gebhart/patrepeval huggingface dataset:
Epigenetic Modulation of Estrogen Receptor-α by pRb Family Proteins: A Novel Mechanism in Breast Cancer (2007)

Estrogen receptor-alpha (ER-alpha) plays a crucial role in normal breast development and has also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients. However, ER-alpha gene expression can change during the course of disease and, consequently, therapy resistance can occur. The molecular mechanism governing ER-alpha transcriptional activity and/or silencing is still unclear. Here, we showed that the presence of a specific pRb2/p130 multimolecular complex on the ER-alpha promoter strongly correlates with the methylation status of this gene. Furthermore, we suggested that pRb2/p130 could cooperate with ICBP90 (inverted CCAAT box binding protein of 90 kDa) and DNA methyltransferases in maintaining a specific methylation pattern of ER-alpha gene. The sequence of epigenetic events for establishing and maintaining the silenced state of ER-alpha gene can be locus- or pathway- specific, and the local remodeling of ER-alpha chromatin structure by pRb2/p130 multimolecular complexes may influence its susceptibility to specific DNA methylation. Our novel hypothesis could provide a basis for understanding how the complex pattern of ER-alpha methylation and transcriptional silencing is generated and for understanding the relationship between this pattern and its function during the neoplastic process.
Identification of the ice‐binding face of antifreeze protein from <i>Tenebrio molitor</i> (2002)

The beetle Tenebrio molitor produces several isoforms of a highly disulfide-bonded beta-helical antifreeze protein with one surface comprised of an array of Thr residues that putatively interacts with ice. In order to use mutagenesis to identify the ice-binding face, we have selected an isoform that folds well and is tolerant of amino acid substitution, and have developed a heating test to monitor refolding. Three different types of steric mutations made to the putative ice-binding face reduced thermal hysteresis activity substantially while a steric mutation on an orthogonal surface had little effect. NMR spectra indicated that all mutations affected protein folding to a similar degree and demonstrated that most of the protein folded well. The large reductions in activity associated with steric mutations in the Thr array strongly suggest that this face of the protein is responsible for ice binding.
New methods for reprocessing of medical devices based on plasma treatment (2012)

The rapid progress in the development of new devices for minimal invasive surgery leads to more complex and fragile instruments including a mixture of different materials most of them thermo labile. In consequence these instruments become more and more expensive which increases the demand for reuse. By now, the manufacturers are obligated to specify the reprocessing procedure which may be a restriction in the development of new products. Therefore, there is a real need for new reprocessing procedures. Especially, plasma processes are commonly discussed as a promising alternative although only few plasma based techniques are currently commercial available. Three examples for plasma based reprocessing are discussed in detail: 1. Classical gas sterilization device: Based on commercial steam sterilizers of low temperature and formaldehyde (LTSF). The formaldehyde unit is replaced by plasma gas generator based on the PLexc® technology developed at INP. This plasma based decontamination technique was tested on long tubes similar to biopsy channels of endoscopes. 2. Atmospheric pressure plasma coating with nanoparticles in order to generate antimicrobial acting surfaces. With a special treatment unit based on the principle of a dielectric barrier discharge the inner surfaces of tubes are coated with nanoparticles. 3. “Plasmoscope”: using special plastic tubes, which include a helical electrode structure it is possible to manufacture endoscopes which allow plasma operation in their biopsy channel. This plasma can either used for decontamination, a reprocessing or under modified operation condition also for therapeutically applications. To simulate the complete reprocessing procedure the “plasmoscope” can be integrated in a reprocessing demonstrator allowing the combination of cleaning and decontamination steps.
Coprecipitation of acid cheese whey and tannery waste and recovery of protein (1978)

Abstract Combining acid cottage cheese whey and the lime–sulfide effluent from tannery unhairing processes spontaneously coprecipitates the whey proteins with the large peptides and proteins of the tannery waste. The floculation of the denatured protein material also carries down the hide pigments, excess lime, and the casein fines from the whey. The clear supernatant contains lactose, sulfur in various states of oxidation, free amino acids, peptides, and ammonium salts, but no detectable macromolecular proteins. The recovered solid products, which contain more than 20% of the original nitrogen, appear to have a good balance of essential amino acids although actual composition varies with the composition of the raw wastes. Feed supplements may possibly by obtained by this method from two presently wasted industrial effluents.
Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape (2018)

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the "out" position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections.<b>IMPORTANCE</b> MERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally defined probes for the MERS-CoV spike glycoprotein (S), the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized nonhuman primates (NHPs). MAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining MAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed MAbs. These data suggest that antibody responses to multiple domains on CoV spike protein may improve immunity and will guide future vaccine and therapeutic development efforts.
Isolating a pure population of epidermal stem cells for use in tissue engineering (2001)

Continuously renewing tissues, such as the epidermis, are maintained by stem cells that slowly proliferate and remain in the tissue for life. Although it has been known for decades that epithelial stem cells can be identified as label-retaining cells (LRCs) by long term retention of a nuclear label, isolating a pure population of stem cells has been problematic. Using a Hoechst and propidium iodide dye combination and specifically defined gating, we sorted mouse epidermal basal cells into three fractions, which we have now identified as stem, transient amplifying (TA), and non-proliferative basal cells. More than 90% of freshly isolated stem cells showed a G0/G1 cell cycle profile, while greater than 20% of the TA cells were actively dividing. Both stem and TA cells retained proliferative capacity, but the stem cells formed larger, more expandable colonies in culture. Both populations could be transduced with a retroviral vector and used to bioengineer an epidermis. However, only the epidermis from the stem cell population continued to grow and express the reporter gene for 6 months in organotypic culture. The epidermis from the transient amplifying cell fraction completely differentiated by 2 months. This novel sorting method yields pure viable epithelial stem cells that can be used to bioengineer a tissue and to test permanent recombinant gene expression.
Some Practical Issues on Real-Time Reservoir Model Updating Using Ensemble Kalman Filter (2007)

Summary The concept of "closed-loop" reservoir management is currently receiving considerable attention in the petroleum industry. A "realtime" or "continuous" reservoir model updating technique is a critical component for the feasible application of any closed-loop, model-based reservoir management process. This technique should be able to rapidly and continuously update reservoir models assimilating the up-to-date observations of production data so that the performance predictions and the associated uncertainty are up-to-date for optimization of future development/operations. The ensemble Kalman filter (EnKF) method has been shown to be quite efficient for this purpose in large-scale nonlinear systems. Previous studies show that a relatively large ensemble size is required for EnKF to reliably assess the uncertainty, and a confirming step is recommended to ensure the consistency of the updated static and dynamic variables with the flow equations. In this paper, we further explore the capability of EnKF, focusing on some practical issues including the correction of the linear and Gaussian assumptions during filter updating with iteration, the reduction of ensemble size with a resampling scheme, and the impact of data assimilation time interval. Results from the example in this paper demonstrate that the proposed iterative EnKF performs better with more accurate predictions and less uncertainty than the traditional noniterative EnKF. The use of iteration reduces the impact of nonlinearity and non-Gaussianity. Results also show that iteration may only be required when predictions are considerably deviated from the observations. The proposed resampling scheme can significantly reduce the ensemble size necessary for reliable assessment of uncertainty with improved accuracy. Finally, we show that the noniterative EnKF is sensitive to the size of time interval between the assimilation steps. Using the proposed iterative EnKF, results are more stable, more accurate reservoir models and predictions can be obtained even when a large time interval is used. This also indicates that iteration within the EnKF updating serves as a process that corrects the stronger nonlinear and non-Gaussian behaviors when larger time interval is used.
An Adaptive Architecture for Control of Uncertain Dynamical Systems with Unknown Actuator Bandwidths (2018)

Closed-loop system stability of adaptive control architectures for autonomous aerospace vehicles can be seriously degraded by the presence of actuator dynamics. To this end, recent research by the authors focuses on a new reference model design approach such that not only closed-loop system stability is rigorously addressed using linear matrix inequalities, but also the proposed reference model achieves better performance characteristics as compared with a well-adopted method in the literature called pseudo-control hedging. Yet, this reference model assumes the exact knowledge of the actuator bandwidth parameter, where such an assumption may not always hold for practical aerospace applications. Motivated from this standpoint, this paper generalizes our recent results such that the exact knowledge of the actuator bandwidth parameter is no longer necessary. Specifically, we utilize an online estimate of the actuator bandwidth parameter in the proposed reference model and show the stability of the closed-loop dynamical system using tools and methods from Lyapunov theory and linear matrix inequalities. An illustrative numerical example involving the short-period dynamics of a hypersonic vehicle model is also included in this paper to elucidate the proposed adaptive architecture for control of uncertain dynamical systems with unknown actuator bandwidths.
Giant magnetoresistive spin valve bridge sensor (1996)

