Nonlocality, Bell's Ansatz and Probability

Quantum Mechanics lacks an intuitive interpretation, which is the cause of a generally formalistic approach to its use. This in turn has led to a certain insensitivity to the actual meaning of many words used in its description and interpretation. Herein, we analyze carefully the possible mathematical meanings of those terms used in analysis of EPR's contention, that Quantum Mechanics is incomplete, as well as Bell's work descendant therefrom. As a result, many inconsistencies and errors in contemporary discussions of nonlocality, as well as in Bell's Ansatz with respect to the laws of probability, are identified. Evading these errors precludes serious conflicts between Quantum Mechanics and both Special Relativity and Philosophy.Comment: 8&1/2 pages revtex; v2: many corrections, clairifications & extentions, all small; v3: editorial scru

TGFβ(1 )signaling via α(V)β(6 )integrin

BACKGROUND: Transforming growth factor β(1 )(TGFβ(1)) is a potent inhibitor of epithelial cell growth, thus playing an important role in tissue homeostasis. Most carcinoma cells exhibit a reduced sensitivity for TGFβ(1 )mediated growth inhibition, suggesting TGFβ(1 )participation in the development of these cancers. The tumor suppresor gene DPC4/SMAD4, which is frequently inactivated in carcinoma cells, has been described as a key player in TGFβ(1 )mediated growth inhibition. However, some carcinoma cells lacking functional SMAD4 are sensitive to TGFβ(1 )induced growth inhibition, thus requiring a SMAD4 independent TGFβ(1 )pathway. RESULTS: Here we report that mature TGFβ(1 )is a ligand for the integrin α(V)β(6), independent of the common integrin binding sequence motif RGD. After TGFβ(1 )binds to α(V)β(6 )integrin, different signaling proteins are activated in TGFβ(1)-sensitive carcinoma cells, but not in cells that are insensitive to TGFβ(1). Among others, interaction of TGFβ(1 )with the α(V)β(6 )integrin resulted in an upregulation of the cell cycle inhibitors p21/WAF1 and p27 leading to growth inhibition in SMAD4 deleted as well as in SMAD4 wildtype carcinoma cells. CONCLUSIONS: Our data provide support for the existence of an alternate TGFβ(1 )signaling pathway that is independent of the known SMAD pathway. This alternate pathway involves α(V)β(6 )integrin and the Ras/MAP kinase pathway and does not employ an RGD motif in TGFβ(1)-sensitive tumor cells. The combined action of these two pathways seems to be necessary to elicit a complete TGFβ(1 )signal

Is "entanglement" always entangled?

Entanglement, including ``quantum entanglement,'' is a consequence of correlation between objects. When the objects are subunits of pairs which in turn are members of an ensemble described by a wave function, a correlation among the subunits induces the mysterious properties of ``cat-states.'' However, correlation between subsystems can be present from purely non-quantum sources, thereby entailing no unfathomable behavior. Such entanglement arises whenever the so-called ``qubit space'' is not afflicted with Heisenberg Uncertainty. It turns out that all optical experimental realizations of EPR's \emph{Gedanken} experiment in fact do not suffer Heisenberg Uncertainty. Examples will be analyzed and non-quantum models for some of these described. The consequences for experiments that were to test EPR's contention in the form of Bell's Theorem are drawn: \emph{valid tests of EPR's hypothesis have yet to be done.}Comment: 5 p. LaTeX + 3 eps & 1 ps fig; v2:typos fixe

A realist view of the canonical EPRB experiment based on quantum theory and its consequences

A realist view of the Einstein-Podolsky-Rosen-Bohm experiment with spins based on quantum theory is presented. This view implies that there is no action at a distance. It also implies that the measurement result A (B) for particle 1 (2) depends on both magnet angles, and hence the probability of obtaining the result A (B) also depends on both magnet angles. In light of these realist implications, it is clear that what is wrong at least with local realistic theory is not the locality or no action-at-a-distance assumption itself but rather the formal implementation of that assumption.Comment: To be published in the Journal of Optics B as part of the proceeedings of the Garda 2001 Workshop on Mysteries, Puzzles and Paradoxes in Quantum Mechanic

The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles – the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions

Spontaneous, pro-arrhythmic calcium signals disrupt electrical pacing in mouse pulmonary vein sleeve cells

The pulmonary vein, which returns oxygenated blood to the left atrium, is ensheathed by a population of unique, myocyte- like cells called pulmonary vein sleeve cells (PVCs). These cells autonomously generate action potentials that propagate into the left atrial chamber and cause arrhythmias resulting in atrial fibrillation; the most common, often sustained, form of cardiac arrhythmia. In mice, PVCs extend along the pulmonary vein into the lungs, and are accessible in a lung slice preparation. We exploited this model to study how aberrant Ca2+ signaling alters the ability of PVC networks to follow electrical pacing. Cellular responses were investigated using real-time 2-photon imaging of lung slices loaded with a Ca2+- sensitive fluorescent indicator (Ca2+ measurements) and phase contrast microscopy (contraction measurements). PVCs displayed global Ca2+ signals and coordinated contraction in response to electrical field stimulation (EFS). The effects of EFS relied on both Ca2+ influx and Ca2+ release, and could be inhibited by nifedipine, ryanodine or caffeine. Moreover, PVCs had a high propensity to show spontaneous Ca2+ signals that arose via stochastic activation of ryanodine receptors (RyRs). The ability of electrical pacing to entrain Ca2+ signals and contractile responses was dramatically influenced by inherent spontaneous Ca2+ activity. In PVCs with relatively low spontaneous Ca2+ activity (2+ activity (>1.5 Hz), electrical pacing was less effective; PVCs became unpaced, only partially-paced or displayed alternans. Because spontaneous Ca2+ activity varied between cells, neighboring PVCs often had different responses to electrical pacing. Our data indicate that the ability of PVCs to respond to electrical stimulation depends on their intrinsic Ca2+ cycling properties. Heterogeneous spontaneous Ca2+ activity arising from stochastic RyR opening can disengage them from sinus rhythm and lead to autonomous, pro-arrhythmic activity

In Vitro Phenotypic, Genomic and Proteomic Characterization of a Cytokine-Resistant Murine β-TC3 Cell Line

Type 1 diabetes mellitus (T1DM) is caused by the selective destruction of insulin-producing β-cells. This process is mediated by cells of the immune system through release of nitric oxide, free radicals and pro-inflammatory cytokines, which induce a complex network of intracellular signalling cascades, eventually affecting the expression of genes involved in β-cell survival

Extracellular Hsp90 and TGFP regulate adhesion, migration and anchorage independent growth in a paired colon cancer cell line model

Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-ß pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-ß pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown