gebhart/patrepeval huggingface dataset:
Periplasmic expression of human interferon-α 2c in Escherichia coli results in a correctly folded molecule (1994)

Human interferon-alpha 2c (IFN-alpha 2c) was produced in Escherichia coli under the control of the alkaline phosphatase promoter using a periplasmic expression system. Compared with other leader sequences, the heat-stable enterotoxin II leader of E. coli (STII) resulted in the highest rate of correct processing as judged by Western-blot analysis. The fermentation was designed as a batch-fed process in order to obtain a high yield of biomass. The processing rate of IFN-alpha 2c could be increased from 25% to more than 50% by shifting the fermentation pH from 7.0 to 6.7. IFN-alpha 2c extracted from the periplasm was purified by a new four-step chromatographic procedure. Whereas cytoplasmically produced IFN-alpha 2c does not have its full native structure, IFN-alpha 2c extracted from the periplasm was found to be correctly folded, as shown by c.d. spectroscopy. Peptide-map analysis in combination with m.s. revealed the correct formation of disulphide bridges. N-terminal sequence analysis showed complete removal of the leader sequence, creating the authentic N-terminus starting with cysteine.
Circulating miRNAs in myasthenia gravis: miR‐150‐5p as a new potential biomarker (2013)

WE PROPOSE THAT THE VALIDATED MIRNAS: hsa-miR150-5p, hsa-miR21-5p, and hsa-miR27a-3p can serve as novel serum biomarkers in AChR+ MG. Hsa-miR-150-5p could be a helpful marker to monitor disease severity.
Supported Hybrid Bilayer Membranes as Rugged Cell Membrane Mimics (1999)

Supported planar lipid bilayers based on alkanethiol-tethering chemistry are becoming increasingly important biomimetic materials. Hybrid bilayers containing thiol-derivatized alkane moieties plus natural lipids provide a biomimetic matrix that permits the successful reconstitution of membrane protein activity. The hybrid membrane is self-assembled and sufficiently rugged to be of practical use in research and in commercial sensing applications. The coupling of the bilayer to a metal support allows a wide range of analytical techniques to be applied to this model membrane. This article reviews some of the fundamental studies of the formation, structure, and response of hybrid bilayer membranes.
Combinations of CD45 Isoforms Are Crucial for Immune Function and Disease (2006)

Expression of the CD45 Ag in hemopoietic cells is essential for normal development and function of lymphocytes, and both mice and humans lacking expression exhibit SCID. Human genetic variants of CD45, the exon 4 C77G and exon 6 A138G alleles, which alter the pattern of CD45 isoform expression, are associated with autoimmune and infectious diseases. We constructed transgenic mice expressing either an altered level or combination of CD45 isoforms. We show that the total level of CD45 expressed is crucial for normal TCR signaling, lymphocyte proliferation, and cytokine production. Most importantly, transgenic lines with a normal level, but altered combinations of CD45 isoforms, CD45(RABC/+) and CD45(RO/+) mice, which mimic variant CD45 expression in C77G and A138G humans, show more rapid onset and increased severity of experimental autoimmune encephalomyelitis. CD45(RO/+) cells produce more TNF-alpha and IFN-gamma. Thus, for the first time, we have shown experimentally that it is the combination of CD45 isoforms that affects immune function and disease.
Genetic aberrations of gastrointestinal stromal tumors (2008)

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract and is associated with mutations of the KIT or PDGFRA gene. In addition, other genetic events are believed to be involved in GIST tumorigenesis. Cytogenetic aberrations associated with these tumors thus far described include loss of 1p, 13q, 14q, or 15q, loss of heterozygosity of 22q, numeric chromosomal imbalances, and nuclear/mitochondrial microsatellite instability. Molecular genetic aberrations include loss of heterozygosity of p16(INK4A) and p14(ARF), methylation of p15(INK4B), homozygous loss of the Hox11L1 gene, and amplification of C-MYC, MDM2, EGFR1, and CCND1. GISTs in patients with neurofibromatosis type 1 appear to lack the KIT and PDGFRA mutations characteristic of GISTs and may have a different pathogenetic mechanism. Gene mutations of KIT or PDGFRA are critical in GISTs, because the aberrant versions not only are correlated with the specific cell morphology, histologic phenotype, metastasis, and prognosis, but also are the targets of therapy with imatinib and other agents. Furthermore, specific mutations in KIT and PDGFR appear to lead to differential drug sensitivity and may in the future guide selection of tyrosine kinase inhibitors. Activation of the receptor tyrosine kinases involves a signal transduction pathway whose components (mitogen-activated protein kinase, AKT, phosphoinositide 3-kinase, mammalian target of rapamycin, and RAS) are also possible targets of inhibition. A new paradigm of classification, integrating the standard clinical and pathological criteria with molecular aberrations, may permit personalized prognosis and treatment.
Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications (2008)

This tutorial review discusses a new class of colloidal metal nanoparticles that is able to enhance the efficiencies of surface-enhanced Raman scattering (SERS) by as much as 10(14)-10(15) fold. This enormous enhancement allows spectroscopic detection and identification of single molecules located on the nanoparticle surface or at the junction of two particles under ambient conditions. Considerable progress has been made in understanding the enhancement mechanisms, including definitive evidence for the single-molecule origin of fluctuating SERS signals. For applications, SERS nanoparticle tags have been developed based on the use of embedded reporter molecules and a silica or polymer encapsulation layer. The SERS nanoparticle tags are capable of providing detailed spectroscopic information and are much brighter than semiconductor quantum dots in the near-infrared spectral window. These properties have raised new opportunities for multiplexed molecular diagnosis and in vivo Raman spectroscopy and imaging.
Multi-task Learning Using Uncertainty to Weigh Losses for Scene Geometry and Semantics (2018)

Numerous deep learning applications benefit from multitask learning with multiple regression and classification objectives. In this paper we make the observation that the performance of such systems is strongly dependent on the relative weighting between each task's loss. Tuning these weights by hand is a difficult and expensive process, making multi-task learning prohibitive in practice. We propose a principled approach to multi-task deep learning which weighs multiple loss functions by considering the homoscedastic uncertainty of each task. This allows us to simultaneously learn various quantities with different units or scales in both classification and regression settings. We demonstrate our model learning per-pixel depth regression, semantic and instance segmentation from a monocular input image. Perhaps surprisingly, we show our model can learn multi-task weightings and outperform separate models trained individually on each task.
Adaptively sampled distance fields (2000)

Adaptively Sampled Distance Fields (ADFs) are a unifying representation of shape that integrate numerous concepts in computer graphics including the representation of geometry and volume data and a broad range of processing operations such as rendering, sculpting, level-of-detail management, surface offsetting, collision detection, and color gamut correction. Its structure is uncomplicated and direct, but is especially effective for quality reconstruction of complex shapes, e.g., artistic and organic forms, precision parts, volumes, high order functions, and fractals. We characterize one implementation of ADFs, illustrating its utility on two diverse applications: 1) artistic carving of fine detail, and 2) representing and rendering volume data and volumetric effects. Other applications are briefly presented.
Catalytic Homologation of Vinyltributylstannane to Allyltributylstannane by Mo(IV) Complexes in the Presence of Ethylene (2004)

We have found that CH2=CHSnBu3 is converted into CH2=CHCH2SnBu3 catalytically in the presence of Mo(IV) olefin complexes such as Mo(NAr)(CH2CH2)[biphen] (where Ar = 2,6-i-Pr2C6H3 and [biphen]2- = 3,3'-di-tert-butyl-5,5',6,6'-tetramethyl-1,1'-biphenyl-2,2'-diolate). The proposed mechanism involves formation of a metalacyclopentane (MC4) complex from ethylene and CH2=CHSnBu3, "contraction" of this MC4 complex to a metalacyclobutane (MC3) complex, and finally metathesis of the MC3 complex to give CH2=CHCH2SnBu3 and Mo(NAr)(CH2)[biphen]. These new findings suggest (inter alia) that contraction of an MC4 ring to an MC3 ring may be a much more common mode of decomposition of metalacyclopentane rings in d0 complexes than previously believed.
A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1 (1990)

Recent cDNA cloning and sequencing of two Epstein-Barr virus (EBV)-specific mRNAs from latently infected cultures revealed that these RNAs are encoded across the fused terminal repeats of the viral genome and that they are likely to encode two nearly identical proteins with the same transmembrane domains. The smaller predicted protein (LMP2B) lacks 119 amino-terminal amino acids found in the larger one (LMP2A). To test whether these proteins are expressed in latently infected lymphocytes, antibodies to the LMP2 proteins were derived by immunizing rabbits with TrpE-LMP2A fusion proteins. Affinity-purified LMP2-specific antibodies recognized 54- and 40-kilodalton proteins, corresponding to LMP2A and LMP2B, in immunoblots of rodent fibroblasts stably transfected with eucaryotic expression plasmids containing either the LMP2A or LMP2B cDNA. Similar-size proteins were also identified in immunoblots of latently infected lymphocytes. LMP2A localized to membranes in cellular fractionation studies. In immunofluorescent studies, LMP2 localized in the plasma membrane of EBV-infected lymphocytes, with the majority of reactivity confined to the region of the LMP1 patch. This reactivity was detected in almost all lymphoblastoid cells latently infected with EBV.
Sequence-independent amplification and labeling of yeast artificial chromosomes for fluorescence in situ hybridization (1994)

We have developed a method that allows reliable construction of high quality FISH probes from yeast artificial chromosomes (YACs) based on the separation of YACs by pulse-field gel electrophoresis and a rapid sequence-independent amplification procedure (SIA). These probes can be used to localize YACs on metaphase chromosomes and also with high efficiency, in interphase nuclei.
Genetically Encoded Cyclopropene Directs Rapid, Photoclick‐Chemistry‐Mediated Protein Labeling in Mammalian Cells (2012)

We just click: Genetic incorporation of a cyclopropene amino acid CpK (see scheme) site-specifically into proteins in E. coli and mammalian cells was achieved using an orthogonal aminoacyl-tRNA synthetase/tRNA(CUA) pair (CpKRS/MbtRNA(CUA)). Cyclopropene exhibited fast reaction kinetics in the photoclick reaction and allowed rapid (ca. 2 min) labeling of proteins.
STUDY OF THE STABILITY IN REAL TIME OF CRYOPRESERVED STRAIN BANKS (2004)

The stability in real time of four strains cryopreserved in 10% v/v of glycerol was evaluated during a 6-month period. The strains studied were Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae and Aspergillus niger. The Master Cell Bank (MCB), cryopreserved at -70ºC and -20ºC, was activated using two thawing protocols, a fast one (F) and a slow one (S). A better cell recovery was achieved with the -70ºC (F) protocol reaching a viability for Escherichia coli of 97.6% in the first 48 hours (p: 7.2x10-4). The viability was retained in the 4 th (p: 1.5 x10 -4), 5 th (p: 4.6 x10-3) and 6 th months (p: 1.9 x10-2). Bacillus subtilis retained a viability of 92.5% after the 2nd (p: 4.7x10-4), 4th (p: 1.76x10-1), 5th (p: 3.4x10-5) and 6th months (p: 3x10-2). Saccharomyces cerevisiae demonstrated a viability of 95% in the second month (p:9x10-3) and for Aspergillus niger, the viability was 94.8%, in the first 48 hours (p: 7.2 x10-4) and after the 4th month (p: 2.79x10-2). With the other protocols, -20ºC F and S, some changes in viability were observed due probably to the formation of eutectic mixtures, nucleation and re-crystallization processes. The Master Bank microbial purity was maintained at 100% during the time of the study.
Quantitative determination of Streptococcus mutans by using competitive polymerase chain reaction (1999)

Mutans streptococci are among the range of pathogens strongly related to human dental caries. The determination of total amounts of these pathogens as well as their proportion in relation to other oral bacteria is of interest for the assessment of the risk that a patient runs of developing dental caries. This paper presents a competitive polymerase chain reaction (PCR) method for the specific quantitative determination of Streptococcus mutans which uses a homologous DNA for internal standardisation. For quantification of these bacteria, calibration curves were obtained by coamplification of known amounts of S. mutans DNA in the presence of different known amounts of the competitor DNA. The same procedure was performed with known amounts of cultured S. mutans cells. In a clinical study, the reliability of the newly developed quantitative PCR method was assessed by comparing its results with those obtained in parallel with a standard chair side culture method. The described method enables a rapid and exact determination of unknown amounts of S. mutans and could provide an efficient tool for evaluating the caries risk in a patient and to monitor the efficiency of preventive and therapeutic measures.
Neural Network Control Of Robot Manipulators And Non-Linear Systems (2020)

There has been great interest in "universal controllers" that mimic the functions of human processes to learn about the systems they are controlling on-line so that performance improves automatically. Neural network controllers are derived for robot manipulators in a variety of applications including position control, force control, link flexibility stabilization and the management of high-frequency joint and motor dynamics.The first chapter provides a background on neural networks and the second on dynamical systems and control. Chapter three introduces the robot control problem and standard techniques such as torque, adaptive and robust control. Subsequent chapters give design techniques and Stability Proofs For NN Controllers For Robot Arms, Practical Robotic systems with high frequency vibratory modes, force control and a general class of non-linear systems. The last chapters are devoted to discrete- time NN controllers. Throughout the text, worked examples are provided.
Inertial sensor technology trends (2001)

This paper presents an overview of how inertial sensor technology is applied in current applications and how it is expected to be applied in nearand far-term applications. The ongoing trends in inertial sensor technology development are discussed, namely interferometric fiber-optic gyros, micro-mechanical gyros and accelerometers, and micro-optical sensors. Micromechanical sensors and improved fiber-optic gyros are expected to replace many of the current systems using ring laser gyroscopes or mechanical sensors. The successful introduction of the new technologies is primarily driven by cost and cost projections for systems using these new technologies are presented. Externally aiding the inertial navigation system (INS) with the global positioning system (GPS) has opened up the ability to navigate a wide variety of new large-volume applications, such as guided artillery shells. These new applications are driving the need for extremely low-cost, batch-producible sensors.
Mechanically Tough Pluronic F127/Laponite Nanocomposite Hydrogels from Covalently and Physically Cross-Linked Networks (2011)

Mechanical properties of polymer hydrogels are critical to their performance as tissue engineering scaffolds especially in load bearing tissues and wound sealants. In this study, we aim to synthesize mechanically tough nanocomposite hydrogels by photo-cross-linking PEO–PPO–PEO triblock copolymer diacrylates (Pluronic F127 diacrylate) in the presence of silicate nanoparticles, Laponite. The resulting hydrogels have high elongations and improved toughness when compared to their polymer hydrogel counterparts. Oscillatory shear and creep experiments suggest that the silicate nanoparticles physically interact with the covalently cross-linked polymer networks and impart viscoelasticity to the hydrogels. Imaging the structures of deformed nanocomposite hydrogels with cryo-scanning electron microscopy (cryo-SEM) leads us to believe that stretched hydrogels have finer network structures with smaller pore sizes when compared to the unstretched ones. The structural transitions observed in cryo-SEM and the viscoelastic properties measured suggest that noncovalent, physical interactions between Pluronic F127 and Laponite may contribute to rearrangements of network structures at high deformations. Overall, we expect the relationships between mechanical properties and network structures to provide valuable knowledge for the future design of high-performance hydrogels with use in a variety of biotechnological, biomedical, and pharmaceutical applications.
Circannual variations of circadian periodicity in murine colony-forming cells. (1984)

The circadian and circannual rhythms of committed stem cells (CFUc) were investigated by using the agar colony technique. There was a marked circadian rhythmicity, with variations between maximum and minimum colony yields of 2-5.5 times; such variations could also be seen throughout the year. A phase shift was observed for the plating efficiency during the year, with the maximum (acrophase) found at different times of the day. At specific times the plating efficiency varied considerably from month to month, with almost no variations at 4:00 P.M. to highly significant variations at other times, e.g., 4:00 A.M. Such changes in proliferation should be taken into consideration especially in long-term studies of hematopoiesis.
α-Galactosides of Sucrose in Foods: Composition, Flatulence-Causing Effects, and Removal (1997)

