gebhart/patrepeval huggingface dataset:
Gaseous-fuel nuclear reactor research for multimegawatt power in space (1977)

In the gaseous-fuel reactor concept, the fissile material is contained in a moderator-reflector cavity and exists in the form of a flowing gas or plasma separated from the cavity walls by means of fluid mechanical forces. Temperatures in excess of structural limitations are possible for low-specific-mass power and high-specific-impulse propulsion in space. Experiments have been conducted with a canister filled with enriched UF6 inserted into a beryllium-reflected cavity. A theoretically predicted critical mass of 6 kg was measured. The UF6 was also circulated through this cavity, demonstrating stable reactor operation with the fuel in motion. Because the flowing gaseous fuel can be continuously processed, the radioactive waste in this type of reactor can be kept small. Another potential of fissioning gases is the possibility of converting the kinetic energy of fission fragments directly into coherent electromagnetic radiation, the nuclear pumping of lasers. Numerous nuclear laser experiments indicate the possibility of transmitting power in space directly from fission energy. The estimated specific mass of a multimegawatt gaseous-fuel reactor power system is from 1 to 5 kg/kW while the companion laser-power receiver station would be much lower in specific mass.
A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor–Resistant Lung Tumors (2016)

Non-small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor-binding antibodies. In NSCLC tumor models driven by EGFR and/or cMet, JNJ-61186372 treatment resulted in tumor regression through inhibition of signaling/receptor downmodulation and Fc-driven effector interactions. Complete and durable regression of human lung xenograft tumors was observed with the combination of JNJ-61186372 and a third-generation EGFR TKI. Interestingly, treatment of cynomolgus monkeys with JNJ-61186372 resulted in no major toxicities, including absence of skin rash observed with other EGFR-directed agents. These results highlight the differentiated potential of JNJ-61186372 to inhibit the spectrum of mutations driving EGFR TKI resistance in NSCLC. Cancer Res; 76(13); 3942-53. ©2016 AACR.
Age‐associated chromosome 21 loss in Down syndrome: Possible relevance to mosaicism and Alzheimer disease (1993)

We previously observed low level mosaicism (2-4% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population.
On Modelling and Estimation of Curl and Twist in Multi-Ply Paperboard (2002)

This thesis describes a grey-box model for the dimensionalstability properties (i.e. curl and twist) of the carton boardproduced at AssiDomän Frövi paper mill in Sweden.AssiDomän Frövi AB is one of Sweden major cartonboard manufacturer, and produces some 350000 ton of board peryear. Curl is defined as the departure from a at form, and it mayseriously affect the processing of the paper. For this reason,customers impose quite restrictive limits on the allowedcurvatures of the board. So, it is becoming more and moreimportant to be able to produce a carton board with a curlwithin certain limits. Due to the economic significance of thecurl problem, much research has been performed to find sheetdesign and processing strategies to eliminate or reducecurl. The approach we used to tackle this problem is based ongrey-box modelling. The reasons for such an approach is thatthe physical process is very complex and nonlinear. The inuenceof some inputs is not entirely understood, and besides itdepends on a number of unknown parameters andunmodelled/unmesurable disturbances. One of the main part of the model is based on classicallaminate theory which is used to model the dimensionalstability of multi-ply board. The main assumption is that eachlayer is considered as an homogeneous elastic medium. The model is then complemented with a sub-model forunmodelled/umeasurable disturbances which are described asstates of a dynamical system, and estimated by means of anextended Kalman filter. The simulated curvatures show a general agreement with themeasurements. However, the prediction errors are too large forthe model to be used in an effective way, and a bigger efforthas to be carried out in order to improve the physicalsub-models. A chapter of this thesis discusses the modelling of thewet-end part of the paper machine with Dymola, a modelling toolfor simulation of large systems based on Modelica language.
Vectors for the expression of PCR-amplified immunoglobulin variable domains with human constant regions (1993)

Cassette vectors have been constructed for mammalian expression of complete immunoglobulin heavy and light chain genes whose variable regions are produced by the polymerase chain reaction (PCR). The light and heavy chain vectors have promoter, leader, partial intron, enhancer and constant region segments within modified pSV2-gpt and pSV2-neo plasmids, respectively. Variable (V) regions are obtained by PCR using a two step process: 1) the V gene is amplified from genomic or cDNA, cloned into an intermediate vector and sequenced; 2) the first PCR product serves as the template for a second amplification in which restriction enzyme recognition sites and limited flanking intron sequence are added. The second PCR product is inserted into the expression vector, which is then transfected into mouse myeloma cells. These vectors contain human constant regions and may be used to express chimeric, humanized or human Ig genes. This report describes the design of these vectors and their application for the expression of chimeric 60.3, an anti-CD18 antibody.
Pyrene-functionalized oligonucleotides and locked nucleic acids (LNAs): Tools for fundamental research, diagnostics, and nanotechnology (2011)

Pyrene-functionalized oligonucleotides (PFOs) are increasingly explored as tools in fundamental research, diagnostics and nanotechnology. Their popularity is linked to the ability of pyrenes to function as polarity-sensitive and quenchable fluorophores, excimer-generating units, aromatic stacking moieties and nucleic acid duplex intercalators. These characteristics have enabled development of PFOs for detection of complementary DNA/RNA targets, discrimination of single nucleotide polymorphisms (SNPs), and generation of π-arrays on nucleic acid scaffolds. This critical review will highlight the physical properties and applications of PFOs that are likely to provide high degree of positional control of the chromophore in nucleic acid complexes. Particular emphasis will be placed on pyrene-functionalized Locked Nucleic Acids (LNAs) since these materials display interesting properties such as fluorescence quantum yields approaching unity and recognition of mixed-sequence double stranded DNA (144 references).
Transcriptional activation potential of normal and tumor-associated myb isoforms does not correlate with their ability to block GCSF-induced terminal differentiation of murine myeloid precursor cells. (1996)

The myb gene has been shown to be an important regulator of hematopoietic cell proliferation, differentiation and apoptosis. Activation of the myb gene into an oncogenic form has involved structural alterations to the coding sequences. Thus, the v-myb gene encoded by the Avian Myeloblastosis Virus, is truncated at both the 5' and 3' ends. Additionally, tumor cells containing rearrangements in the myb locus, such as the ABPL tumors or NFS60 tumor cell line have recently been shown to display a heterogeneity of structure. In this study, we examined the growth and differentiation properties of clonal cell lines derived from 32Dcl3 which harbor myb transgenes; derived from v-myb, and the ABPL-1, ABPL-2, ABPL-4 and NFS-60 cell lines. Retroviral vectors containing the appropriate myb cDNAs were produced, transfected into packaging cell lines, and the viruses were used to generate the 32D derivative cell clones. Abrogation of IL-3 dependence was never observed in any cell line. Expression of c-myb, ABPL-1-myb and ABPL-2-myb isoforms in 32D cells resulted in a block to their ability to terminally differentiate into granulocytes at the pro-myelocytic stage. However, expression of ABPL-4-myb or NFS60-myb in these cells failed to result in a similar effect. These cells differentiated into granulocytes in the presence of G-CSF, albeit more slowly than control 32Dcl3 cells. We also examined the ability of various Myb-isoforms to transactivate transcription of reporter genes containing Myb-binding elements in their promoter/enhancer sequences, to determine whether the phenotypic effects produced by these various isoforms correlate with their ability to transactivate transcription. Our results show that while v-myb and c-myb transactivated transcription equally well, the NFS60-myb exhibited the highest levels of transcriptional transactivation. The ABPL-1, ABPL-2 and ABPL-4-myb isoforms showed very low levels of transcriptional transactivation potential with the same reporter genes. These results suggest that the ability of various Myb-isoforms to transactivate transcription does not by itself correlate with their ability to induce a block to G-CSF-induced terminal differentiation of myeloid precursor cells.
The Acute Respiratory Distress Syndrome (1996)

