Optical pulse compression in a cholesteric liquid crystal

A 20‐ns laser pulse is compressed to nearly 2.5 ns in a 10‐cm‐long sample of liquid‐crystal cholesteryl oleate in the isotropic phase. Pulse compression in a length as short as only 5 cm has been observed. A semiquantitative explanation is given in terms of stimulated Brillouin scattering

DON as a source of bioavailable nitrogen for phytoplankton

Relative to inorganic nitrogen, concentrations of dissolved organic nitrogen ( DON) are often high, even in regions believed to be nitrogen-limited. The persistence of these high concentrations led to the view that the DON pool was largely refractory and therefore unimportant to plankton nutrition. Any DON that was utilized was believed to fuel bacterial production. More recent work, however, indicates that fluxes into and out of the DON pool can be large, and that the constancy in concentration is a function of tightly coupled production and consumption processes. Evidence is also accumulating which indicates that phytoplankton, including a number of harmful species, may obtain a substantial part of their nitrogen nutrition from organic compounds. Ongoing research includes ways to discriminate between autotrophic and heterotrophic utilization, as well as a number of mechanisms, such as cell surface enzymes and photochemical decomposition, that could facilitate phytoplankton use of DON components

Cellular Inhibitor of Apoptosis (cIAP)-mediated ubiquitination of Phosphofurin Acidic Cluster Sorting protein 2 (PACS-2) negatively regulates Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) cytotoxicity

Lysosomal membrane permeabilization is an essential step in TRAIL-induced apoptosis of liver cancer cell lines. TRAIL-induced lysosomal membrane permeabilization is mediated by the multifunctional sorting protein PACS-2 and repressed by the E3 ligases cIAP-1 and cIAP-2. Despite the opposing roles for PACS-2 and cIAPs in TRAIL-induced apoptosis, an interaction between these proteins has yet to be examined. Herein, we report that cIAP-1 and cIAP-2 confer TRAIL resistance to hepatobiliary cancer cell lines by reducing PACS-2 levels. Under basal conditions, PACS-2 underwent K48-linked polyubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. Single c-Iap-1 or c-Iap-2 gene knock-outs in mouse hepatocytes did not lead to PACS-2 accumulation. However, deletion of both cIAP-1 and cIAP-2 reduced PACS-2 ubiquitination, which increased PACS-2 levels and sensitized HuH-7 cells to TRAIL-induced lysosomal membrane permeabilization and apoptosis. Correspondingly, deletion of cIAPs sensitized wild-type, but not PACS-2-deficient hepatocarcinoma cells or Pacs-2-/- mouse hepatocytes to TRAIL-induced apoptosis. Together, these data suggest cIAPs constitutively downregulate PACS-2 by polyubiquitination and proteasomal degradation, thereby restraining TRAIL-induced killing of liver cancer cells. © 2014 Guicciardi et al

BH3-only protein mimetic obatoclax sensitizes cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis.

Human cholangiocarcinomas evade apoptosis by overexpression of Mcl-1. The drug obatoclax (GX15-070) inhibits antiapoptotic members of the Bcl-2 family including Mcl-1. The purpose of this study is to determine if obatoclax sensitizes human cholangiocarcinoma cells to apoptosis. The human cholangiocarcinoma cell lines, KMCH, KMBC, and TFK, were employed for these studies. Protein expression was assessed by immunoblot and protein-protein interactions detected by coprecipitation of the polypeptide of interest with S-tagged Mcl-1. Activation of Bak and Bax was observed by immunocytochemistry with conformation-specific antisera. Obatoclax induced minimal apoptosis alone; however, it increased apoptosis 3- to 13-fold in all three cancer cell lines when combined with Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Obatoclax did not alter cellular expression of Bid, Bim, Puma, Noxa, Bak, Bax, Mcl-1, or cFLIP. Mcl-1 binding to Bak was readily identified in untreated cells, and this association was disrupted by treating the cells with obatoclax. Additionally, Bim binding to Mcl-1 was markedly decreased by obatoclax treatment. We also identified alterations in Bak and Bax conformation following treatment with obatoclax plus Apo2L/TRAIL but not with either Apo2L/TRAIL or obatoclax alone. In conclusion, obatoclax releases Bak and Bim from Mcl-1 and sensitizes human cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis. Obatoclax is a potentially promising adjunctive agent for the treatment of this cancer

Random matrix ensembles with an effective extensive external charge

Recent theoretical studies of chaotic scattering have encounted ensembles of random matrices in which the eigenvalue probability density function contains a one-body factor with an exponent proportional to the number of eigenvalues. Two such ensembles have been encounted: an ensemble of unitary matrices specified by the so-called Poisson kernel, and the Laguerre ensemble of positive definite matrices. Here we consider various properties of these ensembles. Jack polynomial theory is used to prove a reproducing property of the Poisson kernel, and a certain unimodular mapping is used to demonstrate that the variance of a linear statistic is the same as in the Dyson circular ensemble. For the Laguerre ensemble, the scaled global density is calculated exactly for all even values of the parameter $\beta$, while for $\beta = 2$ (random matrices with unitary symmetry), the neighbourhood of the smallest eigenvalue is shown to be in the soft edge universality class.Comment: LaTeX209, 17 page

The chronology of reindeer hunting on Norway's highest ice patches.

The melting of perennial ice patches globally is uncovering a fragile record of alpine activity, especially hunting and the use of mountain passes. When rescued by systematic fieldwork (glacial archaeology), this evidence opens an unprecedented window on the chronology of high-elevation activity. Recent research in Jotunheimen and surrounding mountain areas of Norway has recovered over 2000 finds-many associated with reindeer hunting (e.g. arrows). We report the radiocarbon dates of 153 objects and use a kernel density estimation (KDE) method to determine the distribution of dated events from ca 4000 BCE to the present. Interpreted in light of shifting environmental, preservation and socio-economic factors, these new data show counterintuitive trends in the intensity of reindeer hunting and other high-elevation activity. Cold temperatures may sometimes have kept humans from Norway's highest elevations, as expected based on accessibility, exposure and reindeer distributions. In times of increasing demand for mountain resources, however, activity probably continued in the face of adverse or variable climatic conditions. The use of KDE modelling makes it possible to observe this patterning without the spurious effects of noise introduced by the discrete nature of the finds and the radiocarbon calibration process

Noxa mediates hepatic stellate cell apoptosis by proteasome inhibition.

Aim: Induction of hepatic stellate cell (HSC) apoptosis is a viable therapeutic strategy to reduce liver fibrogenesis. Although BH3-only proteins of the Bcl-2 family trigger pro-apoptotic pathways, the BH3-only proteins mediating HSC apoptosis have not been well defined. Our aim, using proteasome inhibition as a model to induce HSC apoptosis, was to examine the BH3-only proteins contributing to cell death of this key liver cell subtype. Methods: Apoptosis was induced by treating LX-2 cells, an immortalized human hepatic stellate cell line, and primary rat stellate cells with the proteasome inhibitor MG-132. Results: Treatment with proteasome inhibitors increased expression of Noxa both at the mRNA (16-fold) and protein (22-fold) levels indicating that both transcriptional and post-translational mechanisms contributed to the increase in cellular Noxa levels. Knockdown of Noxa by siRNA significantly attenuated cell death, mechanistically implicating Noxa as a key apoptotic mediator of proteasome inhibitor-induced cell death. Given the pivotal role for the anti-apoptotic Bcl-2 protein A1 in activated HSC survival, we determined if Noxa bound to this survival protein. Noxa was shown to physically bind the anti-apoptotic Bcl-2 protein A1 by co-immunoprecipitation. Conclusions: Noxa contributes to proteasome inhibitor-induced apoptosis of stellate cells likely by binding A1. Strategies to therapeutically increase Noxa expression may be useful for inducing HSC apoptosis

Correlation functions of eigenvalues of multi-matrix models, and the limit of a time dependent matrix

We consider the correlation functions of eigenvalues of a unidimensional chain of large random hermitian matrices. An asymptotic expression of the orthogonal polynomials allows to find new results for the correlations of eigenvalues of different matrices of the chain. Eventually, we consider the limit of the infinite chain of matrices, which can be interpreted as a time dependent one-matrix model, and give the correlation functions of eigenvalues at different times.Comment: Tex-Harvmac, 27 pages, submitted to Journ. Phys.

Asymptotic Level Spacing of the Laguerre Ensemble: A Coulomb Fluid Approach

We determine the asymptotic level spacing distribution for the Laguerre Ensemble in a single scaled interval, $(0,s)$, containing no levels, E_{\bt}(0,s), via Dyson's Coulomb Fluid approach. For the $\alpha=0$ Unitary-Laguerre Ensemble, we recover the exact spacing distribution found by both Edelman and Forrester, while for $\alpha\neq 0$, the leading terms of $E_{2}(0,s)$, found by Tracy and Widom, are reproduced without the use of the Bessel kernel and the associated Painlev\'e transcendent. In the same approximation, the next leading term, due to a ``finite temperature'' perturbation (\bt\neq 2), is found.Comment: 10pp, LaTe