Completely bounded bimodule maps and spectral synthesis

We initiate the study of the completely bounded multipliers of the Haagerup tensor product $A(G)\otimes_{\rm h} A(G)$ of two copies of the Fourier algebra $A(G)$ of a locally compact group $G$. If $E$ is a closed subset of $G$ we let $E^{\sharp} = \{(s,t) : st\in E\}$ and show that if $E^{\sharp}$ is a set of spectral synthesis for $A(G)\otimes_{\rm h} A(G)$ then $E$ is a set of local spectral synthesis for $A(G)$. Conversely, we prove that if $E$ is a set of spectral synthesis for $A(G)$ and $G$ is a Moore group then $E^{\sharp}$ is a set of spectral synthesis for $A(G)\otimes_{\rm h} A(G)$. Using the natural identification of the space of all completely bounded weak* continuous $VN(G)'$-bimodule maps with the dual of $A(G)\otimes_{\rm h} A(G)$, we show that, in the case $G$ is weakly amenable, such a map leaves the multiplication algebra of $L^{\infty}(G)$ invariant if and only if its support is contained in the antidiagonal of $G$.Comment: 44 page

Local Operator Multipliers and Positivity

We establish an unbounded version of Stinespring's Theorem and a lifting result for Stinespring representations of completely positive modular maps defined on the space of all compact operators. We apply these results to study positivity for Schur multipliers. We characterise positive local Schur multipliers, and provide a description of positive local Schur multipliers of Toeplitz type. We introduce local operator multipliers as a non-commutative analogue of local Schur multipliers, and obtain a characterisation that extends earlier results concerning operator multipliers and local Schur multipliers. We provide a description of the positive local operator multipliers in terms of approximation by elements of canonical positive cones.Comment: 31 page

Unbounded representations of qq-deformation of Cuntz algebra

We study a deformation of the Cuntz-Toeplitz $C^*$-algebra determined by the relations $a_i^*a_i=1+q a_ia_i^*, a_i^*a_j=0$. We define well-behaved unbounded *-representations of the *-algebra defined by relations above and classify all such irreducible representations up to unitary equivalence.Comment: 13 pages, Submitted to Lett. Math. Phy

Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme

BACKGROUND : The most prevalent phenotype of asthma is characterized by eosinophil-dominated inflammation that is driven by a type 2 helper T cell (Th2). Therapeutic targeting of GATA3, an important transcription factor of the Th2 pathway, may be beneficial. We evaluated the safety and efficacy of SB010, a novel DNA enzyme (DNAzyme) that is able to cleave and inactivate GATA3 messenger RNA (mRNA). METHODS : We conducted a randomized, double-blind, placebo-controlled, multicenter clinical trial of SB010 involving patients who had allergic asthma with sputum eosinophilia and who also had biphasic early and late asthmatic responses after laboratory-based allergen provocation. A total of 40 patients could be evaluated; 21 were assigned to receive 10 mg of SB010, and 19 were assigned to receive placebo, with each study drug administered by means of inhalation once daily for 28 days. An allergen challenge was performed before and after the 28-day period. The primary end point was the late asthmatic response as quantified by the change in the area under the curve (AUC) for forced expiratory volume in 1 second (FEV1). RESULTS : After 28 days, SB010 attenuated the mean late asthmatic response by 34%, as compared with the baseline response, according to the AUC for FEV1, whereas placebo was associated with a 1% increase in the AUC for FEV1 (P = 0.02). The early asthmatic response with SB010 was attenuated by 11% as measured by the AUC for FEV1, whereas the early response with placebo was increased by 10% (P = 0.03). Inhibition of the late asthmatic response by SB010 was associated with attenuation of allergen-induced sputum eosinophilia and with lower levels of tryptase in sputum and lower plasma levels of interleukin-5. Allergen-induced levels of fractional exhaled nitric oxide and airway hyperresponsiveness to methacholine were not affected by either SB010 or placebo. CONCLUSIONS : Treatment with SB010 significantly attenuated both late and early asthmatic responses after allergen provocation in patients with allergic asthma. Biomarker analysis showed an attenuation of Th2-regulated inflammatory responses

Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis