gebhart/patrepeval huggingface dataset:
Characterization of tRNA precursor splicing in mammalian extracts. (1983)

Transcription of a Xenopus laevis tRNATyr gene and splicing of the transcript have been studied in HeLa cell extracts. This tRNATyr gene has a 13-base intervening sequence and is expressed as mature tRNA when transfected into mammalian cells. The tRNATyr gene is transcribed under conditions of low concentrations of magnesium and ATP, but is processed by splicing only when both of these cofactors are added at higher concentrations. The endonucleolytic activity of the tRNA-splicing system in the HeLa extract produces exons with 3'-phosphate and 5'-hydroxyl groups. The 3'-phosphate is retained during the ligation reaction and forms the phosphodiester bond in the mature tRNA. Retention of the 3'-phosphate during tRNA splicing differs from the more extensively studied process in yeast extracts where a phosphate group from an ATP cofactor is used to form the phosphodiester bond joining the exons. Thus, eucaryotic organisms can splice tRNA precursors by at least two distinguishable mechanisms.
Uniform and non uniform optical leaky-wave antennas for field shaping (2015)

The concept of optical leaky wave antennas based on periodic perturbations in a dielectric waveguide has been demonstrated to provide directive radiation in far field. Moreover the radiated field from such silicon-on-insulator and CMOS compatible antenna systems can be modulated through controlling the excess carrier density in silicon inclusions, and the radiation modulation with high extinction ratios were achieved by integrating the antennas in resonator topologies. In this paper we extend this concept to optical waveguides with non uniformly distributed perturbations as a method of shaping the antenna near field. The scattering of electromagnetic waves through such perturbed waveguides can be engineered using array theory or a leaky wave model. The resonator integration and Si-based designs combined with the near-field shaping technique proposed here can lead to applications such as tunable near field detection. In this paper we present a theoretical framework as a proof of the proposed concept with a CMOS compatible optical antenna.
Molecular genetic analysis of Arabidopsis seed quality. (2011)

Improvement of seed quality may greatly benefit from the characterization of genes involved in seed development and seed germination. To study the effect of genes on seed quality, a comparison was made among genetically different lines. Ideally, the genetic difference should be known at the DNA sequence level. For this purpose Arabidopsis thaliana offers a potentially powerful model system. The complete genome sequence of this plant species will soon become available, a large amount of genetic variation is present and daily new mutants are produced. To exploit Arabidopsis as a model system for genetic analysis of seed quality, appropriate seed quality assays were developed. Several mutants and ecotypes were compared for storability, using a controlled deterioration assay. Large variation was observed with regard to this trait. Seeds from abscisic acid deficient or insensitive mutants deteriorated faster compared to wild-type seeds. Seeds from the ecotype Landsberg erecta and the ecotype Cape Verde Island differ in dormancy, controlled deterioration tolerance and their content of raffinose and stachyose. A quantitative trait loci analysis of recombinant inbred lines derived from a cross between these two ecotypes showed that stachyose and raffinose content were linked to a single locus in the genome. The traits for dormancy, controlled deterioration tolerance and content of the sugars were not genetically linked. A very strong reduction in stachyose and raffinose content had no effect on the controlled deterioration tolerance of the seeds. It is concluded that Arabidopsis offers a powerful tool to study genetic variation in seed quality and the effect of modification of seed composition on seed quality.
Absence of canine oral papillomavirus DNA following prophylactic L1 particle-mediated immunotherapeutic delivery vaccination (2002)

In the canine oral papillomavirus (COPV) model, following wart regression, COPV DNA was detected by PCR at the challenge site. However, following particle-mediated immunotherapeutic delivery (PMID) of COPV L1 and subsequent challenge, no COPV DNA could be detected. These data support PMID of COPV L1 as a protective vaccine and suggest that PMID of L1 may induce virus clearance.
Cinacalcet in the Management of Tumor-Induced Osteomalacia (2007)

Abstract Both FGF-23 and PTH inhibit renal phosphate reabsorption. We treated two patients with TIO and FGF-23–mediated hypophosphatemia with cinacalcet to test the hypothesis that medicinally induced hypoparathyroidism would decrease renal phosphate wasting. Cinacalcet treatment resulted in increased renal phosphate reabsorption, allowed for a decrease in phosphate supplementation, and showed evidence of bone healing in one of the two patients. Introduction: Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting, which results in hypophosphatemia and osteomalacia. It is caused by mesenchymal tumors that produce the phosphate and vitamin D–regulating hormone, fibroblast growth factor (FGF)-23. Removal of the tumor is curative, but the tumors are often difficult to locate. Medical treatment involves high doses of oral phosphate and calcitriol, but the phosphate is often poorly tolerated and leads to diarrhea. Because PTH also promotes phosphaturia, and patients with hypoparathyroidism are hyperphosphatemic in the setting of elevated serum FGF-23, we postulated that the calcium-sensing receptor agonist, cinacalcet, which can induce hypoparathyroidism, would be an effective adjuvant in the treatment of TIO. Materials and Methods: Two subjects with presumed TIO in whom the tumor was not located after extensive testing and who did not tolerate medical therapy with phosphorus and calcitriol were treated with cinacalcet. Results: Neither treatment with phosphorus nor combined treatment with phosphorus and calcitriol had an effect on serum FGF-23 levels. Treatment with cinacalcet resulted in increased renal phosphate reabsorption and serum phosphorus and allowed for a decrease in phosphate supplementation to a dose that was tolerated. On this regimen, one patient showed significant bone healing as shown by resolution of activity on bone scan and lack of osteomalacia as assessed by histomorphometry. Conclusions: These data show that medically induced hypoparathyroidism with cinacalcet is a therapeutic option for disorders of FGF-23–mediated hypophosphatemia and that, in the absence of PTH, the phosphaturic effect of FGF-23 is decreased.
Interactions between mannose-binding lectin and MASPs during complement activation by the lectin pathway (2006)

The lectin pathway of complement performs a key role within the immune system by recognising pathogens through patterns of sugar moieties displayed on their cell surfaces and neutralising them via an antibody-independent reaction cascade. While particularly important during early childhood before the adaptive immune system is established, or when adaptive immunity is compromised, it has a protective function throughout life, neutralising invading pathogens directly and helping to stimulate and direct an effective immune response. Complement activation is initiated when complexes comprising mannose-binding lectin (MBL) or serum ficolins and MBL-associated serine protease-2 (MASP-2) bind to pathogens. Binding induces conformational changes in these complexes, leading to autoactivation of the MASPs, which in turn activate the downstream reaction cascade. A major goal in complement research is to understand the molecular events that trigger complement activation. Over the last few years, structure-function studies have improved our knowledge of the way in which MBL binds to MASPs by defining the portions of these proteins that interact and by solving the structures of key protein fragments. In this review, I will summarise the main findings of these studies and describe current theories to explain how the components combine to initiate the reaction cascade.
Identification of α-Fodrin as a Candidate Autoantigen in Primary Sjögren's Syndrome (1997)

It is unclear whether organ-specific autoantigens are critical for the development of primary Sjögren's syndrome (SS). A 120-kilodalton organ-specific autoantigen was purified from salivary gland tissues of an NFS/sld mouse model of human SS. The amino-terminal residues were identical to those of the human cytoskeletal protein alpha-fodrin. The purified antigen induced proliferative T cell responses and production of interleukin-2 and interferon-gamma in vitro. Neonatal immunization with the 120-kilodalton antigen prevented the disease in mice. Sera from patients with SS reacted positively with purified antigen and recombinant human alpha-fodrin protein, whereas those from patients with systemic lupus erythematosus and rheumatoid arthritis did not. Thus, the immune response to 120-kilodalton alpha-fodrin could be important in the initial development of primary SS.
Viruses in Human Cancers (1991)

Viruses may contribute to the development of human tumors by different mechanisms: indirectly by inducing immunosuppression or by modifying the host cell genome without persistence of viral DNA; directly by inducing oncoproteins or by altering the expression of host cell proteins at the site of viral DNA integration. Human cancers associated with papillomavirus, hepatitis B virus, Epstein-Barr virus, and human T cell leukemia-lymphoma virus infections are responsible for approximately 15 percent of the worldwide cancer incidence. Cancer of the cervix and hepatocellular carcinoma account for about 80 percent of virus-linked cancers. Because experimental and epidemiologic data imply a causative role for viruses, particularly in cervical and liver cancer, viruses must be thought of as the second most important risk factor for cancer development in humans, exceeded only by tobacco consumption.
Principles of MicroRNA–Target Recognition (2005)

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression in plants and animals. Although their biological importance has become clear, how they recognize and regulate target genes remains less well understood. Here, we systematically evaluate the minimal requirements for functional miRNA-target duplexes in vivo and distinguish classes of target sites with different functional properties. Target sites can be grouped into two broad categories. 5' dominant sites have sufficient complementarity to the miRNA 5' end to function with little or no support from pairing to the miRNA 3' end. Indeed, sites with 3' pairing below the random noise level are functional given a strong 5' end. In contrast, 3' compensatory sites have insufficient 5' pairing and require strong 3' pairing for function. We present examples and genome-wide statistical support to show that both classes of sites are used in biologically relevant genes. We provide evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 3' ends are key determinants of target specificity within miRNA families.
Synthesis of Novel Poly(amido ethylenimine) (PAMEIM) Dendrimer and Its Self-assembly with Plasmid DNA (2006)

A lot of non-viral gene delivery carriers including cationic lipids and polymers have been developed due to their advantages such as easy introduction of specific bio-functionalities, convenient handling, non-immunogenicity and unlimited capacity of genes delivered. Poly(ethylenimine) (PEI) and poly(amido amine) (PAMAM) dendrimer are representative and commercialized polymeric gene delivery carriers. PEI shows very high transfection efficiency caused by its ‘endosome buffering’ capacity but its severe cytotoxicity limited its application for gene delivery and led its chemical modification for reducing the cytotoxicity. Recently, interesting strategies based on the preincubation of potent glucocorticoid, dexamethasone before transfection and the conjugation of mitochondrial leader peptide to PEI have been also tried in order to enhance the transfection efficiency of PEI by glucocorticoid ligand-receptor interaction and to perform selective delivery of genes to mitochondria, respectively. The transfection efficiency of PAMAM dendrimer is lower than that of PEI. However, its controllable multivalent functionality, defined structure and biocompatibility is still arising many scientists’ interest for gene delivery systems. So, we intended to design a novel hybrid dendrimer, poly(amido ethylenimine) (PAMEIM) dendrimer possessing the endosome buffering capacity of PEI and the defined structure, biocompatibility of PAMAM dendrimer in order to combine their advantages. Here, we report synthesis of a novel PAMEIM dendrimer and characterization of its self-assembly with plasmid DNA in order to identify its potential as a gene delivery carrier.
Post‐translational regulation of expression and conformation of an immunoglobulin domain in yeast surface display (2005)

Display of heterologous proteins on the surface of Saccharomyces cerevisiae is increasingly being exploited for directed evolution because of straightforward cell screens. However, yeast post-translationally modifies proteins in ways that must be factored into library engineering and refinement. Here, we express the extracellular immunoglobulin domain of an ubiquitous mammalian membrane protein, CD47, which is implicated in cancer, immunocompatibility, and motility. CD47 has multiple sites of glycosylation and a core disulfide bond. We assess the effects of both of these post-translational modifications on expression and antibody binding. CD47's extracellular domain is fused to the yeast mating protein Aga2p on the cell wall, and the resulting fusion protein binds several key antibodies, including a conformation-sensitive antibody. Site-by-site mutagenesis of CD47's five N-linked glycosylation sites progressively decreases expression levels on yeast, but folding appears stable. Cysteine mutations disrupt the expected core disulfide, and also decrease protein expression levels, though not to the extent seen with complete deglycosylation. However, with the core disulfide mutants, antibody binding proves to be lower than expected from expression levels and glycosylation is clearly reduced compared to wild-type. The results indicate that glycosylation regulates heterologous display on yeast more than core disulfides do and thus suggest bounds on directed evolution by post-translational processing.
The relationship between different high proliferative potential colony-forming cells in mouse bone marrow. (1994)

