gebhart/patrepeval huggingface dataset:
Live Cell Imaging: Approaches for Studying Protein Dynamics in Living Cells (2002)

In the last decade, the long-standing biologist's dream of seeing the molecular events within the living cell came true. This technological achievement is largely due to the development of fluorescence microscopy technologies and the advent of green fluorescent protein as a fluorescent probe. Such imaging technologies allowed us to determine the subcellular localization, mobility and transport pathways of specific proteins and even visualize protein-protein interactions of single molecules in living cells. Direct observation of such molecular dynamics can provide important information about cellular events that cannot be obtained by other methods. Thus, imaging of protein dynamics in living cells becomes an important tool for cell biology to study molecular and cellular functions. In this special issue of review articles, we review various imaging technologies of microscope hardware and fluorescent probes useful for cell biologists, with a focus on recent development of live cell imaging.
Ultraviolet-induced phosphorylation of p70(S6K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C. (2002)

The p70 S6 kinase (p70(S6k)) is a Ser/Thr kinase that plays an important role in cell growth, transformation, and the transition of the cell cycle in mammalian cells. Because UV radiation has been reported to induce activation of p70(S6k), which is believed to play some role in the carcinogenic effects of sun exposure, the present study investigated the signaling pathways involved in this activation induced by UV radiation in mouse epidermal JB6 Cl41 cells. Exposure of cells to UV radiation led to marked increases in p70(S6k) activity and phosphorylation at Thr(389) and Thr(421)/Ser(424). UV radiation also generated reactive oxygen species as measured by electron spin resonance and by H(2)O(2) and O( minus sign, dot below )(2) fluorescence staining assays in JB6 Cl 41 cells. The scavenging of UV-generated H(2)O(2) by N-acety-L-cyteine (a general antioxidant) or catalase (a specific H(2)O(2) scavenger) inhibited p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424), whereas pretreatment of cells with sodium formate (an.OH radical scavenger) or superoxide dismutase (an O( minus sign, dot below )(2) radical scavenger) did not show any inhibitory effects. Importantly, UV-induced increases in p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424) were dramatically inhibited by pretreatment of cells with rapamycin, LY294002, or PD98059, whereas overexpression of dominant-negative mutants of PKClambda/iota and Akt1 did not inhibit p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424). These results demonstrated that H(2)O(2), phosphatidylinositol 3-kinase, and mammalian target of rapamycin were important players for UV-induced p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424), whereas Akt and atypical protein kinase C were not involved in this activation. The role of H(2)O(2) in p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424) was further supported by the findings that treatment of cells with H(2)O(2) also caused p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424).
Hyperdimensional Computing Exploiting Carbon Nanotube FETs, Resistive RAM, and Their Monolithic 3D Integration (2018)

The field of machine learning is witnessing rapid advances along several fronts: new machine learning models, new machine learning algorithms utilizing these models, new hardware architectures for these algorithms, and new technologies for creating energy-efficient implementations of such hardware architectures. Hyperdimensional (HD) computing represents one such model. Emerging nanotechnologies, such as carbon nanotube field-effect transistors (CNFETs), resistive random-access memory (RRAM), and their monolithic 3D integration, enable energyand area-efficient hardware implementations of HD computing architectures. Such efficient implementations are achieved by exploiting several characteristics of the component nanotechnologies (e.g., energy-efficient logic circuits, dense memory, and incrementers naturally enabled by gradual reset of RRAM cells) and their monolithic 3D integration (enabling tight integration of logic and memory), as well as various characteristics of the HD computing model (e.g., embracing randomness that allows us to utilize rather than avoid inherent variations in RRAM and CNFETs, resilience to errors in the underlying hardware). We experimentally demonstrate and characterize an end-to-end HD computing nanosystem built using monolithic 3D integration of CNFETs and RRAM. Using our nanosystem, we experimentally demonstrate the pairwise classification of 21 languages with measured mean accuracy of up to 98% on 20000 sentences (6.4 million characters), training using one text sample (~100000 characters) per language, and resilient operation (98% accuracy) despite 78% of bits in HD representation being stuck at 0 or 1 in hardware. We also show that the monolithic 3D implementations of HD computing can have 35× improved energy-execution time product for training and inference of language classification data sets (while using 3× less area) compared to silicon CMOS implementations.
Abstract 2663: Characterization of the pharmacodynamic immune response to a novel immunotherapeutic agent, ALKS 4230, in mice and non-human primates (2017)

Abstract ALKS 4230 is a selective agonist of the intermediate-affinity IL-2 receptor (IL-2R). A phase 1 study is ongoing to evaluate the safety and tolerability of ALKS 4230 in the treatment of patients with refractory solid tumors. The selectivity of ALKS 4230 is achieved through the stable fusion of circularly permuted IL-2 to the extracellular portion of the IL-2Rα chain, CD25. The resulting fusion protein is sterically prevented from binding to the high-affinity IL-2R complex, comprised of IL-2Rα, IL-2Rβ, and common gamma chain, expressed preferentially on CD4+ FOXP3+ regulatory T cells (CD4+ Tregs) yet retains full ability to signal through the intermediate-affinity IL-2R complex, comprised of IL-2Rβ and common gamma chain, expressed on memory CD8+ T cells and NK cells. Repeated dosing of ALKS 4230 drives the significant expansion of various CD8+ T cell and NK cell populations without activation and minimal expansion of CD4+ Tregs in mice and non-human primates (NHP). The kinetics of the immunological responses in mice and NHP demonstrate that the pharmacodynamic effects persist beyond systemic exposure of ALKS 4230. Data demonstrating the effects of ALKS 4230 on tumor-infiltrating lymphocyte populations in syngeneic tumor models will also be presented. Citation Format: Jared E. Lopes, Heather C. Losey, Reginald L. Dean, Heather L. Flick, Michael R. Huff, Rosemarie A. Moroso, Lei Sun, Juan C. Alvarez. Characterization of the pharmacodynamic immune response to a novel immunotherapeutic agent, ALKS 4230, in mice and non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2663. doi:10.1158/1538-7445.AM2017-2663
Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development (2016)

The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small molecule inhibitor selective for ERK kinase activity.
The human IgM pentamer is a mushroom-shaped molecule with a flexural bias (2009)

The textbook planar model of pentameric IgM, a potent activator of complement C1q, is based upon the crystallographic structure of IgG. Although widely accepted, key predictions of this model have not yet been directly confirmed, which is particularly important since IgG lacks a major Ig fold domain in its Fc region that is present in IgM. Here, we construct a homology-based structural model of the IgM pentamer using the recently obtained crystallographic structure of IgE Fc, which has this additional Ig domain, under the constraint that all of the cysteine residues known to form disulfide bridges both within each monomer and between monomers are bonded together. In contrast to the planar model, this model predicts a non-planar, mushroom-shaped complex, with the central portion formed by the C-terminal domains protruding out of the plane formed by the Fab domains. This unexpected conformation of IgM is, however, directly confirmed by cryo-atomic force microscopy of individual human IgM molecules. Further analysis of this model with free energy calculations of out-of-plane Fab domain rotations reveals a pronounced asymmetry favoring flexions toward the central protrusion. This bias, together with polyvalent attachment to cell surface antigen, would ensure that the IgM pentamer is oriented on the cell membrane with its C1q binding sites fully exposed to the solution, and thus provides a mechanistic explanation for the first steps of C1q activation by IgM.
Optical system design issues in development of projection camera for EUV lithography (1995)

Optical system design issues are described in development of a four- mirror 4x reduction ring-field system for EUV projection lithography at 13 nm wavelength.
Shifts in human skin and nares microbiota of healthy children and adults (2012)

Significant shifts in the microbiota associated with progressive sexual maturation as measured by Tanner staging suggest that puberty-dependent shifts in the skin and nares microbiomes may have significant implications regarding prevention and treatment of pediatric disorders involving microbial pathogens and colonization.
Degradation of Ginseng Saponins under Mild Acidic Conditions (1982)

Ginseng saponins, ginsenosides Rg (1), Re and Rb (1), decomposed under mild acidic conditions to yield prosapogenins. The structures of the prosapogenins were investigated by (13)C-NMR spectroscopy and Rg (1)-prosapogenin II was shown to be a mixture of ginsenoside Rh (1), and its C-20 epimer, produced by hydrolysis followed by epimerization at C-20. Rg (1)-prosapogenin III, the other prosapogenin derived from ginsenoside Rg (1); was a C-25,26 hydrated derivative of Rg (1)-prosapogenin II. Re-prosapogenin II was identified as a mixture of ginsenoside Rg (2) and its C-20 epimer, and Re-prosapogenine III as a C-25,26 hydrated derivative of Re-prosapogenin II.
[Prednisolone treatment for Duchenne muscular dystrophy]. (2011)

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is the most common form of muscular dystrophy. Affected children develop muscle weakness in early childhood. Only steroids have been shown with evidence to improve muscle function in patients with DMD. We report the long-term effects of prednisolone treatment in patients with DMD, comparing the age at which 14 treated patients and 15 control patients lost their ability to walk. The prednisolone-treated patients were assigned to one of five regimens: 0.5 mg/kg/day given for the first 10 days of every month (n = 6), 0.75 mg/kg/day given for the first 10 days of every month (n = 3), 0.5 mg/kg on alternate days (n = 1), 0.75 mg/kg on alternate days (n = 1), or 5 mg/kg twice a week (n = 3). No significant difference in age of losing ambulation ability was observed between the treated group and the untreated group (mean age; 10 years and 6 months in both groups). However, 13 of the 14 patients showed an improvement in their activity of daily living other than ambulation in the treated group. The results of this study showed that the prednisolone treatment regimens used in this study did not prolong the period of ambulation.
Drug Dependence as a Disorder of Neural Plasticity: Focus on Dopamine and Glutamate (2001)

Drug addiction, as a disease, has grown to reach the level of a social illness. Psychostimulants, opiates, alcohol, nicotine and cannabis abuse affects millions worldwide and virtually all classes of modern society. In spite of the enormous proportions of its spread, intimate neurobiological mechanisms leading to distintictive features of this pathological status, such as craving for the abused substance and loss of control over intake, remain largely obscure and pharmacotherapies sadly unsatisfactory. In the last decade, preclinical and clinical research in this field has made great progress to improve our understanding of the brain mechanisms which form the basis of this illness. The review of recent literature, which represents the focus of the present paper, leads to the emerging consensus that an alteration of physiological mechanisms of neural plasticity within the brain dopamine and glutamate systems may underlie some of the behavioral abnormalities occurring during the dependence cycle. In particular, a reduction of dopamine neuronal activity and glutamate neurotransmission at the level of the ventrotegmental area, after withdrawal from chronic administration of drugs of abuse, may work in concert with alterations in other forebrain areas, such as the nucleus accumbens and the amygdaloid complex. In addition, following prolonged periods of abstinence, even after somatic withdrawal signs have vanished, responsiveness of these systems to drugs of abuse remains abnormal. This suggests that these two neurotransmitters may play a substantial role in the long-lasting, enduring changes typical of the addictive process and may represent ideal targets for pharmacological intervention aimed at normalizing forms of neural plasticity impaired after chronic drug intake.
Expression of the amino-terminal half-molecule of human serum transferrin in cultured cells and characterization of the recombinant protein (1990)

