Breast tumor kinase (Brk/PTK6) plays a role in the differentiation of primary keratinocytes

This work was supported by a project grant from the Biotechnology and Biological Sciences Research Council, UKBreast Tumor Kinase (Brk/PTK6) has a relatively limited expression profile in normal tissue. Its expression is restricted to epithelial cells that are differentiating such as those in the epidermis, and Brk expression appears to be absent from proliferating cells in normal tissue. Also, there is now some evidence to suggest that Brk plays a functional role in the differentiation of the keratinocytes in the epidermis. We have, therefore, investigated the role that Brk/PTK6 plays in normal human primary keratinocytes by suppressing protein levels using RNA interference. We show that as primary human keratinocytes are induced to differentiate in vitro, Brk levels decrease. Decreasing Brk protein levels lead to an increase in the number of cells with a permeable plasma membrane, a decrease in epidermal growth factor receptor (EGFR) and a parallel increase in keratin 10 levels, but classical markers of apoptosis or terminal differentiation are not affected. We propose Brk, Keratin 10 and EGFR are co-regulated during differentiation and that manipulating Brk expression can influence the differentiation of normal primary human keratinocytes.This article is available through the Brunel University Open Access Publishing Fund

Brk expression may affect the differentiation status of breast cancer cells

The breast tumour kinase Brk (PTK6) is found in over two-thirds of breast cancer cell lines and tumours but is not expressed in normal mammary cells. Brk has previously been shown to play a role in regulating proliferation in breast tumour cells [1]. However, in vivo, the site of Brk expression in normal tissues is restricted to nonproliferating cells that are undergoing terminal differentiation such as those in the gut or the skin [2,3]. This led us to hypothesise that Brk expression in breast tumours could be reflective of a differentiation phenotype, especially as a previous study had shown that involucrin, a marker of terminal keratinocyte differentiation, was expressed in a subset of tumours [4]. We therefore examined involucrin expression in breast tumour cells lines and patient biopsy samples. In addition we investigated whether inducers of differentiation in keratinocytes such as prolonged culture in suspension or vitamin D3 treatment could also affect differentiation of breast tumour cells. We found that the expression of Brk in cultured cell lines correlated with involucrin expression. In addition the change in Brk expression, as a result of culture conditions, was accompanied by a change in involucrin levels. Moreover, treatment with vitamin D3 resulted in a decrease in cell numbers in the Brk-positive cell lines relative to the control treatments. The Brk-negative cell line was unaffected by vitamin D3 treatment. These data suggest that Brk and involucrin may be coregulated and that inducers of differentiation such as vitamin D3 could be considered potential therapeutic strategies

Simple Encrypted Arithmetic Library - SEAL v2.1

Achieving fully homomorphic encryption was a longstanding open problem in cryptography until it was resolved by Gentry in 2009. Soon after, several homomorphic encryption schemes were proposed. The early homomorphic encryption schemes were extremely impractical, but recently new implementations, new data encoding techniques, and a better understanding of the applications have started to change the situation. In this paper we introduce the most recent version (v2.1) of Simple Encrypted Arithmetic Library - SEAL, a homomorphic encryption library developed by Microsoft Research, and describe some of its core functionality

Magnetospheric Response Times Following Southward IMF Turnings

We analyze the response times of various regions of the magnetosphere-ionosphere system to sudden southward turnings of the IMF. Our data set consists of 26 events during which the IMP BZ component was observed by WIND to change from a stea northward field to a southward field, which subsequently led to a substorm. The magnetospheric response to such IMF southward turnings is examined using data from the POLAR EFI experiment, the GOES 9 magnetometer, and ground magnetometers. The POLAR/EFI was used to investigate changes in the polar cap electric field which occurred in response to the changing interplanetary electric field, and these results are compared with response timings derived from high-latitude ground magnetometers. POLAR/EFI data show responses in the polar cap about 15 minutes after the arrival of the IMF change at the magnetopause. Auroral zone magnetograms and geosynchronous spacecraft measurements are utilized to evaluate the response timing within the closed field line region. In one event examined in detail, the start of a substorm growth phase was observed by GOES 9 in the midnight sector of geosynchronous orbit about two minutes before POLAR observed a response in the polar cap. Using superposed epoch analysis, we calculate typical response times in the polar cap, in the nightside plasma sheet, and in the ionosphere in order to discuss the various suggested mechanisms for information propagation from the subsolar magnetopause into the magnetosphere. We find that for the set of ten events for which the GOES 9 and the CANOPUS array are in the midnight sector, the field at geosynchronous as measured by GOES responds at or before the time of response in the polar cap as measured by POLAR, suggesting different methods of information propagation

New Gauged Linear Sigma Models for 8D HyperKahler Manifolds and Calabi-Yau Crystals

