Catalytically active peptide–gold nanoparticle conjugates: Prospecting for artificial enzymes

The self‐assembly of peptides onto the surface of gold nanoparticles has emerged as a promising strategy towards the creation of artificial enzymes. The resulting high local peptide density surrounding the nanoparticle leads to cooperative and synergistic effects, which result in rate accelerations and distinct catalytic properties compared to the unconjugated peptide. This Minireview summarizes contributions to and progress made in the field of catalytically active peptide–gold nanoparticle conjugates. The origin of distinct properties, as well as potential applications, are also discussed

Coassembly Generates Peptide Hydrogel with Wound Dressing Material Properties

Multicomponent self-assembly of peptides is a powerful strategy to fabricate novel functional materials with synergetic properties that can be used for several nanobiotechnological applications. In the present study, we used a coassembly strategy to generate an injectable ultrashort bioactive peptide hydrogel formed by mixing a dipeptide hydrogelator with a macrophage attracting short chemotactic peptide ligand. Coassembly does not impede hydrogelation as shown by cryo-transmission electron microscopy (cryo-TEM), scanning electron microscopy, and rheology. Biocompatibility was shown by cytotoxicity assays and confocal microscopy. The hydrogels release the entrapped skin antibiotic ciprofloxacin, among others, in a slow and continuous manner. Such bioinspired advanced functional materials can find applications as wound dressing materials to treat chronic wound conditions like diabetic foot ulcer

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

Testing maximal electron and muon neutrino oscillations with sub-GeV SuperKamiokande atmospheric neutrino data

Motivated by the Exact Parity Model and other theories, the hypothesis that each of the known neutrinos oscillates maximally with a sterile partner has been put forward as an explanation of the atmospheric and solar neutrino anomalies. We provide detailed predictions for muon and electron flux ratios induced in the Kamiokande and SuperKamiokande detectors by sub-GeV atmospheric neutrinos. Several different, carefully chosen cuts on momentum and zenith angle are proposed, emphasizing the role of up-down flux asymmetries.Comment: LaTeX, 8 figures, 17 pages, version to appear in Phys. Rev. D Rapid Communication

Are Messages of R-parity Violating Supersymmetry Hidden within Top Quark Signals ?

In an R-parity nonconserving supersymmetric theory, the lighter stop can dominantly decay into $b\mu$ and $b\tau$ if R-parity breaking has to explain the neutrino mass and mixing pattern suggested by the data on atmospheric muon neutrinos. This should give rise to $dilepton+dijet$ and $single-lepton+jets$, signals resembling those of the top quark at the Fermilab Tevatron. One can thus constrain the stop parameter space using the current top search data, and similarly look for the first signals of supersymmetry at the upgraded runs of the Tevatron.Comment: 13 pages, RevTeX, 2 PS figures, uses epsfig.sty, few comments and references added, version to appear in Phys. Rev. Let

Neutron- and muon-induced background in underground physics experiments

Background induced by neutrons in deep underground laboratories is a critical issue for all experiments looking for rare events, such as dark matter interactions or neutrinoless 2-beta decay. Neutrons can be produced either by natural radioactivity, via spontaneous fission or (alpha,n) reactions, or by interactions initiated by high-energy cosmic rays. In all underground experiments, Monte Carlo simulations of neutron background play a crucial role for the evaluation of the total background rate and for the optimization of rejection strategies. The Monte Carlo methods that are commonly employed to evaluate neutron-induced background and to optimize the experimental setup, are reviewed and discussed. Focus is given to the issue of reliability of Monte Carlo background estimates.Comment: 10 pages, 8 figures. Presented in the IV ILIAS Annual Meeting. Accepted for publication on EPJ

Comparing and contrasting the νμ→ντ\nu_{\mu} \to \nu_{\tau} and νμ→νs\nu_{\mu} \to \nu_s solutions to the atmospheric neutrino problem with SuperKamiokande data

The $\nu_{\mu} \to \nu_{\tau}$ and $\nu_{\mu} \to \nu_s$ solutions to the atmospheric neutrino problem are compared with SuperKamiokande data. The differences between these solutions due to matter effects in the Earth are calculated for the ratio of $\mu$-like to $e$-like events and for up-down flux asymmetries. These quantities are chosen because they are relatively insensitive to theoretical uncertainties in the overall neutrino flux normalisation and detection cross-sections and efficiencies. A $\chi^2$ analysis using these quantities is performed yielding $3\sigma$ ranges which are approximately given by $(0.725 - 1.0, 4 \times 10^{-4} - 2 \times 10^{-2} eV^2)$ and $(0.74 - 1.0, 1 \times 10^{-3} - 2 \times 10^{-2} eV^2)$ for $(\sin^2 2\theta,\Delta m^2)$ for the $\nu_{\mu} \to \nu_{\tau}$ and $\nu_{\mu} \to \nu_s$ solutions, respectively. Values of $\Delta m^2$ smaller than about $2 \times 10^{-3}$ eV$^2$ are disfavoured for the $\nu_{\mu} \to \nu_s$ solution, suggesting that future long baseline experiments should see a positive signal if this scenario is the correct one.Comment: revtex, 22 pages, 12 figure

Solutions of the atmospheric, solar and LSND neutrino anomalies from TeV scale quark-lepton unification

There is a unique $SU(4) \otimes SU(2)_L \otimes SU(2)_R$ gauge model which allows quarks and leptons to be unified at the TeV scale. It is already known that the neutrino masses arise radiatively in the model and are naturally light. We study the atmospheric, solar and LSND neutrino anomalies within the framework of this model.Comment: Minor changes, 31 page

Parameterization-based tracking for the P2 experiment

The P2 experiment in Mainz aims to determine the weak mixing angle θW at low momentum transfer by measuring the parity-violating asymmetry of elastic electronproton scattering. In order to achieve the intended precision of Δ(sin2 θW)/sin2θW = 0:13% within the planned 10 000 hours of running the experiment has to operate at the rate of 1011 detected electrons per second. Although it is not required to measure the kinematic parameters of each individual electron, every attempt is made to achieve the highest possible throughput in the track reconstruction chain. In the present work a parameterization-based track reconstruction method is described. It is a variation of track following, where the results of the computation-heavy steps, namely the propagation of a track to the further detector plane, and the fitting, are pre-calculated, and expressed in terms of parametric analytic functions. This makes the algorithm extremely fast, and well-suited for an implementation on an FPGA. The method also takes implicitly into account the actual phase space distribution of the tracks already at the stage of candidate construction. Compared to a simple algorithm, that does not use such information, this allows reducing the combinatorial background by many orders of magnitude, down to O(1) background candidate per one signal track. The method is developed specifically for the P2 experiment in Mainz, and the presented implementation is tightly coupled to the experimental conditions

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands