Coarse-grained model of tropoelastin self-assembly into nascent fibrils.

Elastin is the dominant building block of elastic fibers that impart structural integrity and elasticity to a range of important tissues, including the lungs, blood vessels, and skin. The elastic fiber assembly process begins with a coacervation stage where tropoelastin monomers reversibly self-assemble into coacervate aggregates that consist of multiple molecules. In this paper, an atomistically based coarse-grained model of tropoelastin assembly is developed. Using the previously determined atomistic structure of tropoelastin, the precursor molecule to elastic fibers, as the basis for coarse-graining, the atomistic model is mapped to a MARTINI-based coarse-grained framework to account for chemical details of protein-protein interactions, coupled to an elastic network model to stabilize the structure. We find that self-assembly of monomers generates up to ∼70 â€‹nm of dense aggregates that are distinct at different temperatures, displaying high temperature sensitivity. Resulting assembled structures exhibit a combination of fibrillar and globular substructures within the bulk aggregates. The results suggest that the coalescence of tropoelastin assemblies into higher order structures may be reinforced in the initial stages of coacervation by directed assembly, supporting the experimentally observed presence of heterogeneous cross-linking. Self-assembly of tropoelastin is driven by interactions of specific hydrophobic domains and the reordering of water molecules in the system. Domain pair orientation analysis throughout the self-assembly process at different temperatures suggests coacervation is a driving force to orient domains for heterogeneous downstream cross-linking. The model provides a framework to characterize macromolecular self-assembly for elastin, and the formulation could easily be adapted to similar assembly systems.

Inclusive Production of the X(4140) State in pp[over ¯] Collisions at D0.

We present a study of the inclusive production of the X(4140) state with the decay to the J/ψϕ final state in hadronic collisions. Based on 10.4 fb^{-1} of pp[over ¯] collision data collected by the D0 experiment at the Fermilab Tevatron collider, we report the first evidence for the prompt production of an X(4140) state and find the fraction of X(4140) events originating from b hadrons to be f_{b}=0.39±0.07(stat)±0.10(syst). The ratio of the nonprompt X(4140) production rate to the B_{s}^{0} yield in the same channel is R=0.19±0.05(stat)±0.07(syst). The values of the mass M=4152.5±1.7(stat)_{-5.4}^{+6.2}(syst) MeV and width Γ=16.3±5.6(stat)±11.4(syst) MeV are consistent with previous measurements.

Search for Violation of CPT and Lorentz Invariance in Bs(0) Meson Oscillations.

We present the first search for CPT-violating effects in the mixing of Bs(0) mesons using the full Run II data set with an integrated luminosity of 10.4 fb(-1) of proton-antiproton collisions collected using the D0 detector at the Fermilab Tevatron Collider. We measure the CPT-violating asymmetry in the decay Bs(0)→µ(±)Ds(±) as a function of celestial direction and sidereal phase. We find no evidence for CPT-violating effects and place limits on the direction and magnitude of flavor-dependent CPT- and Lorentz-invariance violating coupling coefficients. We find 95% confidence intervals of Δa⊥<1.2×10(-12) GeV and (-0.8<ΔaT-0.396ΔaZ<3.9)×10(-13) GeV.

Structure-mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model.

The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry.

Measurement of the Effective Weak Mixing Angle in pp[over ¯]→Z/γ

We present a measurement of the fundamental parameter of the standard model, the weak mixing angle sin^{2}θ_{eff}^{ℓ} which determines the relative strength of weak and electromagnetic interactions, in pp[over ¯]→Z/γ^{*}→e^{+}e^{-} events at a center of mass energy of 1.96 TeV, using data corresponding to 9.7 fb^{-1} of integrated luminosity collected by the D0 detector at the Fermilab Tevatron. The effective weak mixing angle is extracted from the forward-backward charge asymmetry as a function of the invariant mass around the Z boson pole. The measured value of sin^{2}θ_{eff}^{ℓ}=0.23147±0.00047 is the most precise measurement from light quark interactions to date, with a precision close to the best LEP and SLD results.

Measurement of the forward-backward asymmetry in the production of B(±) mesons in pp̄ collisions at √s=1.96 TeV.

