gebhart/patrepeval huggingface dataset:
Acute Sensorineural Deafness in Lassa Fever (1990)

A prospective audiometric evaluation of 69 hospitalized febrile patients in Sierra Leone, West Africa, revealed a sensorineural hearing deficit (SNHD) in 14 (29%) of 49 confirmed cases of Lassa fever and in 0 of 20 febrile controls. An SNHD was present in nine (17.6%) of 51 people who had evidence of previous Lassa virus infection. Twenty-six of 32 local residents who had previously sustained a sudden deafness had antibody titers to Lassa virus of 16 or greater, compared with six of 32 matched controls. Lassa fever is associated with an incidence of SNHD, which considerably exceeds that previously reported with any other postnatally acquired infection, and accounts for a prevalence of virus-related hearing impairment in the eastern province of Sierra Leone that is greater than that reported from anywhere else in the world.
Identification and characterisation of human apoptosis inducing proteins using cell-based transfection microarrays and expression analysis (2006)

This study reports the design and use of the first truly large-scale cell-based microarrays for over-expression studies. Ten genes were confirmed to induce apoptosis, some of which were not previously known to possess this activity. Transcriptome analysis on three of the 10 genes demonstrated their use of similar pathways to invoke apoptosis.
Imidazo [4,5‐c] ‐ and [4,5‐6] pyridines (1977)

Abstract The synthesis of novel imidazo[4,5‐ c ]pyridines 11‐13 and imidazo[4,5‐ b ]pyridines 18‐20 is described using 2 as the starting material. The synthesis is generally applicable for the introduction of a wide variety of substituents.
Pregnancy‐associated plasma protein‐A (PAPP‐A) cleaves insulin‐like growth factor binding protein (IGFBP)‐5 independent of IGF: implications for the mechanism of IGFBP‐4 proteolysis by PAPP‐A (2001)

Pregnancy-associated plasma protein-A (PAPP-A) has recently been identified as the proteinase responsible for cleavage of insulin-like growth factor binding protein (IGFBP)-4, an inhibitor of IGF action, in several biological fluids. Cleavage of IGFBP-4 by PAPP-A is believed to occur only in the presence of IGF. We here report that in addition to IGFBP-4, PAPP-A also cleaves IGFBP-5. Cleavage occurs at one site, between Ser-143 and Lys-144 of IGFBP-5. In the presence of IGF, IGFBP-4 and -5 are cleaved with similar rates by PAPP-A. Interestingly, cleavage of IGFBP-5 by PAPP-A does not require the presence of IGF, but is slightly inhibited by IGF. These findings have implications for the mechanism of proteolysis of IGFBP-4 by PAPP-A, suggesting that IGFBP-4 binds IGF, which then becomes a PAPP-A substrate. Using highly purified, recombinant proteins, we establish that (1) PAPP-A cleavage of IGFBP-4 can occur in the absence of IGF, although the rate of hydrolysis is very slow, and (2) IGF is unable to bind to PAPP-A. We thus conclude that IGF enhances proteolysis by binding to IGFBP-4, not by interaction with PAPP-A, which could not previously be ruled out.
Biochemical and genetic characterization of the membrane‐associated malate dehydrogenase (acceptor) from Corynebacterium glutamicum (1998)

In addition to a cytoplasmic, NAD-dependent malate dehydrogenase (EC 1.1.1.37), Corynebacterium glutamicum possesses a highly active membrane-associated malate dehydrogenase (acceptor) (EC 1.1.99.16). This enzyme also takes part in the citric acid cycle. It oxidizes L-malate to oxaloacetate and donates electrons to ubiquinone-1 and other artificial acceptors or, via the electron transfer chain, to oxygen. NAD is not an acceptor and the natural direct acceptor for the enzyme is most likely a quinone. The enzyme is therefore called malate:quinone oxidoreductase, abbreviated to Mqo. Mqo is a peripheral membrane protein and can be released from the membrane by addition of chelators. The solubilized form was partially purified and characterized biochemically. FAD is probably a tightly but non-covalently bound prosthetic group, and the enzyme is activated by lipids. A C. glutamicum mutant completely lacking Mqo activity was isolated. It grows poorly on several substrates tested. The mutant possesses normal levels of cytoplasmic NAD-dependent malate dehydrogenase. A plasmid containing the gene from C. glutamicum coding for Mqo was isolated by complementation of the Mqo-negative phenotype. It leads to overexpression of Mqo activity in the mutant. The nucleotide sequence of the mqo gene was determined and is the first sequence known for this enzyme. The derived protein sequence is similar to hypothetical proteins from Escherichia coli, Klebsiella pneumoniae, and Mycobacterium tuberculosis.
Development of an Efficient Transdermal Delivery System of Small Interfering RNA Using Functional Peptides, Tat and AT-1002 (2011)

Topical use of small interfering RNA (siRNA) as a therapeutic nucleic acid is increasingly studied for the treatment of skin diseases and for the improvement of skin properties. However, naked siRNA transdermal delivery is limited by its low stability in the body and low permeability into target cells. This is due to various skin barriers such as the stratum corneum that has multiple lipid bilayers and epidermal layers that have tight junctions. In this study, we investigate non-invasive transdermal siRNA delivery using two functional peptides: AT1002, which is a tight junction modulator and 6-mer synthetic peptide belonging to a novel class of compounds that reversibly increases paracellular transport of molecules across the epithelial barrier; and Tat, which is a cell-penetrating peptide applicable as a transdermal siRNA delivery enhancer. We examined whether expression of the tight junction protein zonula occludens protein 1 (ZO-1) was detected in mouse skin applied with AT1002. Additionally, siRNA stabilities for RNaseA using Tat and AT1002 were assessed. We also determined the intradermal delivery efficiency of siRNA using functional peptides by confocal laser microscopy of fluorescently labeled siRNA in mouse skin. We found that the Tat analog and AT1002 strongly increased siRNA stability against RNaseA. In addition, ZO-1 disappeared from the skin after treatment with AT1002, yet recovered with time after washing. Finally, we also found that Tat and AT1002 peptides accelerate transdermal siRNA delivery both widely and effectively. Thus, combination of Tat and AT1002 is expected to be a transdermal delivery enhancer of siRNA.
The proteasome: a macromolecular assembly designed for controlled proteolysis (1999)

In eukaryotic cells, the vast majority of proteins in the cytosol and nucleus are degraded via the proteasome-ubiquitin pathway. The 26S proteasome is a huge protein degradation machine of 2.5 MDa, built of approximately 35 different subunits. It contains a proteolytic core complex, the 20S proteasome and one or two 19S regulatory complexes which associate with the termini of the barrel-shaped 20S core. The 19S regulatory complex serves to recognize ubiquitylated target proteins and is implicated to have a role in their unfolding and translocation into the interior of the 20S complex where they are degraded into oligopeptides. While much progress has been made in recent years in elucidating the structure, assembly and enzymatic mechanism of the 20S complex, our knowledge of the functional organization of the 19S regulator is rather limited. Most of its subunits have been identified, but specific functions can be assigned to only a few of them.
L’article 1843-4 à tout prix !, note sous Cass. com. 4 déc. 2012 (2013)

Commentaire 41
Optimized gradient waveforms for spiral scanning (1995)

Spiral scanning gradient waveforms can be optimized with respect to blurring from off-resonance effects by minimizing the readout time. This is achieved by maximizing the gradient amplitude during the scan so that the edge of k-space is reached as quickly as possible. Gradient hardware constraints are incorporated by considering a circuit model for the gradient coil and amplifier. The optimized gradient waveforms are determined by a set of coupled differential equations. The resulting solutions have shorter readout time than solutions that do not consider the circuit model.
The neuroendocrine precursor 7B2 is a sulfated protein proteolytically processed by a ubiquitous furin-like convertase. (1994)

The neuroendocrine granule-associated protein 7B2, unlike many other neuroendocrine precursor proteins stored in secretory granules, carries in its primary structure the Arg-Xaa-Arg/Lys-Arg processing site usually found in constitutively secreted precursor proteins and recognized by the ubiquitously expressed convertase, furin. pro7B2 (30 kDa), when expressed in endocrine (AtT-20, PC12, and GH4C1) or non-endocrine (Ltk-) cell lines using recombinant vaccinia viruses, was converted to a 23-kDa form. Mutation of the P4 Arg to Gly completely prevented this conversion. When excess pro7B2 was coexpressed with the pro-protein convertases PC1, PC2, or furin, only furin could induce complete processing. In addition, coexpression of pro7B2 in LoVo cells, which are devoid of endogenous furin activity, with each one of the three convertases, showed that only furin was able to induce processing of this precursor. pro7B2 processing in AtT-20 was completely abolished when protein transport into Golgi compartments was blocked by cell incubation at either 15 or 37 degrees C in the presence of monensin or brefeldin A. Furthermore, pulse-chase experiments in the presence of Na2[35S]SO4 showed that pro7B2 is Tyr-sulfated in the trans-Golgi network before it is processed. These results demonstrate that pro7B2 is first processed by a furin-like enzyme within the trans-Golgi network into a 23-kDa form that is then sequestered into secretory granules.
Effects of Initiator Structure on Activation Rate Constants in ATRP (2007)

Activation rate constants (kact) for a variety of initiators for Cu-mediated ATRP have been determined under the same conditions. The ratio of the activation rate constants for the studied alkyl (pseudo)halides exceeds 1 million times. The activation rate constants increase with initiator substitution (e.g., for primary, secondary, and tertiary α-bromoesters the ratios are ∼1:10:80), with the radical stabilizing α-substituent (e.g., alkyl bromides with −C(O)NEt2, −Ph, −C(O)OMe, and −CN groups the ratios are ∼1:4:8:600 but with both α-Ph and α-C(O)OEt ∼ 140 000), and with the leaving atom/group (e.g., for methyl 2-halopropionates: chloro:bromo:iodo ∼1:20:35, but benzyl bromide is ∼10 000 more reactive than the corresponding isothiocyanate/thiocyanate).
KARDIALE BELDGEBUNG UND ELEKTROPHYSIOLOGIE – WAS LEISTEN NEUE DREIDIMENSIONALE MAPPINGVERFAHREN? (2002)

Article KARDIALE BELDGEBUNG UND ELEKTROPHYSIOLOGIE – WAS LEISTEN NEUE DREIDIMENSIONALE MAPPINGVERFAHREN? was published on January 1, 2002 in the journal Biomedical Engineering / Biomedizinische Technik (volume 47, issue s1a).
Designing biosensors for Rho family proteins — deciphering the dynamics of Rho family GTPase activation in living cells (2004)

Rho family GTPases are molecular switches that couple changes in the extracellular environment to intracellular signal transduction pathways. Their ability to regulate behaviors such as cell motility suggests very tight kinetic and spatial control of their activity, which is missed in most biochemical assays. Fluorescent probes that non-invasively report the changing subcellular location of Rho GTPase activity in single living cells are now allowing us to examine spatio-temporal regulation of the activity of these proteins, and are providing new biological insights. Several strategies can be used to construct such probes, and there are advantages and disadvantages associated with the diverse probe designs.
Activation of beta-catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade. (2001)

Mutations affecting phosphorylation sites in the beta-catenin gene have been implicated in the development of human and rodent hepatocellular carcinomas (HCCs). To further investigate the involvement of this gene in hepatocarcinogenesis, we used several transgenic mouse models of hepatic tumors induced by overexpression of c-myc in the liver either alone or in combination with transforming growth factor (TGF) alpha or TGF-beta1. Activation of beta-catenin, as judged by the presence of mutations and/or nuclear translocation of the protein, was most frequent in liver tumors from c-myc (4/17; 23.5%) and c-myc/TGF-beta1 (6/18; 33.3%) transgenic mice. However, it was very rare in faster growing and histologically more aggressive HCCs developed in c-myc/TGF-alpha mice (1/20; 5%). Administration of diethylnitrosamine, phenobarbital, or 2-amino-3,8-diethylimidazo[4,5-f]quinoxaline did not significantly affect the occurrence of beta-catenin mutations. Notably, nuclear accumulation of beta-catenin was observed only in adenomas and highly differentiated carcinomas with eosinophilic phenotype. Furthermore, preneoplastic lesions with eosinophilic phenotype frequently displayed focal nuclear positivity, colocalized with areas of high proliferation. In contrast, basophilic and clear-cell foci, as well as pseudo-glandular and poorly differentiated HCCs, exhibited a normal or reduced membranous immunoreactivity for beta-catenin. These studies suggest that nuclear translocation of beta-catenin and activation of Wingless/Wnt signaling may represent an early event in liver carcinogenesis, providing a growth advantage in a subset of hepatic tumors with a more differentiated phenotype.
Adiposity, Fat Distribution, and Cardiovascular Risk (1989)

Intra-abdominal fat deposition constitutes a greater cardiovascular risk than obesity alone. Hyperinsulinemia may constitute an important component of the increased cardiovascular risk of abdominal obesity.
Protective Antitumor Immunity Induced by a Costimulatory Thalidomide Analog in Conjunction with Whole Tumor Cell Vaccination Is Mediated by Increased Th1-Type Immunity (2002)

Thalidomide and its novel T cell costimulatory analogs (immunomodulatory drugs) are currently being assessed in the treatment of patients with advanced cancer. However, neither tumor-specific T cell costimulation nor effective antitumor activity has been demonstrated in vivo. In this study, we assessed the ability of an immunomodulatory drug (CC-4047/ACTIMID) to prime a tumor-specific immune response following tumor cell vaccination. We found that the presence of CC-4047 during the priming phase strongly enhanced antitumor immunity in the vaccinated group, and this correlated with protection from subsequent live tumor challenge. Protection was associated with tumor-specific production of IFN-gamma and was still observed following a second challenge with live tumor cells 60 days later. Furthermore, CD8(+) and CD4(+) splenocyte fractions from treated groups secreted increased IFN-gamma and IL-2 in response to tumor cells in vitro. Coculture of naive splenocytes with anti-CD3 mAb in the presence of CC-4047 directly costimulated T cells and increased Th1-type cytokines. Our results are the first to demonstrate that a costimulatory thalidomide analog can prime protective, long-lasting, tumor-specific, Th1-type responses in vivo and further support their ongoing clinical development as novel anti-cancer agents.
Expression and processing of biologically active fibroblast growth factors in the yeast Saccharomyces cerevisiae. (1988)

Chemically synthesized genes for bovine and human fibroblast growth factors (FGFs) were expressed in heterologous microorganisms. Although the intracellular expression or secretion of acidic and basic FGFs in Escherichia coli or Saccharomyces cerevisiae yielded recombinant growth factors with high biological activity, the resulting proteins had structural microheterogeneity due to modified amino termini. Expression of amino-terminal extended forms of human acidic and basic FGFs in S. cerevisiae gave rise to soluble, but cell-associated polypeptides, with potent biological activity. These yeast-derived proteins were processed in vivo by removal of initiation codon-derived methionine residues and by amino-terminal acetylation. Both of these processes have been observed in mammalian tissues. The yeast systems described here, therefore, provide a good model system for the expression of FGFs as intracellular proteins, but more importantly they give high levels of authentically processed human FGFs with many potential medical applications. Since the recombinant proteins have all the biological activities of their native counterparts, their possible applications in wound healing, tissue grafting, nerve regeneration, and treatment of ischemia are discussed.
Physical and biochemical characterization of Albunex, a new ultrasound contrast agent consisting of air‐filled albumin microspheres suspended in a solution of human albumin (1994)

Albunex is a new ultrasound contrast agent for medical imaging. The product consists of air-filled albumin microspheres suspended in a solution of 5% (w/v) human albumin. The suspension is sterile, non-pyrogenic and isotonic, with a pH of 7.0 and a viscosity of 1.4 relative to water. The contrast effect is caused by the air-filled microspheres, which range in diameter from 1 to 15 microns, with less than 5% being larger than 10 microns. The product contains a total of about 7 x 10(8) microspheres/ml of suspension. The number concentration of microspheres with diameters between 4 and 10 microns is about 2 x 10(8)/ml. The latter microsphere fraction is assumed to give the main contribution to the ultrasound signal in the left ventricle of the heart after intravenous injection. The air-filled microspheres are prepared by sonication of a heated solution of 5% (w/v) human albumin. During the sonication process, microbubbles of air are formed which become encapsulated in a thin shell of aggregated albumin about 15 nm in thickness. Due to the stabilizing effect of the albumin shell, the air-filled microsphere suspension is stable for at least 2 years when stored refrigerated. The microsphere protein represents about 1.5% of the total protein in the suspension. The remaining protein is soluble albumin molecules which behave like the albumin molecules in the starting material when analysed by a number of biochemical techniques.
Phytochemical, pharmacological and toxicological aspects ofHibiscus sabdariffa L.: a review (2005)

This article reviews the reported phytochemical, pharmacological and toxicological properties of Hibiscus sabdariffa L. (English: roselle, red sorrel; Arabic: karkade), the calyces of which are used in many parts of the world to make cold and hot drinks. Nutritionally, these contain ascorbic acid (vitamin C). In folk medicine, the calyx extracts are used for the treatment of several complaints, including high blood pressure, liver diseases and fever. The pharmacological actions of the calyx extracts include strong in vitro and in vivo antioxidant activity. In rats and rabbits, the extract showed antihypercholesterolaemic, antinociceptive and antipyretic, but not antiinflammatory activities. In rat and man a strong antihypertensive action has been demonstrated. The effects of the calyx extracts on smooth muscles in vitro are variable, but they mostly inhibit the tone of the isolated muscles. In healthy men, consumption of H. sabdariffa has resulted in significant decreases in the urinary concentrations of creatinine, uric acid, citrate, tartrate, calcium, sodium, potassium and phosphate, but not oxalate. Oil extracted from the plant's seeds has been shown to have an inhibitory effect on some bacteria and fungi in vitro. The plant extracts are characterized by a very low degree of toxicity. The LD50 of H. sabdariffa calyx extract in rats was found to be above 5000 mg/kg. A single report has suggested that excessive doses for relatively long periods could have a deleterious effect on the testes of rats. In view of its reported nutritional and pharmacological properties and relative safety, H. sabdariffa and compounds isolated from it (for example, anthocyanins and Hibiscus protocatechuic acid) could be a source of therapeutically useful products.
Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral Sclerosis (2010)

Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects. Trial Registration clinicaltrials.gov Identifier: NCT00781872.
Recovery of gold from computer circuit board scraps: the study of the effect of different reductants (2013)

Computer circuit boards (CCBs) are valuable because of their precious metal contents. In this regard, the recovery of gold from CCBs has attracted great interest. In this work, we report the recovery of gold from CCBs with different reductants. The CCBs were first crushed mechanically to obtain particles with sizes less than 0.1 mm. The powders were then leached with nitric acid to remove undesired metals. The remaining was then treated with aqua regia to dissolve gold ion. The dissolved gold was then precipitated from the leachate with hydrazine, ferrous sulfate or oxalic acid and the effect of these reductants on the recovery of gold was studied. We were able to recover more than 99% of gold from CCBs with purity of about 99.5%.
Megakaryocyte Growth and Development Factor-Induced Proliferation and Differentiation Are Regulated by the Mitogen-Activated Protein Kinase Pathway in Primitive Cord Blood Hematopoietic Progenitors (1999)

In several erythroleukemia cell lines, activation of mitogen-activated protein kinases (MAPK) by phorbol esters or megakaryocyte growth and development factor (MGDF) is required for induction of megakaryocytic phenotype and growth arrest. To support this model, we have examined the effect of a specific inhibitor of this pathway (PD98059) on human CD34(+) hematopoietic progenitors isolated from cord blood (CB), induced to differentiate along the megakaryocytic lineage in liquid cultures supplemented with rhuMGDF. RhuMGDF induced a sustained activation of MAPK in megakaryocytes and this activation was completely inhibited in the presence of low concentrations of PD98059 (6 to 10 micromol/L). At this concentration, PD98059 induced an increase in cell proliferation, resulting in accumulation of viable cells and a prolongation of the life time of the cultures. This increase correlated with an increase in DNA synthesis rather than with a reduction in apoptosis. This effect was combined with developmental changes indicative of delayed megakaryocytic differentiation: (1) PD98059-treated cells tended to retain markers of immature progenitors as shown by the increased proportion of both CD34(+) and CD41(+)CD34(+) cells. (2) PD98059-treated cultures were greatly enriched in immature blasts cells. (3) PD98059 increased megakaryocytic progenitors able to form colonies in semisolid assays. Thus, the MAPK pathway, although not required for megakaryocyte formation, seems to be involved in the transition from proliferation to maturation in megakaryocytes. Inhibition of MAPK activation also led to an increase in the number and size of erythroid colonies without affecting granulocyte/macrophage progenitor numbers suggesting that, in addition to the megakaryocytic lineage, the MAPK pathway could play a role in erythroid lineage differentiation.