gebhart/patrepeval huggingface dataset:
A simple answer for a splicing conundrum (2005)

A Simple Answer for a Splicing Conundrum. Douglas L. Black The medieval philosopher William of Occam admonished that it is best to minimize the postulated entities needed to explain a system. This concept of choosing the simplest explanation of unknown phenomena is now known as the Principle of Parsimony or Occam's Razor. However, in biology, where systems tend to evolve towards states of greater complexity, Occam's Razor can be a dangerous tool. Most often the known components of a biological process increase with study. It is not always safe to assume a limited number of factors are involved. Sometimes though, we do find a simple explanation of a puzzling phenomenon that requires no new unknowns to be added to the model. Such an event is described in this issue of PNAS, where three groups nicely explain a long-standing puzzle in eukaryotic mRNA processing [1]. Specifically, they demonstrate a plausible mechanism for how exons are always linked in order during the pre-mRNA splicing process, without a single exon being skipped. Eukaryotic mRNAs are transcribed as long precursor molecules containing intervening sequences, or introns separating the coding or otherwise functional portions of the transcript called exons (Figure 1A). To form a mature mRNA ready for translation, the cell must precisely excise the introns and ligate the exons together. This process of pre-mRNA splicing is carried out in the cell nucleus by a large macromolecular complex called the spliceosome [2]. Components of the spliceosome recognize special sequences at the intron ends called splice sites. The 5' splice site (at the 5' end of the intron) is initially bound by the U1 snRNP, and the 3' splice site is bound by the protein U2 Auxiliary Factor (U2AF) [3, 4]. These components interact to bring the two ends of the intron together, before going on to assemble the rest of the spliceosome that ultimately catalyzes the cleavage/ligation reactions. Early on, two questions of how splice sites are chosen for pairing during splicing were seen as particularly mysterious [5-7]. First, introns can be very long (>1000 nt.) and have within them many copies of the splice site consensus sequences. It was not understood how the correct sites at the intron ends were recognized, while the other cryptic sites were avoided. Second, pre-mRNAs can contain many exons that must
Sequence Requirements of the 5-Enolpyruvylshikimate-3-phosphate Synthase 5[prime]-Upstream Region for Tissue-Specific Expression in Flowers and Seedlings. (1990)

We have analyzed expression from deletion derivatives of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) 5[prime]-upstream region in transgenic petunia flowers and seedlings. In seedlings, expression was strongest in root cortex cells and in trichomes. High-level expression in petals and in seedling roots was conferred by large (>500 base-pair) stretches of sequence, but was lost when smaller fragments were analyzed individually. This apparent requirement for extensive sequence suggests that combinations of cis-elements that are widely separated control tissue-specific expression from the EPSPS promoter. We have also used the high-level, petal-specific expression of the EPSPS promoter to change petal color in two mutant petunia lines.
Fringe Modifies O-Fucose on Mouse Notch1 at Epidermal Growth Factor-like Repeats within the Ligand-binding Site and the Abruptex Region (2003)

Fringe plays a key role in the specification of boundaries during development by modulating the ability of Notch ligands to activate Notch receptors. Fringe is a fucose-specific beta1,3-N-acetylglucosaminyltransferase that modifies O-fucose moieties on the epidermal growth factor-like (EGF) repeats of Notch. To investigate how the change in sugar structure caused by Fringe modulates Notch activity, we have analyzed the sites of O-fucose and Fringe modification on mouse Notch1. The extracellular domain of Notch1 has 36 tandem EGF repeats, many of which are predicted to be modified with O-fucose. We recently proposed a broadened consensus sequence for O-fucose, C(2)X(3-5)(S/T)C(3) (where C(2) and C(3) represent the second and third conserved cysteines), significantly expanding the potential number of modification sites on Notch. Here we demonstrate that sites predicted using this broader consensus sequence are modified with O-fucose on mouse Notch1, and we present evidence suggesting that the consensus can be further refined to C(2)X(4-5)(S/T)C(3). In particular, we demonstrate that EGF 12, a portion of the ligand-binding site, is modified with O-fucose and that this site is evolutionarily conserved. We also show that endogenous Fringe proteins in Chinese hamster ovary cells (Lunatic fringe and Radical fringe) as well as exogenous Manic fringe modify O-fucose on many but not all EGF repeats of mouse Notch1. These findings suggest that the Fringes show a preference for O-fucose on some EGF repeats relative to others. This specificity appears to be encoded within the amino acid sequence of the individual EGF repeats. Interestingly, our results reveal that Manic fringe modifies O-fucose both at the ligand-binding site (EGF 12) and in the Abruptex region. These findings provide insight into potential mechanisms by which Fringe action on Notch receptors may influence both the affinity of Notch-ligand binding and cell-autonomous inhibition of Notch signaling by ligand.
Irreversible electroporation on the small intestine (2012)

