Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ~5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression

Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits

The accessory olfactory system controls social and sexual behavior. In the mouse accessory olfactory bulb, the first central stage of information processing along the accessory olfactory pathway, projection neurons (mitral cells) display infra-slow oscillatory discharge with remarkable periodicity. The physiological mechanisms that underlie this default output state, however, remain controversial. Moreover, whether such rhythmic infra-slow activity patterns exist in awake behaving mice and whether such activity reflects the functional organization of the accessory olfactory bulb circuitry remain unclear. Here, we hypothesize that mitral cell ensembles form synchronized microcircuits that subdivide the accessory olfactory bulb into segregated functional clusters. We use a miniature microscope to image the Ca2+ dynamics within the apical dendritic compartments of large mitral cell ensembles in vivo. We show that infra-slow periodic patterns of concerted neural activity, indeed, reflect the idle state of accessory olfactory bulb output in awake male and female mice. Ca2+ activity profiles are distinct and glomerulus-specific. Confocal time-lapse imaging in acute slices reveals that groups of mitral cells assemble into microcircuits that exhibit correlated Ca2+ signals. Moreover, electrophysiological profiling of synaptic connectivity indicates functional coupling between mitral cells. Our results suggest that both intrinsically rhythmogenic neurons and neurons entrained by fast synaptic drive are key elements in organizing the accessory olfactory bulb into functional microcircuits, each characterized by a distinct default pattern of infra-slow rhythmicity

Projection methods in conic optimization

There exist efficient algorithms to project a point onto the intersection of a convex cone and an affine subspace. Those conic projections are in turn the work-horse of a range of algorithms in conic optimization, having a variety of applications in science, finance and engineering. This chapter reviews some of these algorithms, emphasizing the so-called regularization algorithms for linear conic optimization, and applications in polynomial optimization. This is a presentation of the material of several recent research articles; we aim here at clarifying the ideas, presenting them in a general framework, and pointing out important techniques

Diet and ovarian cancer risk: a case–control study in China

This case–control study, conducted in Zhejiang, China during 1999–2000, investigated whether dietary factors have an aetiological association with ovarian cancer. Cases were 254 patients with histologically confirmed epithelial ovary cancer. The 652 controls comprised 340 hospital visitors, 261 non-neoplasm hospital outpatients without long-term diet modifications and 51 women recruited from the community. A validated food frequency questionnaire was used to measure the habitual diet of cases and controls. The risks of ovarian cancer for the dietary factors were assessed by adjusted odds ratios based on multivariate logistic regression analysis, accounting for potential confounding demographic, lifestyle, familial factors and hormonal status, family ovarian cancer history and total energy intake. The ovarian cancer risk declined with increasing consumption of vegetables and fruits but vice versa with high intakes of animal fat and salted vegetables. The adjusted upper quartile odds ratio compared to the lower quartile was 0.24 (0.1–0.5) for vegetables, 0.36 (0.2–0.7) for fruits, 4.6 (2.2–9.3) for animal fat and 3.4 (2.0–5.8) for preserved (salted) vegetables with significant dose-response relationship. The risk of ovarian cancer also appeared to increase for those women preferring fat, fried, cured and smoked food

Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer

Background: Prone whole breast irradiation (WBI) leads to reduced heart and lung doses in breast cancer patients receiving adjuvant radiotherapy. In this feasibility trial, we investigated the prone position for whole breast + lymph node irradiation (WB + LNI). Methods: A new support device was developed for optimal target coverage, on which patients are positioned in a position resembling a phase from the crawl swimming technique (prone crawl position). Five left sided breast cancer patients were included and simulated in supine and prone position. For each patient, a treatment plan was made in prone and supine position for WB + LNI to the whole axilla and the unoperated part of the axilla. Patients served as their own controls for comparing dosimetry of target volumes and organs at risk (OAR) in prone versus in supine position. Results: Target volume coverage differed only slightly between prone and supine position. Doses were significantly reduced (P < 0.05) in prone position for ipsilateral lung (Dmean, D2, V5, V10, V20, V30), contralateral lung (Dmean, D2), contralateral breast (Dmean, D2 and for total axillary WB + LNI also V5), thyroid (Dmean, D2, V5, V10, V20, V30), oesophagus (Dmean and for partial axillary WB + LNI also D2 and V5), skin (D2 and for partial axillary WB + LNI V105 and V107). There were no significant differences for heart and humeral head doses. Conclusions: Prone crawl position in WB + LNI allows for good breast and nodal target coverage with better sparing of ipsilateral lung, thyroid, contralateral breast, contralateral lung and oesophagus when compared to supine position. There is no difference in heart and humeral head doses

Estimation and projection of the national profile of cancer mortality in China: 1991–2005

There are no national-level data on cancer mortality in China since two surveys in 1973-1975 and 1990-1992 (a 10% sample), but ongoing surveillance systems, based on nonrandom selected populations, give an indication as to the trends for major cancers. Based on a log-linear regression model with Poisson errors, the annual rates of change for 10 cancers and all other cancers combined, by age, sex and urban/rural residence were estimated from the data of the surveillance system of the Center for Health Information and Statistics, covering about 10% of the national population. These rates of change were applied to the survey data of 1990-1992 to estimate national mortality in the year 2000, and to make projections for 2005. Mortality rates for all cancers combined, adjusted for age, are predicted to change little between 1991 and 2005 (-0.8% in men and +2.5% in women), but population growth and ageing will result in an increasing number of deaths, from 1.2 to 1.8 million. The largest predicted increases are for the numbers of female breast (+155.4%) and lung cancers (+112.1% in men, +153.5% in women). For these two sites, mortality rates will almost double. Cancer will make an increasing contribution to the burden of diseases in China in the 21st century. The marked increases in risk of cancers of the lung, female breast and large bowel indicate priorities for prevention and control. The increasing trends in young age groups for cancers of the cervix, lung and female breast suggest that their predicted increases may be underestimated, and that more attention should be paid to strategies for their prevention and control

New Measurement of Parity Violation in Elastic Electron-Proton Scattering and Implications for Strange Form Factors

We have measured the parity-violating electroweak asymmetry in the elastic scattering of polarized electrons from the proton. The result is A = -15.05 +- 0.98(stat) +- 0.56(syst) ppm at the kinematic point theta_lab = 12.3 degrees and Q^2 = 0.477 (GeV/c)^2. The measurement implies that the value for the strange form factor (G_E^s + 0.392 G_M^s) = 0.025 +- 0.020 +- 0.014, where the first error is experimental and the second arises from the uncertainties in electromagnetic form factors. This measurement is the first fixed-target parity violation experiment that used either a `strained' GaAs photocathode to produce highly polarized electrons or a Compton polarimeter to continuously monitor the electron beam polarization.Comment: 8 pages, 4 figures, Tex, elsart.cls; revised version as accepted for Phys. Lett.

Structural hierarchies define toughness and defect-tolerance despite simple and mechanically inferior brittle building blocks

Mineralized biological materials such as bone, sea sponges or diatoms provide load-bearing and armor functions and universally feature structural hierarchies from nano to macro. Here we report a systematic investigation of the effect of hierarchical structures on toughness and defect-tolerance based on a single and mechanically inferior brittle base material, silica, using a bottom-up approach rooted in atomistic modeling. Our analysis reveals drastic changes in the material crack-propagation resistance (R-curve) solely due to the introduction of hierarchical structures that also result in a vastly increased toughness and defect-tolerance, enabling stable crack propagation over an extensive range of crack sizes. Over a range of up to four hierarchy levels, we find an exponential increase in the defect-tolerance approaching hundred micrometers without introducing additional mechanisms or materials. This presents a significant departure from the defect-tolerance of the base material, silica, which is brittle and highly sensitive even to extremely small nanometer-scale defects