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Recent Advances in Basic Research for Brain Arteriovenous Malformation.
Arteriovenous malformations (AVMs) are abnormal connections of vessels that shunt blood directly from arteries into veins. Rupture of brain AVMs (bAVMs) can cause life-threatening intracranial bleeding. Even though the majority of bAVM cases are sporadic without a family history, some cases are familial. Most of the familial cases of bAVMs are associated with a genetic disorder called hereditary hemorrhagic telangiectasia (HHT). The mechanism of bAVM formation is not fully understood. The most important advances in bAVM basic science research is the identification of somatic mutations of genes in RAS-MAPK pathways. However, the mechanisms by which mutations of these genes lead to AVM formation are largely unknown. In this review, we summarized the latest advance in bAVM studies and discussed some pathways that play important roles in bAVM pathogenesis. We also discussed the therapeutic implications of these pathways
Core-Level X-Ray Photoemission Satellites in Ruthenates: A New Mechanism Revealing the Mott Transition
Ru 3d core-level x-ray photoemission spectra of various ruthenates are
examined. They show in general two-peak structures, which can be assigned as
the screened and unscreened peaks. The screened peak is absent in a Mott
insulator, but develops into a main peak in the metallic regime. This spectral
behavior is well explained by the dynamical mean-field theory calculation for
the single-band Hubbard model with on-site core-hole potential using the exact
diagonalization method. The new mechanism of the core-level photoemission
satellite can be utilized to reveal the Mott transition phenomenon in various
strongly correlated electron systems, especially in nano-scale devices and
phase-separated materials.Comment: 4 pages, 5 figures, submitted to PR
Napabucasin plus nab-paclitaxel with gemcitabine versus nab-paclitaxel with gemcitabine in previously untreated metastatic pancreatic adenocarcinoma: an adaptive multicentre, randomised, open-label, phase 3, superiority trial
Adenocarcinoma; Napabucasin; Pancreatic cancerAdenocarcinoma; Napabucasin; Càncer de pàncreesAdenocarcinoma; Napabucasin; Cáncer de páncreasBackground
Compared with normal cells, tumour cells contain elevated levels of reactive oxygen species (ROS). Increased levels of the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) correlate negatively with the survival of patients with pancreatic cancer. Napabucasin is an investigational, orally administered ROS generator bioactivated by NQO1.
Methods
In the open-label, phase 3 CanStem111P study (NCT02993731), adults with previously untreated metastatic pancreatic adenocarcinoma (mPDAC) were randomised (1:1) to napabucasin plus nab-paclitaxel with gemcitabine or nab-paclitaxel with gemcitabine alone. The primary endpoint was overall survival (OS). In exploratory analyses, OS was evaluated in the subgroup of patients with tumours positive for pSTAT3 (biomarker-positive).
Findings
Between 30 January 2017 and 20 February 2019, a total of 1779 patients were screened across 165 study sites in Austria, Australia, Belgium, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Russia, Singapore, Spain, Taiwan, Ukraine, and the US. Of the 565 and 569 patients randomised to the napabucasin and control treatment arms, respectively, 206 and 176 were biomarker-positive. Median (95% confidence interval [CI]) OS in the napabucasin and control treatment arms was 11.4 (10.5–12.2) and 11.7 (10.7–12.7) months, respectively (hazard ratio, 1.07; 95% CI, 0.93–1.23). Due to the lack of OS improvement in the napabucasin arm, CanStem111P was terminated due to futility. In the biomarker-positive subgroup, no difference between treatment arms was found for OS. Grade ≥3 adverse events were reported in 85.4% and 83.9% of napabucasin-treated and control-treated patients, respectively. The incidence of gastrointestinal-related grade ≥3 events was higher with napabucasin (diarrhoea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%).
Interpretation
Our findings suggested that although the addition of napabucasin to nab-paclitaxel with gemcitabine did not improve efficacy in patients with previously untreated mPDAC, the safety profile of napabucasin was consistent with previous reports. CanStem111P represents the largest cohort of patients with mPDAC administered nab-paclitaxel with gemcitabine in the clinical trial setting. Our data reinforce the value of nab-paclitaxel plus gemcitabine as a platform for novel therapeutics approaches in mPDAC.This study was supported by Sumitomo Pharma Oncology, Inc
High-resolution Ce 3d-edge resonant photoemission study of CeNi_2
Resonant photoemission (RPES) at the Ce 3d -> 4f threshold has been performed
for alpha-like compound CeNi_2 with extremely high energy resolution (full
width at half maximum < 0.2 eV) to obtain bulk-sensitive 4f spectral weight.
The on-resonance spectrum shows a sharp resolution-limited peak near the Fermi
energy which can be assigned to the tail of the Kondo resonance. However, the
spin-orbit side band around 0.3 eV binding energy corresponding to the f_{7/2}
peak is washed out, in contrast to the RPES spectrum at the Ce 3d -> 4f RPES
threshold. This is interpreted as due to the different surface sensitivity, and
the bulk-sensitive Ce 3d -> 4f RPES spectra are found to be consistent with
other electron spectroscopy and low energy properties for alpha-like
Ce-transition metal compounds, thus resolves controversy on the interpretation
of Ce compound photoemission. The 4f spectral weight over the whole valence
band can also be fitted fairly well with the Gunnarsson-Schoenhammer
calculation of the single impurity Anderson model, although the detailed
features show some dependence on the hybridization band shape and (possibly) Ce
5d emissions.Comment: 4 pages, 3 figur
Singular Cucker-Smale Dynamics
The existing state of the art for singular models of flocking is overviewed,
starting from microscopic model of Cucker and Smale with singular communication
weight, through its mesoscopic mean-filed limit, up to the corresponding
macroscopic regime. For the microscopic Cucker-Smale (CS) model, the
collision-avoidance phenomenon is discussed, also in the presence of bonding
forces and the decentralized control. For the kinetic mean-field model, the
existence of global-in-time measure-valued solutions, with a special emphasis
on a weak atomic uniqueness of solutions is sketched. Ultimately, for the
macroscopic singular model, the summary of the existence results for the
Euler-type alignment system is provided, including existence of strong
solutions on one-dimensional torus, and the extension of this result to higher
dimensions upon restriction on the smallness of initial data. Additionally, the
pressureless Navier-Stokes-type system corresponding to particular choice of
alignment kernel is presented, and compared - analytically and numerically - to
the porous medium equation
X-ray absorption spectroscopy study of diluted magnetic semiconductors: Zn1-xMxSe (M = Mn, Fe, Co) and Zn1-xMnxY (Y = Se, Te)
We have investigated 3d electronic states of doped transition metals in II-VI
diluted magnetic semiconductors, Zn1-xMxSe (M = Mn, Fe, Co) and Zn1-xMnxY (Y =
Se, Te), using the transition-metal L2,3-edge X-ray absorption spectroscopy
(XAS) measurements. In order to explain the XAS spectra, we employed a
tetragonal cluster model calculation, which includes not only the full ionic
multiplet structure but also configuration interaction (CI). The results show
that CI is essential to describe the experimental spectra adequately,
indicating the strong hybridization between the transition metal 3d and the
ligand p orbitals. In the study of Zn1-xMnxY (Y = Se, Te), we also found
considerable spectral change in the Mn L2,3-edge XAS spectra for different
ligands, confirming the importance of the hybridization effects in these
materials.Comment: This paper consists of 22 pages including 4 figures. This paper is
submitted to Physical Review
Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways
The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4– (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as follows: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1 ± 0.1) was measured from both (E)-C6H5CH═C(CH3)CONHCH3 and (E)-C6H5CD═C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7 ± 0.1) was observed from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene and styrene-d8. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH═CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH═CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH═CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH═CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1 ± 0.1 and +1.5 ± 0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, ΔH⧧ = 20 ± 2 kcal mol–1 and ΔS⧧ = −42 ± 5 eu. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies
Localized Character of 4f Electrons in CeRh(x=2,3) and CeNi(x=2,5)
We have measured Ce 4f spectral weights of extremely -like
Ce-transition metal intermetallic compounds CeRh (x=2,3) and CeNi
(x=2,5) by using the {\it bulk-sensitive} resonant photoemission technique at
the Ce ()-edge. Unprecedentedly high energy resolution and
longer escape depth of photoemitted electron at this photon energy enabled us
to distinguish the sharp Kondo resonance tails at the Fermi level, which can be
well described by the Gunnarsson-Sch\"onhammer(GS) calculation based on the
Anderson Impurity Hamiltonian. On the other hand, the itinerant 4f band
description shows big discrepancies, which implies that Ce 4f electrons retain
localized characters even in extremely -like compounds.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let
Systematic review and meta-analysis of intravascular temperature management vs. surface cooling in comatose patients resuscitated from cardiac arrest
Objective: To systematically review the effectiveness and safety of intravascular temperature management (IVTM) vs. surface cooling methods (SCM) for induced hypothermia (IH). Methods: Systematic review and meta-analysis. English-language PubMed, Embase and the Cochrane Database of Systematic Reviews were searched on May 27, 2019. The quality of included observational studies was graded using the Newcastle-Ottawa Quality Assessment tool. The quality of included randomized trials was evaluated using the Cochrane Collaboration's risk of bias tool. Random effects modeling was used to calculate risk differences for each outcome. Statistical heterogeneity and publication bias were assessed using standard methods. Eligibility: Observational or randomized studies comparing survival and/or neurologic outcomes in adults aged 18 years or greater resuscitated from out-of-hospital cardiac arrest receiving IH via IVTM vs. SCM were eligible for inclusion. Results: In total, 12 studies met inclusion criteria. These enrolled 1573 patients who received IVTM; and 4008 who received SCM. Survival was 55.0% in the IVTM group and 51.2% in the SCM group [pooled risk difference 2% (95% CI - 1%, 5%)] Good neurological outcome was achieved in 40.9% in the IVTM and 29.5% in the surface group [pooled risk difference 5% (95% CI 2%, 8%)]. There was a 6% (95% CI 11%, 2%) lower risk of arrhythmia with use of IVTM and 15% (95% CI 22%, 7%) decreased risk of overcooling with use of IVTM vs. SCM. There was no significant difference in other evaluated adverse events between groups. Conclusions: IVTM was associated with improved neurological outcomes vs. SCM among survivors resuscitated following cardiac arrest. These results may have implications for care of patients in the emergency department and intensive care settings after resuscitation from cardiac arrest.Peer reviewe
The Far-Infrared Surveyor (FIS) for AKARI
The Far-Infrared Surveyor (FIS) is one of two focal plane instruments on the
AKARI satellite. FIS has four photometric bands at 65, 90, 140, and 160 um, and
uses two kinds of array detectors. The FIS arrays and optics are designed to
sweep the sky with high spatial resolution and redundancy. The actual scan
width is more than eight arcmin, and the pixel pitch is matches the diffraction
limit of the telescope. Derived point spread functions (PSFs) from observations
of asteroids are similar to the optical model. Significant excesses, however,
are clearly seen around tails of the PSFs, whose contributions are about 30% of
the total power. All FIS functions are operating well in orbit, and its
performance meets the laboratory characterizations, except for the two longer
wavelength bands, which are not performing as well as characterized.
Furthermore, the FIS has a spectroscopic capability using a Fourier transform
spectrometer (FTS). Because the FTS takes advantage of the optics and detectors
of the photometer, it can simultaneously make a spectral map. This paper
summarizes the in-flight technical and operational performance of the FIS.Comment: 23 pages, 10 figures, and 2 tables. Accepted for publication in the
AKARI special issue of the Publications of the Astronomical Society of Japa
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