gebhart/patrepeval huggingface dataset:
Lack of DNA Polymerase θ (POLQ) Radiosensitizes Bone Marrow Stromal CellsIn Vitroand Increases Reticulocyte Micronuclei after Total-Body Irradiation (2009)

Abstract Mammalian POLQ (pol theta) is a specialized DNA polymerase with an unknown function in vivo. Roles have been proposed in chromosome stability, as a backup enzyme in DNA base excision repair, and in somatic hypermutation of immunoglobulin genes. The purified enzyme can bypass AP sites and thymine glycol. Mice defective in POLQ are viable and have been reported to have elevated spontaneous and radiation-induced frequencies of micronuclei in circulating red blood cells. To examine the potential roles of POLQ in hematopoiesis and in responses to oxidative stress responses, including ionizing radiation, bone marrow cultures and marrow stromal cell lines were established from Polq(+/+) and Polq(-/-) mice. Aging of bone marrow cultures was not altered, but Polq(-/-) cells were more sensitive to gamma radiation than were Polq(+/+) cells. The D(0) was 1.38 +/- 0.06 Gy for Polq(+/+) cells compared to 1.27 +/- 0.16 and 0.98 +/- 0.10 Gy (P = 0.032) for two Polq(-/-) clones. Polq(-/-) cells were moderately more sensitive to bleomycin than Polq(+/+) cells and were not hypersensitive to paraquat or hydrogen peroxide. ATM kinase activation appeared to be normal in gamma-irradiated Polq(-/-) cells. Inhibition of ATM kinase activity increased the radiosensitivity of Polq(+/+) cells slightly but did not affect Polq(-/-) cells. Polq(-/-) mice had more spontaneous and radiation-induced micronucleated reticulocytes than Polq+/+ and (+/-) mice. The sensitivity of POLQ-defective bone marrow stromal cells to ionizing radiation and bleomycin and the increase in micronuclei in red blood cells support a role for this DNA polymerase in cellular tolerance of DNA damage that can lead to double-strand DNA breaks.
Acquired resistance to MET inhibition in MET driven NSCLC. (2019)

9030 Background: MET mutations ( MET∆ ex14 ), amplifications or translocations can activate oncogenic signaling in lung cancer and are sensitive to MET inhibition. Acquired resistance to therapy with MET tyrosine kinase inhibitors (TKI) occurs inevitably. Methods: Between 2015 and 2018, eighteen patients with MET-driven NSCLC were treated with capmatinib or crizotinib as single agent at our site. Rebiopsy samples from five patients were analyzed by NGS and fluoreszenz-in-situ hybridization (FISH) at time of progression. Results: Of the five patients with rebiopsy samples at time of progression, two had initially a MET amplification (one patient with low-level and one patient with high-level amplification), two patients had a MET∆ ex14 and one patient had a KIF5B-MET fusion. Patient 1 (low-level MET amplification) showed a partial response to crizotinib. The rebiopsy revealed an acquired KRAS mutation as a potential mechanism of resistance. Patient 2 (high-level MET amplification) showed stable disease as best response to capmatinib and patient 3 (MET∆ ex14 ) showed a partial response to capmatinib. Both patients developed acquired HER2 amplifications. Patient 4 ( MET∆ ex14 ) showed initially a partial response to crizotinib. The rebiopsy sample revealed an acquired MET kinase domain mutation (p.D1246N). As preclinical findings suggested that D1246N confers resistance to type I MET inhibitors but remains sensitive to type II inhibitors, cabozantinib was started. A CT six weeks after therapy initiation showed progressive disease. Patient 5 ( KIF5B-MET) had a partial response to crizotinib. An acquired MET p.Y1248H mutation was found at time of progression. Therapy was changed to cabozantinib. A new CT scan is pending. Conclusions: Resistance to MET inhibition is heterogeneous with on- and off-target-mechanisms occurring. We found HER2 amplification as a potential new bypass mechanism. The MET mutation D1246N conferred resistance to type I and type II inhibitors. We describe the first case of an acquired mutation of the MET tyrosine kinase domain in a patient with an oncogenic MET fusion. Further investigations are needed to collect comprehensive data to understand resistance mechanisms in MET inhibition and to develop novel therapeutic strategies.
N-Heterocyclic carbene-based C-centered Au(I)-Ag(I) clusters with intense phosphorescence and organelle-selective translocation in cells (2022)

Photoluminescent gold clusters are functionally variable chemical modules by ligand design. Chemical modification of protective ligands and introduction of different metals into the gold clusters lead to discover unique chemical and physical properties based on their significantly perturbed electronic structures. Here we report the synthesis of carbon-centered Au(I)-Ag(I) clusters with high phosphorescence quantum yields using N-heterocyclic carbene ligands. Specifically, a heterometallic cluster [(C)(Au<sup>I</sup>-L)<sub>6</sub>Ag<sup>I</sup><sub>2</sub>]<sup>4+</sup>, where L denotes benzimidazolylidene-based carbene ligands featuring N-pyridyl substituents, shows a significantly high phosphorescence quantum yield (Φ = 0.88). Theoretical calculations suggest that the carbene ligands accelerate the radiative decay by affecting the spin-orbit coupling, and the benzimidazolylidene ligands further suppress the non-radiative pathway. Furthermore, these clusters with carbene ligands are taken up into cells, emit phosphorescence and translocate to a particular organelle. Such well-defined, highly phosphorescent C-centered Au(I)-Ag(I) clusters will enable ligand-specific, organelle-selective phosphorescence imaging and dynamic analysis of molecular distribution and translocation pathways in cells.
An Overview of Current Approaches to Mashup Generation. (2009)

Abstract: Mashups allow users to bring together data and services from various web applications in order to create anew integrated tool that serves their needs. In the last few years, avariety of mashups frameworks has been proposed that promise to simplify the mashup creation process so that every user is able to create mashups. In this paper, wegive anoverview about these approaches and identify their limitations. The main insight is that the average user will not possess the necessary skills to create mashups that meet his needs with these tools. We therefore propose that atool is needed that allows for the automatic ad-hoc generation of mashups. 1
Synthesis of volatile, fluorinated β-ketoiminato copper(I) complexes (1992)

The fluorinated β-ketoimines, 4-(alkyl)imino-1,1,1,5,5,5-hexafluoropentan-2-one, where alkly = isopropyl 3 or trifluoroethyl 6, have been obtained in high yield from the reaction of a silyl ether of hexafluoroacetylacetone with isopropylamine and trifluoroethylamine, respectively, and used to prepare volatile, monomeric copper(I)β-ketoiminate complexes.
Isolation of bovine kidney leucine aminopeptidase cDNA: Comparison with the lens enzyme and tissue-specific expression of two mRNAs (1993)

Aminopeptidases catalyze the hydrolysis of amino acid residues from the amino terminus of peptide substrates. Leucine aminopeptidase (LAP) from bovine lens is the best characterized aminopeptidase and the only LAP for which the amino acid sequence was determined by protein sequencing. Using this sequence information, we isolated a bovine kidney LAP cDNA and compared its deduced amino acid sequence to the published amino acid sequence for bovine lens LAP. Overall, the sequences are highly conserved. However, several differences are observed. The kidney LAP cDNA indicates a 26 amino acid extension at the amino terminus which is not found in the mature purified lens LAP. The cDNA also indicates an additional octapeptide in the C-terminal region which was not indicated in the published lens LAP amino acid sequence but which was required for best fit of crystallographic data regarding bovine lens LAP. Several other single amino acid changes were also noted. Levels of LAP transcripts were examined in bovine lens and kidney tissue as well as in cultured lens cells. Lens epithelial tissue showed only one LAP transcript (2.4 kb) whereas two transcripts (2.0 and 2.4 kb) were observed in cultured lens cells derived from epithelial tissue and in kidney tissue. Using Northern blot analysis, we correlated LAP mRNA levels with previously determined changes of LAP activity in aging lens tissue and in progressively passaged lens epithelial cells which were used to simulate aging in vitro. No differences were found in LAP mRNA levels in epithelial tissue from old and young lenses.(ABSTRACT TRUNCATED AT 250 WORDS)
Integration of surface and logging NMR data to map hydraulic conductivity (2013)

We investigate elements of a framework to efficiently map hydraulic conductivity (K) over wide areas by integrating surface and logging NMR data. Central to the broader framework is the need to characterize site- and measurement-specific relationships between surface NMR, logging NMR, and hydraulic conductivity data sets. We outline progress toward this goal focusing separately on the relationship between each of the three data types, emphasizing most recent findings. We identify well-development as an important factor affecting the relationship between NMR logging data and K. We also present results showing that multi-pulse surface NMR sequences provide access to NMR parameters more closely related to K. Finally, we present data examples illustrating extension of the framework to wide-scale acquisition of 2D surface NMR data.
Incidence and consequences of periprocedural occlusion. The 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. (1990)

