gebhart/patrepeval huggingface dataset:
Role for highly regulated rep gene expression in adeno-associated virus vector production (1997)

Recent success achieving long-term in vivo gene transfer without a significant immune response by using adeno-associated virus (AAV) vectors (X. Xiao, J. Li, and R. J. Samulski, J. Virol. 70:8098-8108, 1996) has encouraged further development of this vector for human gene therapy. Currently, studies focus on the generation of high-titer vectors by using the two-plasmid helper-vector system in adenovirus (Ad)-infected cells. To examine the effects of the AAV replication (rep) genes on recombinant AAV (rAAV) vector production, we have constructed a series of AAV helper plasmids that contain strong heterologous promoters in place of the endogenous p5 promoter. Although high-level rep gene expression was achieved, rAAV DNA failed to replicate in the absence of Ad infection. Moreover, unregulated overexpression of Rep78/68 led to substantially lower rAAV yields in the presence of Ad (10(4-5) versus 10(7-8)). In contrast, under similar conditions, reduced Rep78/68 expression resulted in much higher rAAV yields (10(9)). Molecular characterization showed that overexpression of the rep gene decreased rAAV DNA replication and severely inhibited capsid (cap) gene expression. Interestingly, a reduced rep level enhanced cap gene expression and supported normal rAAV DNA replication. These studies suggest a critical role for regulated rep gene expression in rAAV production and have facilitated the development of a new AAV helper plasmid that increases vector production eightfold over currently used constructs.
Gene Expression Profiles and B-Type Natriuretic Peptide Elevation in Heart Transplantation (2006)

In the clinically quiescent heart transplant recipient, an elevated BNP concentration is associated with molecular patterns that point to ongoing active cardiac structural remodeling, vascular injury, inflammation, and alloimmune processes. Thus, these findings allude to the notion that BNP elevation is not merely a hemodynamic marker but should be considered reflective of integrated processes that determine the balance between active cardiac allograft injury and repair.
Dysbiosis of Gut Fungal Microbiota is Associated With Mucosal Inflammation in Crohn’s Disease (2013)

This study first demonstrates that the fungal microbiota in the inflamed mucosa is distinguishable from that of the noninflamed area. Shifts of gut fungal microbiota composition may be associated with mucosal inflammation and disease activity of CD. Our data would provide novel insights into understanding the potential of gut fungal microbiota in the pathogenesis of CD.
Cleavage of Kininogen and Subsequent Bradykinin Release by the Complement Component: Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 (2011)

Bradykinin (BK), generated from high-molecular-weight kininogen (HK) is the major mediator of swelling attacks in hereditary angioedema (HAE), a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×10(2) and 2.7×10(2) M(-1) s(-1), respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients.
Streptomyces griseus protease C. A novel enzyme of the chymotrypsin superfamily. (1994)

In this report we describe a novel chymotrypsin-like serine protease produced by Streptomyces griseus.The enzyme has been tentatively named S. griseus protease C (SGPC).The gene encoding the enzyme (sprC) was identified and isolated on the basis of its homology to the previously characterized S. griseus protease B (SGPB).The sprC gene encodes a 457-amino acid prepro-mature protein of which only the 255 carboxyl-termmal amino acids are present in the mature enzyme.Mature SGPC contains two distinct domains connected by a 19-amino acid linker region rich in threonines and prolines.While the amino-terminal domain is homologous to S. griseus proteases A, B, and E and the a-lytic protease of Lysobacter enzymogenes, the carboxyl-terminal domain is not homologous with any known protease.However, the carboxyl-terminal domain shares extensive homology with chitin-binding domains of Bacillus circulans chitinases A1 and D, suggesting that the enzyme is specialized for the degradation of chitin-linked proteins.Recombinant expression and preliminary characterization of the catalytic properties of the enzyme are also reported.The primary specificity of SGPC is similar to that of SGPB; both enzymes preferentially cleave peptide bonds following large hydrophobic side chains.The soil microorganism Streptomyces griseus secretes a variety of hydrolytic enzymes.Consequently, it is the source of a commercial, crude enzyme preparation known as Pronase.Several members of the chymotrypsin-like serine protease family have been purified from Pronase.The corresponding genes have been isolated using synthetic oligonucleotide probes based on the amino acid sequences of the enzymes.Past studies uncovered the enzymes S. griseus protease A (SGPA),' S. griseus protease B (SGPB) (1, 21, S. griseus protease E (SGPE) (3, 4), and S. griseus trypsin (SGT) (1, 5); however, the full breadth and divergence of enzymes secreted from S. griseus has not been determined.As part of an evolutionary study of the S. griseus proteases, we adopted a strategy for cloning protease
Tuning the affinity of a synthetic sialic acid receptor using combinatorial chemistry (1998)

