gebhart/patrepeval huggingface dataset:
Development of a Practical and Reliable Synthesis of Laquinimod (2007)

Laquinimod (5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide) is a drug candidate for treatment of Multiple Sclerosis. A short and industrially feasible process for the preparation of laquinimod starting from 2-amino-6-chlorobenzoic acid, in essentially four steps, is dis-cussed. The key step is a novel reaction in which a methyl ester is converted to an amide in very high yield and with excellent purity. The present article elucidates the scale-up process along with safety aspects and the impurity profiles of the intermediates and product. Initial laboratory conditions are described as well as the changes made on transfer to pilot-plant scale.
Pharmacokinetics and Toxicity of Intravitreal Chemotherapy for Primary Intraocular Lymphoma (2001)

Although responsive to conventional chemotherapy or radiotherapy, recurrence of ocular involvement with primary central nervous system lymphoma occurs in more than 50% of treated cases. Anecdotal reports of the use of intravitreal chemotherapy for primary intraocular lymphoma have been encouraging. However, animal data on the pharmacokinetics and toxicity of combined intravitreal agents for the treatment of this disease are lacking.
Spliceostatin hemiketal biosynthesis in Burkholderia spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase (2014)

Spliceostatins are potent spliceosome inhibitors biosynthesized by a hybrid nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) system of the trans-acyl transferase (AT) type. Burkholderia sp. FERM BP-3421 produces hemiketal spliceostatins, such as FR901464, as well as analogs containing a terminal carboxylic acid. We provide genetic and biochemical evidence for hemiketal biosynthesis by oxidative decarboxylation rather than the previously hypothesized Baeyer-Villiger oxidative release postulated to be catalyzed by a flavin-dependent monooxygenase (FMO) activity internal to the last module of the PKS. Inactivation of Fe(II)/α-ketoglutarate-dependent dioxygenase gene fr9P led to loss of hemiketal congeners, whereas the mutant was still able to produce all major carboxylic acid-type compounds. FMO mutants, on the other hand, produced both hemiketal and carboxylic acid analogs containing an exocyclic methylene instead of an epoxide, indicating that the FMO is involved in epoxidation rather than Baeyer-Villiger oxidation. Moreover, recombinant Fr9P enzyme was shown to catalyze hydroxylation to form β-hydroxy acids, which upon decarboxylation led to hemiketal FR901464. Finally, a third oxygenase activity encoded in the biosynthetic gene cluster, the cytochrome P450 monooxygenase Fr9R, was assigned as a 4-hydroxylase based on gene inactivation results. Identification and deletion of the gene involved in hemiketal formation allowed us to generate a strain--the dioxygenase fr9P(-) mutant--that accumulates only the carboxylic acid-type spliceostatins, which are as potent as the hemiketal analogs, when derivatized to increase cell permeability, but are chemically more stable.
Use of the BD PHOENIX Automated Microbiology System for Direct Identification and Susceptibility Testing of Gram-Negative Rods from Positive Blood Cultures in a Three-Phase Trial (2004)

The present study describes the use of the automated BACTEC 9240 blood culture system, the Serum Separator Tube (SST), and the BD PHOENIX Automated Microbiology System in combination for the direct identification and antimicrobial susceptibility testing (AST) of gram-negative rods (GNRs) from positive blood cultures (BCs) without subculture. The study was conducted in three phases: (i) the recovery yield of Escherichia coli ATCC 25922 was determined with the SST between 0 and 8 h after spiked BC bottles turned positive; (ii) the identifications and susceptibility testing results obtained with the PHOENIX system for nine American Type Culture Collection strains of GNRs processed by the SST procedure and for colonies from agar medium were compared; and (iii) the procedure with the BACTEC system, SSTs, and the PHOENIX system was applied to positive cultures of blood from 309 patients during a 3-month period. The SST procedure with E. coli yielded sufficient numbers of cells to perform direct inoculation at any time between 0 and 8 h after a BC bottle turned positive. By using the identities obtained from pure cultures with the PHOENIX system and other biochemical identification systems as reference methods, the agreement between the reference methods and the PHOENIX system tested directly by using cultures of blood from patients was 92.9%. The 7.1% discrepant results were due to 6.5% incorrect identifications with the PHOENIX system with BC samples and 0.6% incorrect identifications with the PHOENIX system with samples from agar cultures. By AST the overall categorical accuracy was 99.0%, with 0.1% very major errors, 0.1% major errors, and 0.8% minor errors. In conclusion, use of the combination of the BACTEC system, SSTs, and the PHOENIX system has the potential to allow the agar isolation step to be skipped and the procedures for rapid direct identification and susceptibility testing of GNRs from positive BCs to be improved both in hospital-based and in central non-hospital-based laboratories.
Oceano-SLA based management of a computing utility (2002)

Oceano is a prototype of a highly available, scaleable, and manageable infrastructure for an e-business computing utility. It enables multiple customers to be hosted on a collection of sequentially shared resources. The hosting environment is divided into secure domains, each supporting one customer. These domains are dynamic: the resources assigned to them may be augmented when the load increases and reduced when load dips. This dynamic resource allocation enables flexible service level agreements (SLAs) with customers in an environment where peak loads are an order of magnitude greater than the normal steady state.
Cloning of the genes for and characterization of the early stages of toluene and o-xylene catabolism in Pseudomonas stutzeri OX1 (1996)

In order to study the toluene and o-xylene catabolic genes of Pseudomonas stutzeri OX1, a genomic library was constructed. A 28-kb EcoRI restriction endonuclease DNA fragment, cloned into the vector plasmid pLAFR1 and designated pFB3401, permitted Pseudomonas putida PaW340 to convert toluene and o-xylene into the corresponding meta-ring fission products. Physical and functional endonuclease restriction maps have been derived from the cloned DNA fragment. Further subcloning into and deletion analysis in the Escherichia coli vector pGEM-3Z allowed the genes for the conversion of toluene or o-xylene into the corresponding catechols to be mapped within a 6-kb region of the pFB3401 insert and their direction of transcription to be determined. Following exposure to toluene, E. coli cells carrying this 6-kb region produce a mixture of o-cresol, m-cresol, and p-cresol, which are further converted to 3-methylcatechol and 4-methylcatechol. Similarly, a mixture of 2,3-dimethylphenol and 3,4-dimethylphenol, further converted into dimethylcatechols, was detected after exposure to o-xylene. The enzyme involved in the first step of toluene and o-xylene degradation exhibited a broad substrate specificity, being able to oxidize also benzene, ethylbenzene, m-xylene, p-xylene, styrene, and naphthalene. Deletions of the 6-kb region which affect the ability to convert toluene or o-xylene into the corresponding methylphenols compromise also their further oxidation to methylcatechols. This suggests that a single enzyme system could be involved in both steps of the early stages of toluene and o-xylene catabolism.
La atribución causal antecedente y consecuente con el rendimiento experimental como proceso mediador (1997)

Se aborda el estudio de la atribucion causal desde una doble perspectiva: 

bien como variable independiente o atribucion causal antecedente (A.C.A.), administrada desde fuera del sujeto mediante instrucciones de adscripcion del posible exito o fracaso en la subsiguiente tarea, a causas internas, externas y ausencia de atribucion; 
bien como variable dependiente o atribucion causal consecuente (A.C.C.) en cuanto respuesta de adscripcion tras el rendimiento obtenido en la realizacion de la tarea y que el sujeto vivencia como exito o fracaso. 
Las conclusiones manifiestan que la A.C.A. resulta efectiva en el rendimiento. Y por lo que respecta a la A.C.C., los sujetos atribuyen el exito o el fracaso, no con exclusividad a una u otra causa, sino a todas ellas en un determinado orden de preferencia.
Directed Assembly of DNA Molecules Via Simultaneous Ligation and Digestion (2007)

DNA ligation is a routine laboratory practice, yet the yield of the desired product is often very low due to competing off-pathway reactions. The sensitivity of subsequent manipulations (e.g., selection via bacterial transformation) often obviates the need for a high yield of correctly ligated products. However the ability to perform high-yield, preparative-scale DNA ligations would benefit a number of downstream applications ranging from standard molecular cloning to biophysics and DNA computing. We describe here a ligation technique that specifically converts off-pathway ligation products back into substrate. We term this second-chance strategy enzymatic ligation assisted by nucleases (ELAN) and demonstrate the ordered assembly of four DNA fragments via simultaneous ligation and digestion in the presence of eight restriction enzymes. Use of ELAN increased the yield of the desired product by more than 30-fold.
Strain‐Induced Formation of Subsurface Species in Transition Metals (2004)

Expansive surface strain facilitates the formation of subsurface heteroatoms in transition metals. Density functional calculations show that subsurface hydrogen atoms form more rapidly, as depicted schematically in the picture, and are thermodynamically stable at much lower pressures and higher temperatures in stretched (as opposed to unstretched) nickel surfaces.
Molecular Modeling of Antibody-Combining Sites (2003)

Antibodies possess a vast repertoire of specificity and affinity. To understand the molecular basis of antibody function, we require high-resolution X-ray crystallographic structures and good solution structures of free and antigen-bound antibodies. The number of reported antibody structures grows each year. Yet the number of structures deposited with the Brookhaven Protein Database (PDB) (1) remains relatively small, with 43 deposited entries at the time of writing, when compared to the available sequence data. It is therefore important to develop an effective method of predicting the structure of antibody-combining sites. The validity of predicted structures can then be confirmed by mutagenesis in the combining site. The models can also provide valuable structural information to “humanize” antibodies for therapy effectively, to develop immunosensors, and even for the complete de novo design of new antibodies with different functions.
The cytotoxic synergy of nanosecond electric pulses and low temperature leads to apoptosis (2016)

Electroporation by nanosecond electric pulses (nsEP) is an emerging modality for tumor ablation. Here we show the efficient induction of apoptosis even by a non-toxic nsEP exposure when it is followed by a 30-min chilling on ice. This chilling itself had no impact on the survival of U-937 or HPAF-II cells, but caused more than 75% lethality in nsEP-treated cells (300 ns, 1.8-7 kV/cm, 50-700 pulses). The cell death was largely delayed by 5-23 hr and was accompanied by a 5-fold activation of caspase 3/7 (compared to nsEP without chilling) and more than 60% cleavage of poly-ADP ribose polymerase (compared to less than 5% in controls or after nsEP or chilling applied separately). When nsEP caused a transient permeabilization of 83% of cells to propidium iodide, cells placed at 37 °C resealed in 10 min, whereas 60% of cells placed on ice remained propidium-permeable even in 30 min. The delayed membrane resealing caused cell swelling, which could be blocked by an isosmotic addition of a pore-impermeable solute (sucrose). However, the block of swelling did not prevent the delayed cell death by apoptosis. The potent enhancement of nsEP cytotoxicity by subsequent non-damaging chilling may find applications in tumor ablation therapies.
Computer automated structure evaluation of quinolone antibacterial agents (1987)

The Computer Automated Structure Evaluation (CASE) program was used to study a series of quinolone antibacterial agents for which experimental data pertaining to DNA gyrase inhibition as well as MICs against several strains of gram-positive and gram-negative bacteria are available. The result of the analysis was the automatic generation of molecular fragments relevant to the respective biological endpoints. The potential significance of these major activating-inactivating fragments to the biological activity is discussed.
Experimental Shigella Infections in Laboratory Animals I. Antagonism by Human Normal Flora Components in Gnotobiotic Mice (1972)