We present a measurement of the forward-backward asymmetry in the production of B(±) mesons, A(FB)(B(±)), using B(±)→J/ψK(±) decays in 10.4 fb(-1) of pp̄ collisions at sqrt[s]=1.96 TeV collected by the D0 experiment during Run II of the Tevatron collider. A nonzero asymmetry would indicate a preference for a particular flavor, i.e., b quark or ̄b antiquark, to be produced in the direction of the proton beam. We extract A(FB)(B(±)) from a maximum likelihood fit to the difference between the numbers of forward- and backward-produced B(±) mesons. We measure an asymmetry consistent with zero: A(FB)(B(±))=[-0.24±0.41 (stat)±0.19 (syst)]%.

Measurement of the B(s)(0) lifetime in the flavor-specific decay channel B(s)(0)→D(s)(-)µ(+)νX.

We present an updated measurement of the B(s)(0) lifetime using the semileptonic decays B(s)(0)→D(s)(-)µ(+)νX, with D(s)(-)→ϕπ(-) and ϕ→K(+)K(-) (and the charge conjugate process). This measurement uses the full Tevatron Run II sample of proton-antiproton collisions at √[s]=1.96 TeV, comprising an integrated luminosity of 10.4 fb(-1). We find a flavor-specific lifetime τ(fs)(B(s)(0))=1.479±0.010(stat)±0.021(syst) ps. This technique is also used to determine the B(0) lifetime using the analogous B(0)→D(-)µ(+)νX decay with D(-)→ϕπ(-) and ϕ→K(+)K(-), yielding τ(B(0))=1.534±0.019(stat)±0.021(syst) ps. Both measurements are consistent with the current world averages, and the B(s)(0) lifetime measurement is one of the most precise to date. Taking advantage of the cancellation of systematic uncertainties, we determine the lifetime ratio τ(fs)(B(s)(0))/τ(B(0))=0.964±0.013(stat)±0.007(syst).

Constraints on models for the Higgs boson with exotic spin and parity in VH → Vbb final states.

We present constraints on models containing non-standard-model values for the spin J and parity P of the Higgs boson H in up to 9.7 fb(-1) of pp collisions at sqrt[s] = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. These are the first studies of Higgs boson J(P) with fermions in the final state. In the ZH → ℓℓbb, WH → ℓνbb, and ZH → ννbb final states, we compare the standard model (SM) Higgs boson prediction, J(P) = 0(+), with two alternative hypotheses, J(P) = 0(-) and J(P) = 2(+). We use a likelihood ratio to quantify the degree to which our data are incompatible with non-SM J(P) predictions for a range of possible production rates. Assuming that the production rate in the signal models considered is equal to the SM prediction, we reject the J(P) = 0(-) and J(P) = 2(+) hypotheses at the 97.6% CL and at the 99.0% CL, respectively. The expected exclusion sensitivity for a J(P) = 0(-) (J(P) = 2(+)) state is at the 99.86% (99.94%) CL. Under the hypothesis that our data are the result of a combination of the SM-like Higgs boson and either a J(P) = 0(-) or a J(P) = 2(+) signal, we exclude a J(P) = 0(-) fraction above 0.80 and a J(P) = 2(+) fraction above 0.67 at the 95% CL. The expected exclusion covers J(P) = 0(-) (J(P) = 2(+)) fractions above 0.54 (0.47).

Combinatorial molecular optimization of cement hydrates.

Despite its ubiquitous presence in the built environment, concrete's molecular-level properties are only recently being explored using experimental and simulation studies. Increasing societal concerns about concrete's environmental footprint have provided strong motivation to develop new concrete with greater specific stiffness or strength (for structures with less material). Herein, a combinatorial approach is described to optimize properties of cement hydrates. The method entails screening a computationally generated database of atomic structures of calcium-silicate-hydrate, the binding phase of concrete, against a set of three defect attributes: calcium-to-silicon ratio as compositional index and two correlation distances describing medium-range silicon-oxygen and calcium-oxygen environments. Although structural and mechanical properties correlate well with calcium-to-silicon ratio, the cross-correlation between all three defect attributes reveals an indentation modulus-to-hardness ratio extremum, analogous to identifying optimum network connectivity in glass rheology. We also comment on implications of the present findings for a novel route to optimize the nanoscale mechanical properties of cement hydrate.

Precision measurement of the top quark mass in lepton + jets final States.

We measure the mass of the top quark in lepton+jets final states using the full sample of pp collision data collected by the D0 experiment in Run II of the Fermilab Tevatron Collider at sqrt[s] = 1.96 TeV, corresponding to 9.7 fb(-1) of integrated luminosity. We use a matrix element technique that calculates the probabilities for each event to result from tt production or background. The overall jet energy scale is constrained in situ by the mass of the W boson. We measure m(t) = 174.98 ± 0.76 GeV. This constitutes the most precise single measurement of the top-quark mass.

Measurement of the W boson production charge asymmetry in pp̄→W+X→eν+X events at √s=1.96 TeV.

We present a measurement of the W boson production charge asymmetry in pp̄→W+X→eν+X events at a center of mass energy of 1.96 TeV, using 9.7 fb-1 of integrated luminosity collected with the D0 detector at the Fermilab Tevatron Collider. The neutrino longitudinal momentum is determined by using a neutrino weighting method, and the asymmetry is measured as a function of the W boson rapidity. The measurement extends over wider electron pseudorapidity region than previous results and is the most precise to date, allowing for precise determination of proton parton distribution functions in global fits.

Measurement of the direct CP-violating charge asymmetry in Ds ± → ϕ π ± decays.

We present a measurement of the direct CP-violating charge asymmetry in Ds+ → ϕ π(±) decays where the ϕ meson decays to K(+)K(-), using the full Run II data set with an integrated luminosity of 10.4 fb-1 of proton-antiproton collisions collected using the D0 detector at the Fermilab Tevatron Collider. The normalized difference A(CP) in the yield of D(s)(+) and D(s)(-) mesons in these decays is measured by fitting the difference between their reconstructed invariant mass distributions. This results in an asymmetry of A(CP) = [-0.38 ± 0.27]%, which is the most precise measurement of this quantity to date. The result is consistent with the standard model prediction of zero CP asymmetry in this decay.

Measurement of associated production of z bosons with charm quark jets in pp collisions at √s=1.96 TeV.

We present the first measurements of the ratios of cross sections σ(pp → Z+c jet)/σ(pp → Z+jet) and σ(pp → Z+c jet)/σ(pp → Z+b jet) for the associated production of a Z boson with at least one charm or bottom quark jet. Jets have transverse momentum ​pT(jet)​>20 GeV and pseudorapidity |​η(jet)​|<2.5. These cross section ratios are measured differentially as a function of jet and Z boson transverse momenta, based on 9.7 fb(-1) of pp collisions collected with the D0 detector at the Fermilab Tevatron Collider at √s=1.96 TeV. The measurements show significant deviations from perturbative QCD calculations and predictions from various event generators.

Measurement of direct CP violation parameters in B± → J/ψK± and B± → J/ψπ± decays with 10.4 fb-1 of Tevatron data.

We present a measurement of the direct CP-violating charge asymmetry in B(±) mesons decaying to J/ψK(±) and J/ψπ(±) where J/ψ decays to µ(+) µ(-), using the full run II data set of 10.4 fb(-1) of proton-antiproton collisions collected using the D0 detector at the Fermilab Tevatron Collider. A difference in the yield of B(-) and B(+) mesons in these decays is found by fitting to the difference between their reconstructed invariant mass distributions resulting in asymmetries of A(J/ψK) = [0.59 ± 0.37]%, which is the most precise measurement to date, and A(J/ψπ) = [-4.2 ± 4.5]%. Both measurements are consistent with standard model predictions.

Vascularized free tissue transfer for reconstruction of ablative defects in oral and oropharyngeal cancer patients undergoing salvage surgery following concomitant chemoradiation.

The purpose of this study was to determine whether chemotherapy delivered concurrently with external beam radiation therapy for loco-regionally advanced head and neck cancer affects the rate or severity of postoperative complications in patients who underwent salvage surgery for recurrent or persistent disease with simultaneous microvascular free flap reconstruction. The primary study group consisted of patients with head and neck malignancies that had undergone surgical salvage with microvascular free flap reconstruction for persistent or recurrent disease following definitive radiation or concomitant chemoradiation treatment. A group of demographically matched patients who underwent microvascular free flap reconstruction for non-malignant and malignant conditions who never received radiation were randomly selected to serve as a control group. The study cohort was divided according to radiation treatment. The overall success rate of flap reconstruction was 92%, with an overall complication rate of 23%. Concurrently administered chemotherapy did not appear to affect the type of or the complication rate. The results of this investigation indicate that microvascular free flap reconstruction of head and neck defects is highly predictable, results in relatively few major complications, and suggests that neither radiation alone nor concomitant chemoradiation has a statistically significant effect on overall flap survival or complication rate.

