gebhart/patrepeval huggingface dataset:
Abstract 3223: Novel tubulin inhibitor DJ101 targets the colchicine binding site and suppresses melanoma growth and metastasis (2017)

Abstract Interfering with microtubule dynamics is a validated approach for anticancer treatment and by selectively targeting the colchicine binding site on tubulin, microtubule destabilizing agents can evade mechanisms of drug resistance that commonly develop with other antimitotic agents such as taxanes and vinca alkaloids. We have recently reported the discovery of a potent and metabolically stable tubulin inhibitor (DJ101) that specifically targets the colchicine binding site on the beta tubulin subunit, disrupts tubulin polymerization and effectively circumvents drug efflux pumps that decrease the efficacy of existing tubulin inhibitors. To further pre-clinically evaluate DJ101 as a novel tubulin inhibitor and confirm its mechanism of action, we first visually demonstrated the ability of DJ101 to disrupt microtubule dynamics and elucidated the changes in microtubule structure and cell morphology through immunofluorescence techniques. Furthermore, we solved the crystal structure of DJ101 in complex with tubulin to determine its molecular interactions with the protein. We then demonstrated the significant in vitro potency of DJ101 against a panel of metastatic melanoma cell lines harboring major clinically relevant mutations observed in tumors and also validated its cytotoxicity against a broader array of NCI-60 cell lines. Further analysis revealed that DJ101 effectively thwarted anchorage-dependent melanoma colony formation and drastically hindered cell mobility and motility of those cancer cells. We further ascertained that DJ101 shows negligible off-target effects for major physiologically important receptors and ion channels, suggesting a good safety profile. Encouraged by the preliminary results from our in vitro assessment, we evaluated the in vivo activity of DJ101 in two different mouse models. At a dose of 30 mg/kg via i.p. injections, DJ101 nearly completely suppressed tumor growth in a human A375 melanoma xenograft model. It also appreciably inhibited metastasis potential in a murine B16F10 lung metastasis model at the same dose. In conclusion, we have described a microtubule destabilizing agent that targets the colchicine binding site on tubulin, confirmed its mechanism action, determined its potency in a vast array of cancer cell lines, particularly metastatic melanoma, demonstrated its inhibitory effect on cellular proliferation, motility and migration, and evaluated its anticancer potential in terms of tumor growth inhibition and metastasis in two in vivo models. Our findings offer a compelling rationale to further develop and advance DJ101 as a tubulin inhibitor for cancer therapy. Citation Format: Kinsie Arnst, Dong-Jin Hwang, Duane D. Miller, Wei Li. Novel tubulin inhibitor DJ101 targets the colchicine binding site and suppresses melanoma growth and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3223. doi:10.1158/1538-7445.AM2017-3223
Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils (2015)

Ceramides are mediators of inflammatory processes. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that CerS6 mRNA expression was upregulated 15-fold in peripheral blood leukocytes before the onset of EAE symptoms. In peripheral blood leukocytes from MS patients, a 3.9-fold upregulation was found. Total genetic deletion of CerS6 and the selective deletion of CerS6 in peripheral blood leucocytes exacerbated the progression of clinical symptoms in EAE mice. This was associated with enhanced leukocyte, predominantly neutrophil infiltration and enhanced demyelination in the lumbar spinal cord of EAE mice. Interferon-gamma/tumor necrosis factor alpha (IFN-γ/TNF-α) and granulocyte colony-stimulating factor (G-CSF) both drive EAE development and induce expression of the integrin CD11b and the chemokine receptor C-X-C motif chemokine receptor 2 (CXCR2), and we found they also induce CerS6 expression. In vivo, the genetic deletion of CerS6 enhanced the activation/migration of neutrophils, as reflected by an enhanced upregulation of CD11b and CXCR2. In vitro, the genetic deletion of CerS6 enhanced the activation status of IFN-γ/TNF-α-stimulated neutrophils, as shown by increased expression of nitric oxide and CD11b and an increased adhesion capacity. In G-CSF-stimulated neutrophils, the migration status was enhanced, as reflected by an elevated level of CXCR2 and an increased migration capacity. These data suggest that CerS6/C16-Cer mediates feedback regulation by inhibiting the formation of CD11b and CXCR2, which are induced either by IFN-γ/TNF-α or by G-CSF, respectively. We conclude that CerS6/C16-Cer mediates anti-inflammatory effects during the development of EAE and MS possibly by suppressing the migration and deactivation of neutrophils.
Multiclass Anomaly Detection in GI Endoscopic Images using Optimized Deep One-class Classification in an Imbalanced Dataset. (2021)