Alpha-galactosides of sucrose, namely raffinose, stachyose and verbascose, are widely distributed in higher plants, especially leguminous seeds. In addition the presence of galactopinitol, galactinol, mannitriose and melibiose in Brassica campestris, soybean and some legumes has been reported. Due to the absence of α-galactosidase activity in human and animal intestine mucosa, these oligosaccharides escape digestion and they are metabolized by bacteria to hydrogen, carbon dioxide and methane. Thus, they are considered to be the principal flatulence-causing factors present in food of plant origin. Furthermore, starch and hemicellulose may contribute to flatulence. A significant positive correlation, between the hydrogen production by rat and the content of α-galactosides of sucrose in legumes consumed, has been reported. Various methods for the removal of flatulence causing oligosaccharides including dehulling, soaking and/or cooking in water and in buffer solutions, irradiation, enzymatic treatment, germination and solvent extraction have been investigated. The pros and cons of these procedures are discussed.
Efficacy of entrectinib in patients (pts) with solid tumors and central nervous system (CNS) metastases: Integrated analysis from three clinical trials. (2019)

3017 Background: Entrectinib potently inhibits kinases encoded by the NTRK and ROS1 genes. It achieves therapeutic levels in the CNS with antitumor activity in intracranial tumor models. We report integrated data (31 May 2018 cut-off) from 3 Phase 1/2 entrectinib trials (ALKA-372-001, EudraCT 2012-000148-88; STARTRK-1, NCT02097810; STARTRK-2, NCT02568267) for a large cohort of adults with ROS1 fusion-positive NSCLC ( ROS1+) or NTRK fusion-positive solid tumors ( NTRK+), with/without baseline CNS metastases. Methods: Pts had locally advanced/metastatic NTRK+ or ROS1+ tumors by nucleic acid-based confirmation. Baseline CNS metastases were identified by CT/MRI. Tumor assessments were at wk 4, then every 8 wk by blinded independent central review (RECIST v1.1). Primary endpoints: ORR, DOR. Secondary endpoints: CBR, PFS, OS, intracranial efficacy and safety. Results: Most pts had ≥1 prior therapy; 33% had baseline CNS metastases. Outcomes for the ROS1+ NSCLC (n = 53) and NTRK+ solid tumors (n = 54; 24% sarcoma, 18% NSCLC) efficacy evaluable data sets are shown (table). Entrectinib was tolerable with a manageable safety profile; most treatment-related AEs were grade 1–2. Conclusions: Entrectinib induced clinically meaningful durable responses in pts with ROS1+ NSCLC or NTRK+ solid tumors with or without CNS disease. Clinical trial information: NCT02097810; NCT02568267. [Table: see text]
cis-acting elements involved in photoregulation of an oat phytochrome promoter in rice. (1990)

Phytochrome negatively regulates the transcription of its own phyA genes. High levels of Pfr, the active, far-red-light absorbing form of phytochrome, repress phyA transcription; low Pfr levels result in derepression. We have utilized microprojectile-mediated gene transfer to identify regions of an oat phyA3 gene involved in this autoregulation. Chimeric constructs containing various deletion and sequence substitution mutants of the oat phyA3 gene fused to a chloramphenicol acetyltransferase reporter (phyA3/CAT) have been introduced into etiolated rice seedlings by particle bombardment. Low Pfr concentrations induce high phyA3/CAT expression, whereas high Pfr represses activity to near basal levels. Removal of phyA3 sequences 3' to the transcription start site reduces expression about fivefold, suggesting that intron 1 of the phyA3 gene may be required for high activity. The degree of high-Pfr-imposed repression is unaffected by any of a series of deletions or sequence substitutions in the phyA3 promoter, thus providing no evidence of any Pfr-activated negative elements. In contrast, 5' and internal deletions identify a minimum of three major positive promoter elements, designated PE1 [-381 base pairs (bp) to -348 bp], PE2 (-635 bp to -489 bp), and PE3 (-110 bp to -76 bp) that are necessary for high-level expression in low-Pfr cells. The data indicate that PE1 and PE2 are functionally redundant, but that PE3 is required in conjunction with either PE1 or PE2 for activity. PE3 contains a sequence element that is highly conserved between monocot phyA promoters, indicative of a critical role in phyA expression.