374 research outputs found
On the formation of hot Neptunes and super-Earths
The discovery of short-period Neptune-mass objects, now including the
remarkable system HD69830 (Lovis et al. 2006) with three Neptune analogues,
raises difficult questions about current formation models which may require a
global treatment of the protoplanetary disc. Several formation scenarios have
been proposed, where most combine the canonical oligarchic picture of core
accretion with type I migration (e.g. Terquem & Papaloizou 2007) and planetary
atmosphere physics (e.g. Alibert et al. 2006). To date, published studies have
considered only a small number of progenitors at late times. This leaves
unaddressed important questions about the global viability of the models. We
seek to determine whether the most natural model -- namely, taking the
canonical oligarchic picture of core accretion and introducing type I migration
-- can succeed in forming objects of 10 Earth masses and more in the innermost
parts of the disc. This problem is investigated using both traditional
semianalytic methods for modelling oligarchic growth as well as a new parallel
multi-zone N-body code designed specifically for treating planetary formation
problems with large dynamic range (McNeil & Nelson 2009). We find that it is
extremely difficult for oligarchic tidal migration models to reproduce the
observed distribution. Even under many variations of the typical parameters, we
form no objects of mass greater than 8 Earth masses. By comparison, it is
relatively straightforward to form icy super-Earths. We conclude that either
the initial conditions of the protoplanetary discs in short-period Neptune
systems were substantially different from the standard disc models we used, or
there is important physics yet to be understood.Comment: 19 pages, 18 figures. Final version accepted to MNRAS 30 September
200
Structure-based development of specific inhibitors for individual cathepsins and their medical applications
Specific inhibitors for individual cathepsins have been developed based on their tertiary structures of X-ray crystallography. Cathepsin B-specific inhibitors, CA-074 and CA-030, and cathepsin L specific inhibitors, CLIK-148 and CLIK-195, were designed as the epoxysuccinate derivatives. Cathepsin S inhibitor, CLIK-060, and cathepsin K inhibitor, CLIK-166, were synthesized. These inhibitors can use in vitro and also in vivo, and show no toxicity for experimental animals by the amounts used as the cathepsin inhibitor
SCF Ensures Meiotic Chromosome Segregation Through a Resolution of Meiotic Recombination Intermediates
The SCF (Skp1-Cul1-F-box) complex contributes to a variety of cellular events including meiotic cell cycle control, but its function during meiosis is not understood well. Here we describe a novel function of SCF/Skp1 in meiotic recombination and subsequent chromosome segregation. The skp1 temperature-sensitive mutant exhibited abnormal distribution of spindle microtubules in meiosis II, which turned out to originate from abnormal bending of the spindle in meiosis I. Bent spindles were reported in mitosis of this mutant, but it remained unknown how SCF could affect spindle morphology. We found that the meiotic bent spindle in skp1 cells was due to a hypertension generated by chromosome entanglement. The spindle bending was suppressed by inhibiting double strand break (DSB) formation, indicating that the entanglement was generated by the meiotic recombination machinery. Consistently, Rhp51/Rad51-Rad22/Rad52 foci persisted until meiosis I in skp1 cells, proving accumulation of recombination intermediates. Intriguingly bent spindles were also observed in the mutant of Fbh1, an F-box protein containing the DNA helicase domain, which is involved in meiotic recombination. Genetic evidence suggested its cooperation with SCF/Skp1. Thus, SCF/Skp1 together with Fbh1 is likely to function in the resolution of meiotic recombination intermediates, thereby ensuring proper chromosome segregation
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Identification of Genes Affecting the Toxicity of Anti-Cancer Drug Bortezomib by Genome-Wide Screening in S. pombe
Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive. We aimed to identify genes affecting the cytotoxicity of Bortezomib in the fission yeast S.pombe as the drug inhibits this organism's cell division cycle like proteasome mutants. Among the 2815 genes screened (covering 56% of total ORFs), 19 genes, whose deletions induce strong synthetic lethality with Bortezomib, were identified. The products of the 19 genes included four ubiquitin enzymes and one nuclear proteasome factor, and 13 of them are conserved in humans. Our results will provide useful information for understanding the actions of Bortezomib within cells
Angular momentum exchange during secular migration of two-planet systems
We investigate the secular dynamics of two-planet coplanar systems evolving
under mutual gravitational interactions and dissipative forces. We consider two
mechanisms responsible for the planetary migration: star-planet (or
planet-satellite) tidal interactions and interactions of a planet with a
gaseous disc. We show that each migration mechanism is characterized by a
specific law of orbital angular momentum exchange. Calculating stationary
solutions of the conservative secular problem and taking into account the
orbital angular momentum leakage, we trace the evolutionary routes followed by
the planet pairs during the migration process. This procedure allows us to
recover the dynamical history of two-planet systems and constrain parameters of
the involved physical processes.Comment: 20 pages, 9 figures, accepted for publication in Celestial Mechanics
and Dynamical Astronomy (special issue on Exoplanets
Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe
Proteasomes must efficiently remove their substrates throughout the cells in a timely manner as many of these proteins can be toxic. This study shows that proteasomes can do so efficiently because they are highly mobile. Furthermore this study uncovers that proteasome mobility requires functional Arc3, a subunit of the Arp2/3 complex
Proteasome Activator Enhances Survival of Huntington's Disease Neuronal Model Cells
In patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' skin fibroblasts or mutant huntingtin-expressing striatal neurons. Following compromise of the UPS, overexpression of the proteasome activator subunit PA28γ, but not subunit S5a, recovered proteasome function in the HD cells. PA28γ also improved cell viability in mutant huntingtin-expressing striatal neurons exposed to pathological stressors, such as the excitotoxin quinolinic acid and the reversible proteasome inhibitor MG132. These results demonstrate the specific functional enhancements of the UPS that can provide neuroprotection in HD cells
On the synchronization of IEEE 802.15.5 wireless mesh sensor networks: Shortcomings and improvements
- …