Membrane-protein interactions in mechanosensitive channels

In this paper, we examine the mechanical role of the lipid bilayer in ion channel conformation and function with specific reference to the case of the mechanosensitive channel of large conductance (MscL). In a recent paper (Wiggins and Phillips, 2004), we argued that mechanotransduction very naturally arises from lipid-protein interactions by invoking a simple analytic model of the MscL channel and the surrounding lipid bilayer. In this paper, we focus on improving and expanding this analytic framework for studying lipid-protein interactions with special attention to MscL. Our goal is to generate simple scaling relations which can be used to provide qualitative understanding of the role of membrane mechanics in protein function and to quantitatively interpret experimental results. For the MscL channel, we find that the free energies induced by lipid-protein interaction are of the same order as the free energy differences between conductance states measured by Sukharev et al. (1999). We therefore conclude that the mechanics of the bilayer plays an essential role in determining the conformation and function of the channel. Finally, we compare the predictions of our model to experimental results from the recent investigations of the MscL channel by Perozo et al. (2002), Powl et al. (2003), Yoshimura et al. (2004), and others and suggest a suite of new experiments

A neural network approach to predicting price negotiation outcomes in business-to-business contexts

Price premiums are a key profit driver for long-term business relationships. For sellers in business-to-business (B2B) relationships, it is important to have appropriate strategies to negotiate price increases without trading off the relationships with their buyers. This paper aims to understand the annual price negotiation processes of companies by predicting whether a seller’s reservation price, target price, and initial offer positively affect the price negotiation outcome between the sellers and buyers. Data from 284 B2B relationships of a chemicals supplier based in Germany was used to examine our research model. In order to capture the non-linear decisions that are involved in price negotiations and to address collinearity among negotiations’ determinants, neural network analysis was used to predict the factors that influence price negotiation outcome. The neural network model was then compared with the results from regression analysis. Compared to regression analysis, the neural network has a lower standard error, and it showed that target price played a more important role in B2B price negotiations. The neural network was also able measure non-linear, non-compensatory decisions that are involved in price negotiations. The results imply that neural networks should be more widely used by researchers to address the threats that multi-collinearity poses. For companies, the results imply that price targets should be actively managed, e.g. through clear financial aims or through seminars aiming to help sales personnel to establish more challenging negotiation aims

A discrete geometric approach for simulating the dynamics of thin viscous threads

We present a numerical model for the dynamics of thin viscous threads based on a discrete, Lagrangian formulation of the smooth equations. The model makes use of a condensed set of coordinates, called the centerline/spin representation: the kinematical constraints linking the centerline's tangent to the orientation of the material frame is used to eliminate two out of three degrees of freedom associated with rotations. Based on a description of twist inspired from discrete differential geometry and from variational principles, we build a full-fledged discrete viscous thread model, which includes in particular a discrete representation of the internal viscous stress. Consistency of the discrete model with the classical, smooth equations is established formally in the limit of a vanishing discretization length. The discrete models lends itself naturally to numerical implementation. Our numerical method is validated against reference solutions for steady coiling. The method makes it possible to simulate the unsteady behavior of thin viscous jets in a robust and efficient way, including the combined effects of inertia, stretching, bending, twisting, large rotations and surface tension

Study of Upsilon(3S,2S) -> eta Upsilon(1S) and Upsilon(3S,2S) -> pi+pi- Upsilon(1S) hadronic trasitions

We study the Upsilon(3S,2S)->eta Upsilon(1S) and Upsilon(3S,2S)->pi+pi- Upsilon(1S) transitions with 122 million Upsilon(3S) and 100 million Upsilon(2S) mesons collected by the BaBar detector at the PEP-II asymmetric energy e+e- collider. We measure B[Upsilon(2S)->eta Upsilon(1S)]=(2.39+/-0.31(stat.)+/-0.14(syst.))10^-4 and Gamma[Upsilon(2S)->eta Upsilon(1S)]/Gamma[Upsilon(2S)-> pi+pi- Upsilon(1S)]=(1.35+/-0.17(stat.)+/-0.08(syst.))10^-3. We find no evidence for Upsilon(3S)->eta Upsilon(1S) and obtain B[Upsilon(3S)->eta Upsilon(1S)]<1.0 10^-4 and Gamma[Upsilon(3S)->eta Upsilon(1S)]/Gamma[Upsilon(3S)->pi+pi- Upsilon(1S)]<2.3 10^-3 as upper limits at the 90% confidence level. We also provide improved measurements of the Upsilon(2S) - Upsilon(1S) and Upsilon(3S) - Upsilon(1S) mass differences, 562.170+/-0.007(stat.)+/-0.088(syst.) MeV/c^2 and 893.813+/-0.015(stat.)+/-0.107(syst.) MeV/c^2 respectively.Comment: 8 pages, 16 encapsulated postscript figures, submitted to Phys.Rev.

