gebhart/patrepeval huggingface dataset:
Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. (1979)

Plasma membrane vesicles were isolated from col- chicine-resistant mutant lines and sensitive wild type and revertant lines of Chinese hamster ovary cells after controlled cell disruptions. The pressures required to disrupt the mutant cells (150 p.s.i.) similarly were less than for the wild type (350 p.s.i.) or revertant (300 p.s.i.) cells indicating an increased fragility of the drug-re- sistant mutants. In all three cases, however, the final plasma membrane preparations consisted of homoge- neous populations of vesicles ranging between 0.1 and 0.7 pm in diameter and were enriched lo-fold in 5’- nucleotidase and (Na+ + K’)-Mti+ATPase. An integral membrane glycoprotein with a molecular weight of approximately 170,000 (“P-glycoprotein”) was present in vesicles from the drug-resistant cells but not the others. The amount of this protein was related to the degree of drug resistance. The protein was purified by the following procedure: removal of peripheral mem- brane proteins with 35 lll~ lithium diiodosalicylate, solubilization in 0.5% N-dodecylsarcosinate, and frac- tionation by lectin-agarose affinity chromatography using Ricinus communis-I which bound the P-glycopro- tein and Lens culinaris and Pisum sativum lectins which bound other membrane glycoproteins. The amount of purified P-glycoprotein thus obtained ac- counted for approximately 3 to 4% of the total plasma membrane protein in one colchicine-resistant mutant line.
Indication for CDKN2A-mutation analysis in familial pancreatic cancer families without melanomas (2012)

CDKN2A-mutation can be found in a considerable proportion of families with FPC. CDKN2A-mutation analysis should therefore be included in genetic testing in FPC families, even in the absence of reported melanomas. This strategy will enhance the recognition of individuals at risk for PC and facilitate the early detection of melanomas.
Realistic Prospects for Stem Cell Therapeutics (2003)

Studies of the regenerating hematopoietic system have led to the definition of many of the fundamental principles of stem cell biology. Therapies based on a range of tissue stem cells have been widely touted as a new treatment modality, presaging an emerging new specialty called regenerative medicine that promises to harness stem cells from embryonic and somatic sources to provide replacement cell therapies for genetic, malignant, and degenerative conditions. Insights borne from stem cell biology also portend development of protein and small molecule therapeutics that act on endogenous stem cells to promote repair and regeneration. Much of the newfound enthusiasm for regenerative medicine stems from the hope that advances in the laboratory will be followed soon thereafter by breakthrough treatments in the clinic. But how does one sort through the hype to judge the true promise? Are stem cell biologists and the media building expectations that cannot be met? Which diseases can be treated, and when can we expect success? In this review, we outline the realms of investigation that are capturing the most attention, and consider the current state of scientific understanding and controversy regarding the properties of embryonic and somatic (adult) stem cells. Our objective is to provide a framework for appreciating the promise while at the same time understanding the challenges behind translating fundamental stem cell biology into novel clinical therapies.
Shiga-Like Toxin II Derived fromEscherichia coliO157:H7 Modifies Renal Handling of Levofloxacin in Rats (2002)

The effect of Shiga-like toxin II (SLT-II) (2 microg/animal), which was derived from Escherichia coli O157:H7, on renal handling of levofloxacin (LVX), a model drug for quinolone antimicrobial agents, was investigated in rats 24 h after intravenous injection. In histopathological examination, acute tubular injury was observed in SLT-II-treated rats, but the glomeruli were not injured. SLT-II significantly increased the steady-state concentration of LVX in plasma to 1.5-fold that of control rats. SLT-II induced significant decreases in the glomerular filtration rate (GFR) and renal clearance (CL(R)) of LVX. SLT-II slightly, but significantly, increased the unbound fraction and decreased renal plasma flow with no change in the extraction ratio of p-aminohippurate. SLT-II significantly increased concentrations of tumor necrosis factor alpha (TNF-alpha) and nitrite and nitrate (NOx) in plasma. The TNF-alpha inhibitor pentoxifylline partly, but significantly, inhibited SLT-II-induced decreases in the GFR and CL(R) of LVX; in contrast, S-methylisothiourea, a selective inhibitor of inducible nitric oxide synthase, did not. Western blotting analysis revealed that SLT-II did not alter the levels of multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein in kidneys 24 h after injection, assuming the lack of involvement of Mrp2 and P-glycoprotein in SLT-II-induced acute renal tubular injury and renal handling of LVX observed 24 h after SLT-II injection. The present study suggests that SLT-II impairs the renal handling of LVX by decreasing GFR and causing decreased renal plasma flow.
A de novo 13 nt deletion, a newly identified C647W missense mutation and a deletion of exon 18 in infantile onset glycogen storage disease type II (GSDII) (1994)

We identified the presumably rare event of de novo mutation in an autosomal recessive disorder, glycogen storage disease type II (GSDII). GSDII results from inherited deficiency of acid alpha-glucosidase (acid maltase) and both the expressed and structural gene (designated GAA) have been isolated. The mutation was a deletion of 13 nt of coding sequence (delta nt 1456-1468) on the paternally derived allele of the proband. The delta nt 1456-1468 results in a reading frameshift and a premature termination signal upstream of the enzyme catalytic site. Paternity was confirmed by presence of two downstream, uncommon amino acid substitutions (E689K, W746C) in both proband and father and by comparison of nine short tandem repeats. The maternal allele carried a newly identified deleterious C647W missense mutation in a highly conserved area of the protein. The C647W mutation was also found in a second unrelated proband, heteroallelic with a deletion extending from IVS17 to IVS18.
Supporting Location-Awareness in Open Distributed Systems (1998)

Mobile computers and communication devices are establishing themselves as ubiquitous features of daily life. This development is linked to tremendous growth in the number and sophistication of mobile and mobile-aware software applications. Increasingly, such applications need access to information about their own and other objects&amp;apos; physical locations, a requirement known as location-awareness. Existing location-aware applications and systems are typically tailored to a particular type of positioning technology. This is unsatisfactory considering that no technology provides ubiquitous coverage. Equally, there are few accepted models and abstractions for building location-aware applications, making their design and implementation costly and error-prone. Location-awareness raises legitimate concerns about personal and organisational privacy. These vary widely across administrative and application domains. Hence, there is a need to find a model allowing a balance between protection and fu...
Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. (1990)

The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers. We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing. Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor specimens, but not in the corresponding normal lung, were distributed between codons 132 to 283, and included tumors with and without 17p allele loss. Fifteen of the 23 mutations lay in the predicted binding regions for SV40 large T antigen, and 14 were located in regions highly conserved between species. G to T transversions were a common result of p53 mutations in lung cancer compared to other cancers suggesting exposure to different mutagens. In univariate and multivariate analysis the presence of p53 mutations was associated with younger age and squamous histology. However, the presence of p53 mutations was not significantly associated with tumor stage, nodal status or sex and was found in all histologic types of lung cancer. We conclude that somatic mutations in the p53 gene play an important role in the pathogenesis of early stage non-small cell lung cancer.
Obliterative bronchiolitis: varying presentations and clinicopathological correlation (2002)

In obliterative bronchiolitis, inflammation and fibrosis lead to narrowing or occlusion of bronchiolar lumina. To determine how bronchiolar structural alterations relate to lung physiology, 19 patients with a pathological diagnosis of obliterative bronchiolitis were studied. The bronchiolar inflammatory and fibrotic features were correlated to the clinical presentation, and lung function tests. Eleven patients demonstrated airflow limitation, one had a restrictive pattern and one had a mixed pattern, two had isolated gas trapping, but four had normal spirometry. Mild-to-moderate bronchiolar inflammation was invariably present. It involved 60% of bronchioles subepithelially and 54% in the adventitia. Subepithelial fibrosis was observed in 15 patients and adventitial in 12. Adventitial bronchiolar inflammation correlated with forced expiratory volume in one second and forced vital capacity and inversely correlated with residual volume. Subepithelial fibrosis inversely correlated with subepithelial and adventitial inflammation. High-resolution computed tomography in 10 patients revealed inspiratory (five out of 10) and expiratory air trapping (five out of five), ground glass opacities (seven out of 10), bronchial wall thickening (five out of 10), bronchiectasis (two out of 10) and centrilobular nodules (two out of 10). The present study suggests that inflammation and fibrosis occurs in bronchioles at different time points in the disease process, or that there is no transition between these types of pathology in the same patient. No correlation was observed between the degree of bronchiolar fibrosis and the degree of airflow limitation.
The structure and function of food webs in soil (2004)