Combinatorial libraries of carbohydrate receptors were produced by first derivatizing poly(allylamine) with the fluorescent boronic acid 1 followed by various mixtures of carboxylic acids. The libraries were screened for members that exhibited a larger response for sialic acid than glucose or fructose. The derivatized polymers appear to bind sialic acid by a cooperative mechanism.
Gathering insights on disease etiology from gene expression profiles of healthy tissues (2011)

Supplementary data are available at Bioinformatics online.
Generation of T cells from cytokine-mobilized peripheral blood and adult bone marrow CD34+ cells (1994)

The present study compared the T-cell progenitor content of CD34+ lineage (Lin)- cells isolated from normal adult bone marrow (ABM) and mobilized peripheral blood (MPB). Both cell populations were found to differentiate into T cells when injected into human fetal thymi implanted into severe combined immunodeficient mice. Cytokine-MPB cells were less efficient than ABM cells in engrafting in the fetal human thymus, although both gave rise to thymocytes with identical phenotypes based on the analysis of CD1a, CD3, CD4, and CD8 expression. Thymocytes derived from adult CD34+ Lin- cells were capable of fully differentiating into mature CD3+ T cells expressing either the T-cell receptor (TCR) gamma delta or the TCR alpha beta (the later associated with CD4 or CD8), showing that the T-cell progenies of adult CD34+ cells were polyclonal and functional. Our data indicate that human MPB CD34+ cells are qualitatively identical to their BM counterparts, and demonstrate the existence of T-lymphoid progenitor cell activity in MPB.
A GFP‐mouse talin fusion protein labels plant actin filamentsin vivoand visualizes the actin cytoskeleton in growing pollen tubes (1998)

The C-terminus of mouse talin (amino acids 2345-2541) is responsible for all of the protein's f-actin binding capacity. Unlike full-length talin, the C-terminal f-actin binding domain is unable to nucleate actin polymerization. We have found that transient and stable expression of the talin actin-binding domain fused to the C-terminus of the green fluorescent protein (GFP-mTn) can visualize the actin cytoskeleton in different types of living plant cells without affecting cell morphology or function. Transiently expressed GFP-mTn co-localized with rhodamine-phalloidin in permeabilized tobacco BY-2 suspension cells, showing that the fusion protein can specifically label the plant actin cytoskeleton. Constitutive expression of GFP-mTn in transgenic Arabidopsis thaliana plants visualized actin filaments in all examined tissues with no apparent effects on plant morphology or development at any stage during the life cycle. This demonstrates that in a number of different cell types GFP-mTn can serve as a non-invasive marker for the actin cytoskeleton. Confocal imaging of GFP-mTn labeled actin filaments was employed to reveal novel information on the in vivo organization of the actin cytoskeleton in transiently transformed, normally elongating tobacco pollen tubes.
Targeting the growth factors and angiogenesis pathways: Small molecules in solid tumors (2011)

Research over the last decades has provided us with a better understanding of the biology of solid tumors. In some solid tumor malignancies single molecular events leading to malignant transformation have been identified, whilst in others multiple pathways seem to play a role simultaneously. The delineation of such pathways has led to the identification of therapeutic targets. Multiple compounds are available now to treat those molecular aberrations. With the wider use of newer biologic therapies, the understanding of biologic characteristics predicting a clinical response has broadened. This review focuses on the clinical management of gastrointestinal stromal tumors as well as hepatocellular, non small cell lung, renal cell and breast cancer with small molecule tyrosine kinase inhibitors, integrating some of the clinical advances with monoclonal antibody therapies in solid tumor malignancies. It highlights recent advances in relevant biomarkers to predict efficacy of biologic therapies and elaborates on their relevance in the clinical management of patients with solid tumor malignancies.
32 Kbps CCITT Compatible split band coding scheme (2005)

This paper deals with the application of the SVCS (Split band Voice Coding Scheme) concept to the coding of a PCM channel at half the rate of the presently used 64 kbps CCITT standard. This 32 kbps coder is shown to meet the specifications as recommended by the CCITT for a PCM channel operating at 64 kbps (8kHz sampling, 8 bits/sample A-Law). In addition, channel performances have been evaluated with and without transmission errors for different types of signals ranging from tones and modem signals to voice signals. It has been observed that transparency and apparent channel performances are not affected and that the behavior of the proposed 32 kbps is considerably less affected by transmission errors than the 64 kbps. Examples of taped results assuming different error rates on a voice signal with both the 32 kbps SVCS and the 64 kbps A-Law will be played at the conference.
Security modelling using hierarchical state machines (2002)

The paper defines a modelling scheme that allows for abstraction to simplify security analysis, while at the same time permitting a full description of detailed system behaviour. The basis for the model is a hierarchy of state machines. The security equivalence of the varying levels of abstraction is proven, thereby demonstrating the validity of the model. Also, practical considerations regarding the application of the model to real systems are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis (1996)

Epidemiological evidence suggests that ulcerative colitis is a disease of nonsmokers, while Crohn's disease is a disease of smokers. The relative risk of developing ulcerative colitis is not only greater in nonsmokers, in addition there appears to be a rebound effect in smokers who quit, with the heaviest (ex-)smokers increasing their relative risk of the disease the most. This factor poses an ethical dilemma for health professionals giving advice on stopping smoking, which may thus have a serious detrimental effect on the health of some patients. Nicotine is believed to be the pharmacological ingredient of tobacco that is responsible for this beneficial effect and several clinical trials using nicotine have demonstrated it to be an effective therapeutic agent in the treatment of ulcerative colitis. Although the aetiology of ulcerative colitis is unclear, current research using nicotine-based products has produced some interesting clues, together with the possibility of some form of therapeutic treatment based on nicotine administration.
Smoothing variable-bit-rate video in an internetwork (1999)

The burstiness of compressed video complicates the provisioning of network resources for emerging multimedia services. For stored video applications, the server can smooth the variable-bit-rate stream by transmitting frames into the client playback buffer in advance of each burst. Drawing on prior knowledge of the frame lengths and client buffer size, such bandwidth-smoothing techniques can minimize the peak and variability of the rate requirements while avoiding underflow and overflow of the playback buffer. However, in an internetworking environment, a single service provider typically does not control the entire path from the stored-video server to the client buffer. This paper presents efficient techniques for transmitting variable-bit-rate video across a portion of the route, from an ingress node to an egress node. We develop efficient techniques for minimizing the network bandwidth requirements by characterizing how the peak transmission rate varies as a function of the playback delay and the buffer allocation at the two nodes. We present an efficient algorithm for minimizing both the playback delay and the buffer allocation, subject to a constraint on the peak transmission rate. We then describe how to compute an optimal transmission schedule for a sequence of nodes by solving a collection of independent single-link problems, and show that the optimal resource allocation places all buffers at the ingress and egress nodes. Experiments with motion-JPEG and MPEG traces show the interplay between buffer space, playback delay, and bandwidth requirements for a collection of full-length video traces.
Reactions of polyclonal and neutralizing anti-p54 monoclonal antibodies with an isolated, species-specific 54-kilodalton protein of Chlamydia pneumoniae (1997)

A recently described 54-kDa protein has been detected in six type strains and three patient isolates of Chlamydia pneumoniae by immunoblotting with sera from patients positive for antibodies to C. pneumoniae by the microimmunofluorescence test. This protein was not found in either C. trachomatis E or C. psittaci Z 432 as an antigen, confirming its species specificity. The 54-kDa protein was isolated by continuous-elution electrophoresis and immunoglobulin G monoclonal antibodies (MAbs) against the isolated antigen were produced. MAb 8B11E6 reacted only with the 54-kDa band of C. pneumoniae and not with C. trachomatis E or C. psittaci in a Western immunoblot assay. This antibody was purified and tested for neutralizing activity together with three additional anti-p54-active MAbs (8B11E6, 8B11B4, and 10F1C1). In Buffalo green monkey cells, all of the MAbs significantly reduced the infectivity of C. pneumoniae elementary bodies, whereas no neutralizing activity could be observed with C. trachomatis E or C. psittaci Z 432. These results not only confirm the species specificity of the 54-kDa protein but also indicate that this protein might play an important role in the pathogenesis of C. pneumoniae infection. Furthermore, the results suggest a possible protective role of anti-p54 antibodies in an adaptive immune response.
Lung Overexpression of the Vascular Endothelial Growth Factor Gene Induces Pulmonary Edema (2000)

We hypothesized that the angiogenic mediator, vascular endothelial growth factor (VEGF), known to be expressed in the lung and to be capable of inducing local edema in skin, might evoke the development of lung edema if expressed in excess amounts. To test this hypothesis, we developed an in vivo model of VEGF overexpression in the lung on the basis of delivery to the respiratory epithelium of the VEGF165 complementary DNA by an E1(-) adenovirus vector (AdVEGF165). Administration of AdVEGF165 by the intratracheal route (10(9) plaque-forming units [pfu]) to C57Bl/6 mice showed increased expression of VEGF messenger RNA in lung tissue by Northern analysis. Overexpression of VEGF protein in the lung at Days 1 to 10 was confirmed by enzyme-linked immunosorbent assay. Intratracheal administration of AdVEGF165 resulted in a dose-dependent increase in lung wet/dry weight ratios over time, lung histology showed widespread intra- alveolar edema, and pulmonary capillary permeability was significantly increased as quantified by the Evans blue dye assay and [(131)I]albumin permeability. To confirm the specificity of these observations, mice were pretreated with intranasal administration of an adenovirus vector expressing a truncated soluble form of the VEGF receptor flt-1 (Adsflt). Adsflt (10(9) pfu) pretreatment completely abrogated the increased lung wet/dry weight ratio caused by AdVEGF165 administration, whereas an identical adenovirus vector with an irrelevant transgene had no effect upon subsequent AdVEGF165-induced pulmonary edema. Together, these data suggest that overexpression of VEGF in the lung may be one mechanism of increased pulmonary vascular permeability in the early stages of acute lung injury.
CCCXXIX.—The tautomerism of amidines. Part VI. Methylation of 4-anilino-2-phenyl-6-methylpyrimidine (1926)

R. Forsyth and F. L. Pyman, J. Chem. Soc., 1926, 129, 2502 DOI: 10.1039/JR9262902502
Activation of retinoic acid receptor‐α favours regulatory T cell induction at the expense of IL‐17‐secreting T helper cell differentiation (2007)

Autoimmunity is thought to reflect an imbalance between regulatory T helper lymphocytes (Treg) and pathogenic, IL-17-secreting T helper (Th17) cells. Induction of both adaptive Treg and Th17 cells requires signalling from TGF-beta. We now show that, in the context of TGF-beta signalling, all-trans retinoic acid (ATRA) leads to increased induction of CD4(+) T cells expressing the Treg specification factor forkhead box protein P3 (FoxP3) and decreased frequency of cells expressing IL-17, even in the presence of IL-6. Using a specific agonist and antagonist, as well as retroviral over-expression, we also provide evidence that the effects of ATRA are likely to be at least partially mediated by the nuclear retinoic acid receptor-alpha (RARalpha). These findings indicate that signalling through a specific nuclear retinoic acid receptor can favour the decision to adopt the Treg fate at the expense of Th17 fate. Specific agonists of RARalpha could, therefore, be considered candidates for the treatment of autoimmunity.
A profile refinement method for nuclear and magnetic structures (1969)

A structure refinement method is described which does not use integrated neutron powder intensities, single or overlapping, but employs directly the profile intensities obtained from step-scanning measurements of the powder diagram. Nuclear as well as magnetic structures can be refined, the latter only when their magnetic unit cell is equal to, or a multiple of, the nuclear cell. The least-squares refinement procedure allows, with a simple code, the introduction of linear or quadratic constraints between the parameters.
Molybdenum cofactor negative mutants ofEscherichia coliuse citrate anaerobically (1990)

Anaerobically, Escherichia coli cannot grow using either glycerol or citrate as sole carbon and energy source. However, it has been reported that a mixture of glycerol and citrate will support growth. We have found that wild-type strains of E. coli K-12 do not grow on glycerol plus citrate anaerobically. However, growth eventually occurs due to the frequent appearance of mutants. We found that such Cit+ mutants were defective in anaerobic respiration with nitrate or trimethylamine-N-oxide and were chlorate resistant (i.e. molybdenum cofactor deficient). Conversely, well characterized mutants in any of chlA, B, D, E, G and N were also able to use citrate anaerobically. No anaerobic growth differences between wild type and chl mutants were observed either with fermentable sugars or with glycerol plus fumarate or glycerol plus tartrate. Citrate lyase was induced anaerobically by citrate and repressed by glucose in both wild type strains and chl mutants. Furthermore, levels of citrate lyase, fumarate reductase, malate dehydrogenase, fumarase and alcohol dehydrogenase were similar in both types of strains under anaerobic conditions. It is conceivable that a functioning molybdenum cofactor prevents use of citrate by keeping citrate lyase in the inactive form.
Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin's Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study (2010)

With long-term follow-up, we confirm the superior PFS with rituximab maintenance in relapsed/resistant FL. The improvement of OS did not reach statistical significance, possibly because of the unbalanced use of rituximab in post-protocol salvage treatment.
Identification and characterization of bacteriophages specific to the catfish pathogen,Edwardsiella ictaluri (2008)

This is the first report of bacteriophages specific to Edw. ictaluri, an important fish pathogen affecting farm-raised channel catfish. Initial characterization of these bacteriophages has demonstrated their potential use as biotherapeutic and diagnostic agents associated with ESC.