gebhart/patrepeval huggingface dataset:
Childhood acute leukemia with t(11;19) (q23;p13). (1991)

From 583 cases of acute lymphoblastic leukemia (ALL) and 181 cases of acute myeloid leukemia (AML) in childhood, seven patients were identified to have t(11;19) (q23;p13) by sequential cytogenetic analyses. The t(11;19) was associated with B-precursor ALL at diagnosis in three patients and at relapse in one patient. All four tested patients with B-precursor failed to express the CD10 antigen when the t(11;19) was detected, and one of three patients tested expressed myeloid-associated markers. In three other patients the translocation was detected either at lineage conversion from ALL to M5 AML (n = 2) or from AML to CD10- B-precursor ALL (n = 1). Leukemic blasts of four patients had an entirely different karyotype at the time of lineage conversion or loss of CD10 expression, suggesting an induction of a second neoplasm. Thus the t(11;19) can be found in de novo or secondary acute leukemia with lymphoid (CD10-) or myeloid (monoblastic) phenotype. Further investigation of the gene(s) involved in the 11q23 chromosomal region and the breakpoints in the 19p13 region is needed to understand the leukemogenesis of this apparently heterogeneous group of disorders.
Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability (2014)

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NO x ; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NO(x) and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.
MADE4: an R package for multivariate analysis of gene expression data (2005)

MADE4, microarray ade4, is a software package that facilitates multivariate analysis of microarray gene-expression data. MADE4 accepts a wide variety of gene-expression data formats. MADE4 takes advantage of the extensive multivariate statistical and graphical functions in the R package ade4, extending these for application to microarray data. In addition, MADE4 provides new graphical and visualization tools that aid in interpretation of multivariate analysis of microarray data.
Programmed Gene Rearrangements Altering Gene Expression (1987)

Programmed gene rearrangements are used in nature to to alter gene copy number (gene amplification and deletion), to create diversity by reassorting gene segments (as in the formation of mammalian immunoglobulin genes), or to control the expression of a set of genes that code for the same function (such as surface antigens). Two major mechanisms for expression control are DNA inversion and DNA transposition. In DNA inversion a DNA segment flips around and is rejoined by site-specific recombination, disconnecting or connecting a gene to sequences required for its expression. In DNA transposition a gene moves into an expression site where it displaces its predecessor by gene conversion. Gene rearrangements altering gene expression have mainly been found in some unicellular organisms. They allow a fraction of the organisms to preadapt to sudden changes in environment, that is, to alter properties such as surface antigens in the absence of an inducing stimulus. The antigenic variation that helps the causative agents of African trypanosomiasis, gonorrhea, and relapsing fever to elude host defense is controlled in this way.
A novel derivative of the chelon desferrioxamine for site‐specific conjugation to antibodies (1989)

We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.
Relationship of Acetabular Wear to Osteolysis and Loosening in Total Hip Arthroplasty (1999)

Polyethylene wear and the subsequent development of periprosthetic osteolysis are the major factors limiting the longevity of total hip arthroplasties. A minority eventually loosen, but no clinically applicable system exists for accurate early prediction of failure. The relationship between acetabular wear and the development of loosening, osteolysis, and revision was investigated in 235 Charnley low friction arthroplasties. The average age of the patient at surgery was 31.7 years (range, 17-39 years), and the duration of followup averaged 234 months (19.5 years; range, 74-364 months). Total wear averaged 2.1 mm (range, 0-7.2 mm), and the average wear rate was 0.11 mm per year (range, 0-0.55 mm/year), with the wear rate of revised components being twice that of surviving ones (0.19 mm/year versus 0.09 mm/year). The prevalence of osteolysis (33 hips, 14%) and of acetabular and femoral component loosening and revision rose significantly with increasing wear. Osteolysis also was associated significantly with femoral component loosening and revision, but the presence of calcar changes was not (90 hips, 38%). Twenty-five year survivorship exceeded 90% for arthroplasties with a wear rate less than 0.1 mm per year, but 20-year survivorship of acetabular components with a rate greater than 0.2 mm per year was below 30%, and none survived 25 years. For every additional millimeter of wear, the risk of acetabular revision in any one year increased by 45% and for the femur increased by 32%.
HYPERTENSION AND INSULIN RESISTANCE: ROLE OF PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR γ (1999)

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma. 3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression. 5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression. 6. The modulation of PPAR gamma expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.
S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions (2008)

Dendritic cells (DCs) are antigen-presenting cells that play an essential role in mucosal tolerance. They regularly encounter beneficial intestinal bacteria, but the nature of these cellular contacts and the immune responses elicited by the bacteria are not entirely elucidated. Here, we examined the interactions of Lactobacillus acidophilus NCFM and its cell surface compounds with DCs. L. acidophilus NCFM attached to DCs and induced a concentration-dependent production of IL-10, and low IL-12p70. We further demonstrated that the bacterium binds to DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC- specific receptor. To identify the DC-SIGN ligand present on the bacterium, we took advantage of a generated array of L. acidophilus NCFM mutants. A knockout mutant of L. acidophilus NCFM lacking the surface (S) layer A protein (SlpA) was significantly reduced in binding to DC-SIGN. This mutant incurred a chromosomal inversion leading to dominant expression of a second S layer protein, SlpB. In the SlpB-dominant strain, the nature of the interaction of this bacterium with DCs changed dramatically. Higher concentrations of proinflammatory cytokines such as IL-12p70, TNFalpha, and IL-1beta were produced by DCs interacting with the SlpB-dominant strain compared with the parent NCFM strain. Unlike the SlpA-knockout mutant, T cells primed with L. acidophilus NCFM stimulated DCs produced more IL-4. The SlpA-DC-SIGN interaction was further confirmed as purified SlpA protein ligated directly to the DC-SIGN. In conclusion, the major S layer protein, SlpA, of L. acidophilus NCFM is the first probiotic bacterial DC-SIGN ligand identified that is functionally involved in the modulation of DCs and T cells functions.
Molecular sequelae of histone deacetylase inhibition in human malignant B cells (2003)

Histone acetylation modulates gene expression, cellular differentiation, and survival and is regulated by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC inhibition results in accumulation of acetylated nucleosomal histones and induces differentiation and/or apoptosis in transformed cells. In this study, we characterized the effect of suberoylanilide hydroxamic acid (SAHA), the prototype of a series of hydroxamic acid-based HDAC inhibitors, in cell lines and patient cells from B-cell malignancies, including multiple myeloma (MM) and related disorders. SAHA induced apoptosis in all tumor cells tested, with increased p21 and p53 protein levels and dephosphorylation of Rb. We also detected cleavage of Bid, suggesting a role for Bcl-2 family members in regulation of SAHA-induced cell death. Transfection of Bcl-2 cDNA into MM.1S cells completely abrogated SAHA-induced apoptosis, confirming its protective role. SAHA did not induce cleavage of caspase-8, -9, or -3 in MM.1S cells during the early phase of apoptosis, and the pan-caspase inhibitor ZVAD-FMK did not protect against SAHA. Conversely, poly(ADP)ribose polymerase (PARP) was cleaved in a pattern indicative of calpain activation, and the calpain inhibitor calpeptin abrogated SAHA-induced cell death. Importantly, SAHA sensitized MM.1S cells to death receptor-mediated apoptosis and inhibited the secretion of interleukin 6 (IL-6) induced in bone marrow stromal cells (BMSCs) by binding of MM cells, suggesting that it can overcome cell adhesion-mediated drug resistance. Our studies delineate the mechanisms whereby HDAC inhibitors mediate anti-MM activity and overcome drug resistance in the BM milieu and provide the framework for clinical evaluation of SAHA, which is bioavailable, well tolerated, and bioactive after oral administration, to improve patient outcome.
Population Pharmacokinetic Analysis of Tocilizumab in Patients With Rheumatoid Arthritis (2010)

