gebhart/patrepeval huggingface dataset:
Somatic Superenhancer Duplications and Hotspot Mutations Lead to Oncogenic Activation of the KLF5 Transcription Factor (2017)

The Krüppel-like family of transcription factors plays critical roles in human development and is associated with cancer pathogenesis. Krüppel-like factor 5 gene (<i>KLF5</i>) has been shown to promote cancer cell proliferation and tumorigenesis and to be genomically amplified in cancer cells. We recently reported that the <i>KLF5</i> gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here, we show that these alterations activate KLF5 by three distinct mechanisms: (i) Focal amplification of superenhancers activates <i>KLF5</i> expression in squamous cell carcinomas; (ii) Missense mutations disrupt KLF5-FBXW7 interactions to increase KLF5 protein stability in colorectal cancer; (iii) Cancer type-specific hotspot mutations within a zinc-finger DNA binding domain of KLF5 change its DNA binding specificity and reshape cellular transcription. Utilizing data from CRISPR/Cas9 gene knockout screening, we reveal that cancer cells with <i>KLF5</i> overexpression are dependent on KLF5 for their proliferation, suggesting KLF5 as a putative therapeutic target.<b>Significance:</b> Our observations, together with previous studies that identified oncogenic properties of KLF5, establish the importance of KLF5 activation in human cancers, delineate the varied genomic mechanisms underlying this occurrence, and nominate KLF5 as a putative target for therapeutic intervention in cancer. <i>Cancer Discov; 8(1); 108-25. ©2017 AACR.</i><i>This article is highlighted in the In This Issue feature, p. 1</i>.
Phosphorescence characteristics of ruthenium complex as an optical transducer for biosensors (2008)

The saturation intensity, photobleaching, and decay lifetime of tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) chloride [Ru(dpp)3] are investigated. The saturation point was estimated to be 11.8W∕cm2 and subsequently measured to be 11.5W∕cm2. Photobleaching of this dye at a peak absorbance equivalence of 6.6W∕cm2 is observed over 2days resulting in a 14% decrease in intensity within 20min and 47% decrease over two days yielding an unacceptably short operational lifetime under saturated conditions. Lower optical excitation levels in the application of oxygen sensitive fluorescence type fiber optic enzymatic biosensor systems are required and yield acceptable photobleaching rates.
Crossline Reconstruction Using Aliased 3D Deghosted Up- and Downgoing Wavefields (2013)

This paper formulates a new model for crossline reconstruction that relies on aliased, 3D decomposed, up- and downgoing waves. It also presents a closed form approach to solve the joint reconstruction and 3D deghosting problem. The new model provides additional insight into how the ghost reflection and the vertical component of particle velocity/acceleration are exploited in crossline reconstruction and joint 3D deghosting solutions for towed streamer applications.
HLA class I and II typing using cells positively selected from blood by immunomagnetic isolation ‐ a fast and reliable technique (1986)

This paper describes a new cell isolation and HLA typing technique, which permits cell separation and HLA class I or class II typing to be performed in 70 min. Magnetic monodisperse microspheres (Dynabeads TM) were coated with monoclonal antibodies (MAbs) specific for the CD8 T cell antigen or for HLA class II monomorphic epitopes. They could then be used to obtain HLA class I or class II positive cells directly from ACD blood in approximately 15 min by the use of magnetic separation. The cells (attached to the microspheres) were subsequently used in microcytotoxic HLA typing (total incubation time of 55 min) using acridin orange/ethidiumbromide to stain viable (yellow) and dead (red) cells. It was found that this immunomagnetic (IM) HLA typing technique was specific, has a sensitivity superior to that observed for conventional microcytotoxicity assays and gave low background staining. IM HLA-ABC typing of 50 healthy donors and 10 patients and IM HLA-DR typing of 25 healthy donors and 30 patients gave results corresponding well with that obtained independently by conventional HLA typing (concordancy rates 92-100%). Furthermore, the IM HLA typing technique permitted reliable HLA class II typing of blood cells from six patients where conventional HLA class II typing was impossible. The IM HLA typing technique also enables HLA class I and II typing to be quickly and reliably performed on cells from ACD blood of cadaveric donors.
Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants (2022)

Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. We identified an average of 3.07 million variants per genome, of which an average of 112,512 were rare. We mapped runs of homozygosity (ROHs) in affected individuals and found an average genomic homozygosity of 9.65%, consistent with expectations for multiple generations of consanguineous unions. We identified potentially pathogenic rare exonic or splice site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, ZNF292) and 12 candidate (including CHD5, GRB10, PPP1R13B) ASD genes. Furthermore, we annotated noncoding variants in ROHs with brain-specific regulatory elements and identified putative disease-causing variants within brain-specific promoters and enhancers for 5 known ASD and neurodevelopmental disease genes (ACTG1, AUTS2, CTNND2, CNTNAP4, SPTBN4). We also identified copy number variants in two known ASD and neurodevelopmental disease loci in two affected individuals. In total we identified potentially etiological variants in known ASD or neurodevelopmental disease genes for ~61% (14/23) of affected individuals. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants. Our analyses add to the growing number of ASD genes and variants and emphasize the importance of leveraging recent shared ancestry to map disease variants in complex neurodevelopmental disorders.
Amplification of KIT, PDGFRA, VEGFR2, and EGFR in Gliomas (2006)

Receptor tyrosine kinase aberrations are implicated in the genesis of gliomas. We investigated expression and amplification of KIT, PDGFRA, VEGFR2, and EGFR in 87 gliomas consisting of astrocytomas, anaplastic astrocytomas, oligodendrogliomas, or oligoastrocytomas in tumor samples collected at the time of the diagnosis and in samples of the same tumors at tumor recurrence. Gene amplifications were investigated using either chromogenic in situ hybridization or fluorescence in situ hybridization, and protein expression using immunohistochemistry. In samples collected at glioma diagnosis, KIT and PDGFRA amplifications were more frequent in anaplastic astrocytomas than in astrocytomas, oligodendrogliomas, and oligoastrocytomas [28% versus 5% (P = 0.012) and 33% versus 2% (P = 0.0008), respectively]. VEGFR2 amplifications occurred in 6% to 17% of the gliomas at diagnosis, and EGFR amplifications in 0% to 12%. Amplified KIT was more frequently present in recurrent gliomas than in newly diagnosed gliomas (P = 0.0066). KIT amplification was associated with KIT protein expression and with presence of PDGFRA and EGFR amplifications both at the time of the first glioma diagnosis and at tumor recurrence, and with VEGFR2 amplification at tumor recurrence. Three (4%) primary gliomas and 10 (14%) recurrent gliomas that were evaluable for coamplification of KIT, PDGFRA, and VEGFR2 showed amplification of at least two of these genes; the amplicon contained amplified KIT in all 13 cases. In conclusion, besides glioblastoma, amplified KIT, PDGFRA, and VEGFR may also occur in lower-grade gliomas and in their recurrent tumors. It is currently not known whether specific tyrosine kinase inhibitors are effective in the treatment of such gliomas.
Q‐ball imaging with PROPELLER EPI acquisition (2013)

Q-ball imaging (QBI) is an imaging technique that is capable of resolving intravoxel fiber crossings; however, the signal readout based on echo-planar imaging (EPI) introduces geometric distortions in the presence of susceptibility gradients. This study proposes an imaging technique that reduces susceptibility distortions in QBI by short-axis PROPELLER EPI acquisition. Conventional QBI and PROPELLER QBI data were acquired from two 3T MR scans of the brains of five healthy subjects. Prior to the PROPELLER reconstruction, residual distortions in single-blade low-resolution b0 and diffusion-weighted images (DWIs) were minimized by linear affine and nonlinear diffeomorphic demon registrations. Subsequently, the PROPELLER keyhole reconstruction was applied to the corrected DWIs to obtain high-resolution PROPELLER DWIs. The generalized fractional anisotropy and orientation distribution function maps contained fewer distortions in PROPELLER QBI than in conventional QBI, and the fiber tracts more closely matched the brain anatomy depicted by turbo spin-echo (TSE) T2-weighted imaging (T2WI). Furthermore, for fixed T(E), PROPELLER QBI enabled a shorter scan time than conventional QBI. We conclude that PROPELLER QBI can reduce susceptibility distortions without lengthening the acquisition time and is suitable for tracing neuronal fiber tracts in the human brain.
IGKV3 Proteins as Candidate “Off-the-Shelf” Vaccines for Kappa-Light Chain–Restricted B-Cell Non-Hodgkin Lymphomas (2012)

These results provide the rationale to exploit IGKV3 proteins as "off-the-shelf" vaccines for a large fraction of lymphoma patients.
Mean shift analysis and applications (1999)

A nonparametric estimator of density gradient, the mean shift, is employed in the joint, spatial-range (value) domain of gray level and color images for discontinuity preserving filtering and image segmentation. Properties of the mean shift are reviewed and its convergence on lattices is proven. The proposed filtering method associates with each pixel in the image the closest local mode in the density distribution of the joint domain. Segmentation into a piecewise constant structure requires only one more step, fusion of the regions associated with nearby modes. The proposed technique has two parameters controlling the resolution in the spatial and range domains. Since convergence is guaranteed, the technique does not require the intervention of the user to stop the filtering at the desired image quality. Several examples, for gray and color images, show the versatility of the method and compare favorably with results described in the literature for the same images.
Low-complexity model predictive control of electromagnetic actuators with a stability guarantee (2009)

Electromagnetically driven mechanical systems are characterized by fast nonlinear dynamics that are subject to physical and control constraints, which makes controller design a challenging problem. This paper presents a novel model predictive control (MPC) scheme that can handle both the performance/physical constraints and the strict limits on computational complexity required in control of general electromagnetic (EM) actuators. The novel aspects of the MPC design are a one-step-ahead prediction horizon and an infinity-norm artificial Lyapunov function that is employed to drive the system to a desired reference. An additional optimization variable is introduced to relax the conditions on the Lyapunov function, which is not forced to decrease monotonically. In this way feasibility of the MPC algorithm is improved considerably. While the MPC scheme uses a full nonlinear model, which improves performance, we show that the resulting MPC problem can still be transformed into a low-complexity linear program that can be solved by modern microprocessors within tenths of milliseconds. Moreover, an even simpler piecewise affine explicit controller can be obtained via multiparametric programming. Simulation results are reported and compared with the results achieved by state-of-the-art explicit MPC based on a piecewise affine model.
Finite element analysis of the meniscectomised tibio-femoral joint: implementation of advanced articular cartilage models (2013)

The article presents advanced computer simulations aimed at the accurate modelling of human tibio-femoral joints (TFJs) in terms of anatomy, physiological loading and constitutive behaviour of the tissues. The main objective of this research is to demonstrate the implications that the implementation of different articular cartilage models have on the prediction of the joint response. Several biphasic material constitutive laws are tested using a finite element package and compared to the monophasic linear elastic description, often still used to predict the instantaneous response of the cartilage in 3D knee models. Thus, the importance of adequately capturing the contribution of the interstitial fluid support is proved using a simplified 3D model; subsequently, a biphasic poroviscoelastic non-linear constitutive law is implemented to study the response of a patient-specific TFJ subjected to simplified walking cycles. The time evolution of stresses, pore pressure, contact areas and joint displacements is captured and compared with existing meniscectomised knee models. Contact pressures and areas obtained using the developed numerical simulations are in agreement with the existing experimental evidence for meniscectomised human knee joints. The results are then used to predict the most likely site for the origin of mechanical damage, i.e. the medial cartilage surface for the specific case analysed in the present contribution. Finally, future research directions are suggested.
Freeform illumination sources: an experimental study of source-mask optimization for 22-nm SRAM cells (2010)

The use of customized illumination modes is part of the pursuit to stretch the applicability of immersion ArF lithography. Indeed, a specific illumination source shape that is optimized for a particular design leads to enhanced imaging results. Recently, freeform illumination has become available through pixelated DOEs or through FlexRay<sup>TM</sup>, ASML's programmable illuminator system, allowing for virtually unconstrained intensity distribution within the source pupil. In this paper, the benefit of freeform over traditional illumination is evaluated, by applying source mask co-optimization (SMO) for an aggressive use case, and wafer-based verification. For a 22 nm node SRAM of 0.099 &#956;m² and 0.078 &mu;m<sup>2</sup> bit cell area, the patterning of the full contact and metal layer into a hard mask is demonstrated with the application of SMO and freeform illumination. In this work, both pixelated DOEs and FlexRay are applied. Additionally, the match between the latter two is confirmed on wafer, in terms of CD and process window.
ChemInform Abstract: Short Synthesis of a Bicyclic Mimic of α‐L‐Fucose. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Integrated Spatial Uncertainty Visualization using Off-screen Aggregation (2015)

Visualization of spatial data uncertainties is crucial to the data understanding and exploration process. Scientific measurements, numerical simulations, and user generated content are error prone sources that gravely influence data reliability. When exploring large spatial datasets, we face two main challenges: data and uncertainty are two different sets which need to be integrated into one visualization, and we often lose the contextual overview when zooming or filtering to see details. In this paper, we present an extrinsic uncertainty visualization as well as an off-screen technique which integrates the uncertainty representation and enables the user to perceive data context and topology in the analysis process. We show the applicability and usefulness of our approach in a use case.
Small contact resistance and high-frequency operation of flexible low-voltage inverted coplanar organic transistors (2019)

