gebhart/patrepeval huggingface dataset:
EHMT1 pathogenic variants and 9q34.3 microdeletions share altered DNA methylation patterns in patients with Kleefstra syndrome (2020)

Aim: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the euchromatic histone lysine methyltransferase 1 gene, EHMT1 , due to either a submicroscopic 9q34.3 deletion or a pathogenic EHMT1 variant. KS is characterized by intellectual disability, autistic-like features, heart defects, hypotonia and distinctive facial features. Here, we aimed to (1) identify a unique DNA methylation signature in patients with KS, and (2) demonstrate the efficacy of DNA methylation in predicting the pathogenicity of copy number and sequence variants.
43. Fibrinogen assembly in extracellular matrix is heparan sulfate proteoglycan-dependent (1998)

Departments of 1Medicine-Vascular, 2Microbiology and Immunology and 3Pathology, University of Rochester, Rochester, New York, USA
Supplementary Table 2 from Adipocyte-Derived Fibroblasts Promote Tumor Progression and Contribute to the Desmoplastic Reaction in Breast Cancer (2023)

&lt;p&gt;PDF file, 58K, Sequences and concentrations of the primers used to detect human and murine genes expression by qPCR.&lt;/p&gt;
Secrecy Rates in Broadcast Channels with Confidential Messages and External Eavesdroppers (2014)

In this paper, we consider the broadcast channel with confidential messages and external eavesdroppers (BCCE), where a multi-antenna base station simultaneously communicates to multiple potentially malicious users, in the presence of randomly located external eavesdroppers. Using the proposed model, we study the secrecy rates achievable with regularized channel inversion (RCI) precoding by performing a large-system analysis that combines results from stochastic geometry and random matrix theory, where the number of users K and the number of transmit antennas N both grow to infinity in a fixed ratio. We obtain explicit expressions for the probability of secrecy outage and an upper bound on the rate loss due to the presence of external eavesdroppers. We show that both these quantities scale as \fraclambda_esqrt{N} as the density of external eavesdroppers λ_e grows, irrespective of their collusion strategy. Furthermore, we derive a practical rule for the choice of the regularization parameter, which is agnostic of channel state information and location of eavesdroppers, and yet provides close to optimal performance.
Recombination-enhanced migration of interstitial aluminum in silicon (1979)

We report the first observation of recombination-enhanced recovery of a defect in silicon which is otherwise normally stable at room temperature. This defect, produced by 1.5-MeV electron irradiation of aluminum-doped material at room temperature, is identified as isolated interstitial aluminum through correlated deep-level transient-capacitance spectroscopy and EPR studies. The recovery rate constant in the absence of minority-carrier injection is 3(${10}^{9}$) exp(- 1.2\ifmmode\pm\else\textpm\fi{}0.1 eV/kT) ${\mathrm{sec}}^{\ensuremath{-}1}$. Under saturated injection conditions, it is 70 exp(- 0.27\ifmmode\pm\else\textpm\fi{}0.03 eV/kT) ${\mathrm{sec}}^{\ensuremath{-}1}$. This represents an enhancement of the recovery rate by a factor of \ensuremath{\sim} ${10}^{8}$ at room temperature. We conclude that this enhancement results from an efficient conversion of the electronic energy available upon carrier capture to local vibrational energy of the defect which assists it over the migration barrier. The second donor level of the defect ($\frac{{\mathrm{Al}}_{i}^{+}}{{\mathrm{Al}}_{i}^{++}}$) is determined to be at ${E}_{V}+0.17$ eV. We conclude, however, that the enhancement results from carrier capture and recombination at the first donor level ($\frac{{\mathrm{Al}}_{i}^{0}}{{\mathrm{Al}}_{i}^{+}}$) the position of which has not yet been determined. The implications of these results to the properties of the self-interstitial in silicon are discussed.
SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes (2015)

Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3' UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes.
Urokinase inhibits HL-60 cell proliferation in vitro. (1994)