We propose two kinds of gauged linear sigma models whose moduli spaces are real eight-dimensional hyperKahler and Calabi-Yau manifolds, respectively. Here, hyperKahler manifolds have sp(2) holonomy in general and are dual to Type IIB (p,q)5-brane configurations. On the other hand, Calabi-Yau fourfolds are toric varieties expressed as quotient spaces. Our model involving fourfolds is different from the usual one which is directly related to a symplectic quotient procedure. Remarkable features in newly-found three-dimensional Chern-Simons-matter theories appear here as well, such as dynamical Fayet-Iliopoulos parameters, one dualized photon and its residual discrete gauge symmetry.Comment: 20 pages, 1 figure; v2: minor changes and references added; v3: statements improved, newer than JHEP versio

Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial

We report an extensive 600 MHz NMR trial of a quantitative lipoprotein and small molecule measurements in human blood serum and plasma. Five centers with eleven 600 MHz NMR spectrometers were used to analyze 98 samples including: 20 QCs, 37 commercially sourced, paired serum and plasma samples and 2 National Institute of Science and Technology, NIST, reference material 1951c replicates. Samples were analyzed using rigorous protocols for sample preparation and experimental acquisition. A commercial lipoprotein subclass analysis was used to quantify 105 lipoprotein subclasses and 24 low molecular weight metabolites from the nuclear magnetic resonance, NMR, spectra. For all spectrometers, the instrument specific variance in measuring internal quality controls, QCs, was lower than the percentage described by the National Cholesterol Education Program, NCEP, criteria for lipid testing (triglycerides<2.7%, cholesterol<2.8%; LDL-cholesterol<2.8%; HDL-cholesterol<2.3%), showing exceptional reproducibility for direct quantitation of lipoproteins in both matrices. The average RSD for the 105 lipoprotein parameters in the 11 instruments was 4.6% and 3.9% for the two NIST samples while it was 38% and 40% for the 37 commercially sourced plasmas and sera, respectively, showing negligible analytical compared to biological variation. The coefficient of variance, CV, obtained for the quantification of the small molecules across the 11 spectrometers was below 15% for 20 out of the 24 metabolites analyzed. This study provides further evidence of the suitability of NMR for high-throughput lipoprotein subcomponent analysis and small molecule quantitation with the exceptional reproducibility required for clinical and other regulatory settings

Seiberg duality for Chern-Simons quivers and D-brane mutations

Chern-Simons quivers for M2-branes at Calabi-Yau singularities are best understood as the low energy theory of D2-branes on a dual type IIA background. We show how the D2-brane point of view naturally leads to three dimensional Seiberg dualities for Chern-Simons quivers with chiral matter content: They arise from a change of brane basis (or mutation), in complete analogy with the better known Seiberg dualities for D3-brane quivers. This perspective reproduces the known rules for Seiberg dualities in Chern-Simons-Yang-Mills theories with unitary gauge groups. We provide explicit examples of dual theories for the quiver dual to the Y^{p,q}(CP^2) geometries. We also comment on the string theory derivation of CS quivers dual to massive type IIA geometries.Comment: 32 pages+appendix; v2: added a referenc

Automated whole-cell patch-clamp electrophysiology of neurons in vivo

Whole-cell patch-clamp electrophysiology of neurons is a gold-standard technique for high-fidelity analysis of the biophysical mechanisms of neural computation and pathology, but it requires great skill to perform. We have developed a robot that automatically performs patch clamping in vivo, algorithmically detecting cells by analyzing the temporal sequence of electrode impedance changes. We demonstrate good yield, throughput and quality of automated intracellular recording in mouse cortex and hippocampus.National Institutes of Health (U.S.) (NIH EUREKA Award program (1R01NS075421))National Institutes of Health (U.S.) ((NIH) Director′s New Innovator Award (DP2OD002002)National Science Foundation (U.S.) ((NSF) CAREER award (CBET 1053233))New York Stem Cell Foundation (Robertson Neuroscience Award)Dr. Gerald Burnett and Marjorie BurnettNational Science Foundation (U.S.) (grant CISE 1110947)National Science Foundation (U.S.) (grant EHR 0965945)American Heart Association (10GRNT4430029

Noncommutative Vortices and Instantons from Generalized Bose Operators

Generalized Bose operators correspond to reducible representations of the harmonic oscillator algebra. We demonstrate their relevance in the construction of topologically non-trivial solutions in noncommutative gauge theories, focusing our attention to flux tubes, vortices, and instantons. Our method provides a simple new relation between the topological charge and the number of times the basic irreducible representation occurs in the reducible representation underlying the generalized Bose operator. When used in conjunction with the noncommutative ADHM construction, we find that these new instantons are in general not unitarily equivalent to the ones currently known in literature.Comment: 25 page