analysis and multiple linear regression analysis were performed in order to test associations between gut bacterial species, dietary compounds and blood parameters. Obese children showed an elevated Firmicutes-to-Bacteroidetes ratio compared with lean children. Furthermore, low relative proportions of B. vulgatus and high concentrations of Lactobacillus spp. were observed in the obese microbiota. In all children, Staphylococcus spp. were positively associated with energy intake. Additionally, in obese children, Lactobacillus spp. were positively associated with plasma hs-CRP. Our findings corroborate a significant difference in the gut microbiota composition of important bacterial species between obese and lean children. In future, non-invasive manipulation of gut microbiota composition in early infancy could offer a new approach to manage childhood obesity and associated disorders.
Attraction or Repulsion? London Dispersion Forces Control Azobenzene Switches (2015)

Large substituents are commonly seen as entirely repulsive through steric hindrance. Such groups have additional attractive effects arising from weak London dispersion forces between the neutral atoms. Steric interactions are recognized to have a strong influence on isomerization processes, such as in azobenzene-based molecular switches. Textbooks indicate that steric hindrance destabilizes the Z isomers. Herein, we demonstrate that increasing the bulkiness of electronically equal substituents in the meta-position decreases the thermal reaction rates from the Z to the E isomers. DFT computations revealed that attractive dispersion forces essentially lower the energy of the Z isomers.
Concepts and methods in the theory of open quantum systems (2003)

The central physical concepts and mathematical techniques used in the theory of open quantum systems are reviewed. Particular emphasis is laid on the interrelations of apparently different approaches. Starting from the appropriate characterization of the quantum statistical ensembles naturally arising in the description of open quantum systems, the corresponding dynamical evolution equations are derived for the Markovian as well as for the non-Markovian case.
Neoliberale Steuerrechtslehre und Bundesverfassungsgericht (1999)

Diese Konzeption folgt der Idee eines konservativen Wohlfahrtsstaates. Der allgemeine Gleichheitssatz des Grundgesetzes wird als Argumentationsfigul' zur Rechtfertigemg von sozialen Ungleichheiten im Steuerrecht herangezogen. Der Autor untersucht die Entscheidungen des Bundesverfassungsgerichts daraufhin,
Discovery of 1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2‘-(methylsulfonyl)- [1,1‘-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a Highly Potent, Selective, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa (2001)

Factor Xa (fXa) plays a critical role in the coagulation cascade, serving as the point of convergence of the intrinsic and extrinsic pathways. Together with nonenzymatic cofactor Va and Ca2+ on the phospholipid surface of platelets or endothelial cells, factor Xa forms the prothrombinase complex, which is responsible for the proteolysis of prothrombin to catalytically active thrombin. Thrombin, in turn, catalyzes the cleavage of fibrinogen to fibrin, thus initiating a process that ultimately leads to clot formation. Recently, we reported on a series of isoxazoline and isoxazole monobasic noncovalent inhibitors of factor Xa which show good potency in animal models of thrombosis. In this paper, we wish to report on the optimization of the heterocyclic core, which ultimately led to the discovery of a novel pyrazole SN429 (2b; fXa K(i) = 13 pM). We also report on our efforts to improve the oral bioavailability and pharmacokinetic profile of this series while maintaining subnanomolar potency and in vitro selectivity. This was achieved by replacing the highly basic benzamidine P1 with a less basic benzylamine moiety. Further optimization of the pyrazole core substitution and the biphenyl P4 culminated in the discovery of DPC423 (17h), a highly potent, selective, and orally active factor Xa inhibitor which was chosen for clinical development.
Predictive Data Mining: A Practical Guide (1997)

1 What is Data Mining? 2 Statistical Evaluation for Big Data 3 Preparing the Data 4 Data Reduction 5 Looking for Solutions 6 What's Best for Data Reduction and Mining? 7 Art or Science? Case Studies in Data Mining