gebhart/patrepeval huggingface dataset:
Involvement of MET/TWIST/APC Combination or the Potential Role of Ossification Factors in Pediatric High-Grade Osteosarcoma Oncogenesis (2007)

Dysregulated cell growth or differentiation due to misexpression of developmental critical factors seems to be a decisive event in oncogenesis. As osteosarcomas are histologically defined by malignant osteoblasts producing an osteoid component, we prospected in pediatric osteosarcomas treated with OS94 protocol the genomic status of several genes implied in ossification processes. In 91 osteosarcoma cases, we focused on the analysis of the fibroblast growth factor receptors (FGFRs) TWIST, APC, and MET by allelotyping, real-time quantitative polymerase chain reaction, gene sequencing, and protein polymorphism study. Our study supports the frequent role of TWIST, APC, and MET as osteosarcoma markers (50%, 62%, and 50%, respectively). TWIST and MET were mainly found to be deleted, and no additional APC mutation was identified. Surprisingly, FGFRs are abnormal in only < 30%. Most of these factors and their abnormalities seem to be linked more or less to one clinical subgroup, but the most significant correlation is the link of MET, TWIST, and APC abnormalities to a worse outcome and their combination within abnormal tumors. A wider cohort is mandatory to define more robust molecular conclusions, but these results are to be considered as the beginning of a more accurate basis for diagnosis, in search of targeted therapies, and to further characterize prognostic markers.
An approach for global scanning of single nucleotide variations (2002)

Efficient global scanning of single nucleotide variations in DNA sequences between related, complex DNA samples remains a challenge. In the present article we present an approach to this problem. We have used immobilized thymidine DNA glycosylases to capture and enrich DNA fragments containing internal mismatched base pairs and separate these fragments as a pool from perfectly base-paired fragments as another pool. Enrichments of up to several hundredfold were obtained with one cycle of treatment, and all of the four groups of single nucleotide mismatches were fully covered by combining use of two thymine DNA glycosylases generated here. We have used a heterohybrid-orientating strategy for selective amplification of duplexes with one strand derived from each of two input DNA samples, which can also be used for selective amplification of duplexes with both strands derived from one of two input samples when desired. By combining these methods, the single nucleotide variations either between two DNA pools or within one DNA pool can be obtained in one process. This approach has been applied to the total cDNA from a human cell line and has several potential applications in mapping genetic variations, particularly global scanning of cDNA single nucleotide variations or polymorphisms, and finally high-throughput mapping of complex genetic traits.
Pseudocysts in chronic pancreatitis: a morphological analysis of 57 resection specimens and 9 autopsy pancreata. (1991)

The pathology of chronic pancreatitis is reviewed in order to study the histology and incidence of pseudocysts in relation to the degree of pancreatic fibrosis and calcification. The series consisted of 57 resection specimens (49 partial pancreatectomy specimens and 8 total pancreatectomy specimens) and 9 autopsy pancreata. The histology of cystic lesions observed in the specimens was found to be identical to that of pseudocysts in acute pancreatitis. In 19 of 57, there was concomitant occurrence of focal autodigestive (fat) necrosis and pseudocysts. Pseudocysts were more common in specimens with focal fibrosis and few calcifications (13/25) than in those with diffuse advanced fibrosis and numerous calcifications (15/41). The findings indicate that sequelae of acute pancreatitis are frequently present in chronic pancreatitis, particularly in an early stage when fibrosis is still focal and calcification rare. This suggests that chronic pancreatitis may result from relapses of severe acute pancreatitis. A pathogenetic concept that relates acute pancreatitis with chronic pancreatitis is proposed.
Nitration inhibits fibrillation of human α‐synuclein in vitro by formation of soluble oligomers (2003)

The aggregation of alpha-synuclein in dopaminergic neurons is a critical factor in the etiology of Parkinson's disease (PD). Oxidative and nitrative stress is also implicated in PD. We examined the effect of nitration on the propensity of alpha-synuclein to fibrillate in vitro. Fibril formation of alpha-synuclein was completely inhibited by nitration, due to the formation of stable soluble oligomers (apparently octamers). More importantly the presence of sub-stoichiometric concentrations of nitrated alpha-synuclein led to inhibition of fibrillation of non-modified alpha-synuclein. These observations suggest that nitration of soluble alpha-synuclein may be a protective factor in PD, rather than a causative one.
Spin-dependent tunneling spectroscopy in single-crystal Fe∕MgO∕Fe tunnel junctions (2005)

