gebhart/patrepeval huggingface dataset:
Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. (1996)

Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure-function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.
Expression of Aspergillus nidulans phy Gene in Nicotiana benthamiana Produces Active Phytase with Broad Specificities (2014)

A full-length phytase gene (phy) of Aspergillus nidulans was amplified from the cDNA library by polymerase chain reaction (PCR), and it was introduced into a bacterial expression vector, pET-28a. The recombinant protein (rPhy-E, 56 kDa) was overexpressed in the insoluble fraction of Escherichia coli culture, purified by Ni-NTA resin under denaturing conditions and injected into rats as an immunogen. To express A. nidulans phytase in a plant, the full-length of phy was cloned into a plant expression binary vector, pPZP212. The resultant construct was tested for its transient expression by Agrobacterium-infiltration into Nicotiana benthamiana leaves. Compared with a control, the agro-infiltrated leaf tissues showed the presence of phy mRNA and its high expression level in N. benthamiana. The recombinant phytase (rPhy-P, 62 kDa) was strongly reacted with the polyclonal antibody against the nonglycosylated rPhy-E. The rPhy-P showed glycosylation, two pH optima (pH 4.5 and pH 5.5), an optimum temperature at 45~55 °C, thermostability and broad substrate specificities. After deglycosylation by peptide-N-glycosidase F (PNGase-F), the rPhy-P significantly lost the phytase activity and retained 1/9 of the original activity after 10 min of incubation at 45 °C. Therefore, the deglycosylation caused a significant reduction in enzyme thermostability. In animal experiments, oral administration of the rPhy-P at 1500 U/kg body weight/day for seven days caused a significant reduction of phosphorus excretion by 16% in rat feces. Besides, the rPhy-P did not result in any toxicological changes and clinical signs.
A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections (2017)

This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of <i>Clostridium difficile</i> infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the keywords bacterial vaccines, <i>Clostridium difficile</i>, and vaccine. English-language clinical trials evaluating the efficacy and/or safety of <i>Clostridium difficile</i> toxoid vaccines that were completed and had results posted on ClinicalTrials.gov or in a published journal article were included. Six clinical trials were included. The vaccines were associated with mild self-reported adverse reactions, most commonly injection site reactions and flu-like symptoms, and minimal serious adverse events. Five clinical trials found marked increases in antibody production in vaccinated participants following each dose of the vaccine. Clinical trials evaluating <i>C. difficile</i> toxoid vaccines have shown them to be well tolerated and relatively safe. Surrogate markers of efficacy (seroconversion and geometric mean antibody levels) have shown significant immune responses to a vaccination series in healthy adults, indicating that they have the potential to be used as prophylaxis for CDI. However, more research is needed to determine the clinical benefits of the vaccines.
Plant Disease Resistance Genes: Function Meets Structure. (1996)

The coevolution of interacting plants and microbes has given rise to a diverse array of exchanged signals and responses. Microbes that elicit a host response can be met variously with hospitable acceptance (as is the case with symbionts such as nitrogen-fixing Rhizobium bacteria), with tardy recognition and moderately effective defenses (as for most interactions that result in disease), or with a strong and rapid defense response that blocks further infection (Dixon and Lamb, 1990; Keen, 1990; Long and Staskawicz, 1993). This latter form of disease resistance forms the subject of this review and is known variously as race-specific resistance, gene-for-gene resistance, or hypersensitive resistance. Activation of gene-for-gene resistance typically depends on specific recognition of the invading pathogen by the plant (Keen, 1990). Numerous individual plant genes have been identified that control gene-for-gene resistance, and these genes are known as resistance (R) genes. Study of gene-for-gene resistance might be justified solely by the intrigue of plant-pathogen coevolution or as a model for signal transduction research in which an organism perceives and responds to its environment. However, the topic takes on greater interest dueto its pivotal impact on crop health and food production. Plant diseases cause billions of dollars in lost harvest annually, and in some instances, these losses have severe consequences for humans (Agrios, 1988; Schumann, 1991). One of the most convenient, inexpensive, and environmentally sound ways to control plant disease is to utilize disease-resistam varieties, and plant breeders make extensive use of classically defined R genes (Agrios, 1988). Recent work has revealed the structure of a number of plant R genes, and a striking degree of similarity among these genes has been observed. After briefly introducing the subject of R genes and avirulence (Avo genes, this review provides an overview of the conserved structural components that are predicted in the proteins encoded by R genes. The cloning of R genes has stimulated additional research that is also discussed, including structure-function analysis of R gene-encoded proteins, isolation of additional R genes, identification of functionally related components of the defense signal transduction cascade, and engineering of improved disease resistance in plants. RESISTANCE GENES, AVIRULENCE GENES, AND PLANT DEFENSE
Immunological investigation of the distribution of cytochromes related to the two terminal oxidases of Escherichia coli in other gram-negative bacteria (1985)

Monospecific antibodies were raised against the two terminal oxidase complexes of the aerobic respiratory chain of Escherichia coli. These are the cytochrome d and cytochrome o complexes. The antibodies were used to check for the occurrence of cross-reactive antigens in membrane preparations from a variety of gram-negative bacteria by rocket immunoelectrophoresis and immunoblotting techniques. With these criteria, proteins closely related to the cytochrome d complex of E. coli appeared to be widely distributed. Among the strains containing cytochrome d-related material were Serratia marcescens, Photobacterium phosphoreum, Salmonella typhimurium, Klebsiella pneumoniae, and Azotobacter vinelandii. The data suggest that the d-type terminal oxidase in many of these strains is associated in a complex with b-type and a1-type cytochromes, as has been found to be the case in E. coli. K. pneumoniae and S. typhimurium were also shown to have material cross-reactive to the E. coli cytochrome o complex.
Virtual memory in contemporary microprocessors (1998)

Here, we consider the memory management designs of a sampling of six recent processors, focusing primarily on their architectural differences, and hint at optimizations that someone designing or porting system software might want to consider. We selected examples from the most popular commercial microarchitectures: the MIPS R10000, Alpha 21164, PowerPC 604, PA-8000, UltraSPARC-I, and Pentium II. This survey describes how each processor architecture supports the common features of virtual memory: address space protection, shared memory, and large address spaces.
Synthesis of binuclear phenoxyimino organoaluminum complexes and their use as the catalyst precursors for efficient ring-opening polymerisation of ε-caprolactone (2013)

A series of novel binuclear phenoxyimino organoaluminum complexes of the type [(RN=CH)C6H3OAlMe2]2 [R = C6H5 (2a), 2,6-(i)Pr2C6H3 (2b), 2,6-Ph2C6H3 (2c), adamantyl (2d), (t)Bu (2e)] have been prepared in high yields, and these complexes were identified by (1)H, (13)C NMR and elemental analysis. Structural analysis for 2a-e revealed that these complexes have a distorted tetrahedral geometry around Al and both the Al-O and the Al-N bond distances were considerably influenced by substituents in the imino groups. The complexes were tested as catalyst precursors for ring-opening polymerisation (ROP) of ε-caprolactone (CL) in the presence of BnOH, and their catalytic activities were strongly affected by the catalyst structures and polymerisation conditions. An efficient living ROP has been achieved using the 2b/BnOH system.
Aqueous‐Phase Synthesis of Single‐Crystal Ceria Nanosheets (2010)

The evolution of sheet morphology for single-crystal ceria nanosheets with a thickness of about 2.2 nm and lateral dimensions up to 4 μm (see picture), involves two-dimensional self-organization of the initially formed ceria nanocrystals, followed by recrystallization. Ceria nanosheets exhibit an unusually large optical band gap energy due to the quantum size effect associated with their extremely small thickness.
Patient Satisfaction with Oral versus Nonoral Therapeutic Approaches in Onychomycosis (2001)