Acute respiratory distress syndrome (ARDS) continues to be a major cause of morbidity and mortality in critically ill patients. In this issue of the Journal, Anzueto et al.1 report the results of a large, multicenter, randomized trial that was carried out to evaluate the potential benefit of aerosolized surfactant therapy in patients with ARDS. Disappointingly, there was no benefit. It is important to analyze the results of this trial carefully, so that the possibility of success in future trials can be maximized.Although the cellular and molecular mechanisms that cause injury to the lung may not be the same in . . .
Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase. (1992)

Superoxide dismutase enzymes protect aerobic organisms from oxygen-mediated free-radical damage. Crystallographic structures of recombinant human Cu,Zn superoxide dismutase have been determined, refined, and analyzed at 2.5 A resolution for wild-type and a designed thermostable double-mutant enzyme (Cys-6----Ala, Cys-111----Ser). The 10 subunits (five dimers) in the crystallographic asymmetric unit form an unusual stable open lattice with 80-A-diameter channels. The 10 independently fit and refined subunits provide high accuracy, error analysis, and insights on loop conformations. There is a helix dipole interaction with the Zn site, and 14 residues form two or more structurally conserved side-chain to main-chain hydrogen bonds that appear critical to active-site architecture, loop conformation, and the increased stability resulting from the Cys-111----Ser mutation.
Scopoletin is biosynthesized viaortho‐hydroxylation of feruloyl CoA by a 2‐oxoglutarate‐dependent dioxygenase inArabidopsis thaliana (2008)

Coumarins are derived via the phenylpropanoid pathway in plants. The 2H-1-benzopyran-2-one core structure of coumarins is formed via the ortho-hydroxylation of cinnamates, trans/cis isomerization of the side chain, and lactonization. Ortho-hydroxylation is a key step in coumarin biosynthesis as a branch point from lignin biosynthesis; however, ortho-hydroxylation of cinnamates is not yet fully understood. In this study, scopoletin biosynthesis was explored using Arabidopsis thaliana, which accumulates scopoletin and its beta-glucopyranoside scopolin in its roots. T-DNA insertion mutants of caffeoyl CoA O-methyltransferase 1 (CCoAOMT1) showed significant reduction in scopoletin and scopolin levels in the roots, and recombinant CCoAOMT1 exhibited 3'-O-methyltransferase activity on caffeoyl CoA to feruloyl CoA. These results suggest that feruloyl CoA is a key precursor in scopoletin biosynthesis. Ortho-hydroxylases of cinnamates were explored in the oxygenase families in A. thaliana, and one of the candidate genes in the Fe(II)- and 2-oxoglutarate-dependent dioxygenase (2OGD) family was designated as F6'H1. T-DNA insertion mutants of F6'H1 showed severe reductions in scopoletin and scopolin levels in the roots. The pattern of F6'H1 expression is consistent with the patterns of scopoletin and scopolin accumulation. The recombinant F6'H1 protein exhibited ortho-hydroxylase activity for feruloyl CoA (K(m) = 36.0 +/- 4.27 microM; k(cat) = 11.0 +/- 0.45 sec(-1)) to form 6'-hydroxyferuloyl CoA, but did not hydroxylate ferulic acid. These results indicate that Fe(II)- and 2-oxoglutarate-dependent dioxygenase is the pivotal enzyme in the ortho-hydroxylation of feruloyl CoA in scopoletin biosynthesis.
Chromatographic resolution and immunologic identification of the alpha 40 and alpha 41 subunits of guanine nucleotide-binding regulatory proteins from bovine brain. (1988)

