Tensionless branes and the null string critical dimension

BRST quantization is carried out for a model of p-branes with second class constraints. After extension of the phase space the constraint algebra coincides with the one of null string when p=1. It is shown that in this case one can or can not obtain critical dimension for the null string, depending on the choice of the operator ordering and corresponding vacuum states. When p>1, operator orderings leading to critical dimension in the p=1 case are not allowed. Admissable orderings give no restrictions on the dimension of the embedding space-time. Finally, a generalization to supersymmetric null branes is proposed.Comment: 12 pages, LaTeX 2.09. Title changed. Change in the transition from second class constraints to first class ones. Comments, conclusions, references, acknowledgments and report-no adde

Classification of integrable two-component Hamiltonian systems of hydrodynamic type in 2+1 dimensions

Hamiltonian systems of hydrodynamic type occur in a wide range of applications including fluid dynamics, the Whitham averaging procedure and the theory of Frobenius manifolds. In 1+1 dimensions, the requirement of the integrability of such systems by the generalised hodograph transform implies that integrable Hamiltonians depend on a certain number of arbitrary functions of two variables. On the contrary, in 2+1 dimensions the requirement of the integrability by the method of hydrodynamic reductions, which is a natural analogue of the generalised hodograph transform in higher dimensions, leads to finite-dimensional moduli spaces of integrable Hamiltonians. In this paper we classify integrable two-component Hamiltonian systems of hydrodynamic type for all existing classes of differential-geometric Poisson brackets in 2D, establishing a parametrisation of integrable Hamiltonians via elliptic/hypergeometric functions. Our approach is based on the Godunov-type representation of Hamiltonian systems, and utilises a novel construction of Godunov's systems in terms of generalised hypergeometric functions.Comment: Latex, 34 page

Regulation of anti-apoptotic signaling by Kruppel-like factors 4 and 5 mediates lapatinib resistance in breast cancer

The Kruppel-like transcription factors (KLFs) 4 and 5 (KLF4/5) are coexpressed in mouse embryonic stem cells, where they function redundantly to maintain pluripotency. In mammary carcinoma, KLF4/5 can each impact the malignant phenotype, but potential linkages to drug resistance remain unclear. In primary human breast cancers, we observed a positive correlation between KLF4/5 transcript abundance, particularly in the human epidermal growth factor receptor 2 (HER2)-enriched subtype. Furthermore, KLF4/5 protein was rapidly upregulated in human breast cancer cells following treatment with the HER2/epidermal growth factor receptor inhibitor, lapatinib. In addition, we observed a positive correlation between these factors in the primary tumors of genetically engineered mouse models (GEMMs). In particular, the levels of both factors were enriched in the basal-like tumors of the C3(1) TAg (SV40 large T antigen transgenic mice under control of the C3(1)/prostatein promoter) GEMM. Using tumor cells derived from this model as well as human breast cancer cells, suppression of KLF4 and/or KLF5 sensitized HER2-overexpressing cells to lapatinib. Indicating cooperativity, greater effects were observed when both genes were depleted. KLF4/5-deficient cells had reduced basal mRNA and protein levels of the anti-apoptotic factors myeloid cell leukemia 1 (MCL1) and B-cell lymphoma-extra large (BCL-XL). Moreover, MCL1 was upregulated by lapatinib in a KLF4/5-dependent manner, and enforced expression of MCL1 in KLF4/5-deficient cells restored drug resistance. In addition, combined suppression of KLF4/5 in cultured tumor cells additively inhibited anchorage-independent growth, resistance to anoikis and tumor formation in immunocompromised mice. Consistent with their cooperative role in drug resistance and other malignant properties, KLF4/5 levels selectively stratified human HER2-enriched breast cancer by distant metastasis-free survival. These results identify KLF4 and KLF5 as cooperating protumorigenic factors and critical participants in resistance to lapatinib, furthering the rationale for combining anti-MCL1/BCL-XL inhibitors with conventional HER2-targeted therapies

Steps towards the hyperfine splitting measurement of the muonic hydrogen ground state: pulsed muon beam and detection system characterization

The high precision measurement of the hyperfine splitting of the muonic-hydrogen atom ground state with pulsed and intense muon beam requires careful technological choices both in the construction of a gas target and of the detectors. In June 2014, the pressurized gas target of the FAMU experiment was exposed to the low energy pulsed muon beam at the RIKEN RAL muon facility. The objectives of the test were the characterization of the target, the hodoscope and the X-ray detectors. The apparatus consisted of a beam hodoscope and X-rays detectors made with high purity Germanium and Lanthanum Bromide crystals. In this paper the experimental setup is described and the results of the detector characterization are presented.Comment: 22 pages, 14 figures, published and open access on JINS

Analysis of alternative splicing of cassette exons at single-cell level using two fluorescent proteins

Alternative splicing plays a major role in increasing proteome complexity and regulating gene expression. Here, we developed a new fluorescent protein-based approach to quantitatively analyze the alternative splicing of a target cassette exon (skipping or inclusion), which results in an open-reading frame shift. A fragment of a gene of interest is cloned between red and green fluorescent protein (RFP and GFP)-encoding sequences in such a way that translation of the normally spliced full-length transcript results in expression of both RFP and GFP. In contrast, alternative exon skipping results in the synthesis of RFP only. Green and red fluorescence intensities can be used to estimate the proportions of normal and alternative transcripts in each cell. The new method was successfully tested for human PIG3 (p53-inducible gene 3) cassette exon 4. Expected pattern of alternative splicing of PIG3 minigene was observed, including previously characterized effects of UV light irradiation and specific mutations. Interestingly, we observed a broad distribution of normal to alternative transcript ratio in individual cells with at least two distinct populations with ∼45% and >95% alternative transcript. We believe that this method is useful for fluorescence-based quantitative analysis of alternative splicing of target genes in a variety of biological models

Experimental determination of the energy dependence of the rate of the muon transfer reaction from muonic hydrogen to oxygen for collision energies up to 0.1 eV

We report the first experimental determination of the collision-energy dependence of the muon transfer rate from the ground state of muonic hydrogen to oxygen at near-thermal energies. A sharp increase by nearly an order of magnitude in the energy range 0 - 70 meV was found that is not observed in other gases. The results set a reliable reference for quantum-mechanical calculations of low-energy processes with exotic atoms, and provide firm ground for the measurement of the hyperfine splitting in muonic hydrogen and the determination of the Zemach radius of the proton by the FAMU collaboration.Comment: 30 pages, 10 figure

Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy

Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.Toxicolog