gebhart/patrepeval huggingface dataset:
Therapeutic drug monitoring in dried blood spots using liquid microjunction surface sampling and high resolution mass spectrometry (2016)

Dried blood spots (DBS) are a versatile and stable tool for direct clinical blood analysis. Ambient high-resolution mass spectrometry is emerging as a method of choice for their quantitative analysis, for instance in therapeutic drug monitoring. Here, we coupled liquid microjunction surface sampling technology, a so-called Flowprobe, with an Orbitrap mass spectrometer and demonstrated the utility of this set-up for direct quantification of multiple drugs in DBS on filter paper. A three-layer set-up that we had introduced earlier enabled introduction of internal standards into DBS. We furthermore took an established point-of-care test system a step further and analyzed disposable test fields for blood glucose monitoring also for Flowprobe-based acetaminophen screening without additional sample preparation. Using as little as 2 μL blood, the method had an LOD of 1 μg mL(-1) (coefficient of variation of ≤15%) and acetaminophen recoveries of 82 to 119% for blinded samples, as assessed by LC-MS/MS. Half an hour after ingestions of a single 1000 mg acetaminophen dose, indistinguishable drug levels were measured in three healthy volunteers by LC-MS/MS and Flowprobe-Orbitrap MS analysis of DBS. Flowprobe analysis of DBS was 6- to 100-times more sensitive than corresponding desorption electrospray ionization MS analysis for four drugs. For instance, the LOD for salicylic acid analysis was 0.07 ng mL(-1) with Flowprobe measurement. Furthermore, we showed that multi-component analysis of five different substances, which may mimic polypharmacy in diabetes patients, in one blood sample for screening purposes was feasible. Taken together, our study suggests that microjunction surface sampling of DBS on filter paper and disposable point-of-care test fields may be developed into routine methods for near-patient multi-compound therapeutic drug monitoring that may advance blood screening analysis for patients with polypharmacy.
Developing aged SPICE model for hot carrier reliability simulation (2002)

A systematic method to develop aged SPICE model for hot carrier reliability simulation is proposed in this paper. This method not only simplifies the aged model develop procedure, but also solves the problem of modeling reverse stress mode and have good model scalability.
RECOMBINANT FACTOR VIIa INCREASES THE PRESSURE AT WHICH REBLEEDING OCCURS IN PORCINE UNCONTROLLED AORTIC HEMORRHAGE MODEL (2004)

In trauma patients, resuscitation to endpoints below normal blood pressure (BP) levels may reduce further blood loss due to the rebleeding often caused by more aggressive resuscitation. However, patients whose BP is maintained at lower levels for extended periods are at increased risk for organ failure. The purpose of this study was to determine whether recombinant activated factor VII (rFVIIa) raises the BP level at which rebleeding occurs in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation. Thirty anesthetized 40-kg pigs were assigned to three groups (n = 10/group): control, low-dose rFVIIa (180 microg/kg), or high-dose (720 microg/kg). Vehicle or drug was infused 5 min before creating a 2.0-mm infrarenal aortotomy. Ten minutes later, resuscitation with lactated Ringer's (LR) solution at 100 mL/min was begun. Hemorrhage and LR volumes and BP were recorded continuously. We found that pretreatment with rFVIIa increased the mean arterial pressure at which rebleeding occurred during resuscitation (45 +/- 3, 69 +/- 5, and 66 +/- 6 mmHg in the control, low-dose, and high-dose groups, respectively, P = 0.003). Rebleed hemorrhage volume was reduced with rFVIIa (39 +/- 9, 22 +/- 7, and 26 +/- 5 mL/kg for control, and low and high dose, respectively; P = 0.055). This is the first study to show that rFVIIa increases the BP at which rebleeding occurs during resuscitation in an injury to a major artery, suggesting the formation of a tight, stronger fibrin plug in the presence of high concentrations of rFVIIa.
SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia (2003)

The proliferation and differentiation of hematopoietic precursor cells depend on various cytokines. The suppressor of cytokine signaling-1 (SOCS1) down-regulates Janus kinases/signal transducers and activators of transcription (JAK/STAT) pathway activity and inhibits the biological effects of cytokines. SOCS1 has been shown to have tumor-suppressor activity, and methylation of this gene, resulting in transcriptional silencing, has been found in 65% of hepatocellular carcinoma and has been suggested to play an important role in the development of the cancer. The methylation status of the SOCS1 gene in acute myeloid leukemia (AML) has not been reported before. In this study, we analyzed SOCS1 methylation in 89 patients with newly diagnosed AML and correlated the result with immunophenotypes, cytogenetics, clinical features, and treatment outcome. SOCS1 methylation was found in the leukemic cells from 53 patients (60%). Thirteen (76%) of the 17 patients with t(15;17) had SOCS1 methylation, whereas this gene was methylated in only one (11%) of the nine patients with t(8;21). The frequencies of SOCS1 methylation among various cytogenetic subgroups differed significantly (P = 0.014). Other clinical and laboratory parameters and the disease-free survival and overall survival were similar between patients with and without SOCS1 methylation. In conclusion, SOCS1 methylation occurs in more than half of AML cases, correlates with cytogenetic abnormalities, and may play an important role in the development of subsets of AML.
Office du juge dans la mise en oeuvre de la loi étrangère en matière de droits d'auteur (1995)

International audience
Effects of Gevokizumab on Glycemia and Inflammatory Markers in Type 2 Diabetes (2012)

This novel IL-1β-neutralizing antibody improved glycemia, possibly via restored insulin production and action, and reduced inflammation in patients with type 2 diabetes. This therapeutic agent may be able to be used on a once-every-month or longer schedule.
Characterization of theUstilago maydis sid2Gene, Encoding a Multidomain Peptide Synthetase in the Ferrichrome Biosynthetic Gene Cluster (2001)

Ustilago maydis, the causal agent of corn smut disease, acquires and transports ferric ion by producing the extracellular, cyclic peptide, hydroxamate siderophores ferrichrome and ferrichrome A. Ferrichrome biosynthesis likely proceeds by hydroxylation and acetylation of L-ornithine, and later steps likely involve covalently bound thioester intermediates on a multimodular, nonribosomal peptide synthetase. sid1 encodes L-ornithine N(5)-oxygenase, which catalyzes hydroxylation of L-ornithine, the first committed step of ferrichrome and ferrichrome A biosynthesis in U. maydis. In this report we characterize sid2, another biosynthetic gene in the pathway, by gene complementation, gene replacement, DNA sequence, and Northern hybridization analysis. Nucleotide sequencing has revealed that sid2 is located 3.7 kb upstream of sid1 and encodes an intronless polypeptide of 3,947 amino acids with three iterated modules of an approximate length of 1,000 amino acids each. Multiple motifs characteristic of the nonribosomal peptide synthetase protein family were identified in each module. A corresponding iron-regulated sid2 transcript of 11 kb was detected by Northern hybridization analysis. By contrast, constitutive accumulation of this large transcript was observed in a mutant carrying a disruption of urbs1, a zinc finger, GATA family transcription factor previously shown to regulate siderophore biosynthesis in Ustilago. Multiple GATA motifs are present in the intergenic region between sid1 and sid2, suggesting bidirectional transcription regulation by urbs1 of this pathway. Indeed, mutation of two of these motifs, known to be important to regulation of sid1, altered the differential regulation of sid2 by iron.
High‐resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand (2009)

The Mapkap kinases 2 and 3 (MK2 and MK3) have been implicated in intracellular signaling pathways leading to the production of the pro-inflammatory cytokine tumor necrosis factor alpha. MK2 has been pursued by the biopharmaceutical industry for many years for the development of a small molecule anti-inflammatory treatment and drug-like inhibitors have been described. The development of some of these compounds, however, has been slowed by the absence of a high-resolution crystal structure of MK2. Herein we present a high-resolution (1.9 A) crystal structure of the highly homologous MK3 in complex with a pharmaceutical lead compound. While all of the canonical features of Ser/Thr kinases in general and MK2 in particular are recapitulated in MK3, the detailed analysis of the binding interaction of the drug-like ligand within the adenine binding pocket allows relevant conclusions to be drawn for the further design of potent and selective drug candidates.
Using WordNet to measure semantic orientations of adjectives (2004)

Current WordNet-based measures of distance or similarity focus almost exclusively on WordNet's taxonomic relations.This effectively restricts their applicability to the syntactic categories of noun and verb.We investigate a graph-theoretic model of WordNet's most important relation-synonymy-and propose measures that determine the semantic orientation of adjectives for three factors of subjective meaning.Evaluation against human judgments shows the effectiveness of the resulting measures.
Hypertext Transfer Protocol -- HTTP/1.0 (1996)

The Hypertext Transfer Protocol (HTTP) is an application-level protocol with the lightness and speed necessary for distributed, collaborative, hypermedia information systems. It is a generic, stateless, object-oriented protocol which can be used for many tasks, such as name servers and distributed object management systems, through extension of its request methods (commands). A feature of HTTP is the typing of data representation, allowing systems to be built independently of the data being transferred.
Hybridization of Deoxyribonucleotide Sequences of Yersinia enterocolitica and Other Selected Members of Enterobacteriaceae (1975)

Using Yersinia enterocolitica Becht 18 as a standard reference, we obtained deoxyribonucleic acid base sequence homologies ranging from 79 to 100% for 11 additional isolates of the species representing 9 serotypes. These organisms, many of which exhibited dissimilar biochemical reactions, therefore belong to one and the same species. However, the degree of relatedness between Y. enterocolitica and the established members of the genus (Yersinia pestis and Yesinia pseudotuberculosis) was low (18 to 24%), approaching that obtained for some of 10 selected isolates of 7 other genera of Enterobacteriaceae (2 to 16%). These findings suggest that the proposal to include Y. enterocolitica within the genus Yersinia requires further evaluation.
Disruption of the FA/BRCA pathway in bladder cancer (2007)

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression.
Three-Dimensional Paper Microfluidic Devices Assembled Using the Principles of Origami (2011)

We report a method, based on the principles of origami (paper folding), for fabricating three-dimensional (3-D) paper microfluidic devices. The entire 3-D device is fabricated on a single sheet of flat paper in a single photolithographic step. It is assembled by simply folding the paper by hand. Following analysis, the device can be unfolded to reveal each layer. The applicability of the device to chemical analysis is demonstrated by colorimetric and fluorescence assays using multilayer microfluidic networks.
Sponge (2011)

Graphics processing units (GPUs) provide a low cost platform for accelerating high performance computations. The introduction of new programming languages, such as CUDA and OpenCL, makes GPU programming attractive to a wide variety of programmers. However, programming GPUs is still a cumbersome task for two primary reasons: tedious performance optimizations and lack of portability. First, optimizing an algorithm for a specific GPU is a time-consuming task that requires a thorough understanding of both the algorithm and the underlying hardware. Unoptimized CUDA programs typically only achieve a small fraction of the peak GPU performance. Second, GPU code lacks efficient portability as code written for one GPU can be inefficient when executed on another. Moving code from one GPU to another while maintaining the desired performance is a non-trivial task often requiring significant modifications to account for the hardware differences. In this work, we propose Sponge, a compilation framework for GPUs using synchronous data flow streaming languages. Sponge is capable of performing a wide variety of optimizations to generate efficient code for graphics engines. Sponge alleviates the problems associated with current GPU programming methods by providing portability across different generations of GPUs and CPUs, and a better abstraction of the hardware details, such as the memory hierarchy and threading model. Using streaming, we provide a write-once software paradigm and rely on the compiler to automatically create optimized CUDA code for a wide variety of GPU targets. Sponge's compiler optimizations improve the performance of the baseline CUDA implementations by an average of 3.2x.
The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. (1984)

Tbiological activity of one major class of leukotrienes, originally described as slow reacting substance of anaphylaxis (SRS-A)' (1, 2) and now known to be composed of the sulfidopeptide leukotrienes, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-I 1, 14-cis-eicosatetraenoic acid (leukotriene C4, LTC4), 5S-hydroxy-6R-S-cysteinylglycyl-7,9-trans-11, 14-cis-eicosa- tetraenoic acid (leukotriene D4, LTD4), and 5S-hydroxy-6R-Scysteinyl-7,9-trans-1 1, 14-cis-eicosatetraenoic acid (leukotriene E4, LTE4) (3-7), has been known for over 40 years. The biological activity and structure of the second major class of leukotrienes, represented solely by 5S-12R-dihydroxy-6,14-cis-8, I0-trans- eicosatetraenoic acid (leukotriene B4, LTB4), was recognized only 5 years ago On the basis of the earlier definition of SRS-A in terms ofchromatographic, functional, and chemical characteristics (12-15), it was possible to generate a similar material with radiolabeled constituents by ionophore activation of mouse mastocytoma cells and to achieve a chemical characterization of LTC4 (3). The stereospecific synthesis of both LTC4 (16) and LTB4 ( . Abbreviations used in this paper: 5-HPETE, 5S-hydroperoxy-6-trans-8,1 1,14-cis-eicosatetraenoic acid; LTA4, 5,6-trans-oxido-7,9-trans-1 1,14cis-eicosatetraenoic acid; LTB4, 5S-12R-dihydroxy-6,14-cis-8, 10-transeicosatetraenoic acid; LTC4, 5S-hydroxy-6R-S-glutathionyl-7,9-trans-1 1,14-cis-eicosatetraenoic acid; LTD4, 5S-hydroxy-6R-S-cysteinylglycyl- 7,9-trans-I 1,14-cis-eicosatetraenoic acid; LTE4, 5S
Precocious puberty in a boy with a PRL-, LH- and FSH-secreting pituitary tumour: Hormonal and immunocytochemical studies. (1990)

The case of a 7-year-old boy affected with precocious puberty and a large intra- and suprasellar pituitary tumour is described. He had hyperprolactinemia and elevated serum LH, FSH and testosterone concentrations. Pre-operative dynamic hormonal studies showed a rise of PRL, LH and FSH levels after TRH (200 micrograms iv) and a rise of LH and FSH after GnRH (100 micrograms iv). Dopamine infusion (4 micrograms.kg-1.min-1 for 180 min) did not affect gonadotropins and greatly reduced serum PRL. GnRH analogue (buserelin, 0.5 mg sc t.i.d. for 10 days) administration inhibited both LH and FSH, but did not affect PRL concentration. Serum LH and FSH increased after ethinyl-estradiol (0.5 mg orally) administration, and were not affected by bromocriptine (5-7.5 mg/day for 10 days), which decreased serum PRL levels. The patient underwent transfrontal neurosurgery and a large tumour mass was completely removed. Morphological study of the excised tumour, by electron microscope double label immunotechnique, revealed that a large number of tumour cells (70-85%) were positive for PRL, LH and FSH, co-localized in the same secretory granule. After neurosurgery, serum PRL, LH, FSH and testosterone levels fell to within the normal limits. Two months later the patient was well and signs of precocious puberty had partially regressed; hormone levels were in the normal range and MR imaging control did not demonstrate any residual lesion in the sellar region.
DELISA: sensitive nonisotopic assay for GAD65 autoantibodies, a key risk-assessment marker for insulin-dependent diabetes mellitus (1996)

Nonisotopic assays for the measurement of autoantibodies to 65-kDa glutamic acid decarboxylase (GAD65) have not previously achieved performance equivalent to radiobinding assays (RBA). We have developed a modified ELISA protocol, DELISA, for measuring autoantibodies to GAD65 in serum. The method overcomes the problems of poor sensitivity and specificity associated with conventional ELISAs. Serum containing GAD65 autoantibodies is incubated with biotinylated GAD65 (bGAD65). Sufficient soluble Protein A-dextran conjugate is added to bind the immunoglobulins in the sample, including GAD65 autoantibodies to which GAD65 is bound. After incubation, the mixture is transferred to a streptavidin-p4ated microtiter well, which binds free bGAD65 but not bGAD65 bound to autoantibodies. Streptavidin-bound bGAD65 is detected by means of a peroxidase-GAS65MAb conjugate. The method appears to have comparable sensitivity and specificity to those of RBAs. Reaction of the antibodies with soluble antigen to increase the binding rate and the use of high serum concentrations and very low antigen concentrations to increase sensitivity are critical elements of the method.
[Antimicrobial activity of organic extracts isolated from Aplysina fistularis (Demospongiae: Aplysinidae)]. (2000)

Organic extracts of the sponge Aplysina fistularis (Pallas 1766) were tested for antimicrobial activity against Gram positive bacteria (Staphylococcus aureus) and Gram negative bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa). The minimal inhibitory concentration (MIC) and toxic activity of extract were determined. Susceptibility trials of organic fractions obtained by VLC: Hexane, EtOAc and CHCl3 showed that EtOAc fraction has antibacterial activity against E. coli, while CHCl3 fraction inhibited E. coli and S. aureus growth. The later refractioning of EtOAc fraction and the biodirected assays showed that fractions F12 and F13 of EtOAc/Hex and EtOAc F14 were bioactive against Gram positive and Gram negative bacteria. Only EtOAc/MeOH Sf2 from subfractionig of EtOAc F14 produced inhibition for E. coli and S. aureus. In Sf2 EtOAc/MeOH, MIC was moderate for S. aureus (MIC > 256 g/ml). F4 CHCl3/MeOH produced a high inhibition in S. aureus (MIC = 0.125 g/ml) and for E. coli (MIC > 16 g/ml). F10 CHCl3/MeOH showed a moderate activity against S. aureus (MIC > 128 g/ml) and low activity against E. coli (MIC = 512 g/ml). F10 CHCL3/MeOH did no present toxic activity against Artemia salina. The fractiorts F4 CHCL3/MeOH and Sf2 EtOAc/MeOH were toxic for this organism when the concentration was higher than 100 microg/ml. LC50 in both cases was 548.4 and 243.4 microg/ml respectively. Secondary metabolites of medium polarity obtained from A. fistularis have a wide spectrum of anti bacterial activity. Toxicity analysis suggests that only F10 CHCL3/MeOH has potential as an antimicrobial agent for clinical use.
Genes and genomes (1990)

Genes and Genomes provides a well-directed excursion into the realms of modern-day molecular genetics with all the excitement of new discoveries clearly presented to the reader. The first 215 pages of the book present a review of basic genetic concepts that laid the groundwork for the approaches and techniques that have led to an explosion of knowledge in the field of molecular genetics. The second part is an extensive guide to tools and experimental systems that are being used to explore the mysteries of the eukaryotic genome. With these tools in hand, the authors now launch the reader into a 400-page account of current understanding of the anatomy, the expression, and the regulation of eukaryotic genes. The final section of the book is an introduction to more complex biological systems.