gebhart/patrepeval huggingface dataset:
Utilization of Electrically Reduced Neutral Red by Actinobacillus succinogenes : Physiological Function of Neutral Red in Membrane-Driven Fumarate Reduction and Energy Conservation (1999)

Neutral red (NR) functioned as an electronophore or electron channel enabling either cells or membranes purified from Actinobacillus succinogenes to drive electron transfer and proton translocation by coupling fumarate reduction to succinate production. Electrically reduced NR, unlike methyl or benzyl viologen, bound to cell membranes, was not toxic, and chemically reduced NAD. The cell membrane of A. succinogenes contained high levels of benzyl viologen-linked hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U) activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not. Proton translocation by whole cells was dependent on either electrically reduced NR or H2 as the electron donor and on the fumarate concentration. During the growth of Actinobacillus on glucose plus electrically reduced NR in an electrochemical bioreactor system versus on glucose alone, electrically reduced NR enhanced glucose consumption, growth, and succinate production by about 20% while it decreased acetate production by about 50%. The rate of fumarate reduction to succinate by purified membranes was twofold higher with electrically reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)-4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited succinate production from H2 plus fumarate but not from electrically reduced NR plus fumarate. Thus, NR appears to replace the function of menaquinone in the fumarate reductase complex, and it enables A. succinogenes to utilize electricity as a significant source of metabolic reducing power.
Linked oligodeoxynucleotides show binding cooperativity and can selectively impair replication of deleted mitochondrial DNA templates (2001)

Mutations in mitochondrial DNA (mtDNA) cause a spectrum of human pathologies, which predominantly affect skeletal muscle and the central nervous system. In patients, mutated and wild-type mtDNAs often co-exist in the same cell (mtDNA heteroplasmy). In the absence of pharmacological therapy, a genetic strategy for treatment has been proposed whereby replication of mutated mtDNA is inhibited by selective hybridisation of a nucleic acid derivative to the single-stranded replication intermediate, allowing propagation of the wild-type genome and correction of the associated respiratory chain defect. Previous studies have shown the efficacy of this anti-genomic approach in vitro, targeting pathogenic mtDNA templates with only a single point mutation. Pathogenic molecules harbouring deletions, however, present a more difficult problem. Deletions often occur at the site of two short repeat sequences (4-13 residues), only one of which is retained in the deleted molecule. With the more common larger repeats it is therefore difficult to design an anti-genomic molecule that will bind selectively across the breakpoint of the deleted mtDNA. To address this problem, we have used linker-substituted oligodeoxynucleotides to bridge the repeated residues. We show that molecules can be designed to bind more tightly to the deleted as compared to the wild-type mtDNA template, consistent with the nucleotide sequence on either side of the linker co-operating to increase binding affinity. Furthermore, these bridging molecules are capable of sequence-dependent partial inhibition of replication in vitro.
Literatuur leren lezen door vragen stellen: effect op verhaalwaardering (2007)

In deze bijdrage doen de auteurs verslag van een onderzoek naar het effect van vragen stellen door leerlingen op hun waardering van complexe, literaire verhalen. Twee onderwijsexperimenten zijn uitgevoerd. In Experiment 1 vergeleken de auteurs zelf genereren van vragen met niet zelf genereren (tekst-met-vragen). In Experiment 2 werden twee varianten vergeleken: vragen genereren zonder sturing versus met sturing door middel van vraagvoorbeelden. De resultaten laten zien dat het genereren van vragen door leerlingen een positief effect heeft op hun verhaalwaardering. De resultaten zijn positiever naarmate leerlingen meer vrijheid wordt geboden om eigen vragen te stellen.
Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit exceptional breadth and picomolar potency against HIV-1 (2013)

In the absence of an effective HIV-1 vaccine, passive immunization using broadly neutralizing Abs or Ab-like molecules could provide an alternative to the daily administration of oral antiretroviral agents that has recently shown promise as preexposure prophylaxis. Currently, no single broadly neutralizing Ab (bNAb) or combination of bNAbs neutralizes all HIV-1 strains at practically achievable concentrations in vivo. To address this problem, we created bispecific Abs that combine the HIV-1 inhibitory activity of ibalizumab (iMab), a humanized mAb directed to domain 2 of human CD4, with that of anti-gp120 bNAbs. These bispecific bNAbs (BibNAbs) exploit iMab's potent anti-HIV-1 activity and demonstrated clinical efficacy and safety to anchor and thereby concentrate a second broadly neutralizing agent at the site of viral entry. Two BibNabs, PG9-iMab and PG16-iMab, exhibit exceptional breadth and potency, neutralizing 100% of the 118 viruses tested at low picomolar concentrations, including viruses resistant to both parental mAbs. The enhanced potency of these BibNAbs was entirely dependent on CD4 anchoring, not on membrane anchoring per se, and required optimal Ab geometry and linker length. We propose that iMab-based BibNAbs, such as PG9-iMab and PG16-iMab, are promising candidates for passive immunization to prevent HIV-1 infection.
Extracellular Stimulation in Tissue Engineering (2005)

The field of tissue engineering has created a need for biomaterials that are capable of providing biofunctional and structural support for living cells outside of the body. Most of the commonly used biomaterials in tissue engineering are designed based on their physicochemical properties, thus achieving precise control over mechanical strength, compliance, porosity, and degradation kinetics. Biofunctional signals are added to the scaffold by tethering, immobilizing, or supplementing biofunctional macromolecules, such as growth factors, directly to the scaffold material. The challenge in tissue engineering remains to find the correct balance between the biofunctional and the physical properties of the scaffold material for each application. Moreover, the ability to modulate communication between cells and the extracellular environment using the engineered scaffold as the actuator can provide a significant advantage in tissue engineering. In this study, a unique scaffold material is presented. The material interchangeably combines biofunctional and structural molecules by fusing the two into a single backbone macromolecule. This integration provides the basis for practical, effective, and high-resolution control of both the biofunctional and the physical properties of the scaffold material. This new scaffold material has proven effective with smooth muscle, cardiac, cartilage, and human embryonic stem cell cultures. The advantages of this approach as well as the potential applications of this unique scaffold material are discussed.
Singlemode optical waveguides using a high temperaturestable poylmer with low losses in the 1.55 µm range (1997)

Singlemode polymer waveguides are fabricated using a novel high temperature stable fluorinated polymer. Waveguide losses of &lt;0.25 dB/cm were achieved both at 1300 nm as well as in the entire range from 1515 to 1565 nm.
Molecular design at the calamitic/discotic cross-over point. Mononuclear ortho-metallated mesogens based on the combination of rod-like phenylpyrimidines and -pyridines with bent or half-disc-shaped diketonatesElectronic supplementary information (ESI) available: procedures and analytical data for all compounds not described in the Experimental. See http://www.rsc.org/suppdata/jm/b2/b210250a/ (2003)

Six novel series of mononuclear ortho-palladated and ortho-platinated metallomesogens have been obtained by combination of rod-like heteroaromatic liquid crystals with bent or half-disc-shaped 1,3-diketonate units. The synthesis of these molecules was achieved by ortho-metallation of rod-like 2-phenylpyrimidines and 2-phenylpyridines, with formation of the corresponding chloro-bridged dinuclear metallomesogens. Ligand exchange with alkoxy-substituted thallium 1,3-diphenyl-1,3-diketonates led to the desired mononuclear metallomesogens, incorporating a rod-like ortho-metallated heteroaromatic core and bent or half-disc-shaped 1,3-diketonate ligands. The liquid crystalline properties of these molecules were investigated using polarized light optical microscopy, differential scanning calorimetry and X-ray scattering. By increasing the number of alkyl chains attached to the 1,3-diketonate units, a transition from lamellar (SmA, SmC) and nematic to two distinct types of hexagonal columnar phases (Colh) was found, but no cubic phase could be detected. In the Colh phases, depending on the number of attached chains, either only one or two molecules are organized side-by-side within the columns. However, apart from the number of alkyl chains, their distribution on the 1,3-diketonate units is of importance to the mesophase behavior. Elongation of the calamitic subunit (2,5-diphenylpyrimidines) stabilizes smectic phases and Colh phases having two molecules in their cross-section (edge-to-edge dimers). The ortho-metallated 2-phenylpyridine unit has, for the first time, been introduced into metallomesogens. However, ortho-palladated and ortho-platinated 2-phenylpyridines are either non-mesogenic or have significantly lower mesophase stabilities than the corresponding pyrimidine derivatives. Replacement of palladium by platinum does not significantly influence the mesophase type, but it can have a mesophase-stabilizing effect, due to stronger d8–d8 closed-shell interactions between the Pt atoms.
Nonnegative Matrix Factorization Based on Alternating Nonnegativity Constrained Least Squares and Active Set Method (2008)

Nonnegative matrix factorization (NMF) determines a lower rank approximation of a matrix $A \in \mathbb{R}^{m \times n} \approx WH$ where an integer $k \ll \min(m,n)$ is given and nonnegativity is imposed on all components of the factors $W \in \mathbb{R}^{m \times k}$ and $H \in \mathbb{R}^{k \times n}$. NMF has attracted much attention for over a decade and has been successfully applied to numerous data analysis problems. In applications where the components of the data are necessarily nonnegative, such as chemical concentrations in experimental results or pixels in digital images, NMF provides a more relevant interpretation of the results since it gives nonsubtractive combinations of nonnegative basis vectors. In this paper, we introduce an algorithm for NMF based on alternating nonnegativity constrained least squares (NMF/ANLS) and the active set–based fast algorithm for nonnegativity constrained least squares with multiple right-hand side vectors, and we discuss its convergence properties and a rigorous convergence criterion based on the Karush–Kuhn–Tucker (KKT) conditions. In addition, we also describe algorithms for sparse NMFs and regularized NMF. We show how we impose a sparsity constraint on one of the factors by $L_1$-norm minimization and discuss its convergence properties. Our algorithms are compared to other commonly used NMF algorithms in the literature on several test data sets in terms of their convergence behavior.
Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe (2004)

The genetic polymorphism of Borrelia burgdorferi and Borrelia afzelii, two species that cause Lyme borreliosis, was estimated by sequence typing of four loci: the rrs-rrlA intergenic spacer (IGS) and the outer-membrane-protein gene p66 on the chromosome, and the outer-membrane-protein genes ospA and ospC on plasmids. The major sources of DNA for PCR amplification and sequencing were samples of the B. burgdorferi tick vector Ixodes scapularis, collected at a field site in an endemic region of the north-eastern United States, and the B. afzelii vector Ixodes ricinus, collected at a similar site in southern Sweden. The sequences were compared with those of reference strains and skin biopsy isolates, as well as database sequences. For B. burgdorferi, 10-13 alleles for each of the 4 loci, and a total of 9 distinct clonal lineages with linkage of all 4 loci, were found. For B. afzelii, 2 loci, ospC and IGS, were examined, and 11 IGS genotypes, 12 ospC alleles, and a total of 9 linkage groups were identified. The genetic variants of B. burgdorferi and B. afzelii among samples from the field sites accounted for the greater part of the genetic diversity previously reported from larger areas of the north-eastern United States and central and northern Europe. Although ospC alleles of both species had higher nucleotide diversity than other loci, the ospC locus showed evidence of intragenic recombination and was unsuitable for phylogenetic inference. In contrast, there was no detectable recombination at the IGS locus of B. burgdorferi. Moreover, beyond the signature nucleotides that specified 10 IGS genotypes, there were additional nucleotide polymorphisms that defined a total of 24 subtypes. Maximum-likelihood and parsimony cladograms of B. burgdorferi aligned IGS sequences revealed the subtype sequences to be terminal branches of clades, and the existence of at least three monophyletic lineages within B. burgdorferi. It is concluded that B. burgdorferi and B. afzelii have greater genetic diversity than had previously been estimated, and that the IGS locus alone is sufficient for strain typing and phylogenetic studies.
A First Course in Turbulence (1972)

This is the first book specifically designed to offer the student a smooth transitionary course between elementary fluid dynamics (which gives only last-minute attention to turbulence) and the professional literature on turbulent flow, where an advanced viewpoint is assumed.The subject of turbulence, the most forbidding in fluid dynamics, has usually proved treacherous to the beginner, caught in the whirls and eddies of its nonlinearities and statistical imponderables. This is the first book specifically designed to offer the student a smooth transitionary course between elementary fluid dynamics (which gives only last-minute attention to turbulence) and the professional literature on turbulent flow, where an advanced viewpoint is assumed. Moreover, the text has been developed for students, engineers, and scientists with different technical backgrounds and interests. Almost all flows, natural and man-made, are turbulent. Thus the subject is the concern of geophysical and environmental scientists (in dealing with atmospheric jet streams, ocean currents, and the flow of rivers, for example), of astrophysicists (in studying the photospheres of the sun and stars or mapping gaseous nebulae), and of engineers (in calculating pipe flows, jets, or wakes). Many such examples are discussed in the book. The approach taken avoids the difficulties of advanced mathematical development on the one side and the morass of experimental detail and empirical data on the other. As a result of following its midstream course, the text gives the student a physical understanding of the subject and deepens his intuitive insight into those problems that cannot now be rigorously solved. In particular, dimensional analysis is used extensively in dealing with those problems whose exact solution is mathematically elusive. Dimensional reasoning, scale arguments, and similarity rules are introduced at the beginning and are applied throughout. A discussion of Reynolds stress and the kinetic theory of gases provides the contrast needed to put mixing-length theory into proper perspective: the authors present a thorough comparison between the mixing-length models and dimensional analysis of shear flows. This is followed by an extensive treatment of vorticity dynamics, including vortex stretching and vorticity budgets. Two chapters are devoted to boundary-free shear flows and well-bounded turbulent shear flows. The examples presented include wakes, jets, shear layers, thermal plumes, atmospheric boundary layers, pipe and channel flow, and boundary layers in pressure gradients. The spatial structure of turbulent flow has been the subject of analysis in the book up to this point, at which a compact but thorough introduction to statistical methods is given. This prepares the reader to understand the stochastic and spectral structure of turbulence. The remainder of the book consists of applications of the statistical approach to the study of turbulent transport (including diffusion and mixing) and turbulent spectra.
Sleep deprivation induces the unfolded protein response in mouse cerebral cortex (2005)

Little is known about the molecular mechanisms underlying sleep. We show the induction of key regulatory proteins in a cellular protective pathway, the unfolded protein response (UPR), following 6 h of induced wakefulness. Using C57/B6 male mice maintained on a 12:12 light/dark cycle, we examined, in cerebral cortex, the effect of different durations of prolonged wakefulness (0, 3, 6, 9 and 12 h) from the beginning of the lights-on inactivity period, on the protein expression of BiP/GRP78, a chaperone and classical UPR marker. BiP/GRP78 expression is increased with increasing durations of sleep deprivation (6, 9 and 12 h). There is no change in BiP/GRP78 levels in handling control experiments carried out during the lights-off period. PERK, the transmembrane kinase responsible for attenuating protein synthesis, which is negatively regulated by binding to BiP/GRP78, is activated by dissociation from BiP/GRP78 and by autophosphorylation. There is phosphorylation of the elongation initiation factor 2alpha and alteration in ribosomal function. These changes are first observed after 6 h of induced wakefulness. Thus, prolonging wakefulness beyond a certain duration induces the UPR indicating a physiological limit to wakefulness.
The reductive acetyl coenzyme A pathway: sequence and heterologous expression of active methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase from Clostridium thermoaceticum (1994)

The methyltransferase (MeTr) from Clostridium thermoaceticum transfers the N5-methyl group of (6S)-methyltetrahydrofolate to the cobalt center of a corrinoid/iron-sulfur protein in the acetyl coenzyme A pathway. MeTr was purified to homogeneity and shown to lack metals. The acsE gene encoding MeTr was sequenced and actively expressed in Escherichia coli at a level of 9% of cell protein. Regions in the sequence of MeTr and the E. coli cobalamin-dependent methionine synthase were found to share significant homology, suggesting that they may represent tetrahydrofolate-binding domains.
WT1-mediated Transcriptional Activation Is Inhibited by Dominant Negative Mutant Proteins (1995)

The WT1 tumor suppressor gene encodes four isoforms of a zinc finger transcription factor with both activation and repression functions which are dependent upon promoter architecture. Using a simple HSV-tk promoter containing 5'-Egr-1/WT1-binding sites, we found that WT1 isoforms (A) and (B) strongly activated transcription. WT1(A) and (B) bound equally well to the Egr-1/WT1-binding site, but WT1(B), which contains a 17 amino acid insertion compared to WT1(A), was a consistently stronger activator of transcription than WT1(A). Transcriptional activation by wild-type WT1 was inhibited by coexpression of WT(PM) or WT(AR), genetically defined dominant negative alleles of WT1. In vitro, as well as in the yeast two-hybrid system, WT1 protein associated with itself and with dominant negative mutant proteins. The major domain required for self-association and inhibition of transcriptional activation mapped to the first 182 amino acids of WT1. Dominant negative WT1 alleles may play a role in tumorigenesis by associating with wild-type WT1 proteins and decreasing their transcriptional activity.
Candida albicansSecreted Aspartyl Proteinases in Virulence and Pathogenesis (2003)

Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.
Expression and self-assembly of empty virus-like particles of hepatitis E virus (1997)

Hepatitis E virus (HEV) is a pathogenic agent that causes fecally-orally transmitted acute hepatitis. The genome, a single-stranded positive-sense RNA, encodes three forward open reading frames (ORFs), in which an approximately 2-kb structural protein is located in the 3' end. To produce HEV-like particles the structural protein, with its N terminus truncated (amino acid residues 112 to 660 of ORF2), was expressed in insect Tn5 cells by a recombinant baculovirus. In addition to the primary translation product with a molecular mass of 58 kDa, a large amount of a further-processed molecule with a molecular mass of 50 kDa was generated and efficiently released into the culture medium. Electron microscopic observation of the culture medium revealed that the 50-kDa protein self-assembled to form empty virus-like particles (VLPs). The buoyant density of the VLPs in CsCl was 1.285 g/cm3 and their diameter was 23.7 nm, a little smaller than the 27 nm of native HEV particles secreted into the bile or stools of experimentally infected monkeys. The yield of the VLPs was 1 mg per 10(7) cells as a purified form. The particles possess antigenicity similar to that of authentic HEV particles and, consequently, they appear to be a good antigen for the sensitive detection of HEV-specific immunoglobulin G (IgG) and IgM antibodies. Furthermore, the VLP may be the most promising candidate yet for an HEV vaccine, owing to its potent immunogenicity.