Tocilizumab is a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody that has demonstrated efficacy in the treatment of rheumatoid arthritis (RA). A population pharmacokinetic (PK) model was developed using nonlinear mixed effect modeling to describe the PK profile of tocilizumab and used to estimate interindividual variability and assess the influence of covariates on PK parameters. The model was constructed based on data collected from 1793 patients with moderate to severe RA who received tocilizumab (4 or 8 mg/kg), via intravenous infusion every 4 weeks, during 4 phase III clinical trials. Serum concentration-time profiles of tocilizumab were adequately described by a 2-compartment disposition model with parallel linear and nonlinear elimination kinetics. The 8-mg/kg dose of tocilizumab, compared with the 4-mg/kg dose, resulted in a more pronounced saturation of the nonlinear clearance pathway over the dosing interval, and this nonlinear clearance was representative of target-mediated elimination due to tocilizumab binding to the IL-6 receptor.
α-L-LNA (α-L-ribo Configured Locked Nucleic Acid) Recognition of DNA: An NMR Spectroscopic Study (2002)

We have used NMR and CD spectroscopy to study and characterise two alpha-L-LNA:DNA duplexes, a nonamer that incorporates three alpha-L-LNA nucleotides and a decamer that incorporates four alpha-L-LNA nucleotides, in which alpha-L-LNA is alpha-L-ribo-configured locked nucleic acid. Both duplexes adopt right-handed helical conformations and form normal Watson-Crick base pairing with all nucleobases in the anti conformation. Deoxyribose conformations were determined from measurements of scalar coupling constants in the sugar rings, and for the decamer duplex, distance information was derived from 1H-1H NOE measurements. In general, the deoxyriboses in both of the alpha-L-LNA:DNA duplexes adopt S-type (B-type structure) sugar puckers, that is the inclusion of the modified alpha-L-LNA nucleotides does not perturb the local native B-like double-stranded DNA (dsDNA) structure. The CD spectra of the duplexes confirm these findings, as these display B-type characteristic features that allow us to characterise the overall duplex type as B-like. The 1H-1H NOE distances which were determined for the decamer duplex were employed in a simulated annealing protocol to generate a model structure for this duplex, thus allowing a more detailed inspection of the impact of the alpha-L-ribo-configured nucleotides. In this structure, it is evident that the malleable DNA backbone rearranges in the vicinity of the modified nucleotides in order to accommodate them and present their nucleobases in a geometry suitable for Watson-Crick base pairing.
Gene amplification for c-erbB-2, c-myc, epidermal growth factor receptor, int-2, and N-myc measured by quantitative PCR with a multiple competitor template (1995)

We recently proposed a quantitative PCR procedure for the absolute measurement of c-erbB-2 oncogene amplification, based on the simultaneous polymerase chain reaction (PCR) amplification of the target gene and of a competitor DNA molecule acting as internal standard. To increase the number of assayable oncogenes and the accuracy of the quantitative comparison of gene amplification degree within the same tumor, we have now constructed a single synthetic competitor for int-2, c-myc, N-myc epidermal growth factor receptor, and c-erbB-2 genes, and for the reference gene beta-globin. This competitor was constructed by a two-step recombinant PCR procedure and inserted as a 297-bp sequence in a plasmid. The order of primer insertion was designed to obtain competitors of comparable sizes to those of the respective genomic targets, but still easily recognizable from the latter ones by gel electrophoresis. The clone competitor was tested to evaluate the linearity range for each assay. The present application of quantitative PCR based on a multiple competitor represents the first approach for the achievement of a single reagent for the evaluation of a panel of genes potentially amplified in human tumors.
Large Stokes‐Shift Fluorescent Silica Nanoparticles with Enhanced Emission Over Free Dye for Single Excitation Multiplexing (2009)

Abstract We describe a polycondensation reaction of silica precursors in a modified Stöber‐type basic ethanol solution to produce graded Stokes‐shift core‐shell silica nanoparticles providing bright and spectrally multiplexed sets of fluorescent tags that are excitable using a single excitation source. Dynamic light scattering and scanning electron microscopy demonstrate particle sizes in the sub‐10 nm regime. Absorption matched emission comparisons between encapsulated and free dyes in aqueous solution reveal about an order of magnitude per‐dye brightness enhancements that are apparent by simply looking at the solutions under laser illumination conditions. magnified image
In Praise of Irrational Plaintiffs (2000)

Classical economic analysis suggests that parties in a lawsuit decide whether to settle or litigate an action based solely upon calculations of costs and potential recovery in the pending action.This analysis suggests that the current policy of encouraging settlement is beneficiaL Using statistical analysis and behavioral economics, Professor Cross argues that, in fact, many litigants do not engage in rational decision making and that policies should encourage the "irrational plaintff." The classical economic analysis neglects the negative effect of repeat player litigants upon precedent.This Article notes that repeat player litigants, particularly tort and product liability do fendants, have a strong economic interest to engage in strategic precedent setting and reduce their potential liability in fiture cases.These repeat player litigants manipulate precedent by pursuing settlement in cases with unfrienly facts, while tenaciously litigating cases with favorable facts.In contrast, behavioral economic analysis suggests that many plaintiffs have noneconomic motivations to litigate rather than settle, including vengeance, fairness, or vindication.Professor Cross suggests that the irrational plaintiff may counteract the negative effects of strategic settlement by pursuing litigation in spite of large settlement offers.Professer Cross concludes, through an understanding of behavioral economics and classical economic analysis, that settlement can result in significant inefficiencies, and that the irrational plaintiff holds the greatest corrective potential.
Effects of Bacillus thuringiensis δ-Endotoxins on the Pea Aphid ( Acyrthosiphon pisum ) (2009)

Four Bacillus thuringiensis delta-endotoxins, Cry3A, Cry4Aa, Cry11Aa, and Cyt1Aa, were found to exhibit low to moderate toxicity on the pea aphid, Acyrthosiphon pisum, in terms both of mortality and growth rate. Cry1Ab was essentially nontoxic except at high rates. To demonstrate these effects, we had to use exhaustive buffer-based controls.
Inhibition of the serine proteases leukocyte elastase, pancreatic elastase, cathepsin G, and chymotrypsin by peptide boronic acids. (1984)

Three alpha-aminoboronic acid-containing analogs of good peptide substrates for serine proteases were synthesized, MeO-Suc-Ala-Ala-Pro-boro-Phe-OH, MeO-Suc-Ala-Ala-Pro-boro-Ala-OH, and MeO-Suc-Ala-Ala-Pro-boro-Val-OH. They were effective inhibitors of chymotrypsin, cathepsin G, and both leukocyte and pancreatic elastase at nanomolar concentrations (0.10-20 nM). Except for cathepsin G, inhibition was not simply competitive, but showed kinetic properties corresponding to the mechanism for slow-binding inhibition, i.e. E + I in equilibrium EI in equilibrium EI*, where EI and EI* are enzyme-inhibitor complexes and EI* is more stable than EI. This type of inhibition has not been observed previously for synthetic inhibitors or serine proteases and in this study it was observed only for peptide boronic acids which satisfy the primary specificity requirements of the protease.
Rapid prototyping tools and methods for all-Topas® cyclic olefin copolymer fluidic microsystems (2006)

Topas®, the cyclic olefin copolymer, from Topas Advanced Polymers GmbH has a number of advantages over polymers such as poly(methylmethacrylate), polydimethylsiloxane, and polycarbonate traditionally used in fluid microsystem manufacturing, such as low water absorption, high chemical resistance, good machinability, and good optical properties. A number of different processes for rapid and low-cost prototyping of all-Topas microfluidic systems, made with desktop machinery, are presented. Among the processes are micromilling of fluidic structures with a width down to 25 μm and sealing of fluidic channels by thermal bonding or laser bonding, using a thin, spin-coated layer of carbon particles between the Topas substrate and the lid to absorb the laser light.
Towards an elastic distributed SDN controller (2013)

Distributed controllers have been proposed for Software Defined Networking to address the issues of scalability and reliability that a centralized controller suffers from. One key limitation of the distributed controllers is that the mapping between a switch and a controller is statically configured, which may result in uneven load distribution among the controllers. To address this problem, we propose ElastiCon, an elastic distributed controller architecture in which the controller pool is dynamically grown or shrunk according to traffic conditions and the load is dynamically shifted across controllers. We propose a novel switch migration protocol for enabling such load shifting, which conforms with the Openflow standard. We also build a prototype to demonstrate the efficacy of our design.
Cross-linking of alpha 2-plasmin inhibitor to fibrin by fibrin-stabilizing factor. (1980)

A B S T R A C T The concentration of a2-plasmin inhibitor in blood plasma is higher than that in serum ob- tained from the blood clotted in the presence ofcalcium ions, but is the same as that in serum obtained in the absence of calcium ions.