Our results indicate that this novel procedure can be used for abdominal cancer treatment while minimising collateral damage to adjacent tissues because of the unique ability of the NTIRE ablation method to target the cell membrane.
Improved molecular diagnostics for ornithine transcarbamylase deficiency. (1991)

Since the cloning of the cDNA for X-linked ornithine transcarbamylase (OTC) in 1984, diagnostic accuracy of OTC deficiency for prenatal and carrier detection has been greatly improved by the use of linkage analysis. However, the use of RFLP-based diagnosis is limited in this and in other new mutation diseases. Here we report both the use of direct mutation detection by new PCR-based techniques and our experience with linkage-based diagnosis in 18 families. We have previously reported the use of chemical mismatch cleavage to detect mutations first in amplified mRNA and then in genomic DNA of patients. This technique has now been utilized for prenatal diagnosis. Primers for specific amplification of OTC exons 1, 3, 5, 9, and 10 have been developed and been employed to map deletions of the OTC gene in two families. These primers also have been used to detect alterations in the TaqI sites found in exons 1, 3, 5, and 9. Four novel mutations of the OTC gene leading to abolition of a TaqI site in the OTC cDNA were discovered. One of these mutations is in exon 1; two lie in exon 3; and one is in exon 9. In addition, we have used the PCR products as probes to identify the exon-specific bands seen on Southern blots and to map the polymorphic BamHI and MspI sites, which are commonly used for linkage analysis. This information will facilitate the interpretation of altered band patterns seen in deletion cases and in cases of point mutations affecting restriction sites. Utilization of the appropriate combination of these molecular techniques permitted accurate diagnostic evaluations in 17 of 18 families.
Study of dense FRCs formation and their transport with multistage compression (2013)

Summary form only given. A, pulsed hot dense compact plasma torus (CT) in a Field Reversed Configuration (FRC), of few keV temperature, density (10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">23</sup> -10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">24</sup> ) m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> , and a life time of several microseconds is of great interest for fusion research as an alternative to already canonical inertial, magnetic stationary approaches and magnetized target fusion [1-3]. This paper provides a brief description of prototypical experiments on formation of two FRCs, their transport in a sequence of multistage compressions and final collision in the center of device. The goal of this experiment is to test various alternative pulsed power technologies for FRC formation as well as the evolution of formed CTs at higher stored energies. Furthermore, the experiment may provide a preliminary assessment of the feasibility of such a scheme of distributed magnetic compression/acceleration of plasma CTs for controlled thermonuclear fusion. Analysis of first experimental results with stored energy in the 0.5-1 MJ and their comparison with respective computer simulations will be given.
Stereoscopic 3D copy & paste (2010)

With the increase in popularity of stereoscopic 3D imagery for film, TV, and interactive entertainment, an urgent need for editing tools to support stereo content creation has become apparent. In this paper we present an end-to-end system for object copy & paste in a stereoscopic setting to address this need. There is no straightforward extension of 2D copy & paste to support the addition of the third dimension as we show in this paper. For stereoscopic copy & paste we need to handle depth, and our core objective is to obtain a convincing 3D viewing experience. As one of the main contributions of our system, we introduce a stereo billboard method for stereoscopic rendering of the copied selection. Our approach preserves the stereo volume and is robust to the inevitable inaccuracies of the depth maps computed from a stereo pair of images. Our system also includes an interactive stereoscopic segmentation tool to achieve high quality object selection. Hence, we focus on intuitive and minimal user interaction, and our editing operations perform within interactive rates to provide immediate feedback.
Laser Welding of AZ91 and WE43 Magnesium Alloys for Automotive and Aerospace Industries (2001)

No abstracts
A new era in the treatment of coronary disease? (2003)

The technique of coronary stenting introduced in the early 1990s contributed widely to the enhancement of percutaneous interventions' outcomes in patients with coronary artery disease.

However, the phenomenon of in-stent restenosis has long been the stumbling block of interventional cardiology and the target of many research projects in this field including the use of various devices or radiation therapy, and systemic or local delivery of biochemical substances and drugs.

Indeed, angiographic restenosis, defined as a stenosis or narrowing of the vessel diameter by ≥50% at follow-up evaluation (binary restenosis), is still reported in 17–30% of patients followingcardiac stenting with uncoated or bare stents.1,2 Restenosis following stenting is largely due toneointimal hyperplasia, which is the healingresponse to the vascular injury induced by stent implantation and mechanical dilatation and translates into proliferation of smooth muscle cells.3–6 It is in this context that the technology of site-specific, stent-based drug delivery to inhibit the restenosis process has emerged.

The ability of a wide variety of pharmaceuticals to inhibit restenosis following coronary interventions has been assessed. Evaluation of some of these agents, (actinomycin D, Batismastat and QP2) was discontinued in view of the poor results obtained in the preliminary phases of clinical trials. Among the various drugs investigated, Sirolimus and Paclitaxel stood out as yielding very promising results. So far, however, the longest follow-up study available in the largest group of patients has been conducted with Sirolimus.

Indeed, the local delivery of Sirolimus (rapamycin), a natural macrocyclic lactone whichinhibits cytokine and growth factor-mediated cell proliferation in lymphocytes and smooth muscle cells, was shown to reduce neointimal proliferation in animal models as well as in a small, uncontrolled series of patients with coronary artery disease: the First-in-Man pilot study.7 A total of 45 patients were included in this non-randomized trial conducted in Sao …
Endophytic hyphal compartmentalization is required for successful mycobiont-wheat interaction as revealed by confocal laser microscopy (2009)

Root endophytic fungi are seen as promising alternatives to replace chemical fertilizers and&#13;\npesticides in sustainable and organic agriculture systems. Fungal endophytes structure&#13;\nformations play key roles in symbiotic intracellular association with plant-roots. To compare&#13;\nthe morphologies of Ascomycete endophytic fungi in wheat, we analyzed growth&#13;\nmorphologies during endophytic development of hyphae within the cortex of living vs dead&#13;\nroot cells. Confocal laser scanning microscopy (CLSM) was used to characterize fungal cell&#13;\nmorphology within lactofuchsin-stained roots. Cell form regularity Ireg and cell growth&#13;\ndirection Idir, indexes were used to quantify changes in fungal morphology. Endophyte fungi&#13;\nin living roots had a variable Ireg and Idir values, low colonization abundance and patchy&#13;\ncolonization patterns, whereas the same endophyte species in dead (γ-irradiated) roots had&#13;\nconsistent form of cells and mostly grew parallel to the root axis. Knot, coil and vesicle&#13;\nstructures dominated in living roots, as putative symbiotic functional organs. Finally, an&#13;\nincreased hypha septation in living roots might indicate local specialization within&#13;\nendophytic Ascomycota. Our results suggested that the applied method could be expanded to&#13;\nother septate fungal symbionts.
An analysis of MRI and ultrasound imaging in patients with gout who have normal plain radiographs (2009)