The contact resistance in organic thin-film transistors (TFTs) is the limiting factor in the development of high-frequency organic TFTs. In devices fabricated in the inverted (bottom-gate) device architecture, staggered (top-contact) organic TFTs have usually shown or are predicted to show lower contact resistance than coplanar (bottom-contact) organic TFTs. However, through comparison of organic TFTs with different gate-dielectric thicknesses based on the small-molecule organic semiconductor 2,9-diphenyl-dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene, we show the potential for bottom-contact TFTs to have lower contact resistance than top-contact TFTs, provided the gate dielectric is sufficiently thin and an interface layer such as pentafluorobenzenethiol is used to treat the surface of the source and drain contacts. We demonstrate bottom-contact TFTs fabricated on flexible plastic substrates with record-low contact resistance (29 Ωcm), record subthreshold swing (62 mV/decade), and signal-propagation delays in 11-stage unipolar ring oscillators as short as 138 ns per stage, all at operating voltages of about 3 V.
Multi-resolution deep learning pipeline for dense large scale point clouds (2021)

Recent development of 3D sensors allows the acquisition of extremely dense 3D point clouds of large-scale scenes. The main challenge of processing such large point clouds remains in the size of the data, which induce expensive computational and memory cost. In this context, the full resolution cloud is particularly hard to process, and details it brings are rarely exploited. Although fine-grained details are important for detection of small objects, they can alter the local geometry of large structural parts and mislead deep learning networks. In this paper, we introduce a new generic deep learning pipeline to exploit the full precision of large scale point clouds, but only for objects that require details. The core idea of our approach is to split up the process into multiple sub-networks which operate on different resolutions and with each their specific classes to retrieve. Thus, the pipeline allows each class to benefit either from noise and memory cost reduction of a sub-sampling or from fine-grained details.
Presence of Circulating Suppressive Factor for Muscarinic Acethylcholine Receptor in Senile Dementia. (1991)

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.
Space vector modulated cascade multi-level inverter for PMSG wind generation systems (2009)

Modulation and control of a cascade multilevel inverter, which has a high potential in future wind generation applications, are presented. The inverter is a combination of a high power, three level “bulk inverter” and a low power “conditioning inverter”. To minimize switching losses, the bulk inverter operates at a low frequency producing square wave outputs while high frequency conditioning inverter is used to suppress harmonic content produced by the bulk inverter output. This paper proposes an improved Space Vector Modulation (SVM) algorithm and a neutral point potential balancing technique for the inverter. Furthermore, a maximum power tracking controller for the Permanent Magnet Synchronous Generator (PMSG) is described in detail. The proposed SVM technique eliminates most of the computational burdens on the digital controller and renders a greater controllability under varying DC-link voltage conditions. The DC-link capacitor voltage balancing of both bulk and conditioning inverters is carried out using Redundant State Selection (RSS) method and is explained in detail. Experimental results are presented to verify the proposed modulation and control techniques.
Highly Active Mixed-Metal Nanosheet Water Oxidation Catalysts Made by Pulsed-Laser Ablation in Liquids (2014)

Surfactant-free mixed-metal hydroxide water oxidation nanocatalysts were synthesized by pulsed-laser ablation in liquids. In a series of [Ni-Fe]-layered double hydroxides with intercalated nitrate and water, [Ni1-xFex(OH)2](NO3)y(OH)x-y·nH2O, higher activity was observed as the amount of Fe decreased to 22%. Addition of Ti(4+) and La(3+) ions further enhanced electrocatalysis, with a lowest overpotential of 260 mV at 10 mA cm(-2). Electrocatalytic water oxidation activity increased with the relative proportion of a 405.1 eV N 1s (XPS binding energy) species in the nanosheets.
Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages (2022)

Abstract Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolated 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with an early ancestral strain of SARS-CoV-2 and later boosted with mRNA-1273. We characterized mAb genetic features by sequence assignments to the donors’ personal immunoglobulin genotypes and assessed antibody neutralizing activities against ancestral SARS-CoV-2, Beta, Delta, and Omicron variants. The mAbs used a broad range of immunoglobulin heavy chain (IGH) V genes in the response to all sub-determinants of the spike examined, with similar characteristics observed in both donors. IGH repertoire sequencing and B cell lineage tracing at longitudinal time points revealed extensive evolution of SARS-CoV-2 spike-binding antibodies from acute infection until vaccination five months later. These results demonstrate that highly polyclonal repertoires of affinity-matured memory B cells were efficiently recalled by vaccination, providing a basis for the potent antibody responses observed in convalescent persons following vaccination.