gebhart/patrepeval huggingface dataset:
Reptilian Reovirus Utilizes a Small Type III Protein with an External Myristylated Amino Terminus To Mediate Cell-Cell Fusion (2004)

Reptilian reovirus is one of a limited number of nonenveloped viruses that are capable of inducing cell-cell fusion. A small, hydrophobic, basic, 125-amino-acid fusion protein encoded by the first open reading frame of a bicistronic viral mRNA is responsible for this fusion activity. Sequence comparisons to previously characterized reovirus fusion proteins indicated that p14 represents a new member of the fusion-associated small transmembrane (FAST) protein family. Topological analysis revealed that p14 is a representative of a minor subset of integral membrane proteins, the type III proteins N(exoplasmic)/C(cytoplasmic) (N(exo)/C(cyt)), that lack a cleavable signal sequence and use an internal reverse signal-anchor sequence to direct membrane insertion and protein topology. This topology results in the unexpected, cotranslational translocation of the essential myristylated N-terminal domain of p14 across the cell membrane. The topology and structural motifs present in this novel reovirus membrane fusion protein further accentuate the diversity and unusual properties of the FAST protein family and clearly indicate that the FAST proteins represent a third distinct class of viral membrane fusion proteins.
Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma (2013)

Exosomes are nanovesicles released by a variety of cells and are detected in body fluids including blood. Recent studies have highlighted the critical application of exosomes as personalized targeted drug delivery vehicles and as reservoirs of disease biomarkers. While these research applications have created significant interest and can be translated into practice, the stability of exosomes needs to be assessed and exosome isolation protocols from blood plasma need to be optimized. To optimize methods to isolate exosomes from blood plasma, we performed a comparative evaluation of three exosome isolation techniques (differential centrifugation coupled with ultracentrifugation, epithelial cell adhesion molecule immunoaffinity pull-down, and OptiPrep(TM) density gradient separation) using normal human plasma. Based on MS, Western blotting and microscopy results, we found that the OptiPrep(TM) density gradient method was superior in isolating pure exosomal populations, devoid of highly abundant plasma proteins. In addition, we assessed the stability of exosomes in plasma over 90 days under various storage conditions. Western blotting analysis using the exosomal marker, TSG101, revealed that exosomes are stable for 90 days. Interestingly, in the context of cellular uptake, the isolated exosomes were able to fuse with target cells revealing that they were indeed biologically active.
Benzoyl peroxide enhances the invasive ability of a mouse epidermal carcinoma cell line (1989)

The effect of the skin tumor promoter benzoyl peroxide on the invasive potential of a murine squamous carcinoma cell line was investigated using an in vitro assay based on the capacity of cells to migrate through a porous filter coated with matrigel. Pre-treatment of the murine squamous carcinoma cell line CH72 with benzoyl peroxide added to the tissue culture medium increased the invasive capacity of these cells 5-8 times. No effects were observed on cells from primary cultures of normal murine epidermis. The simultaneous treatment of CH72 cells with benzoyl peroxide and the free radical scavengers, superoxide dismutase or CuSO4, prevented the increase and the values did not differ significantly from the baseline invasive potential. This suggests that activated oxygen species participate in the benzoyl peroxide-induced enhancement of the invasive capacity of these carcinoma cells.
The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation (1976)

Scanning electron microscopic observations of rat bone marrow reveal that the sinusoidal wall is continuous and has no permanent patent apertures allowing free communication between the extravascular and intravascular myeloid compartments. Blood cells migrate into the sinusoids by perforating the endothelial cell body. Platelets are derived from long intrasinusoidal "proplatelet" processes which originate from the cell body of extravascularly located megakaryocytes. Proplatelet processes frequently occur in clusters, with the probability that all processes in a cluster arise from a single megakaryocyte. The release of platelets into the circulation may be initiated by local constriction along these processes, at which places either individual platelets or larger segments of proplatelet cytoplasm are pinched off. The larger segments may subsequently undergo further fragmentation into individual platelets.
Filterbank reconstruction of bandlimited signals from nonuniform and generalized samples (2000)

This paper introduces a filterbank interpretation of various sampling strategies, which leads to efficient interpolation and reconstruction methods. An identity, which is referred to as the interpolation identity, is developed and is used to obtain particularly efficient discrete-time systems for interpolation of generalized samples as well as a class of nonuniform samples, to uniform Nyquist samples, either for further processing in that form or for conversion to continuous time. The interpolation identity also leads to new sampling strategies including an extension of Papoulis' (1977) generalized sampling expansion.
Generation and Characterization of Aggrecanase (1999)

A method was developed for generating soluble, active "aggrecanase" in conditioned media from interleukin-1-stimulated bovine nasal cartilage cultures. Using bovine nasal cartilage conditioned media as a source of the aggrecanase enzyme, an enzymatic assay was established employing purified aggrecan monomers as a substrate and monitoring specific aggrecanase-mediated cleavage products by Western analysis using the monoclonal antibody, BC-3 (which recognizes the new N terminus, ARGS, on fragments produced by cleavage between amino acid residues Glu373 and Ala374). Using this assay we have characterized cartilage aggrecanase with respect to assay kinetics, pH and salt optima, heat sensitivity, and stability upon storage. Aggrecanase activity was inhibited by the metalloprotease inhibitor, EDTA, while a panel of inhibitors of serine, cysteine, and aspartic proteinases had no effect, suggesting that aggrecanase is a metalloproteinase. Sensitivity to known matrix metalloproteinase inhibitors as well as to the endogenous tissue inhibitor of metalloproteinases, TIMP-1, further support the notion that aggrecanase is a metalloproteinase potentially related to the ADAM family or MMP family of proteases previously implicated in the catabolism of the extracellular matrix.
Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low α‐tocopherol diet (1995)

Three series of experiments demonstrated that sesame seed and its lignans cause significant elevation of alpha-tocopherol content in rats. In Experiment 1, 20% sesame seed (with a negligible amount of alpha-tocopherol) supplementing 10 (low), 50 (normal), or 250 (high) mg/kg alpha-tocopherol diets (protein and fat concentrations in diets were adjusted to 200 and 110 g/kg, respectively) all caused a significant increase of alpha-tocopherol in the blood and tissue of rats. In Experiment 2, groups of rats were fed five different diets: a vitamin E-free control diet, a low alpha-tocopherol diet, and three low alpha-tocopherol diets supplemented with 5, 10, and 15% sesame seed. Changes in lipid peroxides in liver, red blood cell hemolysis, and pyruvate kinase activity, as indices of vitamin E deficiency, were examined. These indices were high in the low alpha-tocopherol diet, whereas supplementation with even 5% sesame seed suppressed these indices completely and caused a significant increase of alpha-tocopherol content in the plasma and liver. In Experiment 3, two diets containing sesame lignan (sesaminol or sesamin) and low alpha-tocopherol were tested. Results in both of the sesame lignan-fed groups were comparable to those observed in the sesame seed-fed groups as shown in Experiment 2. These experiments indicate that sesame seed lignans enhance vitamin E activity in rats fed a low alpha-tocopherol diet and cause a marked increase in alpha-tocopherol concentration in the blood and tissue of rats fed an alpha-tocopherol-containing diet with sesame seed or its lignans.
Engineering antibody affinity and specificity (1988)

A combination of ab initio calculations, "knowledge-based prediction", molecular graphics and site-directed mutagenesis has enabled us to probe the molecular details of antibody:antigen recognition and binding and to alter the affinity and specificity of an antibody for its antigen. The significance of electrostatic hydrogen bonding, hydrophilic/hydrophobic patch matching and van der Waals interactions as well as CDR:CDR interactions are discussed in relation to the results of site-directed mutagenesis experiments on the anti-lysozyme antibody Gloop2. The ability to generate reconstructed antibodies, chimeric antibodies, catalytic antibodies and the use of modelled antibodies for the design of drugs is discussed.
Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences (2018)

Here we provide a review of available literature pertaining to these challenges in the 225Acradiopharmaceutical field and also provide insight into how performed and planned efforts at TRIUMF - Canada's particle accelerator centre - aim to address these issues.
Functional discrepancies between tumor necrosis factor and lymphotoxin α explained by trimer stability and distinct receptor interactions (1995)

Tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) are closely related cytokines which bind with nearly identical affinities to the same pair of cell surface receptors, p55 and p75TNFR. Therefore it is assumed that TNF and LT alpha are redundant cytokines. This study, however, demonstrates that TNF and LT alpha differ significantly with regard to their mitogenic and cytotoxic potentials. LT alpha's superior mitogenic effect could be explained by its formation of a more stable trimer. In contrast to the TNF trimer, which disintegrated under physiological conditions into biologically inactive monomers, the LT alpha trimer remained stable for several days. Accordingly, LT alpha more effectively induced fibroblast growth which demands long-term presence of the cytokine. TNF's superior cytotoxicity, which requires only short-term impact of the cytokine, could be attributed to a distinct interaction with the human p55TNFR. This was demonstrated in NIH 3T3 cells transfected with the human p55TNFR, where cytotoxicity is mediated exclusively by the transfected receptor. Although the p55ATNFR had virtually identical affinities for TNF and LT alpha, as defined by Scatchard analysis, it nevertheless discriminated between binding of each cytokine and showed a 200-fold enhanced cytotoxicity mediated by TNF.
Flow Boiling Heat Transfer on Micro Pin Fins Entrenched in a Microchannel (2010)

Flow boiling of 1-methoxyheptafluoropropane (HFE 7000) in 222 μm hydraulic diameter channels containing a single row of 24 inline 100 μm pin fins was studied for mass fluxes from 350 kg/m2 s to 827 kg/m2 s and wall heat fluxes from 10 W/cm2 to 110 W/cm2. Flow visualization revealed the existence of isolated bubbles, bubbles interacting, multiple flow, and annular flow. The observed flow patterns were mapped as a function of the boiling number and the normalized axial distance. The local heat transfer coefficient during subcooled boiling was measured and found to be considerably higher than the corresponding single-phase flow. Furthermore, a thermal performance evaluation comparison with a plain microchannel revealed that the presence of pin fins considerably enhanced the heat transfer coefficient.
Health Care Costs and Mortality Associated with Nosocomial Diarrhea Due to Clostridium difficile (2002)

A total of 271 patients were prospectively followed up to determine whether patients whose hospital stay is complicated by diarrhea due to Clostridium difficile experience differences in cost and length of stay and survival rates when compared with patients whose stay is not complicated by C. difficile-associated diarrhea. Forty patients (15%) developed nosocomial C. difficile-associated diarrhea. These patients incurred adjusted hospital costs of $3669--that is, 54% (95% confidence interval [CI], 17%-103%)--higher than patients whose course was not complicated by C. difficile-associated diarrhea. The extra length of stay attributable to C. difficile-associated diarrhea was 3.6 days (95% CI, 1.5-6.2). C. difficile-associated diarrhea was not associated with excess 3-month or 1-year mortality after adjustment for age, comorbidity, and disease severity. On the basis of the findings of this study, a conservative estimate of the cost of this disease in the United States exceeds $1.1 billion per year.
Mechanisms of TNF-α– and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis (2003)

Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by extensive bone resorption. The mechanisms underlying this matrix loss have not been elucidated. We report here that blood samples from PsA patients, particularly those with bone erosions visible on plain radiographs, exhibit a marked increase in osteoclast precursors (OCPs) compared with those from healthy controls. Moreover, PsA PBMCs readily formed osteoclasts in vitro without exogenous receptor activator of NF-κB ligand (RANKL) or MCSF. Both osteoprotegerin (OPG) and anti-TNF antibodies inhibited osteoclast formation. Additionally, cultured PsA PBMCs spontaneously secreted higher levels of TNF-α than did healthy controls. In vivo, OCP frequency declined substantially in PsA patients following treatment with anti-TNF agents. Immunohistochemical analysis of subchondral bone and synovium revealed RANK-positive perivascular mononuclear cells and osteoclasts in PsA specimens. RANKL expression was dramatically upregulated in the synovial lining layer, while OPG immunostaining was restricted to the endothelium. These results suggest a model for understanding the pathogenesis of aggressive bone erosions in PsA. OCPs arise from TNF-α–activated PBMCs that migrate to the inflamed synovium and subchondral bone, where they are exposed to unopposed RANKL and TNF-α. This leads to osteoclastogenesis at the erosion front and in subchondral bone, resulting in a bidirectional assault on psoriatic bone.
Nutrient Fluxes in Forests of the Eastern Sierra Nevada: Comparisons with Humid Forest Systems1 (1998)

Preliminary results of studies on nutrientfluxes inforests ofthe eastern Sierra Nevada were compared to thosefrom more humid and polluted ecosystems. Snowmelt, soil solution, soil, and streamwater were collectedfrom J@ey and lodgepole pine Pinus jefkeyii [Grev, and Bag] and Pinus contorta Dougl.) stands in Little bllq, Nevada, and from California red$r (Abies rnagnifica A. murr.) andJefiey pine/white fir Pinus jetTreyii/Abies concolor [Gord and Glend.] Lindl.) stands at Sagehen, California. Snowmelt, soil solutions, and streamwaters from both sites were circumneutral and dominated by base cations and bicarbonate. The redfir stand at Sagehen had high NO3' concentrations (approximately 30-100 pol /L) in both snowmelt and soil solution during the relatively dry 1993-4 wateryear. The Little Valley sites had substantially lower NO,- concentrations in both snowmelt (5-20 pol /L) and soil solution (0.5-3 pol /L) in both wet and dryyears. At both sites, a pulse ofstreamwater NO; (from 0.5 to20-40 pol /L) was detected during dry years but not wet years. The Andic soils at the Sagehen site have trace levels of available Pin soils, whereas the Entisols and Inceptisols in Little Valley have10 to 100 timesgreater levels. The results suggest a hypothesis that thegreater mobility $NO; in the Sagehen redfir site was caused by the amount and timing ofN033 releasefrom snowmelt (e.g., too concentrated and early for dormant biota to respond to), and that P may also be limiting at Sagehen. Compared to other forest ecosystems in more humid and polluted environments, N, Sand H+ deposition andfluxes at the Little Valley site are extremely low, but HC03.and base cationfluxes are high. This reveals that the Little Valley site is relatively pristine, and that ionicfluxes at this site are dohinated by natural carbonic acid leaching and weathering reactions.
MAST: Modeling and analysis suite for real time applications (2002)

This paper describes a model for representing the temporal and logical elements of real-time applications, called MAST. This model allows a very rich description of the system, including the effects of event or message-based synchronization, multiprocessor and distributed architectures as well as shared resource synchronization. The model is directly obtainable from a description of the system design using a UML tool. A system representation using this model is analyzable through a set of tools that has been developed within the MAST suite, including worst-case schedulability analysis for hard timing requirements, and discrete-event simulation for soft timing requirements. Although the current model only includes fixed priority systems, it is conceived as an open model and is easily extensible to accommodate other kinds of systems.
An ultra-sensitive DNA assay based on single-molecule detection coupled with hybridization accumulation and its application (2011)

An ultra-sensitive assay for quantification of DNA based on single-molecule detection coupled with hybridization accumulation was developed. In this assay, target DNA (tDNA) in solution was accumulated on a silanized substrate blocked with ethanolamine and bovine serum albumin (BSA) through a hybridization reaction between tDNA and capture DNA immobilized on the substrate. The tDNA on the substrate was labeled with quantum dots which had been modified with detection DNA and blocked with BSA. The fluorescence image of single QD-labeled tDNA molecules on the substrate was acquired using total internal reflection fluorescence microscopy. The tDNA was quantified by counting the bright dots on the image from the QDs. The limit of detection of the DNA assay was as low as 6.4 × 10(-18) mol L(-1). Due to the ultra-high sensitivity, the DNA assay was applied to measure the beta-2-microglobulin messenger RNA level in single human breast cancer cells without a need for PCR amplification.
Mammalian Cell‐Free Protein Synthesis Directed by Viral Ribonucleic Acid (1970)

A cell‐free system from mouse Krebs II ascites cells is described which responds by increased amino acid incorporation into protein on addition of encephalomyocarditis virus (EMC‐RNA). RNA from other sources does not produce this response. The stimulation by EMC‐RNA occurs over a narrow range of Mg 2+ concentrations and is maximal at 5 mM, which is optimal for the endogenous incorporation and lower than that required in the presence of poly(U). The EMC‐RNA‐directed product is distinguished from the endogenous products by its size and composition. After an initial lag of 4 min, during which the nascent chains are too short to be acid‐insoluble, EMC‐RNA‐directed protein synthesis is active for more than 1 h. EMC‐RNA‐directed synthesis is particularly sensitive to the inhibitors cycloheximide and dextran sulphate. Using the latter, it has been shown that the initiation of protein synthesis is completed during the first 15 min of incubation. Only 20–30% of the product of the cell‐free system, whether endogenous or EMC‐RNA‐directed, is released from the ribosomes. Despite the size of the viral RNA, it did not appear to promote the formation of exceptionally large polysomes. It is concluded that the EMC‐RNA is acting as a message for viral proteins in the ascites cell‐free system.
DNA sequencing using differential extension with nucleotide subsets (DENS) (1997)

Here we describe template directed enzymatic synthesis of unique primers, avoiding the chemical synthesis step in primer walking. We have termed this conceptually new technique DENS (differential extension with nucleotide subsets). DENS works by selectively extending a short primer, making it a long one at the intended site only. The procedure starts with a limited initial extension of the primer (at 20-30 degrees C) in the presence of only two out of the four possible dNTPs. The primer is extended by 6-9 bases or longer at the intended priming site, which is deliberately selected, (as is the two-dNTP set), to maximize the extension length. The subsequent termination reaction at 60-65 degrees C then accepts the extended primer at the intended site, but not at alternative sites, where the initial extension (if any) is generally much shorter. DENS allows the use of primers as long as 8mers (degenerate in two positions) which prime much more strongly than modular primers involving 5-7mers and which (unlike the latter) can be used with thermostable polymerases, thus allowing cycle-sequencing with dye-terminators compatible with Taq DNA polymerase, as well as making double-stranded DNA sequencing more robust.
Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A (2013)

Reactivation of fetal hemoglobin (HbF) in adults ameliorates the severity of the common β-globin disorders. The transcription factor BCL11A is a critical modulator of hemoglobin switching and HbF silencing, yet the molecular mechanism through which BCL11A coordinates the developmental switch is incompletely understood. Particularly, the identities of BCL11A cooperating protein complexes and their roles in HbF expression and erythroid development remain largely unknown. Here we determine the interacting partner proteins of BCL11A in erythroid cells by a proteomic screen. BCL11A is found within multiprotein complexes consisting of erythroid transcription factors, transcriptional corepressors, and chromatin-modifying enzymes. We show that the lysine-specific demethylase 1 and repressor element-1 silencing transcription factor corepressor 1 (LSD1/CoREST) histone demethylase complex interacts with BCL11A and is required for full developmental silencing of mouse embryonic β-like globin genes and human γ-globin genes in adult erythroid cells in vivo. In addition, LSD1 is essential for normal erythroid development. Furthermore, the DNA methyltransferase 1 (DNMT1) is identified as a BCL11A-associated protein in the proteomic screen. DNMT1 is required to maintain HbF silencing in primary human adult erythroid cells. DNMT1 haploinsufficiency combined with BCL11A deficiency further enhances γ-globin expression in adult animals. Our findings provide important insights into the mechanistic roles of BCL11A in HbF silencing and clues for therapeutic targeting of BCL11A in β-hemoglobinopathies.