Wireless Capsule Endoscopy helps physicians examine the gastrointestinal (GI) tract noninvasively, with the cost of generating many images. Many available datasets, such as KID2 and Kvasir, suffer from imbalance issue which make it difficult to train an effective artificial intelligence (AI) system. Moreover, increasing number of classes makes the problem worse. In this study, an ensemble of one-class classifiers is used for detecting anomaly. This method focuses on learning single models using samples from only one class, and ensemble all models for multiclass classification. A total of 1,778 normal, 227 inflammation, 303 vascular diseases, and 44 polyp images have been used from the KID2 dataset. In the first step, deep features are extracted based on an autoencoder architecture from the preprocessed images. Then, these features are oversampled using Synthetic Minority Over-sampling Technique and clustered using Ordering Points to Identify the Clustering Structure. To create one-class classification model, the Support Vector Data Descriptions are trained on each cluster with the help of Ant Colony Optimization, which is also used for tuning clustering parameters for improving F1-score. This process is applied on each classes and ensemble of final models used for multiclass classification. The entire algorithm ran 5 times and obtained F1-score 96.3 +- 0.2% and macro-average F1-score 85.0 +- 0.4%, for anomaly detection and multiclass classification, respectively. The results are compared with GoogleNet, AlexNet, Resnet50, VGG16 and other published algorithms, and demonstrate that the proposed method is a competitive choice for multiclass class anomaly detection in GI images.
Modeling and experimental validation of carbon dioxide evolution in alkalophilic cultures (1992)

The chemical reactions involving carbon dioxide in mineral culture media are considered. A mathematic model is set up, based on published data, which is valid at pH values below 9, and in which the nonideality of the solution is taken into account. The crucial parameter is the constant expressing the equilibrium between carbon dioxide and bicarbonate, K(1).The reactions were studied in three different aqueous solutions: water, mineral salt medium, and a suspension with nongrowing bacterial cells. For each situation, three methods were compared for the determination of the bicarbonate concentration in the solution: equilibrium state total carbon analysis, dynamic monitoring of the rate of acid or alkali addition, and dynamic measurement of the carbon dioxide gas phase mole fraction.In a batch-stirred tank reactor, the equilibrium constant K(1) agreed with the published value, and the three bicarbonate analysis methods give the same results. If the nonideality is not taken into account, the result significantly differed from the published value and is likely to be incorrect.A real alkalophilic process, using Acinetobacter calcoaceticus in a continuous stirred tank reactor at steady state, also gave results that are in accord with the literature. However, the results do not allow validation of the equation expressing the nonideality.The steady state in the batch system and in continuous culture can be well described with the mathematical model. However, in the transient state there are some unexplained differences between simulation and measurement.
Dendritic Tip-on Polytriazine-Based Carbon Nitride Photocatalyst with High Hydrogen Evolution Activity (2015)

Developing stable, ubiquitous, and efficient water-splitting photocatalyst material that has extensive absorption in the visible-light range is desired for a sustainable solar energy-conversion device. We herein report a triazine-based carbon nitride (CN) material with different C/N ratios achieved by varying the monomer composition ratio between melamine (Mel) and 2,4,6-triaminopyrimidine (TAP). The CN material with a different C/N ratio was obtained through a two-step synthesis protocol: starting with the solution state dispersion of the monomers via hydrogen-bonding supramolecular aggregate, followed by a salt-melt high temperature polycondensation. This protocol ensures the production of a highly crystalline polytriazine imide (PTI) structure consisting of a copolymerized Mel-TAP network. The observed bandgap narrowing with an increasing TAP/Mel ratio is well simulated by density functional theory (DFT) calculations, revealing a negative shift in the valence band upon substitution of N with CH in the aromatic rings. Increasing the TAP amount could not maintain the crystalline PTI structure, consistent with DFT calculation showing the repulsion associated with additional C–H introduced in the aromatic rings. Because of the high exciton binding energy calculated by DFT for the obtained CN, the cocatalyst must be close to any portion of the material to assist the separation of excited charge carriers for an improved photocatalytic performance. The photocatalytic activity was improved by providing a dendritic tip-on-like shape grown on porous fibrous silica KCC-1 spheres, and highly dispersed Pt nanoparticles (<5 nm) were photodeposited to introduce heterojunction. As a result, the Pt/CN/KCC-1 photocatalyst exhibited an apparent quantum efficiency (AQE) as high as 22.1 ± 3% at 400 nm, and the silica was also beneficial for improving photocatalytic stability. The results obtained by time-resolved transient absorption spectroscopy measurements were consistent with the improved photocatalytic activity with the slowest carrier recombination for the optimized CN photocatalyst.
At-wavelength inspection of defect smoothing in EUVL masks (2002)

Results of at-wavelength inspection of EUVL mask substrate defects that were smoothed by multilayer coatings are presented. Programmed mask substrate defects were made with 80nm gold (Au) spheres, which were deposited on the mask substrate before the Mo/Si reflective multilayer coating. After coating, at-wavelength and visible-light inspection were then performed. The smoothing process was found to be effective in significantly suppressing the EUV visibility of the defects.
Tests of rRNA hybridization to microarrays suggest that hybridization characteristics of oligonucleotide probes for species discrimination cannot be predicted (2006)

Hybridization of rRNAs to microarrays is a promising approach for prokaryotic and eukaryotic species identification. Typically, the amount of bound target is measured by fluorescent intensity and it is assumed that the signal intensity is directly related to the target concentration. Using thirteen different eukaryotic LSU rRNA target sequences and 7693 short perfect match oligonucleotide probes, we have assessed current approaches for predicting signal intensities by comparing Gibbs free energy (DeltaG degrees) calculations to experimental results. Our evaluation revealed a poor statistical relationship between predicted and actual intensities. Although signal intensities for a given target varied up to 70-fold, none of the predictors were able to fully explain this variation. Also, no combination of different free energy terms, as assessed by principal component and neural network analyses, provided a reliable predictor of hybridization efficiency. We also examined the effects of single-base pair mismatch (MM) (all possible types and positions) on signal intensities of duplexes. We found that the MM effects differ from those that were predicted from solution-based hybridizations. These results recommend against the application of probe design software tools that use thermodynamic parameters to assess probe quality for species identification. Our results imply that the thermodynamic properties of oligonucleotide hybridization are by far not yet understood.
Characteristics of infrared imaging systems that benefit from superresolution reconstruction (2007)

There have been numerous applications of superresolution reconstruction algorithms to improve the range performance of infrared imagers. These studies show there can be a dramatic improvement in range performance when superresolution algorithms are applied to undersampled imager outputs. These occur when the imager is moving relative to the target, which creates different spatial samplings of the field of view for each frame. The degree of performance benefit is dependent on the relative sizes of the detector/spacing and the optical blur spot in focal plane space. The minimum blur spot size achievable on the focal plane is dependent on the system F/number. Hence, we provide a range of these sensor characteristics, for which there is a benefit from superresolution reconstruction algorithms. Additionally, we quantify the potential performance improvements associated with these algorithms. We also provide three infrared sensor examples to show the range of improvements associated with provided guidelines.
An <i>in vitro</i> study of the sub‐cellular distribution of nicotinic receptors (2003)

Nicotinic and serotoninergic 5HT3 receptors share important sequence identities except for their cytoplasmic loop. Both ends of this loop display conserved 3D helical structures with distinct primary sequences. We decided to check whether these two helices named F and G play a role in the sub-cellular distribution of different nicotinic receptors. We systematically exchanged each helix with the equivalent sequence of neuronal nicotinic and alpha4, beta2 and alpha7 subunits in the functional chimeric alpha7-5HT3 receptor used as a model system. The new chimeras were expressed in vitro in polarized epithelial cells from pig kidney. We quantified synthesis and export of the receptors to the cell surface by measuring alpha-bungarotoxin binding sites. Immunogold labelling was used, at the electron microscope level, to determine the amount of each chimera present at either domain, apical and/or basolateral, of these cells. We noticed that in epithelial cells the majority of alpha-bungarotoxin binding sites remained sequestered in the cytoplasm as already observed in neurons in vivo. The majority of the pentamers present at the cell surface were located at the apical domain. Our results suggest that helix F and G differently regulate assembly and export to the cell surface of alpha-bungarotoxin binding receptors.
Suitian koetilan mastiittiongelman kartoitus ja saneerausohjelman laatiminen (1991)

Tämä syventävien opintojen tutkielma sisältää taustatietoja utaretulehduksen vastustamisesta ja tutkimusosan, jossa tutkittiin Helsingin yliopiston koetilan navetassa esiintyvän utaretulehdusongelman syitä ja tehtiin saneerausohjelma tilalle ja pantiin se alkuun. \n\nTutkimusosassa aluksi esitetään navetassa tehtyjä tutkimuksia. Navetasta selvitettiin erikseen olosuhteet, utareterveystilanne, lypsykone ja lypsyrutiini. Olosuhteita huononsi eniten navetassa jatkuva remontti. Navettailman lämpötila, kosteus, valaistus ja ilmavirtaus olivat kunnossa. Lypsykoneessa ilmeni selviä vikoja, joista tiedotettiin tilan henkilökunnalle. Utareterveys oli huono, mikä todettiin NAGaasi- ja bakteriologisin kokein. \n\nTilalle laadittiin hoito-ohjelma, johon osallistuivat tilanhoitohenkilökunta, alueen hoitava eläinlääkäri-, Lohjan maitolaboratorio ja VELL. Pääperiaatteena hoidoissa oli, että akuuteista mastiiteista otetaan maitonäytteet bakteerieristystä ja lääkeherkkyysmääritystä varten. Näin antibioottiterapia saadaan suunnattua mahdollisimman tehokkaana ja kapeakirjoisena juuri taudinaiheuttajaan. Tutkimuksen alussa pääasiallisin utaretulehduspatogeenioli S.aureus \n\nPuolen vuoden aikana ei onnistuttu parantamaan tilan utareterveyttä, mikä suureksi osaksi johtuu lypsykoneen jäljellä olevista vioista ja lypsyn virheistä. Tutkimusosan lopussa on esitetty jatko-ohjelma tilan utareterveyden parantamiseksi jatkossa.
Genome-Wide siRNA Screen Reveals a New Cellular Partner of NK Cell Receptor KIR2DL4: Heparan Sulfate Directly Modulates KIR2DL4-Mediated Responses (2013)

KIR2DL4 (CD158d) is a distinct member of the killer cell Ig-like receptor (KIR) family in human NK cells that can induce cytokine production and cytolytic activity in resting NK cells. Soluble HLA-G, normally expressed only by fetal-derived trophoblast cells, was reported to be a ligand for KIR2DL4; however, KIR2DL4 expression is not restricted to the placenta and can be found in CD56(high) subset of peripheral blood NK cells. We demonstrated that KIR2DL4 can interact with alternative ligand(s), expressed by cells of epithelial or fibroblast origin. A genome-wide high-throughput siRNA screen revealed that KIR2DL4 recognition of cell-surface ligand(s) is directly regulated by heparan sulfate (HS) glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1). KIR2DL4 was found to directly interact with HS/heparin, and the D0 domain of KIR2DL4 was essential for this interaction. Accordingly, exogenous HS/heparin can regulate cytokine production by KIR2DL4-expressing NK cells and HEK293T cells (HEK293T-2DL4), and induces differential localization of KIR2DL4 to rab5(+) and rab7(+) endosomes, thus leading to downregulation of cytokine production and degradation of the receptor. Furthermore, we showed that intimate interaction of syndecan-4 (SDC4) HS proteoglycan (HSPG) and KIR2DL4 directly affects receptor endocytosis and membrane trafficking.
Infection and Thrombosis in Total Artificial Heart Technology: Past and Future Challenges–A Historical Review (2000)