Previous work has shown that part of the hierarchical structure of the hematopoietic system can be described by HPP-CFC-1 (primitive high proliferative potential colony-forming cells responding to colony-stimulating factor-1 [CSF-1] + interleukin-3 [IL-3] + IL-1), HPP-CFC-2 (more mature HPP-CFC responding to CSF-1 + IL-3), and mature HPP-CFC responding to the single factors, CSF-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-3. In this study, we have attempted to relate the murine HPP-CFC, stimulated by various combinations of growth factors (GFs)--CSF-1, GM-CSF, IL-3, IL-6, IL-1, stem cell factor (SCF), and transforming growth factor-beta (TGF-beta)--and by CSF-1, GM-CSF, and IL-3 on their own, to these known progenitors. Studies involving regeneration of the bone marrow after 5-fluorouracil (5-FU) treatment, generation of progenitors in liquid cultures in response to different GF combinations, and the HPP-CFC content of lineage-negative rhodamine-sorted bone marrow (BM) fractions have indicated that: 1. the combinations CSF-1 + IL-3 + IL-1 + SCF and CSF-1 + IL-3 + IL-1 + IL-6, and possibly CSF-1 + GM-CSF + IL-3 + IL-1, stimulate pre-HPP-CFC-1; 2. the combinations CSF-1 + IL-1 + GM-CSF, CSF-1 + IL-1 + IL-6, CSF-1 + IL-1 + SCF, CSF-1 + IL-3 + SCF, CSF-1 + IL-6 + SCF, and IL-3 + SCF, appear to overlap with the CSF-1 + IL-3 + IL-1 combination to stimulate the more mature cells of the HPP-CFC-1 compartment; 3. the combinations CSF-1 + GM-CSF, CSF-1 + IL-1, CSF-1 + IL-6, and CSF-1 + SCF may stimulate the more mature cells of the HPP-CFC-2 population, while the single factors CSF-1, GM-CSF, and IL-3, as suggested in other reports, may stimulate HPP-CFC that are more mature than the HPP-CFC-2; 4. the combinations IL-3 + IL-6 and SCF + IL-6 appear to stimulate HPP-CFC that overlap with the HPP-CFC-1 population, while those responding to the combination GM-CSF + TGF-beta overlap with the HPP-CFC-2 population within the hematopoietic hierarchy; and 5. CSF-1 and GM-CSF appear to be interchangeable in the combinations studied.
Hybridization specificity, enzymatic activity and biological (Ha-ras) activity of oligonucleotides containing 2,4-dideoxy-β-D-erythro-hexopyranosyl nucleosides (1993)

Antisense oligonucleotides with a 2,4-dideoxyhexopyranosyl nucleoside incorporated at the 3'-end and at a mutation site of the Ha-ras oncogene mRNA were synthesized. Melting temperature studies revealed that an A*-G mismatch is more stable than an A*-T mismatch with these hexopyranosyl nucleosides incorporated at the mutation site. The oligonucleotides are stable against enzymatic degradation. RNase H mediated cleavage studies revealed selective cleavage of mutated Ha-ras mRNA. The oligonucleotide containing two pyranose nucleosides at the penultimate position activates RNase H more strongly than natural oligonucleotides. No correlation, however, was found between DNA - DNA or RNA - DNA melting temperatures and RNase H mediated cleavage capacity. Although the A*-G mismatch gives more stable hybridization than the A*-T base pairing, only the oligonucleotides containing an A*-T base pair are recognized by RNase H. This modification is situated 3 base pairs upstream to the cleavage site. Finally, the double pyranose modified oligonucleotide was able to reduce the growth of T24 cells (bladder carcinoma) while the unmodified antisense oligonucleotide was not.
Frenetic (2011)

Modern networks provide a variety of interrelated services including routing, traffic monitoring, load balancing, and access control. Unfortunately, the languages used to program today's networks lack modern features - they are usually defined at the low level of abstraction supplied by the underlying hardware and they fail to provide even rudimentary support for modular programming. As a result, network programs tend to be complicated, error-prone, and difficult to maintain. This paper presents Frenetic, a high-level language for programming distributed collections of network switches. Frenetic provides a declarative query language for classifying and aggregating network traffic as well as a functional reactive combinator library for describing high-level packet-forwarding policies. Unlike prior work in this domain, these constructs are - by design - fully compositional, which facilitates modular reasoning and enables code reuse. This important property is enabled by Frenetic's novel run-time system which manages all of the details related to installing, uninstalling, and querying low-level packet-processing rules on physical switches. Overall, this paper makes three main contributions: (1) We analyze the state-of-the art in languages for programming networks and identify the key limitations; (2) We present a language design that addresses these limitations, using a series of examples to motivate and validate our choices; (3) We describe an implementation of the language and evaluate its performance on several benchmarks.
A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence. (1995)

We describe a differential screening method for cDNA libraries which used a combination of subtracted and PCR-amplified cDNA probes, and which can be applied to the selection of genes expressed in multiple tissues. This technique was used to identify genes commonly overexpressed in breast and basal cell carcinomas. These represent stromally dependent, invasive tumors with and without metastatic capacity. Thus, this screening sought to identify genes involved in the early stages of tumor progression. We identified a total of 16 genes, including c-erbB-2 and tissue inhibitor of metalloproteinases 3 whose products have been implicated in tumorigenesis or invasion. We also identified a novel sequence (D52) showing little homology with others described in any species, which maps to the human chromosomal band 8q21. In situ RNA hybridizations of breast carcinoma sections indicated that the D52 gene was expressed in cancer cells, whereas other genes identified in the differential screening were expressed in fibroblastic or inflammatory cells within the tumor stroma. Thus, the procedure developed in this study selected genes expressed in a diversity of cell types, indicating its potential usefulness in other systems.
Lysosomal Integral Membrane Protein II Binds Thrombospondin-1 (1998)

LIMPII (lysosomal integral membrane protein II) is one of a family of proteins structurally related to the cell surface glycoprotein CD36. We recently defined a single structural domain on CD36 that mediates binding to adhesive glycoprotein thrombospondin-1 (TSP1). The CD36-TSP1 interaction is known to play a role in platelet-tumor and platelet-monocyte adhesion, angiogenesis, and in monocyte uptake of apoptotic cells. To test whether LIMPII also binds TSP1, a LIMPII peptide corresponding to the TSP1 binding domain of CD36 was expressed as a recombinant glutathione S-transferase (GST) fusion protein. In solid phase binding assays, purified 125I-TSP1 bound to immobilized GST/LIMPII in a time-dependent and saturable manner. Inhibition by excess unlabeled TSP1 or EDTA demonstrated specificity. LIMPII.TSP1 complex formation was specifically blocked by soluble LIMPII fusion protein, by monospecific rabbit IgG directed against the LIMPII peptide and by CD36 fusion proteins containing the TSP1 binding domain. Transfection of Bowes melanoma cells with a chimeric LIMPII cDNA that targets expression to the plasma membrane conferred the ability to bind 125I-TSP1 and to adhere to TSP1-coated surfaces. This study defines a TSP1 binding site conserved between LIMPII and CD36 and suggests that cell surface LIMPII may function in some circumstances as an adhesion receptor for TSP1. Computer-assisted homology searches suggest that the TSP1 recognition motif identified from study of CD36 family members may be widely expressed in nature.
Elastically Deforming 3D Atlas to Match Anatomical Brain Images (1993)

To evaluate our system for elastically deforming a three-dimensional atlas to match anatomical brain images, six deformed versions of an atlas were generated. The deformed atlases were created by elastically mapping an anatomical brain atlas onto different MR brain image volumes. The mapping matches the edges of the ventricles and the surface of the brain; the resultant deformations are propagated through the atlas volume, deforming the remainder of the structures in the process. The atlas was then elastically matched to its deformed versions. The accuracy of the resultant matches was evaluated by determining the correspondence of 32 cortical and subcortical structures. The system on average matched the centroid of a structure to within 1 mm of its true position and fit a structure to within 11% of its true volume. The overlap between the matched and true structures, defined by the ratio between the volume of their intersection and the volume of their union, averaged 66%. When the gray-white interface was included for matching, the mean overlap improved to 78%; each structure was matched to within 0.6 mm of its true position and fit to within 6% of its true volume. Preliminary studies were also made to determine the effect of the compliance of the atlas on the resultant match.