We describe the design, fabrication, and performance of a "spin valve" magnetic field sensor based on the giant magnetoresistive effect. The sensor is a balanced, four resistor, fully biased, Wheatstone bridge network with bipolar output. The devices described here show magnetoresistance ratios /spl Delta/V/V=/spl Delta/R/R=6%, saturation fields of 25 Oe, and a Johnson limited noise floor of 2.6 /spl mu/Oe/(Hz)/sup 1/2/. The linearity of the device is +/-2% of the full scale amplitude, with a hysteresis of 1% over the linear range. Fabrication of this device requires a novel approach to setting the directions of the antiferromagnetic exchange layers that bias the sensor. As compared to bridges based on the anisotropic magnetoresistance effect, these devices offer superior signal amplitude and linearity. To our knowledge this is the first report of such a device.
The synthesis of a hierarchically porous BEA zeolite via pseudomorphic crystallization (2009)

A synthesis route to a hierarchically meso-/microporous BEA zeolite has been developed with a cyclic diammonium as a structure-directing agent (SDA), which leads to pseudomorphic crystallization of the zeolite by suppressing the mobility of silicates during crystallization.
Virtual Private Wire Service Support in Ethernet VPN (2017)

This document describes how Ethernet VPN (EVPN) can be used to support
the Virtual Private Wire Service (VPWS) in MPLS/IP networks. EVPN
accomplishes the following for VPWS: provides Single-Active as well as
All-Active multihoming with flow-based load-balancing, eliminates the
need for Pseudowire (PW) signaling, and provides fast protection
convergence upon node or link failure.
Selective Activation of the Muscles of Micturition Using Intrafascicular Stimulation of the Pudendal Nerve (2011)

We investigate the hypothesis that intrafascicular stimulation of the pudendal nerve (PN) can be used to selectively activate the detrusor bladder muscle and the external urethral sphincter (EUS). Nine anesthetized male canines were used in this study. Muscle activations were measured via bladder catheter pressure transducers and EUS electromyography (EMG) wires. The PNs were exposed via dissection of the ischioanal fossa and implanted with Utah Slanted Electrode Arrays (USEAs). USEAs consist of 100, 0.5–1.5 mm long microelectrodes that project out from a 4 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\,\times\,$</tex> </formula> 4 mm substrate. Intrafascicular stimulation was delivered via individual USEA microelectrodes in order to map the ability of each electrode to selectively or nonselectively evoke detrusor and/or EUS contractions. We were able to selectively activate the detrusor using 33 Hz stimulation of PN axons with an average of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$4.57 \pm 3.82$</tex></formula> ( <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">${\rm mean }\pm {\rm sd}$</tex></formula> ) USEA electrodes per animal tested. Electrically-evoked and distention-evoked bladder contractions had similar kinetics. Sustained bladder contractions were evoked via 60 s of intrafascicular stimulation. The EUS was activated using 33 Hz stimulation via an average of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex Notation="TeX">$26.14 \pm 19.45$</tex></formula> electrodes per animal tested. High frequency ( <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$> {2}~{\rm kHz}$</tex></formula> ) stimulation delivered via EUS selective electrodes produced nonselective block of PN axons. Examples of how this selective axonal access could be used to restore continence and activate micturition were demonstrated in two animals. We report herein the first study demonstrating selective detrusor and EUS activation via microelectrodes implanted intrafascicularly in the PN. Such selective activation enables new therapeutic possibilities for controlling the muscles of micturition.
Impact of Nature and Length of Linker Incorporated in Agonists on Toll-Like Receptor 9-Mediated Immune Responses (2010)

Oligodeoxynucleotides containing unmethylated CpG motifs act as ligands of Toll-like receptor 9 (TLR9). We previously reported a novel class of TLR9 agonists, referred to as immune-modulatory oligonucleotides (IMOs), in which two 11-mers of the same sequence are attached via their 3'-ends through a 1,2,3-propanetriol linker and contain a synthetic immune-stimulatory motif, Cp7-deaza-dG. In the present study, we have examined the impact of length, nature, and stereochemistry of the linker incorporated in agonists for TLR9 activation. The new linkers studied include (S)-(-)-1,2,4-butanetriol, 1,3,5-pentanetriol, cis,cis-1,3,5-cyclohexanetriol, cis,trans-1,3,5-cyclohexanetriol, 1,3,5-tris(2-hydroxyethyl)isocyanurate, tetraethyleneglycol, and hexaethyleneglycol in place of 1,2,3-propanetriol linker. Agonists with various linkers are studied for TLR9-mediated immune responses in HEK293 cells, human cell-based assays, and in vivo in mice. Results of these studies suggest that C3-C5 linkers, 1,2,3-propanetriol, (S)-(-)-1,2,4-butanetriol, or 1,3,5-pentanetriol, are optimal for stimulation of TLR9-mediated immune responses. Rigid C3 linkers with different stereochemistry have little effect on immune stimulation, while linkers longer than C5 reduced TLR9-mediated immune stimulation.
Plasma etching of III-V compound semiconductors (1983)