We report a detailed spin-dependent tunneling spectroscopy in single-crystal Fe(001)∕MgO(001)∕Fe(001) magnetic tunnel junctions (MTJs) that show a giant tunnel magnetoresistance effect. Spectra for antiparallel magnetic configurations show asymmetry because of extrinsic electron scatterings caused by structural defects at the barrier/electrode interfaces. Surprisingly, spectra for parallel magnetic configurations exhibit a complex oscillatory structure that has never been observed in conventional MTJs with an aluminum-oxide tunnel barrier. The complex spectra reflect the tunneling process via interface resonant states. These results provide some information that helps to elucidate the physics of spin-dependent electron tunneling and to further enhance magnetoresistance.
Softmax to Softassign: neural network algorithms for combinatorial optimization (1996)

A new technique termed softassign is applied to three combinatorial optimization problems - weighted graph matching, the travelling salesman problem and graph partitioning. Softassign, which has emerged from the recurrent neural network/ statistical physics framework, enforces two-way (assignment) constraints without the use of penalty terms in the energy functions. The softassign can also be generalised from two-way winner-take-all constraints to multiple membership constraints which are required for graph partitioning. The softassign technique is compared to softmax (Potts glass) dynamics. Within the statistical physics framework, softmax and a penalty term has been a widely used method for enforcing the two-way constraints common to many combinatorial optimization problems. The benchmarks present evidence that softassign has clear advantages in accuracy, speed, parallelizability and algorithmic simplicity over softmax and a penalty term in optimization problems with two-way constraints.
Interim results from a phase I study of CAL-101, a selective oral inhibitor of phosphatidylinositol 3-kinase p110d isoform, in patients with relapsed or refractory hematologic malignancies. (2010)

3032 Background: The class I phosphatidylinositol 3-kinase (PI3K) p110δ isoform is primarily expressed in cells of hematopoietic origin and has a key role in B cell maturation and function. CAL-101 is a potent and selective inhibitor of p110δ that inhibits PI3K signaling and induces apoptosis of primary CLL and AML cells and a range of leukemia and lymphoma cell lines. Methods: An ongoing phase 1 study enrolled previously treated patients with select hematologic malignancies in a standard sequential dose escalation/cohort expansion design. CAL-101 was administered orally twice-a-day continuously for 28 days per cycle. Results: At data cutoff, 57 patients were enrolled (NHL n=29, CLL n=18, AML n=10), 49% had refractory disease, median number of prior regimens= 4.5. Dose levels were 50 mg (n=3), 100 mg (n=3), 200 mg (n=34) and 350 mg (n=17). Clinical responses were seen at all dose levels. The objective response rate was 9/15 in indolent NHL, 6/7 in mantle cell lymphoma, and 4/17 in CLL, with 14/16 evaluable CLL patients having >50% reduction in lymphadenopathy (mean decrease=75%). Durable responses of >6 months have been reached in 5 patients, with 9/19 responders still on therapy. The dose limiting toxicity was reversible increases in serum transaminases in 21% of patients dosed at 200 mg and 350 mg; 6/8 patients resumed at a lower dose without recurrence of the transaminitis. Hematological toxicity was infrequent. Plasma exposure increased with dose. Phospho-AKT (T308) as a marker of PI3K activation was measured in cells from a subset of CLL patients with circulating lymphocytes and was reduced by >90% following dosing. Accrual is continuing and updated data will be presented. Conclusions: CAL-101, an oral selective PI3K p110δ inhibitor, shows promising activity with acceptable toxicity in patients with relapsed or refractory B-cell malignancies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Calistoga Pharmaceuticals Calistoga Pharmaceuticals Calistoga Pharmaceuticals Calistoga Pharmaceuticals Calistoga Pharmaceuticals
Isolations of a Cartilage Factor That Inhibits Tumor Neovascularization (1976)

