Mechano-transduction: from molecules to tissues.

External forces play complex roles in cell organization, fate, and homeostasis. Changes in these forces, or how cells respond to them, can result in abnormal embryonic development and diseases in adults. How cells sense and respond to these mechanical stimuli requires an understanding of the biophysical principles that underlie changes in protein conformation and result in alterations in the organization and function of cells and tissues. Here, we discuss mechano-transduction as it applies to protein conformation, cellular organization, and multi-cell (tissue) function

Rotational levels in quantum dots

Low energy spectra of isotropic quantum dots are calculated in the regime of low electron densities where Coulomb interaction causes strong correlations. The earlier developed pocket state method is generalized to allow for continuous rotations. Detailed predictions are made for dots of shallow confinements and small particle numbers, including the occurance of spin blockades in transport.Comment: RevTeX, 10 pages, 2 figure

A room temperature 19-channel magnetic field mapping device for cardiac signals

We present a multichannel cardiac magnetic field imaging system built in Fribourg from optical double-resonance Cs vapor magnetometers. It consists of 25 individual sensors designed to record magnetic field maps of the beating human heart by simultaneous measurements on a grid of 19 points over the chest. The system is operated as an array of second order gradiometers using sophisticated digitally controlled feedback loops.Comment: 3 pages, 3 figures, submitted to Applied Physics Letter

Galactic Twins of the Ring Nebula Around SN1987A and a Possible LBV-like Phase for Sk-69 202

Some core-collapse supernovae show clear signs of interaction with dense circumstellar material that often appears to be non-spherical. Circumstellar nebulae around supernova progenitors provide clues to the origin of that asymmetry in immediate pre-supernova evolution. Here I discuss outstanding questions about the formation of the ring nebula around SN1987A and some implications of similar ring nebulae around Galactic B supergiants. Several clues hint that SN1987A's nebula may have been ejected in an LBV-like event, rather than through interacting winds in a transition from a red supergiant to a blue supergiant.Comment: 2 pages, to appear in procedings of "Massive stars: fundamental parameters and circumstellar interactions", conference in honor of Virpi Niemela's 70th birthda

Calculations of the Exclusive Processes 2H(e,e'p)n, 3He(e,e'p)2H and 3He(e,e'p)(pn) within a Generalized Glauber Approach

The exclusive processes 2H(e,e'p)n, 3He(e,e'p)2H and 3He(e,e'p)(pn), have been analyzed using realistic few-body wave functions and treating the final state interaction (FSI) within a Generalized Eikonal Approximation (GEA), based upon the direct calculation of the Feynman diagrams describing the rescattering of the struck nucleon with the nucleons of the A-1 system. The approach represents an improvement of the conventional Glauber approach (GA), in that it allows one to take into account the effects of the nuclear excitation of the $A-1$ system on the rescattering of the struck nucleon. Using realistic three-body wave functions corresponding to the AV18 interaction, the results of our parameter free calculations are compared with available experimental data. It is found that in some kinematical conditions FSI effects represent small corrections, whereas in other kinematics conditions they are very large and absolutely necessary to provide a satisfactory agreement between theoretical calculations and experimental data. It is shown that in the kinematics of the experimental data which have been considered, covering the region of missing momentum and energy with p_m < 0.6 GeV/c and E_m < 100 MeV in the perpendicular kinematics, the GA and GEA predictions differ only by less than 3-4 %.Comment: Typos detected and removed while Proof reading. Physical Review C. in Pres

Signatures of electron correlations in the transport properties of quantum dots

The transition matrix elements between the correlated $N$ and $N\!+\!1$ electron states of a quantum dot are calculated by numerical diagonalization. They are the central ingredient for the linear and non--linear transport properties which we compute using a rate equation. The experimentally observed variations in the heights of the linear conductance peaks can be explained. The knowledge of the matrix elements as well as the stationary populations of the states allows to assign the features observed in the non--linear transport spectroscopy to certain transition and contains valuable information about the correlated electron states.Comment: 4 pages (revtex,27kB) + 3 figures in one file ziped and uuencoded (postscript,33kB), to appear in Phys.Rev.B as Rapid Communicatio

Reaching the quantum limit of sensitivity in electron spin resonance

We report pulsed electron-spin resonance (ESR) measurements on an ensemble of Bismuth donors in Silicon cooled at 10mK in a dilution refrigerator. Using a Josephson parametric microwave amplifier combined with high-quality factor superconducting micro-resonators cooled at millikelvin temperatures, we improve the state-of-the-art sensitivity of inductive ESR detection by nearly 4 orders of magnitude. We demonstrate the detection of 1700 bismuth donor spins in silicon within a single Hahn echo with unit signal-to-noise (SNR) ratio, reduced to just 150 spins by averaging a single Carr-Purcell-Meiboom-Gill sequence. This unprecedented sensitivity reaches the limit set by quantum fluctuations of the electromagnetic field instead of thermal or technical noise, which constitutes a novel regime for magnetic resonance.Comment: Main text : 10 pages, 4 figures. Supplementary text : 16 pages, 8 figure

Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy

Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the ‘response to injury' paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloantigen-independent factors include donor-transmitted coronary artery disease, surgical trauma, ischaemia-reperfusion injury, viral infections, hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic advances include the use of novel immunosuppressive agents such as sirolimus (rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular risk factors remains of paramount importanc

A small-molecule antagonist of the β-catenin/TCF4 interaction blocks the self-renewal of cancer stem cells and suppresses tumorigenesis

Wnt/beta-catenin signaling is a highly conserved pathway essential for embryogenesis and tissue homeostasis. However, deregulation of this pathway can initiate and promote human malignancies, especially of the colon and head and neck. Therefore, Wnt/beta-catenin signaling represents an attractive target for cancer therapy. We performed high-throughput screening (HTS) using AlphaScreen and ELISA techniques to identify small molecules that disrupt the critical interaction between beta-catenin and the transcription factor TCF4 required for signal transduction. We found that compound LF3, a 4-thioureido-benzenesulfonamide derivative, robustly inhibited this interaction. Biochemical assays revealed clues that the core structure of LF3 was essential for inhibition. LF3 inhibited Wnt/beta-catenin signals in cells with exogenous reporters and in colon cancer cells with endogenously high Wnt activity. LF3 also suppressed features of cancer cells related to Wnt signaling, including high cell motility, cell cycle progression, and the overexpression of Wnt target genes. However, LF3 did not cause cell death or interfere with cadherin-mediated cell-cell adhesion. Remarkably, the self-renewal capacity of cancer stem cells was blocked by LF3 in concentration-dependent manners, as examined by sphere formation of colon and head and neck cancer stem cells under non-adherent conditions. Finally, LF3 reduced tumor growth and induced differentiation in a mouse xenograft model of colon cancer. Collectively, our results strongly suggest that LF3 is a specific inhibitor of canonical Wnt signaling with anticancer activity that warrants further development for preclinical and clinical studies as a novel cancer therapy