Putting to rest WISHE-ful misconceptions for tropical cyclone intensification

The purpose of this article is twofold. The first is to point out and correct several misconceptions about the putative WISHE mechanism of tropical cyclone intensification that currently are being taught to atmospheric science students, to tropical weather forecasters, and to laypeople who seek to understand how tropical cyclones intensify. The mechanism relates to the simplest problem of an initial cyclonic vortex in a quiescent environment. This first part is important because the credibility of tropical cyclone science depends inter alia on being able to articulate a clear and consistent picture of the hypothesized intensification process and its dependencies on key flow parameters. The credibility depends also on being able to test the hypothesized mechanisms using observations, numerical models, or theoretical analyses. The second purpose of the paper is to carry out new numerical experiments using a state-of-the-art numerical model to test a recent hypothesis invoking the WISHE feedback mechanism during the rapid intensification phase of a tropical cyclone. The results obtained herein, in conjunction with prior work, do not support this recent hypothesis and refute the view that the WISHE intensification mechanism is the essential mechanism of tropical cyclone intensification in the idealized problem that historically has been used to underpin the paradigm. This second objective is important because it presents a simple way of testing the hypothesized intensification mechanism and shows that the mechanism is neither essential nor the dominant mode of intensification for the prototype intensification problem. In view of the operational, societal, and scientific interest in the physics of tropical cyclone intensification, we believe this paper will be of broad interest to the atmospheric science community and the findings should be useful in both the classroom setting and frontier research

Quasi-stationary chaotic states in multi-dimensional Hamiltonian systems

We study numerically statistical distributions of sums of chaotic orbit coordinates, viewed as independent random variables, in weakly chaotic regimes of three multi-dimensional Hamiltonian systems: Two Fermi-Pasta-Ulam (FPU-$\beta$) oscillator chains with different boundary conditions and numbers of particles and a microplasma of identical ions confined in a Penning trap and repelled by mutual Coulomb interactions. For the FPU systems we show that, when chaos is limited within "small size" phase space regions, statistical distributions of sums of chaotic variables are well approximated for surprisingly long times (typically up to $t\approx10^6$) by a $q$-Gaussian ($1<q<3$) distribution and tend to a Gaussian ($q=1$) for longer times, as the orbits eventually enter into "large size" chaotic domains. However, in agreement with other studies, we find in certain cases that the $q$-Gaussian is not the only possible distribution that can fit the data, as our sums may be better approximated by a different so-called "crossover" function attributed to finite-size effects. In the case of the microplasma Hamiltonian, we make use of these $q$-Gaussian distributions to identify two energy regimes of "weak chaos"-one where the system melts and one where it transforms from liquid to a gas state-by observing where the $q$-index of the distribution increases significantly above the $q=1$ value of strong chaos.Comment: 32 pages, 13 figures, Submitted for publication to Physica

N,N-Dimethyl-4-[(E)-2-(3,6,7-tribromo-9-butyl-9H-carbazol-2-yl)ethen­yl]aniline

In the title mol­ecule, C26H25Br3N2, a dihedral angle of 6.15 (10)° is present between the carbazole and benzene ring systems with an E conformation about the C=C bond [1.335 (4) Å]. The butyl group is almost perpendicular to the carbazole plane [C—N—C—C torsion angle = −98.7 (3)°]. In the crystal, supra­molecular double chains along [-7,18,-16] are formed via C—H⋯Br and π–π inter­actions [centroid(carbazole five-membered ring)⋯centroid(carbazole six-membered ring) distance = 3.6333 (13) Å]

Low expression of gamma-glutamyl hydrolase mRNA in primary colorectal cancer with the CpG island methylator phenotype

Division of Translational and Clinical Oncolog

Using Expression and Genotype to Predict Drug Response in Yeast

Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross

Elastin Peptides Signaling Relies on Neuraminidase-1-Dependent Lactosylceramide Generation

The sialidase activity of neuraminidase-1 (Neu-1) is responsible for ERK 1/2 pathway activation following binding of elastin peptide on the elastin receptor complex. In this work, we demonstrate that the receptor and lipid rafts colocalize at the plasma membrane. We also show that the disruption of these microdomains as well as their depletion in glycolipids blocks the receptor signaling. Following elastin peptide treatment, the cellular GM3 level decreases while lactosylceramide (LacCer) content increases consistently with a GM3/LacCer conversion. The use of lactose or Neu-1 siRNA blocks this process suggesting that the elastin receptor complex is responsible for this lipid conversion. Flow cytometry analysis confirms this elastin peptide-driven LacCer generation. Further, the use of a monoclonal anti-GM3 blocking antibody shows that GM3 is required for signaling. In conclusion, our data strongly suggest that Neu-1-dependent GM3/LacCer conversion is the key event leading to signaling by the elastin receptor complex. As a consequence, we propose that LacCer is an early messenger for this receptor

Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma

<p>Abstract</p> <p>Background</p> <p>Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).</p> <p>Methods</p> <p>An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated <it>in vitro</it>. In addition, the <it>in vivo </it>effect of TS siRNA on tumor progression was assessed using a xenograft model.</p> <p>Results</p> <p>Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.</p> <p>Conclusion</p> <p>TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.</p

Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment