gebhart/patrepeval huggingface dataset:
Synthesis of 3,N4-Etheno, 3,N4-Ethano, and 3-(2-Hydroxyethyl) Derivatives of 2'-Deoxycytidine and Their Incorporation into Oligomeric DNA (1995)

3,N4-Etheno, 3,N4-ethano, and 3-(2-hydroxyethyl)derivatives of 2'-deoxycytidine arise in mammalian DNA that has been exposed to the metabolic products of either vinyl chloride or the antitumor drug bis(chloroethyl)nitrosourea. These chemically-related adducts are thought to be associated with both mutagenesis and carcinogenesis. In this paper we report reliable syntheses of these deoxynucleosides and incorporation of the latter into oligodeoxynucleotides by the phosphoramidite route, using automated methods. It was found that 3-(2-hydroxyethyl)-2'-deoxycytidine is unstable in aqueous solution and undergoes an autoinduced hydrolysis to 3-(2-hydroxyethyl)-2'-deoxyuridine. The rate of this hydrolysis was found to be pH-dependent, having a maximum around pH 8, and a half-life of approximately 5 h. At higher or lower acidities, the reaction rate falls, indicating that the process involves a general acid-base catalysis. Thus in this case, oligomers were obtained that possessed 3-(2-hydroxyethyl)-2'-deoxyuridine residues, rather than the cytidine analogue. It is likely that the former represents the longer-lived species in DNA under physiological conditions. Representative oligomers containing these chemical lesions were analyzed by mass spectrometric and enzymatic degradation methods to confirm their structures.
Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia (2011)

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.
Properties of virion transactivator proteins encoded by primate cytomegaloviruses (2009)

All of the UL82 homolog proteins analysed activated gene expression, but surprising differences in other aspects of their properties were revealed. The results provide new information on early events in infection with cytomegaloviruses.
New cross‐linked and sulfated derivatives of partially deacetylated hyaluronan: Synthesis and preliminary characterization ; (2002)

Abstract Partial chemical deacetylation of hyaluronan (HA) has been carried out using known procedures and carefully controlled experimental conditions in order to minimize chain degradation. The sample described herein (deHA) has a degree of deacetylation of about 17%, which corresponds to what required for its further use, but a molecular weight of about 1/25 with respect to the native, starting material. Chemical gels have been prepared with different degrees of cross‐linking by means of a Ugi multicomponent condensation reaction involving aqueous deHA, formaldehyde, and cyclohexylisocyanide: the gels are mechanically stable and exhibit good water uptake strongly dependent on the extent of cross‐linking, as expected. deHA samples have also been selectively N‐sulfated or O‐sulfated: the former exhibit anticoagulant properties well exceeding those of the latter and not too inferior to heparin. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 86–94, 2002
Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. (1996)

Expression of the E7 oncogene of HPV-16 induces S phase entry of mammalian cells in the presence of antiproliferative signals. In particular, E7 can bypass G0/G1 arrest in response to both serum withdrawal and loss of cell adhesion, two experimental conditions in which cell cycle progression is accompanied by elevated levels of the cdk inhibitor p27KIP1. We show here that E7 can antagonize the ability of p27KIP1 to block cyclin E-associated kinase in vitro and to inhibit transcription from the cyclin A gene in transfection experiments. E7 associates with p27KIP1 both in a reconstituted in vitro system and in extracts of mammalian cells, and association requires the C-terminal part of E7. The interaction between p27KIP1 and E7 can also be demonstrated in a yeast two hybrid system. The data suggest that the ability of E7 to override certain forms of G0/G1 arrest is mediated in part by binding to and subsequent inactivation of the cdk inhibitor p27KIP1.
High-frequency transformation method and library transducing vectors for cloning mammalian cDNAs bytrans-complementation ofSchizosaccharomyces pombe (1990)

We describe a highly efficient alkali cation method and library transducing vectors for cloning mammalian cDNAs by trans-complementation of fission yeast Schizosaccharomyces pombe mutants. cDNA libraries constructed with the pcD or pcD2 vector are transduced into yeast by cotransfection with a linearized vector, which allows an enhanced homologous recombination between the yeast vector and the library plasmid leading to the efficient formation of concatemers containing pcD molecules. The transformation frequencies obtained by the method are 10(6) colonies per 10(8) cells transfected with 2 micrograms of library and 1 microgram of vector, 50-60% of which contain pcD molecules. The high-efficiency alkali cation method circumvents many of the shortcomings of the spheroplast method generally used for Schiz. pombe transfection. The vectors are maximized for the efficiency of library transduction and minimized for the rearrangements of pcD molecules during propagation in yeast. This system allows rapid screening of multi-million cDNA clone libraries for rare cDNAs in a routine scale of experiments. Using this system, various mammalian cDNAs that are extremely difficult, time-consuming, or unclonable to clone by other methods have been cloned.
Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease (2009)

Mature myeloid cells (macrophages and CD11b(+) dendritic cells) form a prominent component of neuroinflammatory infiltrates in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). The mechanism by which these cells are replenished during relapsing and chronic neuroinflammation is poorly understood. Here we demonstrate that CD11b(+)CD62L(+)Ly6C(hi) monocytes with colony-forming potential are mobilized into the bloodstream by a granulocyte-macrophage colony-stimulating factor-dependent pathway immediately before EAE relapses. Circulating Ly6C(hi) monocytes traffic across the blood-brain barrier, up-regulate proinflammatory molecules, and differentiate into central nervous system dendritic cells and macrophages. Enrichment of Ly6C(hi) monocytes in the circulating pool is associated with an earlier onset and increased severity of clinical EAE. Our studies indicate that granulocyte-macrophage colony-stimulating factor-driven release of Ly6C(hi) precursors from the bone marrow prevents exhaustion of central nervous system myeloid populations during relapsing or chronic autoimmune demyelination, suggesting a novel pathway for therapeutic targeting.
Actin Filament Dynamics in Living Glial Cells Imaged by Atomic Force Microscopy (1992)

Observation of filamentous actin (F-actin) in living cells is currently limited to the resolution of the light microscope. Higher resolution procedures require sample fixation and preclude dynamic studies. The atomic force microscope (AFM) can image and manipulate samples at very high, sometimes atomic resolution by scanning a fine tip over the surface of interest and detecting physical interactions between the tip and sample. This study demonstrates that F-actin can be readily resolved in living cells with the AFM and that the dynamic properties of F-actin are easily observed.
Exercise‐induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. VIII. Conclusions and implications (1987)

This paper reviews a series of clinical, post mortem and imaging studies on exercise-induced pulmonary haemorrhage (EIPH) performed on 26 Thoroughbred racehorses. Post mortem techniques included routine gross, subgross and histological examination; coloured latex perfusions of pulmonary and bronchial circulations; and microradiography and computerised tomography scans of lungs with contrast injected vasculature. The major lesions were multiple, separate and coalescing foci of moderately proliferative small airway disease accompanied by intense neovascularisation of the bronchial circulation. As a result of bronchial artery angiogenesis, the systemic circulation dominated the vascular supply of the air exchange structures in affected areas, producing an apparent left to right shunt. Extensive areas of sequestered haemosiderophages indicated previous haemorrhage from vessels apparently supplied by the bronchial arteries. Diffuse and focal parenchymal destruction and connective tissue reactions in affected areas were considered to be secondary to localised haemorrhage and macrophage-induced damage. The aetiology of EIPH was not determined, but the multifocal, small airway-centred lesions indicated that low grade bronchiolitis, possibly of viral origin, was a factor. Gravitational effects also appear to contribute to dorsal distribution of the lesions. The mild focal and subclinical lesions confined to secondary lobules are thought to evolve into the serious lung pathology observed in EIPH cases through the effects of localised hypoxia induced by maximal exercise and partial airway obstruction. Once initiated, a vicious cycle of increasing inflammatory damage and further local bleeding is set in motion.
Hierarchically Porous Silver Monoliths from Colloidal Bicontinuous Interfacially Jammed Emulsion Gels (2011)

Silver monoliths with interconnected hierarchical pore networks and three-dimensional (3D) bicontinuous morphology are synthesized from a colloidal bicontinuous interfacially jammed emulsion gel (bijel) via reduction of silver ions within a nanoporous cross-linked polymer template. The pore sizes may be tuned independently and range from tens of nanometers to over a hundred micrometers. The method is straightforward as well as flexible and can pave the way to a host of hierarchical materials for current technologies.
Electrochemical Origin of Voltage-Controlled Molecular Conductance Switching (2006)

We have studied electron transport in bipyridyl-dinitro oligophenylene-ethynelene dithiol (BPDN) molecules both in an inert environment and in aqueous electrolyte under potential control, using scanning tunneling microscopy. Current-voltage (IV) data obtained in an inert environment were similar to previously reported results showing conductance switching near 1.6 V. Similar measurements taken in electrolyte under potential control showed a linear dependence of the bias for switching on the electrochemical potential. Extrapolation of the potentials to zero switching bias coincided with the potentials of redox processes on these molecules. Thus switching is caused by a change in the oxidation state of the molecules.
Kinetic Mechanism and Cofactor Content of Soybean Root Nodule Urate Oxidase (1997)

The kinetic mechanism of urate oxidase isolated from soybean root nodules has been determined by initial velocity kinetic studies monitoring oxygen uptake, in order to avoid potential artifacts in the spectrophotometric assay which arise from absorbance due to unidentified products of the enzymatic reaction. Urate and O2 bind to the enzyme sequentially; xanthine is a competitive inhibitor versus urate and a noncompetitive inhibitor versus O2, which suggests that urate binds to the enzyme before O2. This kinetic mechanism was confirmed by an 18O isotope-trapping experiment, which demonstrated that O2 does not bind productively to the enzyme in the absence of urate. The pH dependence of V and (V/K)urate reveal the presence of an ionizable residue on the enzyme with a pK of approximately 6.2, which must be unprotonated for the catalytic reaction to occur. The (V/K)O2 profile is pH independent; these data are accomodated by a model in which a unimolecular step intervenes between the binding of urate and O2. The pKi profile for 9-methylurate, a competitive inhibitor versus urate, is pH independent, confirming that the protonation state of the ionizable residue is not important for binding. The pKi profile for xanthine defines a pK of 7.4, which demonstrates that the monoanion of xanthine binds to the enzyme; by analogy, the monoanion of urate is predicted to be the substrate. The four isomeric N-methylurates were examined as potential inhibitors of urate oxidase. Only 9-methylurate showed significant inhibition suggesting that ionization at N9 of urate is not required for binding; it is proposed that the N3-deprotonated urate monoanion is the species which binds to urate oxidase. The gene encoding urate oxidase was cloned from soybeans and expressed in Escherichia coli. The metal content of the recombinant enzyme was examined by inductively coupled argon plasma emission spectroscopy, and only trace quantities of copper were found. The molecular mass of the protein was determined by MALDI-TOF mass spectrometry and found to be 35,059.8 Da. The calculated molecular mass of urate oxidase is 35,052 Da; therefore, these data suggest that there is no covalently bound cofactor in urate oxidase.
A mesoporous nickel counter electrode for printable and reusable perovskite solar cells (2015)

A mesoporous nickel layer is used as the counter electrode in printable perovskite solar cells. A unique reuse process is realized in such perovskite solar cell devices by repeated loading of the perovskite material. Under standard AM1.5 illumination, the fresh device shows a promising power conversion efficiency of 13.6%, and an efficiency of 12.1% is obtained in the reused devices.
Thermally-Induced Formation of Atomic Au Clusters and Conversion into Nanocubes (2004)

A thermal method for converting Au colloids into atomic Au clusters and subsequent growth of Au nanocubes from clusters is reported. Mass spectral analysis shows that these clusters are Au trimers. The Au clusters show distinct optical absorption at 305 and 250 nm and have extraordinary stability under ambient conditions.
Performance analysis of two time-based coordinated checkpointing protocols (2002)

Time-based checkpointing protocols are a recently proposed way to improve a system's dependability. They claim to have the advantages of coordinated protocols without the normal costs of coordination. This paper investigates that claim, by analyzing and comparing two time-based checkpointing protocols. The analysis is performed by determining the forward progress of a system using each protocol, and it is described in such a way as to be easily modifiable for other time-based protocols. By carefully analyzing the behavior of each protocol between renewal points, we are able to obtain a closed-form expression for the forward progress of the two protocols considered. We also determine the checkpoint interval value that will maximize forward progress. A validation of the analytical model is then performed via a detailed simulation. The results obtained from the model show the advantages and disadvantages of each protocol.
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma (2013)

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
Moderated, Water-Based, Condensational Particle Growth in a Laminar Flow (2014)

Presented is a new approach for laminar-flow water condensation that produces saturations above 1.5 while maintaining temperatures of less than 30°C in the majority of the flow and providing an exiting dew point below 15°C. With the original laminar flow water condensation method, the particle activation and growth occurs in a region with warm, wetted walls throughout, which has the side-effect of heating the flow. The "moderated" approach presented here replaces this warm region with a two sections - a short, warm, wet-walled "initiator", followed by a cool-walled "moderator". The initiator provides the water vapor that creates the supersaturation, while the moderator provides the time for particle growth. The combined length of the initiator and moderator sections is the same as that of the original, warm-walled growth section. Model results show that this new approach reduces the added heat and water vapor while achieving the same peak supersaturation and similar droplet growth. Experimental measurements confirm the trends predicted by the modeling.
Copy Number Analysis of c-erb-B2 (HER-2/neu) and Topoisomerase IIα Genes in Breast Carcinoma by Quantitative Real-Time Polymerase Chain Reaction Using Hybridization Probes and Fluorescence In Situ Hybridization (2005)

We conclude that the potentially automatic, real-time PCR analysis using hybridization probes is an efficient method to perform copy number analysis, with results that appear identical to the FISH technique and with the benefit of identifying HER-2 polymorphisms.
Applicability of the time–temperature superposition principle in modeling dynamic response of a polyurea (2007)

This paper addresses the applicability of the Time–Temperature Superposition Principle in the dynamic response of a polyurea polymer at high strain rates and different temperatures. Careful and extensive measurements in the time domain of the relaxation behavior and subsequent deduction of a master-relaxation curve establish the mechanical behavior for quasistatic deformations over a time range of 16 decades. To examine its validity in a highly dynamic environment, experiments with the aid of a split Hopkinson (Kolsky) pressure bar are carried out. The use of a two-material pulse shaper allows for stress equilibrium across the specimen during the compression process, to concentrate on the initial, small deformation part that characterizes linearly viscoelastic behavior. This behavior of polyurea at high strain rates and different temperatures is then investigated by comparing results from a physically fully three-dimensional (axisymmetric) numerical model, employing the quasistatically obtained properties, with corresponding Hopkinson bar measurements. The experimentally determined wave history entering the specimen is used as input to the model. Experimental and simulation results are compared with each other to demonstrate that the Time–Temperature Superposition Principle can indeed provide the requisite data for high strain rate loading of viscoelastic solids, at least to the extent that linear viscoelasticity applies with respect to the polyurea material.
Disulfide Bond Bridge Insertion Turns Hydrophobic Anticancer Prodrugs into Self-Assembled Nanomedicines (2014)

It is commonly observed that hydrophobic molecules alone cannot self-assemble into stable nanoparticles, requiring amphiphilic or ionic materials to support nanoparticle stability and function in vivo. We report herein newly self-assembled nanomedicines through entirely different mechanisms. We present proof-of-concept methodology and results in support of our hypothesis that disulfide-induced nanomedicines (DSINMs) are promoted and stabilized by the insertion of a single disulfide bond into hydrophobic molecules, in order to balance the competition between intermolecular forces involved in the self-assembly of nanomedicines. This hypothesis has been explored through diverse synthetic compounds, which include four first-line chemotherapy drugs (paclitaxel, doxorubicin, fluorouracil, and gemcitabine), two small-molecule natural products and their derivatives, as well as a fluorescent probe. Such an unprecedented and highly reproducible system has the potential to serve as a synthetic platform for a wide array of safe and effective therapeutic and diagnostic nanomedicine strategies.
Spectroscopic and morphological studies of human retinal lipofuscin granules (2003)

The emission properties of ocular lipofuscin granules isolated from human retinal pigment epithelial cells are examined by using steady-state fluorescence spectroscopy and spectrally resolved confocal microscopy. The shape of the emission spectrum of a thick sample of lipofuscin granules dried on glass varies with excitation energy. The polarization of this emission is wavelength-dependent, exhibiting significant polarization near the excitation wavelength and becoming mostly depolarized over the majority of the emission spectrum. These results show that the yellow-emitting fluorophores [e.g., A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium)] are excited as a result of energy transfer within the granules and therefore are not the dominant blue-absorbing chromophores within lipofuscin granules. Atomic force microscopy images show lipofuscin granules to be an aggregated structure. Bulk and in vivo emission measurements must therefore take into account the effect of Raleigh scattering. When corrected for scattering, the emission spectrum of a thick lipofuscin deposit or intracellular lipofuscin resembles that for A2E. The sum of the emission spectra of a collection of individual granules also resembles the emission spectrum of A2E, but the spectrum of individual granules varies significantly. This result suggests that the agreement between the emission spectra of lipofuscin and A2E is fortuitous, and the collective data indicate the presence of several blue-absorbing chromophores in lipofuscin and show A2E is not the dominant yellow-emitting fluorophore in many of the granules studied.