Germfree mice were associated with selected species of human intestinal bacteria and then challenged with a streptomycin-resistant Shigella flexneri strain. Antagonism against Shigella was most pronounced in mice associated with Escherichia coli and least pronounced in mice associated with Bacteroides fragilis. A moderate degree of antagonism could be demonstrated in mice associated with either Streptococcus faecalis or Bifidobacterium adolescentis. Shigella persisted in the cecal contents of E. coli-associated mice at very low, stable levels. Shigella populations were reduced to levels below detection in the ceca of mice diassociated with E. coli and Bacteroides. Upon subsequent administration of streptomycin, Bacteroides disappeared from the ceca. The E. coli population was greatly reduced, and Shigella reappeared at very high population levels as an apparent recombinant which resembled E. coli biochemically. A streptomycin-resistant E. coli population subsequently emerged and became dominant in the ceca. Shigella concomitantly declined to levels below detection.
Linear polymerization of a synthetic peptide of the V3 region from HIV-1 JY1 isolate using acetamidomethyl-protected thiol groups of cysteine residues (2000)

A method to carry out the linear polymerization of a synthetic peptide\nusing acetamidomethyl (Acm)-protected thiol groups of cysteine\nresidues, was developed. This polymer showed to be useful in the\nimprovement of peptide immunogenicity. To achieve the polymerization,\ntwo Cys(Acm) residues were incorporated at both ends of the peptide.\nThe model peptide contains B and T cell epitopes placed in tandem. The\nB cell epitope comprises 15 amino acids of the V3 region from HIV-1 JY1\nisolate, and the helper T cell epitope belongs to the region 830-844 of\nthe tetanus toxoid. The polymerization reaction consisted in an instant\nprocess of deprotection and oxidation of thiol groups at a high monomer\nconcentration. This reaction proceeded quickly with about 80% of\nconversion. The monomer and the polymers were analyzed by gel\nfiltration chromatography, reverse phase-high performance liquid\nchromatography, sodium dodecyl sulfate-polyacrylamide gel\nelectrophoresis, and mass spectrometry. The sera obtained from mice\nimmunized with the monomer and the polymer variants were assayed\nagainst a conjugated BSA-JY1 peptide in an indirect ELISA. The highest\ntiter values corresponded to the polymer variant (p &amp;lt; 0.01). This\nresult emphasizes that this strategy can be used to increase the\nimmunogenicity of synthetic peptides in vaccines or therapeutics.
Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS (2005)

Hepatic peptide hormone hepcidin is the key regulator of iron metabolism and the mediator of anemia of inflammation. Previous studies indicated that interleukin-6 (IL-6) mediates hepcidin increase and consequent hypoferremia during inflammation. Here we used an in vivo human endotoxemia model to analyze the effects of lipopolysaccharide (LPS) as a more upstream inflammation activator. The temporal associations between plasma cytokines, hepcidin levels, and serum iron parameters were studied in 10 healthy individuals after LPS injection. IL-6 was dramatically induced within 3 hours after injection, and urinary hepcidin peaked within 6 hours, followed by a significant decrease in serum iron. Serum prohepcidin showed no significant change within a 22-hour time frame. These in vivo human results confirm the importance of the IL-6-hepcidin axis in the development of hypoferremia in inflammation and highlight the rapid responsiveness of this iron regulatory system.
The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983] (1995)

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.
New commercial trends of nanostructured ferrofluids (2004)

In the realm of nanotech materials, ferrofluids are unique in that their constituents are both liquid and solid. True microsystems based on hydrodynamic principles of ferrofluids may still be some years away. However, ferrofluids are already contributing to nanotechnology, first as components of microproducts and second by their utilization in processes engaged in fabrication of nanostructured materials. This paper focuses on applications of ferrofluids, which are related to the drive towards the new technology. IPC Code: Int. Cl. 7 H 01F 41/30 A nanostructure is an assembly of countable number of atoms or molecules. The linear dimension of these objects ranges from 1 to 100 nm. These are the smallest man-made products promising a new industrial revolution 1,2 . Examples of these materials are: zeolites, ceramics, polymers, nanotubes and layered films. Nature sets the standard for the ultimate structure of this kind, i.e., a human cell that has the ability to both self-assemble and replicate. Miniaturization of existing devices is within the vision of nanotechnology; may it be tiny semiconductor chips or high memory computer systems. The new scientific revolution not only demands unusual materials but also progress in process technology. Ferrofluids have traditionally provided solutions to complex engineering problems facing emerging industries. These colloids are now meeting new challenges of ensuring ultra clean environments crucial to fabrication of nanostructures, in producing microbeads for DNA isolation and in ensuring performance of scale down versions of speakers, hearing aids and memory drives. In this paper, those applications of ferrofluids are presented which are contributing to the advancement of nanosystems, whether it is a process, device, instrument, or structure characterization. Properties of ferrofluids, as well as of particles, are first reviewed and then several applications are discussed. Ferrofluids
Detection of platelet-activating factor in plasma of patients with streptococcal nephritis. (1993)

The purpose of this study was to evaluate whether platelet-activating factor (PAF) is released in the plasma of patients with acute poststreptococcal glomerulonephritis, because previous studies have shown an involvement of platelets in the active phase of this disease. The results of this study indicate that PAF bioactive material is released in significant amounts in the plasma of 49 out of 50 patients with acute poststreptococcal glomerulonephritis. The observed release of PAF was not a direct consequence of the bacterial infection, because it was minimal or absent in patients with streptococcal infection without glomerular involvement. PAF bioactive material extracted and purified from the plasma of patients was shown to be chemically and biologically identical to the synthetic C-16 PAF (1-O-hexadecyl-2-acetyl-sn-glyceryl 3-phosphorylcholine).
Preterm Birth Subtypes among Blacks and Whites (1992)

The differences in preterm birth between blacks and whites are poorly understood. Our study examined subtypes of moderately preterm delivery (34-36 completed weeks of gestation) and very preterm delivery (20-33 weeks) in blacks and whites using North Carolina birth certificate data for 1988-1989. We divided the causes of preterm birth into three categories: preterm premature rupture of the membranes, indication of pregnancy complication, and idiopathic preterm deliveries. The overall prevalence of preterm birth was 8.0% and 16.7% for whites and blacks, respectively. The entire gestational age distribution of blacks was shifted to earlier ages relative to whites. More highly educated blacks still had higher risks of moderately and very preterm deliveries than less educated whites. Multivariate analysis, controlling for other factors, showed that blacks had 3.3, 2.5, and 3.5 times the risk of whites to have preterm premature rupture of the membranes, complication-related, and idiopathic delivery, respectively, among very preterm births, and 1.6, 1.9, and 2.0 times the risk of whites for moderately preterm births of the same three types.
The hypothetical N-glycan charge: a number that characterizes protein glycosylation (1996)

The production of recombinant glycoprotein therapeutics requires characterization of glycosylation with respect to the lot-to-lot consistency. Here we introduce the ¿hypothetical N-glycan charge Z' as a parameter that allows to characterize the protein glycosylation in a simple, however, efficient manner. The hypothetical N-glycan charge of a given glycoprotein is deduced from the N-glycan mapping profile obtained via HPAE-PAD. In HPAEC, N-glycans are clearly separated according to their charge, i.e., their number of sialic acid residues, providing distinct regions for neutral structures as well as for the mono- di-, tri, and tetrasialylated N-glycans (Hermentin et al., 1992a). Z is defined as the sum of the products of the respective areas (A) in the asialo, monosialo, disialo, trisialo, tetrasialo, and pentasialo region, each multiplied by the corresponding charge: [formula: see text] Thus, a glycoprotein with mostly C4-4* structures will provide Z approximately equal to 400 (e.g., rhu EPO (CHO), Z = 361), a glycoprotein carrying largely C3-3* structures will amount to Z approximately equal to 300 (e.g., bovine fetuin, Z = 290), a glycoprotein with mostly C2-2* structures will have Z approximately equal to 200 (e.g., human serum transferrin, Z = 207, or human plasma AT III, Z = 180), and a glycoprotein carrying only high-mannose type or trunkated structures will provide Z approximately equal to 0 (e.g., bovine pancreas ribonuclease B, Z = 15, and hen ovomucoid, Z = 15, respectively). The determination of Z was validated in multiple repetitive experiments and proved to be highly accurate and reliable. Z may therefore be regarded as a new and characteristic parameter for protein N-glycosylation.