A proposed mechanism for autism: an aberrant neuroimmune response manifested as a psychiatric disorder.

Autism, an incurable neurodevelopmental brain disorder, is a complex psychopathology in which the affected individual cannot effectively self-regulate their sensory inputs toward coherent and focused motor outputs. There have been many hypotheses as to the etiology of autism - genetics, neurotransmitter imbalances, early childhood immunizations, xenobiotic and teratogenic agents, and maternal infection; the disorder can perhaps be studied best under the field of "Psychoneuroimmunology", which analyzes systemic and psychopathologies from an integrated approach through the combined effects of the nervous, immune, and endocrine systems. Using principles of psychoneuroimmunology along with previously established but yet un-linked scientific principles and observations, this paper proposes a neuroimmune-based mechanistic hypothesis for the etiology of autism that connects elevated levels of maternal pro-inflammatory cytokines to autistic symptoms in her offspring through a logical sequence of events. While both researchers and clinicians often note correlations between pro-inflammatory cytokine levels and autistic symptoms in affected individuals, no specific mechanism has been documented that logically and directly connects the two. I propose that pro-inflammatory cytokines arising from maternal inflammation, infection, and, possibly, autoimmunity, pass through the placenta; enter the fetal circulation; cross the fetal blood-brain barrier (BBB); and cause aberrant neuronal growth and plasticity within the fetal brain via a "cytokine-storm". Microglia and astrocyte stimulation lead to a positive-feedback loop that also facilitates the development of a chronic inflammatory environment within the fetus, pre-disposing it to lifelong comorbid psychiatric and systemic pathologies. Such a mechanism could account for many of the observed symptoms and behaviors of autistic individuals such as hyper-sensitivity to environmental stimuli, object fixation, echolalia, repetitive physical behaviors, chronic enterocolitis, autoimmune disease, and, at the extreme, savantism. The thiazolidinedione pioglitazone (and possibly rosiglitazone), a non-steroidal anti-inflammatory drug (NSAID), which is commonly used to lower blood glucose levels and associated inflammatory markers in patients with diabetes, and histamine receptor blockers, as well as monitoring and limiting sucrose-containing foods, might prove to be effective preventative therapies for the development of autism in the fetus for pregnant women displaying either a cytokine-induced depression or other elevated systemic inflammatory state conditions.

In vitro effects of bethanechol on smooth muscle preparations from abomasal fundus, corpus, and antrum of dairy cows.

Abomasal displacement has been associated with gastric hypomotility. The supply of prokinetic drugs available to address this problem is insufficient. The goal of the study was to investigate the effect of the muscarinic agonist bethanechol (BeCh) on contractility parameters of smooth muscle preparations from several regions of the bovine abomasum (fundus, corpus, and antrum). Cumulative concentration-response curves were constructed using BeCh in vitro with and without pre-incubation with antagonists targeted at M(2) and M(3) muscarinic acetylcholine receptor (mAChR) subtypes. In all preparations investigated, BeCh induced a significant and concentration-dependent increase in all contractility parameters investigated. The maximal attainable effect (V(max)) was more pronounced in circular specimens, and V(max) of antral specimens in circular orientation were significantly lower when compared to the other preparations. Both antagonists caused a rightward shift of the concentration-response curve, suggesting that the effect of BeCh is mediated at least partly by M(2) and M(3) AChRs.

Investigation of water and ice by ac impedance using electrochemical properties cup.

Water and ice were investigated by ac impedance with the electrochemical properties cup in an effort to develop an in situ instrument for water characterization. In liquid water, the impedance modulus decreased with the increase in charge carriers. In the ice, the impedance measurements were characterized by the dielectric relaxation and its corresponding activation energy. The activation energy of 0.400 eV was determined for pure ice. With ice containing Cl(-) anions, the activation energy was 0.24 eV. H(+) and OH(-) doped ice has the lowest activation energy for dielectric relaxation. Results from previous works are similar to the results reported in this study.