Of 1,801 patients in the 1985-1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry, 122 (6.8%) had periprocedural occlusion (4.9% in the catheterization laboratory, 1.9% outside the laboratory). Baseline patient factors independently associated with increased occlusion rates included triple-vessel disease, high risk status for surgery, and acute coronary insufficiency. Lesion characteristics showing significant positive association included severe stenosis before PTCA, diffuse or multiple discrete morphology, thrombus, and collateral flow from the lesion. Intimal tear and dissection were also very strongly associated with occlusion. Sixty patients (49%) had a transient occlusion that was reopened with PTCA, 43 (35%) were not redilated and managed with bypass surgery, and 19 (16%) were not redilated and managed medically. In-hospital mortality was 5% in each of these treatment groups, compared with 1% in occlusion-free patients. In-hospital infarction rates ranged from 27% in patients with transient occlusion to 56% in the patients managed with surgery, compared with 2% in patients without occlusion. During 2 years of follow-up, somewhat increased mortality continued in patients with occlusion, whereas follow-up infarction rates were comparable for all patients regardless of occlusion. Patients with an occlusion that was reopened or managed medically had increased rates of surgery during follow-up. Rates of repeat PTCA were comparable (about 23% by 2 years) in patients with transient occlusion and those without occlusion. Occlusion remains a serious complication of angioplasty and is associated most strongly with major events and surgical procedures that occur during the in-hospital period.
Hill-Based Model as a Myoprocessor for a Neural Controlled Powered Exoskeleton Arm - Parameters Optimization (2006)

The exoskeleton robot, serving as an assistive device worn by the human (orthotic), functions as a human-amplifier. Setting the human machine interface (HMI) at the neuro-muscular level may lead to seamless integration and an intuitive control of the exoskeleton arm as a natural extension of the human body. At the core of the exoskeleton HMI there is a myoprocessor. It is a model of the human muscle, running in real-time and in parallel to the physiological muscle, that predicts joint torque as a function of the joint kinematics and neural activation levels. The study is focused on developing a myoprocessor based on the Hill phenomenological muscle model. Genetic algorithms were used to optimize model internal parameters using an experimental database that provides inputs to the model and allows for performance assessment. The results indicate high correlation between joint moment predictions of the model and the measured data. Consequently, the myoprocessor seems an adequate model, sufficiently robust for further integration into the exoskeleton control system.
Histology of knees from Pre-PDT treated mice. (2015)

&lt;p&gt;Histopathological images of the intraarticular tissues of the knee joint in the preventive PDT (Pre-PDT) group and the PS-IR- group (hematoxylin-eosin staining and immunostaining using an anti-GR-1 antibody). Bar = 50 µm.&lt;/p&gt;
The adenosine A 2A receptor agonist regadenoson decreases activation of invariant NKT cells in human sickle cell subjects (2012)

Sickle cell disease (SCD) is associated with widely disseminated vaso‐occlusion caused by hyper‐adherent sickle red blood cells and leukocytes. Recurrent episodes of ischemia reperfusion‐injury in the vasculature of SCD individuals promote a pro‐inflammatory state. In a mouse model of SCD, adenosine A 2A receptor (A 2A R) activation significantly decreases pulmonary inflammation and dysfunction. Similar protective effects are produced by depleting invariant NKT (iNKT) cells or by blocking CD1d restricted activation of iNKT cells, indicating that A 2A R agonists mediate their anti‐inflammatory effects primarily by inhibiting iNKT cell activation. We have initiated a clinical trial to investigate the safety and efficacy of a selective A 2A R agonist, regadenoson, in human SCD subjects. Our findings indicate that iNKT cells in blood from normal subjects are fewer in number and less activated than from subjects with SCD. Furthermore, activated iNKT cells from SCD subjects are CD4+ and express elevated levels of phospho‐NFκB (P‐NFκB), CD69, and the A 2A R. Most significantly, infused regadenoson was observed to diminish iNKT cell expression of P‐NFκB and other activation markers in a time dependent manner. These results imply that A 2A R signaling and NFκB regulate iNKT cell activation and that selective A 2A R agonists may be useful for treating acute vaso‐occlusion in SCD.
Similar Manga Retrieval Using Visual Vocabulary Based on Regions of Interest (2011)

Manga, a kind of graphic novels expressed by sequential line drawings, is an important document image publication which is invoking more and more attentions for their copyright protection. Because of simple constructions and abstract expression styles, similar copies are always applied in plagiarisms of mangas. In addition, the enormous volume of copyrighted manga publications issues a challenge to the task of detecting suspicious images. Considering only some regions of interests (ROIs) require copyright protection, we propose a bag-of-features method using visual words based on ROIs for similar manga retrieval. In the experiments, we applied real manga publications as data and proved the effectiveness of the proposed method.
Tietoliikenneoperaattorin vaihto suuressa yrityksessä (2009)

Opinnäytetyössä dokumentoitiin toisen tietoliikenneoperaattorin rinnalle otto Lemminkäinen konsernissa. Projektin tavoitteena oli kahdentaa pääkonttorin tietoliikenneyhteydet toisella operaattorilla, siirtää noin puolet yrityksen toimipisteistä uuden operaattorin verkkoon ja mahdollistaa kahden operaattorin välinen kilpailutus tulevaisuudessa muiden toimipaikkojen liittymien osalta.&#13;\n&#13;\nAloituspalaveri uuden operaattorin kanssa pidettiin alkuvuodesta 2008 ja sen yhteydessä käynnistettiin projekti, jonka aikana suunniteltiin, rakennettiin ja testattiin uuden operaattorin yhteydet pääkonttorille ja pilottina toimivaan Vantaanportin toimipaikkaan. Kun pääkonttorin kahdennettu yhteys ja yhteydet Vantaanporttiin saatiin toimimaan halutulla tavalla, yliheitettiin pilottipaikka uuden operaattorin verkkoon.&#13;\n&#13;\nToimipaikan siirtäminen toisen operaattorin MPLS-verkkoon tehtiin luomalla uusi verkko Lemminkäisen tietojärjestelmiin, jolloin toimipaikan kytkeytyessä toisen operaattorin kautta pääkonttoriin, kaikki oli valmiina ja vain IP-osoitteet muuttuivat. Työssä on esitelty tarvittavat muutokset ja asetukset, joilla uusi verkko luodaan ja varmistutaan, ettei toimipaikan uuteen verkkoon siirtäminen aiheuta pitkää tietoliikennekatkosta tai muita suurempia ongelmia toimipaikan työntekijöille.&#13;\n&#13;\nOnnistuneen pilottipaikan yliheiton jälkeen siirryttiin projektista tuotantovaiheeseen, jolloin yksittäisen toimipaikan yliheitto toisen operaattorin verkkoon oli dokumentoitu ja ”tuotteistettu” Lemminkäisen tietohallinnon osalta.&#13;\n&#13;\nTyössä on esitetty myös ongelmakohtia edellisen operaattorin kanssa, kuin myös ongelmia uuden operaattorin käyttöönotossa.&#13;\n&#13;\nTyötä voidaan käyttää ohjekirjana uusien toimipaikkojen yliheittojen suorittamisessa tai käyttöönotoissa Lemminkäisellä. Työtä voidaan myös hyödyntää vastaavanlaisessa projektissa Lemminkäisellä, samoin kuin myös muussa isossa yrityksessä.
Residual stress versus microstructural effects on the strength and toughness of phase‐separated PbO–B 2 O 3 –Al 2 O 3 glasses (2022)

Abstract A few authors have reasonably proposed that liquid–liquid phase‐separated (LLPS) glasses could show improved fracture strength, S f , and toughness, K Ic , as the second phase could provide a barrier to crack propagation via deflection, bowing, trapping, or bridging. Due to the associated tensile or compressive residual stresses, the second phase could also act as a toughening or a weakening mechanism. In this work, we investigated five glasses of the PbO–B 2 O 3 –Al 2 O 3 system spanning across the miscibility gap: Four of them undergo LLPS—three are binodal (two B 2 O 3 ‐rich and one PbO‐rich) and one is spinodal—and one does not show LLPS (composition outside the miscibility gap). Their compositions were designed in such a way that the amorphous particles are under compressive residual stresses in some and under tensile residual stresses in others. The following mechanical properties were determined: the Vickers hardness, ball on three balls (B3B) strength, and toughness, K Ic‐SEVNB (single‐edge V‐notch beam [SEVNB]). The microstructures and compositions were analyzed using scanning electron microscopy with energy‐dispersive X‐ray spectrometry. The spinodal glass showed, by far, the best mechanical properties. Its K Ic‐SEVNB = 1.6 ± 0.1 MPa m 1/2 , which embodies an increase of almost 50% over the B 2 O 3 ‐rich binodal composition, and 90% considering the PbO‐rich binodal composition. Moreover, its fracture strength, S f = 166 ± 7 MPa, is one of the highest ones ever reported for an LLPS glass. Fracture analyses evidenced that the spinodal composition exhibited the lowest net stress at the fracture point. Moreover, calculations indicate that the internal residual stress level is the lowest in the spinodal glass. The overall results indicate that the microstructural effect of the spinodal glass is the most significant factor for its superior mechanical properties. This work corroborates the idea that LLPS provides a feasible and stimulating solution to improve the mechanical properties of glasses.
VEGF164differentially regulates neutrophil and T cell adhesion through ItgaL- and ItgaM-dependent mechanisms (2010)

Leukocyte recruitment to inflamed tissues is the cornerstone of inflammatory responses and the driving force behind the establishment of inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis. It has been reported that angiogenic cytokines contribute to this inflammatory response that facilitates the chronic nature of disease. We have previously reported (Goebel S, Huang M, Davis WC, Jennings M, Siahaan TJ, Alexander JS, Kevil CG. Am J Physiol Gastrointest Liver Physiol 290: G648-G654, 2006) that vascular endothelial growth factor (VEGF)-A can stimulate neutrophil adhesion to colon microvascular endothelial cells in a β₂-integrin (Itgb2)-dependent manner. However, it is not known which of the specific leukocyte integrins are critical for VEGF-A-dependent neutrophil and T cell recruitment. Here we examine the differential importance of either α-integrin (Itga)L or ItgaM in governing neutrophil and T cell adhesion to VEGF-A-activated colonic endothelium. Using an in vitro parallel-plate flow chamber model, we found that genetic deficiency of ItgaM completely blunted neutrophil adhesion to VEGF-A-stimulated endothelium, whereas ItgaL deficiency only partly blocked neutrophil adhesion. Deficiency of ItgaM did significantly decrease neutrophil rolling, whereas deficiency of ItgaL did not. We found that genetic deficiency of either ItgaL or ItgaM did significantly blunt T cell adhesion to VEGF-A-stimulated colon endothelium. We also found that genetic deficiency of these Itgas significantly attenuated T cell rolling behavior. Lastly, we examined whether VEGF-A-mediated leukocyte recruitment occurred through different VEGF receptor (VEGFR) pathways and found that VEGFR2 activation regulates neutrophil recruitment, whereas both VEGFR1 and VEGFR2 modulate T cell recruitment. Together, these data identify differential molecular mechanisms of VEGF-A-mediated leukocyte recruitment.
On-Demand Deposition of Functional Oxide Microdots by Double-Pulse Laser-Induced Dot Transfer (2014)

We have newly developed a double-pulse laser-induced dot transfer technique to realize ondemand deposition of functional oxide microdots under room-temperature atmospheric conditions. In our double-pulse system, the first pulse was irradiated to preheat an oxide source film, and then the second pulse was more tightly focused on the same position to deposit an oxide microdot onto a receiver substrate. As a model case, indium tin oxide microdots with much smaller lateral dimensions than the laser focal area were reproducibly arrayed on a silica glass substrate by the doublepulse process, while there were microdot vacancies at a rate of approximately 30 % in the case of a single-pulse process without preheating. In order to explore the effect of double-pulse, laser-induced temperature distribution was also investigated from a finite elemental approach.
Ornithine decarboxylase activity in chick duodenum induced by 1 α, 25-dihydroxycholecalciferol (1981)

The effect of cholecalciferol and its metabolites on ornithine decarboxylase activity was investigated in the duodenal mucosa of vitamin D-deficient chicks. The duodenal ornithine decarboxylase activity decreased in animals fed a vitamin D-deficient diet and its retarded activity was increased dose-dependently by a single injection of cholecalciferol. Among various metabolites of cholecalciferol tested, 1 alpha, 25-dihydroxycholecalciferol [ 1 alpha, 25 (OH)2D3] was the most potent stimulator. Stimulation of the enzyme activity was detected as early as 2h after intravenous administration of 1 alpha, 25 (OH)2D3 and a maximal value was attained at 6 h. The maximal value was 27 times higher than the control. In addition, treatment with 1 alpha 25 (OH)2D3 affected the duodenal content of polyamines. The content of putrescine increased to a value of three times that of the control 6 h after the hormone administration. The spermidine content did not change appreciably. The enhancement of duodenal ornithine decarboxylase activity by 1 alpha, 25 (OH)2D3 occurred in parallel with the enhancement of calcium absorption, which was first detected 3 h after the hormone administration. The enhancement appeared to be tissue-specific. It was observed in every intestinal segment, but was highest in the duodenum. Enzyme activity in other tissues was not influenced appreciably by 1 alpha, 25 (OH)2D3. These results clearly indicate that the duodenal biosynthesis of polyamines is regulated by 1 alpha, 25 (OH)2D3, suggesting the possibility that duodenal ornithine decarboxylase may be involved in the calcium absorption mechanism.