A cartilage fraction isolated by guanidine extraction and purified by affinity chromatography inhibits tumor-induced vascular proliferation and consequently restricts tumor growth. This fraction contains several different proteins; the major one has a molecular weight of about 16,000. The fraction strongly inhibits protease activity.
ChemInform Abstract: Synthesis of Novel Azapyridocyanines. (1986)

Abstract Die im Titel genannten Verbindungen (II) werden durch Erhitzen der 2‐Aminopyridine (I) mit Diiodmethan in Acetonitril erhalten.
Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis (2006)

Naturally occurring CD25(+)CD4(+) regulatory T cells (Tregs) actively engage in the maintenance of immunologic self-tolerance and immunoregulation. They specifically express the transcription factor Forkhead box P3 (Foxp3) as a master control molecule for their development and function. Although several cell-surface molecules have been reported as Treg-specific markers, such as CD25, glucocorticoid-induced TNFR family-related gene/protein and CTL-associated molecule-4, they are also expressed on activated T cells derived from CD25(-)CD4(+) naive T cells. To identify Treg-specific molecules controlled by Foxp3, we performed DNA microarray analysis by comparing the following pairs of cell populations: fresh CD25(+)CD4(+) T cells versus fresh CD25(-)CD4(+) T cells, activated CD25(+)CD4(+) T cells versus activated CD25(-)CD4(+) T cells and retrovirally Foxp3-transduced CD25(-)CD4(+) T cells versus mock-transduced CD25(-)CD4(+) T cells. We found that the Gpr83, Ecm1, Cmtm7, Nkg7, Socs2 and glutaredoxin genes are predominantly transcribed in fresh and activated natural Treg as well as in Foxp3-transduced cells, while insulin-like 7, galectin-1, granzyme B and helios genes are natural Treg specific but Foxp3 independent. G protein-coupled receptor 83 (Gpr83) expression on the cell surface of natural Treg was confirmed by staining with Gpr83-specific antibody. Retroviral transduction of either group of genes in CD25(-)CD4(+) T cells failed to confer in vitro suppressive activity. Thus, there are several genes that are expressed in a highly Treg-specific fashion. Some of these genes are controlled by Foxp3, and others are not. These genes, in particular, Gpr83, Ecm1 and Helios, could potentially be used as specific markers for natural Treg.
PI3K-PKB/Akt Pathway (2012)

Protein kinase B (PKB, or Akt) plays a role in cell metabolism, growth, proliferation, and survival. Its activation is controlled by a multi-step process that involves phosphoinositide-3-kinase (PI3K).
Biochemical and Molecular Analysis of Deltamethrin Resistance in the Common Bed Bug (Hemiptera: Cimicidae) (2008)

This study establishes deltamethrin resistance in a common bed bug, Cimex lectularius L., population collected from New York City (NY-BB). The NY-BB population was 264-fold more resistant to 1% deltamethrin in contact bioassay compared with an insecticide-susceptible population collected in Florida (FL-BB). General esterase, glutathione S-transferase, and 7-ethoxycoumarin O-deethylase activities of NY-BB were not statistically different from those of FL-BB. cDNA fragments that encoded the open reading frame of voltage-sensitive sodium channel alpha-subunit genes from the FL-BB and NY-BB populations, respectively, were obtained by homology probing polymerase chain reaction (PCR) and sequenced. Sequence alignment of the internal and 5' and 3' rapid amplification of cDNA ends (RACE) fragments generated a 6500-bp cDNA sequence contig, which was composed of a 6084-bp open reading frame (ORF) encoding 2027 amino acid residues and 186-bp 5' and 230-bp 3' untranslated regions (5' and 3' UTRs, respectively). Sequence comparisons of the open reading frames of the alpha-subunit genes identified two point mutations (V419L and L925I) that were presented only in the NY-BB population. L925I, located the intracellular loop between IIS4 and IIS5, has been previously found in a highly pyrethroid-resistant populations of whitefly (Bemisia tabaci). V419L, located in the IS6 transmembrane segment, is a novel mutation. A Val to Met mutation at the corresponding position of the bed bug V419, however, has been identified in the tobacco budworm as a kdr-type mutation. This evidence suggests that the two mutations are likely the major resistance-causing mutations in the deltamethrin-resistant NY-BB through a knockdown-type nerve insensitivity mechanism.
Analysis of the cathodic region of atmospheric pressure discharges (2002)

The cathodic region of atmospheric pressure arcs is dominated by a number of different mechanisms. This makes a theoretical model extremely difficult. A description of this region based on fundamental physical principles is given. Using a previously published model of the inhomogeneous boundary layer of a Saha plasma (Schmitz H and Riemann K-U 2001 J. Phys. D: Appl. Phys. 34 1193), the description is set on a firm theoretical basis. A number of equations including the energy balances of plasma boundary and cathode body lead to a maximum closure of the system. The values for the boundary conditions toward the plasma column could be motivated by a simple minimum principle argument thus eliminating all arbitrary fitting parameters. Results are given for a variety of external parameters and three different discharge gases. The comparison with experimental results shows excellent agreement.
Unexpected asymmetric epoxidation reactions catalysed by polyleucine-based systems (1996)

W. Kroutil, P. Mayon, M. E. Lasterra-Sánchez, S. J. Maddrell, S. M. Roberts, S. R. Thornton, C. J. Todd and M. Tüter, Chem. Commun., 1996, 845 DOI: 10.1039/CC9960000845
Development of a Radiochemical Cyclooxygenase-1 and -2 in Vitro Assay for Identification of Natural Products as Inhibitors of Prostaglandin Biosynthesis (1998)

A radiochemical enzyme assay for studying cyclooxygenase (COX)-catalyzed prostaglandin biosynthesis in vitro was optimized with respect to both COX-1 and COX-2 activity. The assay can be used to assess the relative selectivity of plant-derived inhibitors on COX-1 and COX-2 Assay conditions were optimized for both enzymes with respect to concentration of cofactors (l-epinephrine, reduced glutathione, and hematin), activation time (enzyme and cofactors), reaction time, and pH. Moreover, the kinetic parameters, Km and Kcat, of both enzymes were estimated. Five COX inhibitors were used to validate the assay, indomethacin, aspirin, naproxen, ibuprofen, and the arylsulfonamide NS-398, all with different COX selectivity and time dependency. Time-dependent inhibition was determined by comparing the inhibition, with and without preincubation of enzyme and inhibitor. Two flavonoids, (+)-catechin and quercitrin, were examined with respect to inhibition of COX-catalyzed prostaglandin biosynthesis. (+)-Catechin showed equal inhibitory effects on the two enzymes. Quercitrin was found to be inactive toward both COX-1- and COX-2-catalyzed prostaglandin biosynthesis. The optimization procedure resulted in a considerable reduction of the amount of enzyme required for adequate prostglandin biosynthesis and a reliable method suited to evaluate natural products on inhibition of COX-2-catalyzed prostaglandin biosynthesis, as well as on COX-1.
Acute Respiratory Infections Among Infants and Children in Japan (1986)

To simplify the procedure of virus isolation, a new microplate method has been attempted. Four kinds of cell, i.e. human embryonic fibroblast (HEF), Hep-2, Vero, MDCK were prepared together in a tissue culture microplate. 657 viruses recovered from throat swabs obtained from 2, 310 infants and children with acute respiratory infections (ARI) tested between December, 1984 and December, 1985. The isolates were influenza viruses, RS virus, parainfluenza viruses, mumps virus, adenoviruses, enteroviruses, herpes simplex virus and cytomegalovirus. Influenza and parainfluenza viruses were isolated by adding trypsin to a medium. The new microplate method is more sensitive to virus isolation, simpler to handle, cheaper economically and more convenient than ordinary tube method for the isolation of viruses from syndrome due to multiple agents such as ARI.
Determination of 25-hydroxyvitamin D3 in human serum by fluorescence labelling and high-performance liquid chromatography (1991)

A method is described for the determination of 25-hydroxyvitamin D3 in human blood serum. The problems of sensitivity and selectivity encountered with previous techniques were avoided by the formation of a highly fluorescent Diels-Alder adduct following solid-phase extraction of the vitamin. After excess of reagent had been eliminated, quantification was achieved by high-performance liquid chromatography. The recovery of the vitamin from serum was 76.4 +/- 1.76%. The precision of the method was determined, and the relative standard deviations were 8.38% at a concentration of 47.0 x 10(-9) mol dm-3, 6.74% at a concentration of 99.8 x 10(-9) mol dm-3 and 3.79% at a concentration of 146.8 x 10(-9) mol dm-3. The detection limit for the adduct was 2.93 x 10(-14) mol injected, for a signal-to-noise ratio of 3:1, and serum concentrations of 0.25 x 10(-9) mol dm-3 could easily be quantified. No interference from endogenous or exogenous substances was observed.
Adenosine deaminase (ADA) deficiency due to deletion of the ADA gene promoter and first exon by homologous recombination between two Alu elements. (1988)

In 15-20% of children with severe combined immunodeficiency (SCID), the underlying defect is adenosine deaminase (ADA) deficiency. The goal of this study was to determine the precise molecular defect in a patient with ADA-deficient SCID whom we previously have shown to have a total absence of ADA mRNA and a structural alteration of the ADA gene. By detailed Southern analysis, we now have determined that the structural alteration is a deletion of approximately 3.3 kb, which included exon 1 and the promoter region of the ADA gene. DNA sequence analysis demonstrates that the deletion created a novel, complete Alu repeat by homologous recombination between two existing Alu repeats that flanked the deletion. The 26-bp recombination joint in the Alu sequence includes the 10-bp "B" sequence homologous to the RNA polymerase III promoter. This is the first example of homologous recombination involving the B sequence in Alu repeats. Similar recombination events have been identified involving Alu repeats in which the recombination joint was located between the A and B sequences of the polymerase III split promoter. The nonrandom location of these events suggests that these segments may be hot spots for recombination.
Characterization of moenomycin antibiotics from medicated chicken feed by ion‐trap mass spectrometry with electrospray ionization (2005)

The antimicrobial moenomycin, commonly used as a growth promoter in livestock, was isolated from medicated chicken feed. The purified extract was subjected to reversed-phase liquid chromatographic separation followed by structural characterization using ion-trap mass spectrometry (ITMS), which allowed identification of five moenomycins (A, A12, C1, C3, and C4) as the major components. The fragmentation patterns of the protonated and deprotonated moenomycin molecules, as well as of a series of sodium adducts, were investigated using ITMS after electrospray ionization. While the protonated molecules [M+H]+ proved highly unstable and underwent extensive in-source fragmentation, isolation and activation of the [M--H]- ions (m/z 1580 for moenomycin-A) yielded simple mass spectra with a dominant base peak corresponding to the loss of the carboxy-glycol and the C25-hydrocarbon chain (m/z 1152 for moenomycin-A). Further study of this fragment ion in an MS3 experiment gave rise to a peculiar product ion (m/z 902 for moenomycin-A) that was attributed to the expulsion of a carbohydrate moiety representing a central building block of the linear molecule. In positive ion mode the generation of the mono-sodiated adduct ions, [M+Na]+, was promoted by amending the mobile phase with 100 microM sodium acetate, but this also resulted in higher adducts of the type [M+2Na--H]+ and [M+3Na--2H]+ arising from the formation of the sodium salts of the phosphate acid diester and subsequently of the carboxylic acid. Substantial differences among the fragment-rich product ion profiles of the three species were observed, and could in part be traced back to the mode of complexation of the additional sodium cation(s).
Comparison of the X‐ray structure of native rubredoxin from pyrococcus furiosus with the NMR structure of the zinc‐substituted protein (1992)

The three-dimensional X-ray structures of the oxidized and reduced forms of rubredoxin from Pyrococcus furiosus, determined at -161 degrees C, and the NMR structure of the zinc-substituted protein, determined in solution at 45 degrees C, are compared. The NMR and X-ray structures, which were determined independently, are very similar and lead to similar conclusions regarding the interactions that confer hyperthermostability.