TWO-DIMENSIONAL PARTICLE-IN-CELL SIMULATIONS OF THE NONRESONANT, COSMIC-RAY-DRIVEN INSTABILITY IN SUPERNOVA REMNANT SHOCKS

In supernova remnants, the nonlinear amplification of magnetic fields upstream of collisionless shocks is essential for the acceleration of cosmic rays to the energy of the "knee" at 10(15.5) eV. A nonresonant instability driven by the cosmic ray current is thought to be responsible for this effect. We perform two-dimensional, particle-in-cell simulations of this instability. We observe an initial growth of circularly polarized nonpropagating magnetic waves as predicted in linear theory. It is demonstrated that in some cases the magnetic energy density in the growing waves can grow to at least 10 times its initial value. We find no evidence of competing modes, nor of significant modification by thermal effects. At late times, we observe saturation of the instability in the simulation, but the mechanism responsible is an artifact of the periodic boundary conditions and has no counterpart in the supernova-shock scenario.

A current-driven instability in parallel, relativistic shocks

Recently, Bell ( 2004 Mon. Not. R. Astron. Soc. 353 550) has reanalysed the problem of wave excitation by cosmic rays propagating in the pre-cursor region of a supernova remnant shock front. He pointed out a strong, non-resonant, current-driven instability that had been overlooked in the kinetic treatments by Achterberg ( 1983 Astron. Astrophys. 119 274) and McKenzie and Volk ( 1982 Astron. Astrophys. 116 191), and suggested that it is responsible for substantial amplification of the ambient magnetic field. Magnetic field amplification is also an important issue in the problem of the formation and structure of relativistic shock fronts, particularly in relation to models of gamma-ray bursts. We have therefore generalized the linear analysis to apply to this case, assuming a relativistic background plasma and a monoenergetic, unidirectional incoming proton beam. We find essentially the same non-resonant instability observed by Bell and show that also, under GRB conditions, it grows much faster than the resonant waves. We quantify the extent to which thermal effects in the background plasma limit the maximum growth rate.

A cosmic ray current-driven instability in partially ionised media

Context. We investigate the growth of hydromagnetic waves driven by streaming cosmic rays in the precursor environment of a supernova remnant shock.

Aims. It is known that transverse waves propagating parallel to the mean magnetic field are unstable to anisotropies in the cosmic ray distribution, and may provide a mechanism to substantially amplify the ambient magnetic field. We quantify the extent to which temperature and ionisation fractions modify this picture.

Methods. Using a kinetic description of the plasma we derive the dispersion relation for a collisionless thermal plasma with a streaming cosmic ray current. Fluid equations are then used to discuss the effects of neutral-ion collisions.

Results. We calculate the extent to which the environment into which the cosmic rays propagate influences the growth of the magnetic field, and determines the range of possible growth rates.

Conclusions. If the cosmic ray acceleration is efficient, we find that very large neutral fractions are required to stabilise the growth of the non-resonant mode. For typical supernova parameters in our Galaxy, thermal effects do not significantly alter the growth rates. For weakly driven modes, ion-neutral damping can dominate over the instability at more modest ionisation fractions. In the case of a supernova shock interacting with a molecular clouds, such as in RX J1713.7-3946, with high density and low ionisation, the modes can be rapidly damped.

ENVIRONMENTAL LIMITS ON THE NONRESONANT COSMIC-RAY CURRENT-DRIVEN INSTABILITY

We investigate the so-called nonresonant cosmic-ray streaming instability, first discussed by Bell (2004). The extent to which thermal damping and ion-neutral collisions reduce the growth of this instability is calculated. Limits on the growth of the nonresonant mode in SN1006 and RX J1713.7-3946 are presented.

Slowly fading super-luminous supernovae that are not pair-instability explosions

Super-luminous supernovae that radiate more than 10 44 ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of 56 Ni are synthesized; this isotope decays to 56 Fe via 56 Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10 -6 times that of the core-collapse rate. © 2013 Macmillan Publishers Limited. All rights reserved.

Modification of the formation of high-Mach number electrostatic shock-like structures by the ion acoustic instability

The formation of unmagnetized electrostatic shock-like structures with a high Mach number is examined with one- and two-dimensional particle-in-cell (PIC) simulations. The structures are generated through the collision of two identical plasma clouds, which consist of equally hot electrons and ions with a mass ratio of 250. The Mach number of the collision speed with respect to the initial ion acoustic speed of the plasma is set to 4.6. This high Mach number delays the formation of such structures by tens of inverse ion plasma frequencies. A pair of stable shock-like structures is observed after this time in the 1D simulation, which gradually evolve into electrostatic shocks. The ion acoustic instability, which can develop in the 2D simulation but not in the 1D one, competes with the nonlinear process that gives rise to these structures. The oblique ion acoustic waves fragment their electric field. The transition layer, across which the bulk of the ions change their speed, widens and their speed change is reduced. Double layer-shock hybrid structures develop.

Semiclassical relativistic fluid theory for electrostatic envelope modes in dense electron-positron-ion plasmas:Modulational instability and rogue waves

A fluid model is used to describe the propagation of envelope structures in an ion plasma under the influence of the action of weakly relativistic electrons and positrons. A multiscale perturbative method is used to derive a nonlinear Schrödinger equation for the envelope amplitude. Criteria for modulational instability, which occurs for small values of the carrier wavenumber (long carrier wavelengths), are derived. The occurrence of rogue waves is briefly discussed. © Cambridge University Press 2013.

BRCA1 Deficiency Exacerbates Estrogen-Induced DNA Damage and Genomic Instability

Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell-cycle arrest, and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here, we report that estrogen and estrogen metabolites can cause DNA double-strand breaks (DSB) in estrogen receptora- negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability.We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolizing enzymes, such as CYP1A1, in breast cells. Finally, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumors in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types. © 2014 American Association for Cancer Research.

Mitotic Arrest Deficiency Protein 2 (MAD2) and Histone Deacetylase 6 (HDAC6) Present a Complex Relationship in Their Regulation and Expression and Subsequent Impact on Chemoresponsiveness

Introduction:
Ovarian cancer patients presenting with advanced stage (III/IV)
canceraretreatedwithcarboplatinumincombinationwithpaclitaxel.Despitea
significant initial response rate, fewer than 20% of patients become long-term
survivors. We have published that low MAD2 expression levels associate with
reduced progression free survival (PFS) in patients with high-grade serous
epithelial ovarian cancer (EOC). Moreover, we have demonstrated that MAD2
expressionisdown-regulatedbythemicroRNAmiR-433(
Furlong et al., 2011
).
Interestingly, miR-433 also down-regulates HDAC6 (
Simon et al., 2010
), which
uniquely deacetylates
a
-tubulin prior to HDAC6s binding to
b
-tubulin.
In vitro
studies have shown that HDAC6 inhibition in combination with paclitaxel
treatment enhances chemoresistant cancer cell death. To date, an interaction
between MAD2 and HDAC6 has not been reported.
Experimental design:
MAD2 and HDAC6 immunohistochemistry (IHC) and
Western blot analyses were performed to investigate the role of HDAC6 and
MAD2 in chemoresistance to paclitaxel in high-grade serous EOC.
Results and Discussion:
In vitro
experiments demonstrated that overex-
pression of pre-miR-433, which targets MAD2, resulted in down-regulation
of HDAC6 in EOC cell lines. High levels of HDAC6 are co-expressed with
MAD2 in the paclitaxel resistant UPN251 and OVCAR7 cell lines. While, all
4 paclitaxel resistant EOC cell lines express higher levels of miR-433 than
the paclitaxel sensitive A2780 cells, only ovca432 and ovca433 demonstrated
down-regulation of both HDAC6 and MAD2. Paclitaxel binds to
b
-tubulin and
causesmicrotubulepolymerizationinpaclitaxelsensitivecellsasdemonstrated
by tubulin acetylation in A2780 cells. However, paclitaxel failed to cause a
significant acetylation of
a
-tubulin and microtubule stabilisation in the resistant
UPN251 cells. Therefore resistance in this cell line may be mediated by
aberrantly high HDAC6 activity. We have previously shown that MAD2 knock-
down cells are resistant to paclitaxel (
Furlong F., et al., 2011; Prencipe M.,
et al., 2009
). We measured HDAC6 protein expression in MAD2 knockdown
cells and showed that MAD2 knockdown is associated with concomitant
up-regulation of HDAC6. We hypothesise that the up-regulation of HDAC6
by MAD2 knockdown renders cancer cells more resistant to paclitaxel and
increases the invasive potential of these cells. On-going experiments will test
this hypothesis. Lastly we have observed differential MAD2 and HDAC6 IHC
staining intensity in formalin fixed paraffin embedded EOC samples.
In conclusion
, we have reported on a novel interaction between MAD2 and
HDAC6 which may have important consequences for paclitaxel resistant EOC.
Moreover, understanding chemo-responsiveness in ovarian tumours will lead
to improved patient management and treatment options for women diagnosed
with this disease

"Republic of Instability":Artifice, Death and the Afterlife in Mark Doty's "Murano"

An article on a single poem by Mark Doty, published as part of the "Hospitable Forms: Post-Secular Thought in New-Century Poetics" feature.

Amplitude modulation of quantum-ion-acoustic wavepackets in electron-positron-ion plasmas: Modulational instability, envelope modes, extreme waves

A semirelativistic fluid model is employed to describe the nonlinear amplitude modulation of low-frequency (ionic scale) electrostatic waves in an unmagnetized electron-positron-ion plasma. Electrons and positrons are assumed to be degenerated and inertialess, whereas ions are warm and classical. A multiscale perturbation method is used to derive a nonlinear Schrödinger equation for the envelope amplitude, based on which the occurrence of modulational instability is investigated in detail. Various types of localized ion acoustic excitations are shown to exist, in the form of either bright type envelope solitons (envelope pulses) or dark-type envelope solitons (voids, holes). The plasma configurational parameters (namely, the relativistic degeneracy parameter, the positron concentration, and the ionic temperature) are shown to affect the conditions for modulational instability significantly, in fact modifying the associated threshold as well as the instability growth rate. In particular, the relativistic degeneracy parameter leads to an enhancement of the modulational instability mechanism. Furthermore, the effect of different relevant plasma parameters on the characteristics (amplitude, width) of these envelope solitary structures is also presented in detail. Finally, the occurrence of extreme amplitude excitation (rogue waves) is also discussed briefly. Our results aim at elucidating the formation and dynamics of nonlinear electrostatic excitations in superdense astrophysical regimes.

BubR1 is required for the mitotic block induced by combretastatin-A4 and a novel cis-restricted ß-lactam analogue in human cancer cells

BubR1 is a well-defined guardian of the mitotic spindle, initiating mitotic arrest in response to the lack of tension and/or chromosome alignment across the mitotic plate. However, the role of BubR1 in combretastatin-induced cell death remains unknown. In this study, we describe the effects of combretastatin A-4 (CA-4) and a synthetic cis-restricted 3,4-diaryl-2-azetidinone (ß-lactam) analogue (CA-432) on the modulation and phosphorylation of BubR1 in human cervical cancer-derived cells. We demonstrate that CA-4 and CA-432 depolymerise the microtubular network of human cervical carcinoma-derived cells. Both compounds induced the disassembly of the microtubules and the loss of microtubule tension led to the early phosphorylation of BubR1 and the late cleavage of BubR1. The phosphorylation of BubR1 correlated with the onset of G2M cell cycle arrest whilst the cleavage of BubR1 coincided with apoptosis induced by the combretastatins. The combretastatin-induced apoptosis and the BubR1 cleavage were caspase-dependent. In vitro enzyme digests demonstrated that combretastatin-activated BubR1 is a substrate for caspase-3. Gene silencing of BubR1 with small interfering RNA severely compromised combretastatin-induced G2M cell cycle arrest with a corresponding increase in the formation of polyploid cells in both cervical and breast cancer-derived cells. In summary, BubR1 is required to maintain the G2M arrest and limit the formation of polyploid cells in response to continued combretastatin exposure. Moreover, substitution of the ethylene bridge with 3,4-diaryl-2-azetidinone did not alter the tubulin depolymerising properties or the subsequent mitotic spindle checkpoint response to CA-4 in human cancer cells.