On the basis of animal testing and a single clinical implant during the 1960s, development of the total artificial heart (TAH) began in earnest in the 1970s. The goal was to produce a pump that could treat biventricular heart failure or any other condition that necessitated removal of the patient's native heart. The early TAHs were pneumatically powered, with externalized drivelines. After undergoing in vivo evaluation in hundreds of sheep and calves at several centers (mainly the Utah Heart Institute), these pumps were implanted in humans, initially for permanent cardiac replacement and later for bridging to transplantation. In both the in vivo experimental setting and the clinical setting, infection and thrombosis were problematic, infection being encountered much more frequently than thrombosis in clinical cases. To minimize these problems, four research groups, funded by NIH, began in 1988 to develop permanent, transcutaneously powered, totally implantable, electromechanical TAHs. For the first time, TAH technology was able to minimize infection and thrombosis, as confirmed by current in vivo studies. These new TAHs will undergo preclinical, pre-IDE studies this year and clinical trials in the near future. This article briefly reviews the evolution of TAH technology, with an emphasis on the prevention and management of infection and thrombosis.
Continuously distributed phase shifts by chirped distributed-feedback gratings for 1.55 µm distributed-feedback lasers (1997)

DFB lasers with axially distributed phase shifts implemented by distributed feedback (DFB) gratings with axially varied pitch lengths (chirped DFB gratings) have been investigated. It is shown that distributed phase shifts can be used to counteract spatial hole burning and reduce the inhomogeneity of the axial photon-density distribution. Different total amounts of phase shift and axial extensions of the phase shift section have been compared by appropriate chirping functions, and also to the behaviour of abrupt phase shifts. It is shown that different design goals can be reached such as minimum threshold gain, reduced axial photon field inhomogeneities, specific spectral positions of the oscillating mode or increased gain margin. The results are obtained for two different ways of implementing DFB gratings with axially varied pitch length such as bent waveguides on homogeneous grating fields or fractal gratings. For identical chirping functions, both implementation possibilities show identical device properties if homogeneous coupling is assumed and bending losses remain negligible. Finally, the influence of facet phase statistics on the device yield is studied.
Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease (2020)

Anti-MDA5-associated ILD occurred predominantly from October to March in individuals residing near freshwater, suggesting an environmental influence on the onset of this disease subset.
3-D model construction using range and image data (2002)

This paper deals with the automated creation of geometric and photometric correct 3-D models of the world. Those models can be used for virtual reality, tele-presence, digital cinematography and urban planning applications. The combination of range (dense depth estimates) and image sensing (color information) provides data-sets which allow us to create geometrically correct, photorealistic models of high quality. The 3-D models are first built from range data using a volumetric set intersection method previously developed by us. Photometry can be napped onto these models by registering features from both the 3-D and 2-D data sets. Range data segmentation algorithms have been developed to identify planar regions, determine linear features from planar intersections that can serve as features for registration with 2-D imagery lines, and reduce the overall complexity of the models. Results are shown for building models of large buildings on our campus using real data acquired from multiple sensors.
Properties of a Novel D-Stereospecific Aminopeptidase from Ochrobactrum anthropi (1989)

A novel aminopeptidase active toward D-amino acid-containing peptides, D-amino acid amides, and D-amino acid esters has been purified 2,800-fold to homogeneity from a bacterium Ochrobactrum anthropi SCRC C1-38, which had been isolated from soil. The enzyme has a molecular weight of about 122,000 and is composed of two identical subunits (Mr = 59,000). The optimal pH for activity was 8.0. It showed strict D-stereospecificity toward substrates including low molecular weight D-amino acid amides such as D-alanine amide, D-alpha-aminobutyric acid amides, and D-serine amide; D-alanine N-alkylamides such as D-alanine-p-nitroanilide, D-alanine benzylamide, and D-alanine n-butylamide; and peptides with a D-alanine at the NH2 terminus such as D-alanylglycine, D-alanylglycylglycine, D-alanyl-L-alanyl-L-alanine, and D-alanine oligomers. Generally, the enzyme did not act on substrates composed of L-amino acid at the NH2 terminus, although it showed low stereospecificity only toward substrates such as the methyl esters of L-alanine, L-serine, and L-alanine-p-nitroanilide. Comparing the Km and Vmax values for the major substrates, it is clear that the enzyme prefers peptides to amino acid arylamides or amino acid amides. The enzyme was tentatively named as "D-aminopeptidase." EDTA and divalent cations have no effect on the enzyme activity. The enzyme appears to be a thiol peptidase.