The follow-up results of a 9-month observational study of 150 onychomycosis patients treated with a variety of mechanical, topical, and oral therapies by podiatric physicians and dermatologists are presented. Changes from baseline in toenail condition and patient satisfaction were assessed at 4- and 9-month follow-up. At 9 months, patients who had received oral therapy reported significantly fewer onychomycosis-related problems in social situations, including embarrassment or self-consciousness about the appearance of nails, avoidance of contact by others, being perceived as unclean or untidy, and the desire to keep their nails concealed. Patient-reported satisfaction with the treatment program was significantly higher for those receiving oral therapy than for those receiving nonoral therapy.
Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection (2011)

IgG is a major Ig subclass in mucosal secretions of the human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about where and how IgG enters the lumen of the genital tract and the exact role local IgG plays in preventing sexually transmitted diseases. We demonstrate here that the neonatal Fc receptor, FcRn, is expressed in female genital tract epithelial cells of humans and mice and binds IgG in a pH-dependent manner. In vitro we show that FcRn mediates bidirectional IgG transport across polarized human endometrial HEC-1-A monolayers and primary human genital epithelial cells. Furthermore, endosomal acidification appears to be a prerequisite for FcRn-mediated IgG transcytosis; IgG transcytosis was demonstrated in vivo by translocation of systemically administered IgG into the genital lumen in WT but not FcRn-KO mice. The biological relevance of FcRn-transported IgG was demonstrated by passive immunization using herpes simplex virus-2 (HSV-2)-specific polyclonal serum, which conferred significantly higher protection against intravaginal challenge infection by the HSV-2 186 strain in WT mice than in FcRn-KO mice. These studies demonstrate that FcRn-mediated transport is a mechanism by which IgG can act locally in the female genital tract in immune surveillance and in host defense against sexually transmitted diseases.
Should the Incorporation of Structural Alerts be Restricted in Drug Design? An Analysis of Structure-Toxicity Trends with Aniline-Based Drugs (2014)

Certain idiosyncratic adverse drug reactions (IADRs) can be triggered by electrophilic protein-reactive metabolites that are formed in the process of drug metabolism. While methodologies (e.g., structural alert concept in drug design, glutathione (GSH) trapping, and protein covalent binding) for examining reactive metabolite (RM) formation are available, predicting the IADR potential applying these parameters remains a significant challenge. The present work examines toxicity trends associated with the aniline structural alert in the top 200 prescribed drugs of 2011 and recently approved (2009-2013) small molecule drugs, in relation with 30 aniline-based drugs withdrawn from commercial use or associated with a black box warning for IADRs. The aniline sub-structure was found in several drugs from the toxic, most prescribed, and recently approved category. RMs resulting from the bioactivation of the aniline alert was also noted in the three categories chosen for comparison. A major discriminator between the toxic drugs and the majority of drugs in the most-prescribed list, however, was the daily dose--drugs most frequented associated with IADRs were the ones with higher daily doses (exceeding hundreds of milligrams). A greater tolerance for IADRs was also noted with certain drugs intended to treat rare, unmet medical needs (e.g., cancer). Overall, the analysis suggests that optimization of pharmacologic potency and pharmacokinetics that would lead to a lower daily dose, and therefore, a lower body burden of parent drug/metabolites, should be taken into consideration in drug discovery.
Comparison of the Oral Direct Thrombin Inhibitor Ximelagatran With Enoxaparin as Prophylaxis Against Venous Thromboembolism After Total Knee Replacement (2001)

Fixed-dose, unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be safe and effective oral prophylaxis against venous thromboembolism after total knee replacement.
Synthetic Reactions via Vanadium-Induced One-Electron Redox. (1994)

VO (OR) Cl2 is revealed to be a Lewis acid with one-electron oxidation capability. The regioselective ringopening oxygenation of cyclic ketones is catalyzed by VO (OEt) Cl2 in ethanol under oxygen to give the diesters or keto esters. The presence of α, β carbon-carbon double bond in the ketones alters the reaction course. 2-Cyclohexen-l-ones undergo dehydrogenative aromatization to give aryl ethers. An oxovanadium compound obtained from VO (OEt) Cl2 and AgOTf or Me3SiOTf works more efficiently. In the cases of 2-cyclopenten-1- ones, 1-acetyl-1-cyclohexene, and β-ionone, allylic oxidation is achieved to introduce an oxo or alkoxyl group at the γ-position. 2-Phenylglycine derivatives are transformed to ethyl benzoate and ethyl phenylglyoxylate by the VO (OEt) Cl2-induced' oxidative deamination and/or decarboxylation. The ring-opening addition of cyclobutanone to olefins bearing an electron-withdrawing group leads to the corresponding E-chloro ester via oxidation of a cyclobutoxide intermediate. Treatment of a mixture of diketene and styrenes with VO (OR) Cl2 gives 3-alkoxycarbony1-2-methyl-5-phenyl-4, 5-dihydrofurans.Oxidative desilylation is selectively realized by one-electron oxidation of organosilicon compounds with VO (OEt) Cl2. Silyl enol ethers undergo the oxidative cross coupling to afford unsymmetrical 1, 4-diketones. Allylic silanes also regioselectively dimerize to 1, 5-hexadienes. Oxidative desilylation of silyl enol ethers and allylic silanes selectively gives γ, δ-unsaturated ketones depending on their redox potentials.The highly stereoselective monodebromination of gem-dibromocyclopropanes is induced or catalyzed by a low valent vanadium species generated from vanadium (III) chloride or CpV (CO) 4 and zinc in dimethoxyethane in a combination with diethyl phosphonate or triethyl phosphite.
Principles of Healthcare Ethics: Consent and the Doctor/Patient Relationship (1993)

(1993). Principles of Healthcare Ethics: Consent and the Doctor/Patient Relationship. Australian Journal of Forensic Sciences: Vol. 25, No. 1, pp. 21-29.
Investigation of 2 inch SiC layers grown in a resistively-heated LP-CVD reactor with horizontal “hot-walls” (2003)

International audience
Multiple Sclerosis Is Not an Autoimmune Disease (2004)

diagnosticcriteria.TheMSplaquehas a well-defined edge and a scant lymphocyticinfiltratethatisabsentinone third of all plaques. In patients with MS, the normal-appearing gray and whitematterarealwaysinvolvedwith thediseaseprocess,extendingwellbeyondthebordersoftheplaqueasseen in the T2-weighted magnetic resonance (MR) brain images. In the diffusion tensor MR imaging, there is a progressive decline in fractional anisotropyextendingfromthenormalappearingwhitemattertotheplaque withthemostextensivechangesseen at the center of the plaque paralleling the decrease in the magnetization transfer ratio. 4 White matter abnormalities in ADEM are different, however, and do not extend beyond the focal areas of injury. Unlike MS, themagnetizationtransferratioofthe uninvolved brain and spinal cord in ADEM is identical to that of normal tissue. The evolution of the plaques in patients with MS as seen in MR spectroscopyisdifferentfromADEM. Extrapolation of EAE data to MS is guided purely by faith rather than by science. Even the most exhaustiveexperimentshaveyieldedinconclusive results. Autoreactive T-cell
Pharmacophore modeling, multiple docking, and molecular dynamics studies on Wee1 kinase inhibitors (2018)