A human liver cDNA library was screened with a synthetic oligonucleotide, complementary to the 5' region of human transferrin mRNA, as a hybridization probe. The full-length human cDNA clone isolated from this screen contained part of the 5' untranslated region, the complete coding region for the signal peptide and the two lobes of transferrin, the 3' untranslated region, and a poly(A) tail. By use of oligonucleotide-directed mutagenesis in vitro, two translational stop codons and a HindIII site were introduced after the codon for Asp-337. This fragment was inserted into two different expression vectors that were then introduced into Escherichia coli. As judged by NaDodSO4-polyacrylamide gel electrophoresis and Western blot analysis, however, recombinant hTF/2N was undetectable in bacteria transformed by these plasmids. Concurrently, we developed a plasmid vector for the expression of recombinant hTF/2N in eukaryotic cells. In this case, a DNA fragment coding for the natural signal sequence, the hTF/2N lobe, and the two stop codons was cloned into the expression vector pNUT, such that the expression of hTF/2N was controlled by the mouse metallothionein promoter and the human growth hormone termination sequences. Baby hamster kidney cells containing this hTF/2N-pNUT plasmid secreted up to 20 mg of recombinant hTF/2N per liter of tissue culture medium. Recombinant hTF/2N was purified from the medium by successive chromatography steps on DEAE-Sephacel, Sephadex G-75, and FPLC on Polyanion SI. The purified protein was characterized by NaDodSO4-PAGE, urea-PAGE, amino-terminal sequence analysis, UV-visible spectroscopy, iron-binding titration, and proton NMR.(ABSTRACT TRUNCATED AT 250 WORDS)
Error-Prone Polymerase, DNA Polymerase IV, Is Responsible for Transient Hypermutation during Adaptive Mutation in Escherichia coli (2003)

The frequencies of nonselected mutations among adaptive Lac(+) revertants of Escherichia coli strains with and without the error-prone DNA polymerase IV (Pol IV) were compared. This frequency was more than sevenfold lower in the Pol IV-defective strain than in the wild-type strain. Thus, the mutations that occur during hypermutation are due to Pol IV.
Positional enhancer-blocking activity of the chicken β-globin insulator in transiently transfected cells (1999)

It is thought that insulators demarcate transcriptionally and structurally independent chromatin domains. Insulators are detected by their ability to block enhancer-promoter interactions in a directional manner, and protect a transgene from position effects. Most studies are performed in stably transformed cells or organisms. Here we analyze the enhancer-blocking activity of the chicken beta-globin insulator in transient transfection experiments in both erythroid and nonerythroid cell lines. We show that four tandem copies of a 90-bp fragment of this insulator were able to block an enhancer in these experiments. In circular plasmids, placement on either side of the enhancer reduced activity, but when the plasmid was linearized, the enhancer-blocking activity was observed only when the insulator was placed between the promoter and the enhancer. These observations are consistent with the position-dependent enhancer-blocking activity of the insulator observed in stable transformation experiments.
STATE OF THE ARGUMENT (2009)

In croffing a heath, fuppofe I pitched my foot againft a ftone, and were afked how the ftone came to be there, I might poffibly anfwer, that, for any thing I knew to the contrary, it had lain there for ever: nor would it perhaps be very eafy to fhew the abfurdity of this anfwer. But fuppofe I had found a watch upon the ground, and it fhould be enquired how the watch happened to be in that place, I fhould hardly think of the anfwer which I had before given, that, for any thing I knew, the watch might have always been there. Yet why fhould not this anfwer ferve for the watch, as well as for the ftone? Why is it not as admiffible in the fecond cafe, as in the firft? For this reafon, and for no other, viz. that, when we come to infpect the watch, we perceive (what we could not difcover in the ftone) that its feveral parts are framed and put together for a purpofe, e. g. that they are fo formed and adjufted as to produce motion, and that motion, fo regulated as to point out the hour of the day; that, if the feveral parts had been differently fhaped from what they are, of a different fize from what they are, or placed after any other manner, or in any other order, than that in which they are placed, either no motion at all would have been carried on in the machine, or none which would have anfwered the ufe, that is now ferved by it.
Treatment of insulin resistance with peroxisome proliferator–activated receptor γ agonists (2000)

Insulin resistance is a characteristic feature of most patients with type 2 diabetes mellitus and is almost a universal finding in type 2 diabetic patients who are overweight (1–3). The presence of insulin resistance leads to increased β-cell insulin secretion with compensatory hyperinsulinemia (1–3). As long as the hyperinsulinemia is adequate to overcome the insulin resistance, glucose tolerance remains normal. In patients destined to develop type 2 diabetes, the β-cell compensatory response declines, and relative, or absolute, insulin insufficiency develops. At this point, insulin secretion cannot keep pace with the underlying insulin resistance, and glucose intolerance and eventually frank type 2 diabetes occur. Based on these observations it is evident that, except for very unusual patients, type 2 diabetes only develops in the context of insulin resistance plus β cell dysfunction. Although there is still some debate as to whether the insulin resistance or the β-cell defect comes first, most epidemiologic studies have indicated that in the early, prediabetic state, insulin resistance is the antecedent abnormality (4, 5).
Short-term tocolytics for preterm delivery &ndash; current perspectives (2014)

Administration of short-term tocolytic agents can prolong pregnancy for women in preterm labor. Prolonging pregnancy has many benefits because it allows for other proven interventions, such as antenatal corticosteroid administration, to be accomplished. This review provides an overview of currently utilized tocolytic agents and the evidence demonstrating their efficacy for prolonging pregnancy by at least 48 hours. General pharmacological principles for the clinician regarding drugs in pregnancy are also briefly discussed. In general, while the choice of the best first-line short-term tocolytic drug is not clear, it is evident that use of these agents has a clear place in current obstetric therapeutics.
Nucleotide sequence of the humanβ-actin promoter 5′ flanking region (1987)

Journal Article Nucleotide sequence of the human β -actin promoter 5′ flanking region Get access Neil G. Miyamoto Neil G. Miyamoto Division of Biological Research, The Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto500 Sherbourne Street, Toronto, Ontario, M4X 1K9, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 15, Issue 21, 11 November 1987, Page 9095, https://doi.org/10.1093/nar/15.21.9095 Published: 11 November 1987 Article history Received: 04 September 1987 Published: 11 November 1987
Molecular cytogenetics of lymphoma: where do we stand in 2010? (2011)

For the past 20 years most malignant lymphomas have been classified as clinicopathological entities, each with its own combination of clinical, morphological, immunophenotypic and molecular genetic characteristics. Molecular and cytogenetic abnormalities can be detected by a wide range of techniques, ranging from conventional karyotyping to single nucleotide polymorphism analysis. In this review, we consider the common genetic abnormalities found in lymphoma and discuss the advantages and disadvantages of individual techniques used in their detection. Finally, we discuss briefly possible novel developments in the field of lymphoma diagnostics.
Efficient tunable luminescence of SiGe alloy sheet polymers (2001)

Crystalline SiGe alloy sheet polymers were topotactically prepared from epitaxially grown calcium germanosilicide Ca(Si1−xGex)2 precursor films in the whole composition range. These polygermanosilynes are found to be a well-defined mixture of the known siloxene and polygermyne sheet polymers with the OH groups exclusively bonded to silicon. The optical properties determined by photoluminescence and optical reflection measurements identify the mixed SiGe sheet polymers as direct semiconductors with efficient luminescence tunable in the energy range between 2.4 and 1.3 eV.
Wavelet transforms and the ECG: a review (2005)

The wavelet transform has emerged over recent years as a powerful time-frequency analysis and signal coding tool favoured for the interrogation of complex nonstationary signals. Its application to biosignal processing has been at the forefront of these developments where it has been found particularly useful in the study of these, often problematic, signals: none more so than the ECG. In this review, the emerging role of the wavelet transform in the interrogation of the ECG is discussed in detail, where both the continuous and the discrete transform are considered in turn.