Plasma etching techniques for III-V compound semiconductors are reviewed, emphasizing design considerations in the choice of gases, discharge parameters, and substrate temperature. Mechanisms are proposed for anisotropic, isotropic, and crystallographic chemical etching. Applications of plasma etching in device fabrication are given.
Real‐Time SNP Analysis in Secondary‐Structure‐Folded Nucleic Acids (2010)

A tricomponent sensor was designed for genotyping stem-loop-structured DNA sequences. DNA adaptor strand f (see picture; red) hybridizes to the analyte (orange) with high affinity and unwinds its secondary structure; strand m (green) forms a stable complex only with the fully complementary analyte sequence. A fluorescing molecular beacon reports complex formation. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Discovery of an Orally Available Diazabicyclooctane Inhibitor (ETX0282) of Class A, C, and D Serine β-Lactamases (2020)

Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases are responsible for a large proportion of the resistance phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with β-lactam antibiotics to negate the action of the β-lactamases, thereby restoring activity of the β-lactam. Newly developed BLIs offer some advantage over older BLIs in terms of enzymatic spectrum but are limited to the intravenous route of administration. Reported here is a novel, orally bioavailable diazabicyclooctane (DBO) β-lactamase inhibitor. This new DBO, ETX1317, contains an endocyclic carbon-carbon double bond and a fluoroacetate activating group and exhibits broad spectrum activity against class A, C, and D serine β-lactamases. The ester prodrug of ETX1317, ETX0282, is orally bioavailable and, in combination with cefpodoxime proxetil, is currently in development as an oral therapy for multidrug resistant and carbapenem-resistant <i>Enterobacterales</i> infections.
Cloning, sequencing, and expression of thermophilic Bacillus sp. strain TB-90 urease gene complex in Escherichia coli (1994)

The urease of thermophilic Bacillus sp. strain TB-90 is composed of three subunits with molecular masses of 61, 12, and 11 kDa. By using synthetic oligonucleotide probes based on N-terminal amino acid sequences of each subunit, we cloned a 3.2-kb EcoRI fragment of TB-90 genomic DNA. Moreover, we cloned two other DNA fragments by gene walking starting from this fragment. Finally, we reconstructed in vitro a 6.2-kb DNA fragment which expressed catalytically active urease in Escherichia coli by combining these three DNA fragments. Nucleotide sequencing analysis revealed that the urease gene complex consists of nine genes, which were designed ureA, ureB, ureC, ureE, ureF, ureG, ureD, ureH, and ureI in order of arrangement. The structural genes ureA, ureB, and ureC encode the 11-, 12-, and 61-kDa subunits, respectively. The deduced amino acid sequences of UreD, UreE, UreF, and UreG, the gene products of four accessory genes, are homologous to those of the corresponding Ure proteins of Klebsiella aerogenes. UreD, UreF, and UreG were essential for expression of urease activity in E. coli and are suggested to play important roles in the maturation step of the urease in a co- and/or posttranslational manner. On the other hand, UreH and UreI exhibited no significant similarity to the known accessory proteins of other bacteria. However, UreH showed 23% amino acid identity to the Alcaligenes eutrophus HoxN protein, a high-affinity nickel transporter.
A Closed Form Solution for a Nonlinear Wiener Filter (2006)

In this paper a nonlinear extension to the Wiener filter is presented. A direct approach has been devised of replacing the autocorrelation function with a novel function called correntropy, derived from ideas on kernel-based learning theory and information theoretic learning. The linear Wiener filter, widely used because of its simplicity and optimality for linear systems and Gaussian distribution, is no longer effective when dealing with nonlinear time series data. The proposed method incorporates higher order moments in the general form of autocorrelation and improves upon the linear filter. Moreover, the computation cost is still lower than some kernel based methods and has a closed form solution to the problem unlike neural network based methods.