A guanine nucleotide-binding regulatory protein (G protein), with subunits designated as alpha 40 beta gamma, was identified and partially resolved from two other purified G proteins, Go (alpha 39 beta gamma) and Gi (alpha 41 beta gamma), found in bovine brain. The alpha 40 G protein subunit served as a substrate for ADP-ribosylation catalyzed by Bordetella pertussis toxin, as did alpha 39 and alpha 41. alpha 40 was shown to be closely related to, but distinct from, alpha 41 by reaction with various peptide antisera. An antiserum generated against a peptide derived from the sequence of a Gi alpha clone isolated from a rat C6 glioma cDNA library (Itoh, H., Kozasa, T., Nagata, S., Nakamura, S., Katada, T., Ui, M., Iwai, S., Ohtsuka, E., Kawasaki, H., Suzuki, K., and Kaziro, Y. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 3776-3780) reacted with alpha 40 to the exclusion of all other alpha subunits tested. Another antiserum generated against a peptide derived from an analogous region of a different Gi alpha clone from a bovine brain cDNA library (Nukuda, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H., and Numa, S. (1986) FEBS Lett. 197, 305-310) reacted exclusively with alpha 41. Evidence is given for the existence of another form of alpha 41 that did not react with either of these two peptide antisera. The antisera were used to survey various rat tissues for the expression of alpha 40 and alpha 41.
Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus (2003)

Systemic lupus erythematosus (SLE) is a complex, inflammatory autoimmune disease that affects multiple organ systems. We used global gene expression profiling of peripheral blood mononuclear cells to identify distinct patterns of gene expression that distinguish most SLE patients from healthy controls. Strikingly, about half of the patients studied showed dysregulated expression of genes in the IFN pathway. Furthermore, this IFN gene expression "signature" served as a marker for more severe disease involving the kidneys, hematopoetic cells, and/or the central nervous system. These results provide insights into the genetic pathways underlying SLE, and identify a subgroup of patients who may benefit from therapies targeting the IFN pathway.
[Diagnosis of blackleg by direct immunofluorescence in bovine bone marrow]. (1994)

On smears of marrow-bone death bovines, presumptively diagnostic of black-leg, we have carried out the direct immunofluorescence test (IF). We used two labelled immunosera with fluorescein isothiocyanate. The immunosera wer prepared with the reference strain 5078 of Clostridium chauvoei as following: a) a cellular extract obtained with veronal buffer 0.045 M pH = 8.6, and b) a flagellar suspension obtained by agitation with glass beads, centrifuged at 3,500 x g, and centrifuged again at 16,000 x g during 20 min at 4 degrees C. Both antigenic preparations were injected into rabbits, five doses (0.2, 0.4, 0.8, 1.6 and 3.2 ml) each by i.v. route. Control positive strain of C. chauvoei were used, and control negative strains of C. septicum and C. perfringens were used too. Of all 56 examined samples, 26 (47.5%) gave positive IF test. These results had a 100% of correlation by culture and biochemical identification.
Protein kinase inhibitors: contributions from structure to clinical compounds (2009)

Protein kinases catalyse key phosphorylation reactions in signalling cascades that affect every aspect of cell growth, differentiation and metabolism. The kinases have become prime targets for drug intervention in the diseased state, especially in cancer. There are currently 10 drugs that have been approved for clinical use and many more in clinical trials. This review summarises the structural basis for protein kinase inhibition and discusses the mode of action for each of the approved drugs in the light of structural results. All but one of the approved compounds target the ATP binding site on the kinase. Both the active and inactive conformations of protein kinases have been used in strategies to produce potent and selective compounds. Targeting the inactive conformation can give high specificity. Targeting the active conformation is favourable where the diseased state has arisen from activating mutations, but such inhibitors generally target several protein kinases. Drug resistance mutations are a potential risk for both conformational states, where drug-binding regions are not directly involved in catalysis. Imatinib (Glivec), the most successful of protein kinase inhibitors, targets the inactive conformation of ABL tyrosine kinase. Newer compounds, such as dasatinib, which targets the ABL active state, have been developed to increase potency and have proved effective for some, but not all, drug-resistant mutations. The first epidermal growth factor receptor (EGFR) inhibitors in clinical use [gefitinib (Iressa) and erlotinib (Tarceva)] targeted the active form of the kinase, and this proved advantageous for patients whose cancer was caused by mutations that resulted in a constitutively active EGFR kinase domain. Newer approved compounds, such as lapatinib (Tykerb), target the inactive conformation with high potency. A further compound that forms a covalent attachment to the kinase has been found to overcome one of the major drug resistance mutations, where the effectiveness of the drug in vivo is dependent on its ability to compete successfully in the presence of cellular concentrations of ATP. Inhibitors of vascular endothelial growth factor receptor (VEGFR) kinase against cancer angiogenesis show the advantage of some relaxation in specificity. Sorafenib, originally developed as RAF inhibitor, is now in clinical use as a VEGFR inhibitor. Temsirolimus (a derivative of rapamycin) is the only example of a drug in clinical use that does not target the kinase ATP site. Instead rapamycin, when in complex with the protein FKBP12, effectively targets mTOR kinase at a site located on a domain, the FRB domain, that appears to be involved in localisation or substrate docking.
Population genetics of polymorphism and divergence. (1992)

Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and Drosophila yakuba. Assuming a synonymous mutation rate of 1.5 x 10(-8) per site per year and 10 generations per year, we obtain estimates for the effective population size (N(e) = 6.5 x 10(6)), the species divergence time (tdiv = 3.74 million years), and an average selection coefficient (sigma = 1.53 x 10(-6) per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2-23 at any one time. The approach provides a theoretical basis for the use of a 2 x 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements.
Periacetabular Osteotomy for the Treatment of Severe Acetabular Dysplasia (2005)

The periacetabular osteotomy is an effective technique for surgical correction of a severely dysplastic acetabulum in adolescents and young adults. In this series, the early clinical results were very good at an average of 4.2 years postoperatively; the two major complications did not compromise the good clinical results.
Electron‐rich 2‐Pyridones, III: Stereochemistry and Reactivity of Phenylsulfonyl‐ substituted 2‐Azabicyclo[2.2.2]octan‐6‐ones (1990)

Abstract [4+2]cycloaddition of electron‐rich 5‐benzyloxy‐2‐pyridone ( 1 ) with phenylvinyl sulfone furnished, after functional group transformation, 2 in a syn/anti ratio of 3/7. Deprotonation with LDA provided the thermodynamic stable 2a . The α‐sulfonyl carbanion can be alkylated to 4 . During reductive desulfonylation complete epimerisation to 5 occured. Synthesis of 5b was also accomplished by conjugate addition of ethylphenylsulfonyl carbanion to 11 .
Dressed for success: Realizing the catalytic potential of RNA (1998)

In this manuscript the catalytic ability of RNA is examined and compared to other biopolymers. Despite having considerably fewer catalytically enabling properties when compared to proteins, the power of in vitro selection has allowed for RNA and DNA catalysts to be isolated. RNA catalysis has been expanded by incorporating modified bases to enrich the structural and functional diversity of RNA. Successful examples of new RNA chemistry using base modifications include carbon–carbon bond forming reactions and creation of highly specific active sites that are capable of recognizing small organic molecules without the need for nucleic acid templating or intercalation. In fact, the scope of functional modifications available for use in the RNA platform may eventually surpass those that are found in proteins and there are already hints that well chosen modifications allow nucleic acid catalysts to take advantage of mechanisms not available to selected protein catalysts for similar reactions. The chemical versatility of RNA is just emerging and future research directions will likely entail more creative methods for functional modification that will lead to new catalysts. © 1998 John Wiley & Sons, Inc. Biopoly 48: 29–37, 1998