Evidence for the η_b(1S) Meson in Radiative Υ(2S) Decay

We have performed a search for the η_b(1S) meson in the radiative decay of the Υ(2S) resonance using a sample of 91.6 × 10^6 Υ(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E_γ = 609.3^(+4.6)_(-4.5)(stat)±1.9(syst) MeV, corresponding to an η_b(1S) mass of 9394.2^(+4.8)_(-4.9)(stat) ± 2.0(syst) MeV/c^2. The branching fraction for the decay Υ(2S) → γη_b(1S) is determined to be [3.9 ± 1.1(stat)^(+1.1)_(-0.9)(syst)] × 10^(-4). We find the ratio of branching fractions B[Υ(2S) → γη_b(1S)]/B[Υ(3S) → γη_b(1S)]= 0.82 ± 0.24(stat)^(+0.20)_(-0.19)(syst)

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

The cooperative sex: Sexual interactions among female bonobos are linked to increases in oxytocin, proximity and coalitions

In some species habitual same-sex sexual behavior co-occurs with high levels of intra-sexual alliance formation, suggesting that these behaviors may be linked. We tested for such a link by comparing behavioral and physiological outcomes of sex with unrelated same- and opposite-sex partners in female bonobos (Pan paniscus). We analyzed behavioral outcomes following 971 sexual events involving n = 19 female and n = 8 male adult and sub-adult members of a wild, habituated bonobo community. We additionally collected n = 143 urine samples before and after sexual interactions to non-invasively measure oxytocin (OT), which modulates female sexual behavior and facilitates cooperation in other species. The majority of sexual events (65%) consisted of female same-sex genito-genital rubbing (or GG-rubbing). Female dyads engaged in significantly more sexual interactions than did inter-sexual dyads, and females were more likely to remain within close proximity to their partners following GG-rubbing. Females also exhibited greater increases in urinary OT following GG-rubbing compared with copulations, indicating a physiological basis for increased motivation to cooperate among females. The frequency of coalitionary support among non-kin was positively predicted by the frequency of sexual interactions for female as well opposite-sex dyads, although coalitionary support tended to be more frequent among females. The emergence of habitual same-sex sexual behavior may have been an important step in the evolution of cooperation outside of kinship and pair-bonds in one of our closest phylogenetic relatives

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications

Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype

PURPOSE: DNA methylation plays a fundamental role in the epigenetic control of carcinogenesis and is, in part, influenced by the availability of methyl donors obtained from the diet. In this study, we developed an in-vitro model to investigate whether methyl donor depletion affects the phenotype and gene expression in head and neck squamous cell carcinoma (HNSCC) cells. METHODS: HNSCC cell lines (UD-SCC2 and UPCI-SCC72) were cultured in medium deficient in methionine, folate, and choline or methyl donor complete medium. Cell doubling-time, proliferation, migration, and apoptosis were analysed. The effects of methyl donor depletion on enzymes controlling DNA methylation and the pro-apoptotic factors death-associated protein kinase-1 (DAPK1) and p53 upregulated modulator of apoptosis (PUMA) were examined by quantitative-PCR or immunoblotting. RESULTS: HNSCC cells cultured in methyl donor deplete conditions showed significantly increased cell doubling times, reduced cell proliferation, impaired cell migration, and a dose-dependent increase in apoptosis when compared to cells cultured in complete medium. Methyl donor depletion significantly increased the gene expression of DNMT3a and TET-1, an effect that was reversed upon methyl donor repletion in UD-SCC2 cells. In addition, expression of DAPK1 and PUMA was increased in UD-SCC2 cells cultured in methyl donor deplete compared to complete medium, possibly explaining the observed increase in apoptosis in these cells. CONCLUSION: Taken together, these data show that depleting HNSCC cells of methyl donors reduces the growth and mobility of HNSCC cells, while increasing rates of apoptosis, suggesting that a methyl donor depleted diet may significantly affect the growth of established HNSCC

Why do we treat adolescent idiopathic scoliosis? What we want to obtain and to avoid for our patients. SOSORT 2005 Consensus paper

BACKGROUND: Medicine is a scientific art: once science is not clear, choices are made according to individual and collective beliefs that should be better understood. This is particularly true in a field like adolescent idiopathic scoliosis, where currently does not exist definitive scientific evidence on the efficacy either of conservative or of surgical treatments. AIM OF THE STUDY: To verify the philosophical choices on the final outcome of a group of people believing and engaged in a conservative treatment of idiopathic scoliosis. METHODS: We performed a multifaceted study that included a bibliometric analysis, a questionnaire, and a careful Consensus reaching procedure between experts in the conservative treatment of scoliosis (SOSORT members). RESULTS: The Consensus reaching procedure has shown to be useful: answers changed in a statistically significant way, and 9 new outcome criteria were included. The most important final outcomes were considered Aesthetics (100%), Quality of life and Disability (more than 90%), while more than 80% of preferences went to Back Pain, Psychological well-being, Progression in adulthood, Breathing function, Scoliosis Cobb degrees (radiographic lateral flexion), Needs of further treatments in adulthood. DISCUSSION: In the literature prevail outcome criteria driven by the contingent treatment needs or the possibility to have measurement systems (even if it seems that usual clinical and radiographic methods are given much more importance than more complex Disability or Quality of Life instruments). SOSORT members give importance to a wide range of outcome criteria, in which clinical and radiographic issues have the lowest importance. CONCLUSION: We treat our patients for what they need for their future (Breathing function, Needs of further treatments in adulthood, Progression in adulthood), and their present too (Aesthetics, Disability, Quality of life). Technical matters, such as rib hump or radiographic lateral alignment and rotation, but not lateral flexion, are secondary outcomes and only instrumental to previously reported primary outcomes. We advocate a multidimensional, comprehensive evaluation of scoliosis patients, to gather all necessary data for a complete therapeutic approach, that goes beyond x-rays to reach the person and the family