Wee1-like protein kinase (Wee1) is a tyrosine kinase that regulates the G<sub>2</sub> checkpoint and prevents entry into mitosis in response to DNA damage. Based on a series of signaling pathways initiated by Wee1, Wee1 has been recognized as a potential target for cancer therapy. To discover potent Wee1 inhibitors with novel scaffolds, ligand-based pharmacophore model has been built based on 101 known Wee1 inhibitors. Then the best pharmacophore model, AADRRR.340, with good partial least square (PLS) statistics (R<sup>2</sup> = 0.9212, Q<sup>2</sup> = 0.7457), was selected and validated. The validated model was used as a three-dimensional (3D) search query for databases virtual screening. The filtered molecules were further analyzed and refined by Lipinski's rule of 5, multiple docking procedures (high throughput virtual screening (HTVS), standard precision (SP), genetic optimization for ligand docking (GOLD), extra precision (XP), and unique quantum polarized ligand docking (QPLD)); absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening; and the Prime/molecular mechanics generalized born surface area (MM-GBSA) method binding free energy calculations. Eight leads were identified as potential Wee1 inhibitors, and a 50 ns molecular dynamics (MD) simulation was carried out for top four inhibitors to predict the stability of ligand-protein complex. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) based on MD simulation and the energy contribution per residue to the binding energy were calculated. In the end, three hits with good stabilization and affinity to protein were identified. Communicated by Ramaswamy H. Sarma.
The Light-Addressable Potentiometric Sensor: Principles and Biological Applications (1994)

PRINCIPLES OF THE LIGHT-ADDRESSABLE POTENTIOMETRIC SENSOR 88 Measurement of pH 89 The Photoeffect 90 Light Addressability 93 Measurement of Other Chemical Species 93 THE LAPS AS A SENSOR IN AN ANALYTICAL SYSTEM 94 Electrical Measurement of Phospholipid Membranes 94 Discrete Sensor Arrays 94 LAPS as an Imaging Sensor 94 Microvolume Systems 95 The Sensor as a Structural Element of Analytical Systems 96 Data Analysis in LAPS Systems 96 APPLICATIONS FOR BIOCHEMICAL ASSAYS 98 Measurement of Enzyme Substrates and lnhibitors 98 Enzyme-Linked lmmunoassays 98 APPLICATIONS FOR CELL-BASED BIOASSAYS: THE MICROPHYSIOMETER 102 Biological Basis 102 Instrumental Characteristics 102 Applications of Microphysiometry 105 Prospects 108 CONCLUDING PERSPECTIVE 109
Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship (2008)

Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer disease (AD). There is controversy regarding the use of current diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to cognitive impairment. Because AD is specific to humans, rigorous and comprehensiveclinicopathologic studies are necessary to test and refine hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but thepredictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration. We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy. There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD. For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function. We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.
Effects of Combined Treatment with Interferon and Mezerein on Melanogenesis and Growth in Human Melanoma Cells (1985)

We have analyzed the effects of various human interferons produced in bacteria and the antileukemic compound mezerein (MEZ) on growth and melanogenesis in human melanoma cells. In four human melanoma cell lines, recombinant human fibroblast interferon (IFN-beta) was more active than recombinant human leukocyte interferons (IFN-alpha A, IFN-alpha D, or IFN-alpha A/D (Bgl] in inhibiting cellular proliferation. When monolayer cultures were exposed to 1000 IU/ml IFN-beta for four days the degree of growth inhibition in the different melanoma cell lines varied between 94 and 26%. Similarly, four days growth in medium containing 10 ng/ml MEZ resulted in either no inhibition of growth or as much as 53% inhibition of growth, depending on the specific melanoma cell line tested. MEZ induced dendrite-like processes, cytoplasmic projections morphologically similar to those normally found in neurons and melanocytes, in all four melanoma cell lines, whereas none of the interferons tested had this effect. The combination of interferon and MEZ resulted in a dramatic inhibition in cellular proliferation in all four melanoma cell lines. When cell extracts were assayed for melanin content, a marker of melanoma cell differentiation, the combination of IFN-beta and MEZ resulted in higher levels of melanin than with either agent alone. Dendrite-like formation was also prominent in the cultures treated with this combination. These results indicate that the antiproliferative effect of interferon toward human melanoma dells can be enhanced by treatment with MEZ and that this effect is associated with an enhancement of terminal differentiation.