A large percentage of patients with gout and normal plain radiographs have occult destructive arthropathy that is only detected by advanced imaging such as MRI and/or US. However, MRI appears to be much more sensitive than US at detecting these findings.
Phenylketonuria Due to a Deficiency of Dihydropteridine Reductase (1975)

The onset of neurologic symptoms in a child who had markedly elevated blood phenylalanine levels during the first two weeks of life and who was promptly treated with a low phenylalanine diet, with excellent control of serum phenylalanine levels, suggested that this child had an unusual form of phenylketonuria. In assays of the components of the phenylalanine hydroxylating system (open liver biopsy at 14 months), the activity of phenylalanine hydroxylase was 20 per cent of the average normal adult value. By contrast, no dihydropteridine reductase activity was detected in the patient's liver, brain or cultured skin fibroblasts. Since dihydropteridine reductase is also essential for the biosynthesis of dopamine, norepinephrine, and serotonin, disturbed neurotransmitter function may be responsible for the patient's neurologic deterioration. On the basis of these results, assay of reductase in cultured skin fibroblasts may be advisable in the initial diagnosis of phenylketonuria.
Relations among Actors in Governmental Projects (2013)

This paper aims to study an eleven-year project of Mobile Government (mGov) in the state of Paraná, Brazil. The precocious experience in Brazil in mGov and the number of cell phones used in the country are not arguments for these to be used in providing mass public services. Mason’s Historical Method was used to get to know the project, raising available information and retrieving happenings and results. To identify events, relevant actors, their roles, aspects in collaboration, setting and density of the relations among these actors, Social Network Analysis was used. The authors conclude it is important to formalize the project, but that will not guarantee its continuity in the long run. Characterizing phases minimizes the importance given to the change of governors after new elections in large corporative projects. The networks forming favors the dissemination of IT knowledge among actors.
Doxycycline Modulates Nitric Oxide Production in Murine Lung Epithelial Cells (2006)

Many effective therapeutic agents exhibit effects that are different from their intended primary mode of action. Antibiotics such as doxycycline and erythromycin A are no exception. They also display anti-inflammatory activity. Using LA4 murine lung alveolar epithelial cells, effects of doxycycline and erythromycin A on inducible NO synthase (iNOS) NO production as well as iNOS protein and mRNA production were investigated. Induction of iNOS was accomplished by treatment with cytomix (TNF-alpha, IL-1beta, and IFN-gamma each at 5 ng/ml). Production of NO or iNOS was not detected in controls with or without erythromycin A. In the presence of cytomix, erythromycin A did not decrease NO, nitrite, iNOS protein, or mRNA production. In contrast, doxycycline caused a dose-dependent decrease in NO, nitrite, iNOS protein, and mRNA production in cytomix-treated cells. Doxycycline at 30 mug/ml produced a 90% decrease in nitrite and NO production and a 52% decrease in iNOS mRNA transcription compared with cytomix treatment alone. Actinomycin D treatment suggests that doxycycline decreases stability of iNOS mRNA in cytomix-treated cells. To determine a mechanism for the decrease in iNOS expression, NF-kappaB and AP-1 transcription regulatory systems and p38 MAPK were examined. Doxycycline treatment gave no statistically significant change in NF-kappaB activation but did decrease p38 MAPK protein in cytomix-treated cells by 50%, suggesting that p38 MAPK may be responsible for stabilization of iNOS mRNA. These results demonstrate that doxycycline decreases NO production from iNOS by destabilization of iNOS mRNA via decreased expression of p38 MAPK.
Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9 (2007)

Hemozoin (HZ) is an insoluble crystal formed in the food vacuole of malaria parasites. HZ has been reported to induce inflammation by directly engaging Toll-like receptor (TLR) 9, an endosomal receptor. "Synthetic" HZ (beta-hematin), typically generated from partially purified extracts of bovine hemin, is structurally identical to natural HZ. When HPLC-purified hemin was used to synthesize the crystal, beta-hematin had no inflammatory activity. In contrast, natural HZ from Plasmodium falciparum cultures was a potent TLR9 inducer. Natural HZ bound recombinant TLR9 ectodomain, but not TLR2. Both TLR9 stimulation and TLR9 binding of HZ were abolished by nuclease treatment. PCR analysis demonstrated that natural HZ is coated with malarial but not human DNA. Purified malarial DNA activated TLR9 but only when DNA was targeted directly to the endosome with a transfection reagent. Stimulatory quantities of natural HZ contain <1 microg of malarial DNA; its potency in activating immune responses was even greater than transfecting malarial DNA. Thus, although the malarial genome is extremely AT-rich, its DNA is highly proinflammatory, with the potential to induce cytokinemia and fever during disease. However, its activity depends on being bound to HZ, which we propose amplifies the biological responses to malaria DNA by targeting it to a TLR9(+) intracellular compartment.
Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate (2015)

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST-weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH-dependent exchange rate followed a dominantly base-catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system.
Elucidation of regulatory elements that control damage induction and competence induction of the Bacillus subtilis SOS system (1993)

A novel consensus sequence (GAAC-N4-GTTC) has been identified within the promoter regions of DNA damage-inducible (din) genes from Bacillus subtilis. This sequence has been proposed to function as an operator site that is required for regulation of the SOS system of B. subtilis. To test this hypothesis, a deletion analysis of the dinA and recA promoter regions was utilized. A single consensus sequence is sufficient and necessary for damage-inducible regulation of the dinA and recA promoters. Deletion of the consensus sequences upstream of these promoters derepressed their expression under uninduced conditions. In addition, this deletion analysis has further defined sequences upstream of the recA promoter that are required for expression of the recA gene in cells that have differentiated to the state of natural competence. Northern (RNA) hybridization and S1 nuclease protection experiments have demonstrated that the damage-inducible and competence-inducible recA-specific transcripts initiate from a single promoter. Mutations within the comA, srfA, and degU loci each completely abolish the competence-inducible expression of the recA gene.
Low-temperature (&lt;450 °C), plasma-assisted deposition of poly-Si thin films on SiO2 and glass through interface engineering (1997)

A low-temperature, two-stage process that employs interface engineering is investigated for deposition of poly-Si thin films on SiO2 and glass. In this two-stage process, film growth is separated into two regimes: (i) interface formation and (ii) bulk film growth. Interface formation (stage 1) was optimized for remote plasma enhanced chemical-vapor deposition (PECVD) of ultra thin (&amp;lt;100 Å) μc-Si films on the oxide. This layer acts as a seed template, providing ordered growth sites for the next stage of film growth. Bulk Si film deposition (stage 2) was then initiated on the seed template using remote PECVD process conditions shown to produce low-temperature (&amp;lt;450 °C), epitaxial-Si films on crystalline silicon substrates, so as to drive a transition to larger grain growth off of the seed crystals. Results showed that the seed layer had a dramatic impact on bulk film crystallinity. Films deposited without a μc-Si seed layer were amorphous, whereas films deposited using a seed layer, in conjunction with the appropriate second stage conditions, were highly oriented (220) poly-Si.
Effect of primrose oil on serum lipids and blood pressure in hyperlipidemic subjects. (1986)

Primrose oil (about 72% of fatty acids 18:2 omega 6 and 9% of 18:3 omega 6) was supplemented in addition to the used diet of 20 hyperlipidemic patients for 3 months in an open study. The dose of primrose oil was 2.4 ml, 4.8 ml and 7.2 ml during the first, second and third month, respectively. Primrose oil increased the proportion of gamma-linolenic acid in serum cholesteryl esters (1.81 vs. 2.13%, p less than 0.05), phospholipids (0.65 vs. 0.82%, p less than 0.01), triglycerides (0.70 vs. 0.99%, p less than 0.01) and free fatty acids (0.80 vs. 0.91%, NS). It did not, however, change serum cholesterol, HDL cholesterol or triglyceride mean values. Blood pressure mean values remained unchanged during the follow-up as well.