The binding of urokinase-type plasminogen activator (u-PA) to its receptor (u-PA-R) is required for morphological and functional maturation during monocyte differentiation of the promyelocytic leukaemia line HL-60. This paper reports that monocyte differentiation of HL-60 cells induced by 1,25 dihydroxyvitamin D2 (vitamin D2) results in a marked increase in expression of u-PA and u-PA-R. This increase in u-PA expression is of greater magnitude than is observed after culture with interferon-gamma (IFN gamma), another potent inducer of monocytic differentiation. Dimethyl sulphoxide (DMSO), an agent that induces granulocytic differentiation, also increased expression of u-PA. However, culture with the granulocyte-inducing all-trans retinoic acid (RA) did not induce an increase in surface expression of u-PA or u-PA-R. The vitamin D2-induced increase in cell-surface u-PA was not coincident with an increase in steady-state levels of u-PA mRNA, suggesting that intracellular stores of this protein, translational or post-translational mechanisms of regulation, or some other regulatory mechanism may be responsible for the increase in u-PA during differentiation. To ascertain an association between the increased expression of cell-surface u-PA and reduced proliferation that accompanies differentiation, the effect of u-PA on cellular proliferation of HL-60 cells was measured. Both pro-u-PA (whole molecule) and fragments of u-PA that retained receptor-binding capability caused a marked inhibition of HL-60 proliferation in the absence of vitamin D2.(ABSTRACT TRUNCATED AT 250 WORDS)
Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects (2020)

Here we present an evaluation of the binding affinity prediction accuracy of the free energy calculation method FEP+ on internal active drug discovery projects and on a large new public benchmark set.&lt;br&gt;
Electrostatic shape-shifting ion optics (2023)

Electrostatic shape-shifting ion optics includes an outer electrode that defines an interior region between first and second opposed open ends. A first inner electrode is positioned within the interior region of the outer electrode at about the first open end. A second inner electrode is positioned within the interior region of the outer electrode at about the second open end. A first end cap electrode is positioned at about a first open end of the first inner electrode so that the first end cap electrode substantially encloses the first open end of the first inner electrode. A second end cap electrode is positioned at about a second open end of the second inner electrode so that the second end cap electrode substantially encloses the second open end of the second inner electrode. A voltage source operatively connected to each of the electrodes applies voltage functions to each of the electrodes to produce an electric field within an interior space enclosed by the electrodes.
Serial multiomic analysis in advanced breast cancer: A novel platform to inform therapeutic decisions. (2023)

e13001 Background: We designed and implemented a platform wherein patients with metastatic treatment-refractory cancer would receive individually tailored treatment informed by multi-omic data and iteratively adapted in real-time. Here we describe the workflow of this platform and quantify operational characteristics for a metastatic breast cancer cohort. Methods: Participants with metastatic breast cancer progressing after standard-of-care therapy were enrolled. Sites demonstrating disease progression were targeted for biopsy. Resultant tissue was analyzed by a next-generation sequencing (NGS) solid tumor panel, whole exome sequencing, whole transcriptomic sequencing, multiplex protein analysis of a panel of cancer-relevant proteins and phosphoproteins, and focused immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) analysis. Results: Between 1/1/2017 to 12/31/2021, 74 participants were consented and 55 were enrolled. Median age at enrollment was 54 years, most were ECOG 0-1, and received a median of 2 lines of therapy in the metastatic setting. There were 95 biopsies collected from 55 individual participants and analytics were successfully generated in 94% of the cases. At the provider’s request, an integrated clinical, molecular, and cancer biology tumor board (TB) was convened for 25 participants. A total of 21 participants received matched therapy based on clinical parameters coupled to a consideration of biologically informed therapeutic vulnerabilities and 6 had a PFS2/PFS1 &gt; 1.3. Twenty-one participants had a median of 2 repeat progression biopsies (range 2-5) and new alterations with potential therapeutic implications were identified. Repeat biopsies could have led to a new treatment in 11 of the participants, though only 3 received a therapy recommended by the tumor board owing to either rapid disease progression, clinical deterioration, or lack of access to drug. Conclusions: We demonstrated the practical feasibility and initial operating characteristics of a platform designed to comprehensively understand and integrate the clinical and molecular characteristics of a cohort with metastatic progressive breast cancer as they evolve on therapy and to use this information to deliver iteratively tailored therapy in real time. Further, clinical responses were observed in a subset of participants. These findings suggest an opportunity to incorporate this platform earlier in a disease course or to design adaptive clinical trials with access to therapies aimed at targeting new biological alteration.
Fine force control based on reaction force observer for electric injection molding machine (2011)

Currently, most plastic products are manufactured by using injection molding machines. The quality of plastic products depends largely on the injection force. In a typical force control system of an injection molding machine, force information from the machine environment is obtained by a force sensor. However, force sensors have a few disadvantages in terms of signal noise, sensor cost and narrow bandwidth. So, a sensor-less force detection method is desirable for electric injection molding machines. We have proposed the use of a reaction force observer based on the two-inertia resonant model. However, this method has some estimated error because of the influence of nonlinear characteristics of the holding process and the screw back-pressure process. This paper proposes a new injection force estimation method based on a proposed high-order reaction force observer (HORFO), which is not influenced by the nonlinear friction phenomenon significantly. This paper evaluates the possibility and versatility of the proposed sensor-less force control system by using proposed HORFO through experiments.
Normal-mode statistics of sound scattering by a rough elastic boundary in underwater wave-guide in a full coupled mode approach, including back-scattering (2017)

The underwater sound scattering by rough sea surface, ice, or rough elastic bottom is studied. The effects of scattering from a rough elastic boundary are included in a coupled mode propagation model by the analytical equation for solid-state layer impedance. A full two-way coupled mode solution was used to derive the stochastic differential equations for the second order statistics in a Markov approximation for a transport theory. The coupled mode matrix was approximated by a linear function of one random parameter such as ice-thickness or the surface perturbation. A one parameter Gaussian model has a form of a two-way differential stochastic equation for the correlation of normal mode coefficients. The derived equation relates the correlation matrix of mode coefficients (for both directions) with the correlation function of the rough boundary and the power spectrum of the its slopes. The theory gives a solution for sound attenuation and horizontal coherence over long-range propagation along random interfaces. The result can be used for the estimation of sound attenuation in long-range under-ice propagation or attenuation of seismic waves in an underwater wave-guide with random bathymetry.
ME-15 * INTERACTION BETWEEN CANCER STEM CELLS AND MYELOID DERIVED SUPPRESSOR CELLS DRIVES IMMUNOSUPPRESSION AND GLIOBLASTOMA GROWTH (2014)

Cellular and molecular regulation of the immune system is exquisitely controlled in the brain and disrupted in neoplasia. Glioblastoma (GBM) has an immunosuppressive phenotype, and despite the accumulation of immune cells in the tumor microenvironment, tumor growth persists. Myeloid derived suppressor cells (MDSCs) are a class of immature immune cells that mitigate cytotoxic T cell responses and promote immunosuppression in a variety of cancers. MDSCs are increased in the peripheral blood of GBM patients, but their role in the GBM microenvironment is undefined. We observed co-localization between arginase (Arg1) producing immunosuppressive MDSCs and cancer stem cells (CSCs) in GBM patient specimens and xenografts, leading to the hypothesis that CSCs stimulate MDSCs to promote immunosuppression. Intracranial injections of CSCs into mice led to GBM formation, expansion of the Arg1-producing MDSCs within the marrow of GBM-bearing mice, and increased levels of MDSCs within the GBM microenvironment. CSC conditioned media increased Arg1 production of murine marrow MDSCs which were then able to modulate cytotoxic T cell responses in co-culture models. Screening of conditioned media revealed cytokines secreted selectively by CSCs that activated MDSCs suppression. Removal of CSC-secreted factors decreased MDSCs in the GBM microenvironment, increased cytotoxic T cell infiltration, and had a pronounced survival benefit. Peripheral targeting of MDSCs through a sub-therapeutic dose of 5-fluorouracil (5-FU) in an immunocompetent syngeneic mouse model led to a similar phenotype to CSC-secreted factor removal in the GBM microenvironment, and an even greater survival benefit. Taken together, our results suggest a critical role of MDSC-mediated immunosuppression in GBM, a novel paradigm of immunomodulation by CSCs, and demonstrate that peripheral removal of MDSCs leads to increased T cell infiltration into GBM, and consequently suggest a novel chemotherapeutic strategy that is not generally toxic to bone marrow and that is not dependent on agents crossing the blood brain barrier.
Nuclear structure and the three‐dimensional organization of DNA (1991)

The organization of DNA within the nucleus has been demonstrated to be both cell and tissue specific and is arranged in a non-random fashion in both sperm and somatic cells. Nuclear structure has a pivotal role in this three-dimensional organization of DNA and RNA and contributes as well to forming fixed organizing sites for nuclear functions, such as DNA replication, transcription, and RNA processing. In sperm, DNA is also organized in a specific fashion by the nuclear matrix and DNA-protamine interactions. Within somatic cells, the nuclear matrix provides a three-dimensional framework for the tissue specific regulation of genes by directed interaction with transcriptional activators. This differential organization of the DNA by the nuclear matrix, in a tissue specific manner, contributes to tissue specific gene expression. The nuclear matrix is the first link from the DNA to the entire tissue matrix system and provides a direct structural linkage to the cytomatrix and extracellular matrix. In summary, the tissue matrix serves as a dynamic structural framework for the cell which interacts to organize and process spatial and temporal information to coordinate cellular functions and gene expression. The tissue matrix provides a structural system for integrating form and function.
Aqueous ozonolysis products of methyl- and dimethylnaphthalenes (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAqueous ozonolysis products of methyl- and dimethylnaphthalenesMichael D. Gaul, Gregor A. Junk, and Harry J. SvecCite this: Environ. Sci. Technol. 1987, 21, 8, 777–784Publication Date (Print):August 1, 1987Publication History Published online1 May 2002Published inissue 1 August 1987https://pubs.acs.org/doi/10.1021/es00162a008https://doi.org/10.1021/es00162a008research-articleACS PublicationsRequest reuse permissionsArticle Views167Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Simulation of high-contrast densitiy-driven transport at field scale (2011)

Recent 2D density-coupled solute transport simulations have revealed the importance of geological dip for predicting subsurface dissolution of halite. In the presented experiments, relevance of additional field parameters such as depth of extraction wells, time-variable permeability, aquifer width, and normal fault width were evaluated. The study site in the Tabular Jura is an approximately 1000m long, and 200m deep 2D field scale model, which represents a setup of two aquifers connected by subvertical normal fault zones. The resulting high contrasts in groundwater density were simulated with a numerical model based on Mixed Finite Elements for the fluid flow problem and a combination of Discontinuous Galerkin Finite Element and Multi-Point Flux Approximation methods for the transport. Steady-state concentration distribution in the upper aquifer is reached in most simulations after a few years, and increased salinities are affecting most parts of the aquifer. Different scenarios were run to study the effect of the well depth on the dissolution process. Well depth in the about 50 m thick upper aquifer varied between 20 m to 50 meters. Results show that the depth of the well has no significant effect on the process (difference is in the order of 1%). The effect of variable permeability, which is due to fracture opening in the evaporitic rock formation, is simulated with a discrete fracture approach, which includes small fractures and bedding partings of a karstic, or fissured aquifer directly into a porous flow model. The fracture aperture, or void opening, is time-dependent and a function of salt dissolution. The results demonstrate that the permeability has a large impact on the dissolved salt mass: the total simulated mass with time-variable permeability is more than 25% larger compared to the dissolved mass with constant permeability. The effect of the normal fault zone thickness of higher permeability is studied by simulating fault zone thicknesses between 10 cm and 40 m. The corresponding simulated dissolution rates sharply increase with fault widening before they apparently start to level out at 40 m. Finally, the range of the unknown lower aquifer thickness above the rock salt is varied from 10 cm to 10 m. Simulated density-driven flow velocities are directly related to the imposed aquifer thickness: if the lower aquifer thickness decreases, then the flow velocity will increase, which leads to more dissolved salt, and vice-versa.
Biomarkers for Progenitor and Differentiated Epithelial Cells in the Human Meibomian Gland (2018)

The meibomian gland (MG) is a sebaceous gland that secretes through a holocrine process. Because such secretion requires the destruction of MG acinar epithelial cells, they need constant renewal and differentiation. The processes that promote these regenerative events in the human MG are unknown, nor is it known how to distinguish MG progenitor and differentiated cells. We discovered that Lrig1 and DNase2 serve as biomarkers for human MG progenitor and differentiated cells, respectively. Lrig1 is expressed in MG basal epithelial cells in the acinar periphery, a location where progenitor cells originate in sebaceous glands. DNase2 is expressed in the differentiated epithelial cells of the MG central acinus. Furthermore, proliferation stimulates, and differentiation suppresses, Lrig1 expression in human MG epithelial cells. The opposite is true for DNase2 expression. Our biomarker identification may have significant value in clinical efforts to restore MG function and to regenerate MGs after disease-induced dropout. Stem Cells Translational Medicine 2018;7:887-892.
Pattern recognition for classification and determination of polychlorinated biphenyls in environmental samples (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPattern recognition for classification and determination of polychlorinated biphenyls in environmental samplesW. J. Dunn, D. L. Stalling, T. R. Schwartz, J. W. Hogan, J. D. Petty, Erik. Johansson, and Svante. WoldCite this: Anal. Chem. 1984, 56, 8, 1308–1313Publication Date (Print):July 1, 1984Publication History Published online1 May 2002Published inissue 1 July 1984https://pubs.acs.org/doi/10.1021/ac00272a026https://doi.org/10.1021/ac00272a026research-articleACS PublicationsRequest reuse permissionsArticle Views162Altmetric-Citations68LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts