The gene expression profiles of human postmortem parietal and prefrontal cortex samples of normal controls and patients with bipolar disease, or human neuroblastoma flat (NBFL) cells treated with the ...mood-stabilizing drug, valproate, were used to compare the performance of Affymetrix oligonucleotide U133A GeneChips
® and Agilent Human 1 cDNA microarrays. Among those genes represented on both platforms, the oligo array identified 26–53% more differentially expressed genes compared to the cDNA array in the three experiments, when identical fold change and
t-test criteria were applied. The increased sensitivity was primarily the result of more robust fold changes measured by the oligonucleotide system. Essentially all gene changes overlapping between the two platforms were co-directional, and ranged from 4 to 19% depending upon the amount of biological variability within and between the comparison groups. Q-PCR validation rates were virtually identical for the two platforms, with 23–24% validation in the prefrontal cortex experiment, and 56% for both platforms in the cell culture experiment. Validated genes included dopa decarboxylase, dopamine beta-hydroxylase, and dihydropyrimidinase-related protein 3, which were decreased in NBFL cells exposed to valproate, and spinocerebellar ataxia 7, which was increased in bipolar disease. The modest overlap but similar validation rates show that each microarray system identifies a unique set of differentially expressed genes, and thus the greatest information is obtained from the use of both platforms.
Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We ...investigated phosphorylated kinases as target in PDAC.
Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Subsequently, we investigated targeting of focal adhesion kinase (FAK) in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling. An orthotopic model of PDAC was used to evaluate the combination of defactinib with nab-paclitaxel.
PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree. The non-receptor kinase, FAK, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo.
Our study shows high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel against this devastating disease.
Metal borides have attracted the attention of researchers due to their useful physical properties and unique ability to form high hydrogen-capacity metal borohydrides. We demonstrate improved ...hydrogen storage properties of a nanoscale Mg–B material made by surfactant ball milling MgB2 in a mixture of heptane, oleic acid, and oleylamine. Transmission electron microscopy data show that Mg–B nanoplatelets are produced with sizes ranging from 5 to 50 nm, which agglomerate upon ethanol washing to produce an agglomerated nanoscale Mg–B material of micron-sized particles with some surfactant still remaining. X-ray diffraction measurements reveal a two-component material where 32% of the solid is a strained crystalline solid maintaining the hexagonal structure with the remainder being amorphous. Fourier transform infrared shows that the oleate binds in a “bridge-bonding” fashion preferentially to magnesium rather than boron, which is confirmed by density functional theory calculations. The Mg–B nanoscale material is deficient in boron relative to bulk MgB2 with a Mg–B ratio of ∼1:0.75. The nanoscale MgB0.75 material has a disrupted B–B ring network as indicated by X-ray absorption measurements. Hydrogenation experiments at 700 bar and 280 °C show that it partially hydrogenates at temperatures 100 °C below the threshold for bulk MgB2 hydrogenation. In addition, upon heating to 200 °C, the H–H bond-breaking ability increases ∼10-fold according to hydrogen–deuterium exchange experiments due to desorption of oleate at the surface. This behavior would make the nanoscale Mg–B material useful as an additive where rapid H–H bond breaking is needed.
Electron cyclotron emission (ECE) imaging is a passive radiometric technique that measures electron temperature fluctuations; and microwave imaging reflectometry (MIR) is an active radar imaging ...technique that measures electron density fluctuations. Microwave imaging diagnostic instruments employing these techniques have made important contributions to fusion science and have been adopted at major fusion facilities worldwide including DIII-D, EAST, ASDEX Upgrade, HL-2A, KSTAR, LHD, and J-TEXT. In this paper, we describe the development status of three major technological advancements: custom mm-wave integrated circuits (ICs), digital beamforming (DBF), and synthetic diagnostic modeling (SDM). These have the potential to greatly advance microwave fusion plasma imaging, enabling compact and low-noise transceiver systems with real-time, fast tracking ability to address critical fusion physics issues, including ELM suppression and disruptions in the ITER baseline scenario, naturally ELM-free states such as QH-mode, and energetic particle confinement (i.e. Alfvén eigenmode stability) in high-performance regimes that include steady-state and advanced tokamak scenarios. Furthermore, these systems are fully compatible with today's most challenging non-inductive heating and current drive systems and capable of operating in harsh environments, making them the ideal approach for diagnosing long-pulse and steady-state tokamaks.
B-flavor tagging at Belle II Akopov, N.; Banerjee, Sw; Bauer, M. ...
The European physical journal. C, Particles and fields,
04/2022, Letnik:
82, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We report on new flavor tagging algorithms developed to determine the quark-flavor content of bottom (
) mesons at Belle II. The algorithms provide essential inputs for measurements of quark-flavor ...mixing and charge-parity violation. We validate and evaluate the performance of the algorithms using hadronic
decays with flavor-specific final states reconstructed in a data set corresponding to an integrated luminosity of 62.8 fb
-
1
, collected at the
resonance with the Belle II detector at the SuperKEKB collider. We measure the total effective tagging efficiency to be
ε
eff
=
(
30.0
±
1.2
(
stat
)
±
0.4
(
syst
)
)
%
for a category-based algorithm and
ε
eff
=
(
28.8
±
1.2
(
stat
)
±
0.4
(
syst
)
)
%
for a deep-learning-based algorithm.
Na+/K+-ATPase (NKA) is essential for maintaining the Na+ and K+ gradients, and supporting the secondary active transport of certain ions/molecules, across the plasma membrane of animal cells. This ...study aimed to clone the NKA α-subunit (NKAα) from the inner mantle adjacent to the extrapallial fluid of Tridacna squamosa, to determine its subcellular localization, and to examine the effects of light exposure on its transcript level and protein abundance. The cDNA coding sequence of NKAα from T. squamosa comprised 3105 bp, encoding 1034 amino acids with an estimated molecular mass of 114 kDa. NKAα had a basolateral localization along the shell-facing epithelium of the inner mantle. Exposure to 12 h of light led to a significantly stronger basolateral NKAα-immunofluorescence at the shell-facing epithelium, indicating that NKA might play a role in light-enhanced calcification in T. squamosa. After 3 h of light exposure, the transcript level of NKAα decreased transiently in the inner mantle, but returned to the control level thereafter. In comparison, the protein abundance of NKAα remained unchanged at hour 3, but became significantly higher than the control after 12 h of light exposure. Hence, the expression of NKAα in the inner mantle of T. squamosa was light-dependent. It is probable that a higher expression level of NKA was needed in the shell-facing epithelial cells of the inner mantle to cope with a rise in Na+ influx, possibly caused by increases in activities of some Na+-dependent ion transporters/channels involved in light-enhanced calcification.
The first simultaneous test of muon-electron universality using B+→K+ℓ+ℓ− and B0→K*0ℓ+ℓ− decays is performed, in two ranges of the dilepton invariant-mass squared, q2. The analysis uses beauty mesons ...produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb−1. Each of the four lepton universality measurements reported is either the first in the given q2 interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.
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