Summary Several soil food webs have been thoroughly described and the importance of nematodes is evident from their representation at different trophic links - as plant-feeders, secondary detritivores, predators and omnivores. Carbon flow models have shown the importance of several pathways, including those through bacterial- and fungal-feeders to predaceous nematodes, and from plant roots through plant-feeders. The herbivory pathway has been observed experimentally by following a pulse of 13C, applied above-ground, through the soil community. Novel observations are also emerging on the effects of root-feeding fauna on above-ground food webs. Disturbance of food web groups causes a loss in stability, reduced biodiversity and changes in soil processes. Consideration of biodiversity in food web models will allow exploration of biodiversity-productivity and biodiversity-stability relationships. Modelling interactions according to function rather than species reveal interesting interactions in above-ground food webs. Current soil food web models group organisms by function and taxa, but for improved understanding of the system information on broader functional groups may be more appropriate. Current initiatives and developments in food web research and theory highlight the importance of soil food webs in biosphere function and are providing insights into the preservation, conservation and management of soil systems.
The β-Glucan Receptor, Dectin-1, Is Predominantly Expressed on the Surface of Cells of the Monocyte/Macrophage and Neutrophil Lineages (2002)

We recently identified dectin-1 (betaGR) as a major beta-glucan receptor on leukocytes and demonstrated that it played a significant role in the non-opsonic recognition of soluble and particulate beta-glucans. Using a novel mAb (2A11) raised against betaGR, we show here that the receptor is not dendritic cell-restricted as first reported, but is broadly expressed, with highest surface expression on populations of myeloid cells (monocyte/macrophage (Mphi) and neutrophil lineages). Dendritic cells and a subpopulation of T cells also expressed the betaGR, but at lower levels. Alveolar Mphi, like inflammatory Mphi, exhibited the highest surface expression of betaGR, indicative of a role for this receptor in immune surveillance. In contrast, resident peritoneal Mphi expressed much lower levels of betaGR on the cell surface. Characterization of the nonopsonic recognition of zymosan by resident peritoneal Mphi suggested the existence of an additional beta-glucan-independent mechanism of zymosan binding that was not observed on elicited or bone marrow-derived Mphi. Although this recognition could be inhibited by mannan, we were able to exclude involvement of the Mphi mannose receptor and complement receptor 3 in this process. These observations imply the existence of an additional mannan-dependent receptor involved in the recognition of zymosan by resident peritoneal Mphi.
Effects of peptide therapy on ex vivo T-cell responses (1998)

Peptide therapy induces a significant, dose-dependent decrease in peptide-stimulated IL-4 production, consistent with either a shift in T-cell phenotype or peptide-specific T-cell tolerance.
RNA-dependent RNA targeting by CRISPR-Cas9 (2018)

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo. We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. These results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications.
Practical prefetching via data compression (1993)

An important issue that affects response time performance in current OODB and hypertext systems is the I/O involved in moving objects from slow memory to cache. A promising way to tackle this problem is to use prefetching , in which we predict the user's next page requests and get those pages into cache in the background. Current databases perform limited prefetching using techniques derived from older virtual memory systems. A novel idea of using data compression techniques for prefetching was recently advocated in [KrV, ViK], in which prefetchers based on the Lempel-Ziv data compressor (the UNIX compress command) were shown theoretically to be optimal in the limit. In this paper we analyze the practical aspects of using data compression techniques for prefetching. We adapt three well-known data compressors to get three simple, deterministic, and universal prefetchers. We simulate our prefetchers on sequences of page accesses derived from the OO1 and OO7 benchmarks and from CAD applications, and demonstrate significant reductions in fault-rate. We examine the important issues of cache replacement, size of the data structure used by the prefetcher, and problems arising from bursts of “fast” page requests (that leave virtually no time between adjacent requests for prefetching and book keeping). We conclude that prediction for prefetching based on data compression techniques holds great promise.
TcVac3 Induced Control of Trypanosoma cruzi Infection and Chronic Myocarditis in Mice (2013)

We characterized the immune responses elicited by a DNA-prime/MVA-boost vaccine (TcVac3) constituted of antigenic candidates (TcG2 and TcG4), shown to be recognized by B and T cell responses in Trypanosoma cruzi (Tc) infected multiple hosts. C57BL/6 mice immunized with TcVac3 elicited a strong antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1); and a robust antigen- and Tc-specific CD8(+)T cell response with type-1 cytokine (IFN-γ(+)TNF-α>IL-4(+)IL-10) and cytolytic effector (CD8(+)CD107a(+)IFN-γ(+)Perforin(+)) phenotype. The vaccine-induced effector T cells significantly expanded upon challenge infection and provided >92% control of T. cruzi. Co-delivery of IL-12 and GMCSF cytokine adjuvants didn't enhance the TcVac3-induced resistance to T. cruzi. In chronic phase, vaccinated/infected mice exhibited a significant decline (up to 70%) in IFN-γ(+)CD8(+)T cells, a predominance of immunoregulatory IL-10(+)/CD4(+)T and IL10(+)/CD8(+)T cells, and presented undetectable tissue parasitism, inflammatory infiltrate, and fibrosis in vaccinated/infected mice. In comparison, control mice responded to challenge infection by a low antibody response, mixed cytokine profile, and consistent activation of pro-inflammatory CD8(+)T cells associated with parasite persistence and pathologic damage in the heart. We conclude that TcVac3 elicited type-1 effector T cell immunity that effectively controlled T. cruzi infection, and subsequently, predominance of anti-inflammatory responses prevented chronic inflammation and myocarditis in chagasic mice.
[Studies of beta-thalassemia mutations and prenatal diagnosis in Guangxi, Guangdong and Sichuan Provinces of south China]. (1990)

beta-Thalassemia is one of the most common single gene disorders in South China, and ten different point mutations and frameshifts have been observed among Chinese. We studied 150 chromosomes of 95 beta-thalassemia patients from Guangxi, Guangdong and Sichuan Provinces using the polymerase chain reaction followed by dot hybridization with specific oligonucleotide probes. The most common mutations were the frameshift at codon 41-42 and the nonsense mutation at codon 17 in Guangxi and Sichuan, and the codon 41-42 frameshift and IVS-II-654 mutation in Guangdong. The A-G mutation at -28 of the promoter was common in Sichuan but not in the other two provinces. Three mutations, -30, IVS-I-1 and IVS-I-5, were not observed. A prenatal diagnosis program using these techniques has been initiated based on these data. Fourteen pregnancies at risk for beta-thalassemia have been diagnosed successfully.
The rational design of a 'type 88' genetically stable peptide display vector in the filamentous bacteriophage fd (2001)

Filamentous bacteriophages are particularly efficient for the expression and display of combinatorial random peptides. Two phage proteins are often employed for peptide display: the infectivity protein, PIII, and the major coat protein, PVIII. The use of PVIII typically requires the expression of two pVIII genes: the wild-type and the recombinant pVIII gene, to generate mosaic phages. 'Type 88' vectors contain two pVIII genes in one phage genome. In this study a novel 'type 88' expression vector has been rationally designed and constructed. Two factors were taken into account: the insertion site and the genetic stability of the second pVIII gene. It was found that selective deletion of recombinant genes was encountered when inserts were cloned into either of the two non-coding regions of the phage genome. The deletions were independent of recA yet required a functional F-episome. Transcription was also found to be a positive factor for deletion. Taking the above into account led to the generation of a novel vector, designated fth1, which can be used to express recombinant peptides as pVIII chimeric proteins in mosaic bacteriophages. The fth1 vector is not only genetically stable but also of high copy number and produces high titers of recombinant phages.
Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection (2003)

Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly. It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood. However, the results of published studies can be interpreted that pneumococci may enter the brain directly from the nasal cavity by axonal transport through olfactory nerves. This hypothesis is based on findings that (i) teichoic acid of the pneumococcal cell wall interact with gangliosides (GLS), (ii) the interaction of GLS with cholera toxin leads to axonal transport through the olfactory nerves into the brain, and (iii) viruses enter the brain through axonal transport into olfactory nerves. After nasal inoculation, we observe high numbers of pneumococci in nasal washes and the olfactory nerves and epithelium. Significant numbers of pneumococci also infected the olfactory bulbs, brain, and the trigeminal ganglia. The absence of bacteremia in this model makes it unlikely that the bacteria entered the brain from the blood stream. Recovery of colony-forming units from the brain, lungs, olfactory nerves, and epithelium and nasal washes was inhibited by incubating pneumococci with GLS before nasal inoculation. These findings, confirmed by PCR and immunohistochemistry, support a GLS-mediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport.
Surface-Initiated Thermal Radical Polymerization on Gold (2001)

We report surface-initiated thermal radical polymerization from cross-linked monolayers of azo-initiators on Au. Initial attempts to graft polymer layers from initiators attached to alkanethiol monolayers yielded polymer films with thicknesses less than 5 nm. Efficient grafting from such surfaces is not possible because initiator-containing monolayers are somewhat unstable under thermal radical polymerization conditions, and desorbed thiols may serve as efficient chain-transfer reagents that inhibit radical polymerization. In addition, reactive radicals can attack the Au−S bonds that link the initiator monolayer to the surface. To overcome these problems, we employed mercaptopropyltrimethoxysilanes to form an adhesion layer for initiator attachment. Cross-linked poly(siloxane) layers apparently stabilize the initiator layer, allowing well-defined surface radical polymerization to occur from Au substrates. We characterized the grafted polymer layers with ellipsometry, reflectance Fourier transform infrared spectroscopy, and atomic force microscopy.