Crystal Structure Analysis of the Polysialic Acid Specific O-Acetyltransferase NeuO

The major virulence factor of the neuroinvasive pathogen Escherichia coli K1 is the K1 capsule composed of α2,8-linked polysialic acid (polySia). K1 strains harboring the CUS-3 prophage modify their capsular polysaccharide by phase-variable O-acetlyation, a step that is associated with increased virulence. Here we present the crystal structure of the prophage-encoded polysialate O-acetyltransferase NeuO. The homotrimeric enzyme belongs to the left-handed β-helix (LβH) family of acyltransferases and is characterized by an unusual funnel-shaped outline. Comparison with other members of the LβH family allowed the identification of active site residues and proposal of a catalytic mechanism and highlighted structural characteristics of polySia specific O-acetyltransferases. As a unique feature of NeuO, the enzymatic activity linearly increases with the length of the N-terminal poly-ψ-domain which is composed of a variable number of tandem copies of an RLKTQDS heptad. Since the poly-ψ-domain was not resolved in the crystal structure it is assumed to be unfolded in the apo-enyzme

Efficacy and Safety of a Low-level Laser Device in the Treatment of Male and Female Pattern Hair Loss: A Multicenter, Randomized, Sham Device-controlled, Double-blind Study

Significance Male and female pattern hair loss are common, chronic dermatologic disorders with limited therapeutic options. In recent years, a number of commercial devices using low-level laser therapy have been promoted, but there have been little peer-reviewed data on their efficacy. Objective: To determine whether treatment with a low-level laser device, the US FDA-cleared HairMax Lasercomb®, increases terminal hair density in both men and women with pattern hair loss. Methods: Randomized, sham device-controlled, double-blind clinical trials were conducted at multiple institutional and private practices. A total of 146 male and 188 female subjects with pattern hair loss were screened. A total of 128 male and 141 female subjects were randomized to receive either a lasercomb (one of three models) or a sham device in concealed sealed packets, and were treated on the whole scalp three times a week for 26 weeks. Terminal hair density of the target area was evaluated at baseline and at 16- and 26-week follow-ups, and analyzed to determine whether the hypothesis formulated prior to data collection, that lasercomb treatment would increase terminal hair density, was correct. The site investigators and the subjects remained blinded to the type of device they dispensed/received throughout the study. The evaluator of masked digital photographs was blinded to which trial arm the subject belonged. Results: Seventy-eight, 63, 49, and 79 subjects were randomized in four trials of 9-beam lasercomb treatment in female subjects, 12-beam lasercomb treatment in female subjects, 7-beam lasercomb treatment in male subjects, and 9- and 12-beam lasercomb treatment in male subjects, compared with the sham device, respectively. Nineteen female and 25 male subjects were lost to follow-up. Among the remaining 122 female and 103 male subjects in the efficacy analysis, the mean terminal hair count at 26 weeks increased from baseline by 20.2, 20.6, 18.4, 20.9, and 25.7 per cm2 in 9-beam lasercomb-treated female subjects, 12-beam lasercomb-treated female subjects, 7-beam lasercomb-treated male subjects, and 9- and 12-beam lasercomb-treated male subjects, respectively, compared with 2.8 (p < 0.0001), 3.0 (p < 0.0001), 1.6 (p = 0.0017), 9.4 (p = 0.0249), and 9.4 (p = 0.0028) in sham-treated subjects (95 % confidence interval). The increase in terminal hair density was independent of the age and sex of the subject and the lasercomb model. Additionally, a higher percentage of lasercomb-treated subjects reported overall improvement of hair loss condition and thickness and fullness of hair in self-assessment, compared with sham-treated subjects. No serious adverse events were reported in any subject receiving the lasercomb in any of the four trials. Conclusions and relevance We observed a statistically significant difference in the increase in terminal hair density between lasercomb- and sham-treated subjects. No serious adverse events were reported. Our results suggest that low-level laser treatment may be an effective option to treat pattern hair loss in both men and women. Additional studies should be considered to determine the long-term effects of low-level laser treatment on hair growth and maintenance, and to optimize laser modality

Indications for Factorization and ReVub<0Re V_{ub} < 0 from Rare B Decay Data

Surveying known hadronic rare B decays, we find that the factorization approximation can give a coherent account of $K\pi$, $\pi\pi$ and $\rho^0\pi^+$ data and give predictions for $\omega^0\pi^+$, $\rho\pi$ and $K^*\pi$ modes, {\it if ${Re}V_{ub}$ is taken as negative} (in standard phase convention) rather than positive. As further confirmation, we expect a lower $\sin2\beta$ value at B Factories as compared to current fits, and $B_s$ mixing close to LEP bounds at SLD and CDF.Comment: 11 pages, revtex, 4 figures (unchanged and eps files included); version (including title and abstract change) to appear in Phys. Rev. Let

Phenomenological Study of Strong Decays of Heavy Hadrons in Heavy Quark Effective Theory

The application of the tensor formalism of the heavy quark effective theory (HQET) at leading order to strong decays of heavy hadrons is presented. Comparisons between experimental and theoretical predictions of ratios of decay rates for B mesons, D mesons and kaons are given. The application of HQET to strange mesons presents some encouraging results. The spin-flavor symmetry is used to predict some decay rates that have not yet been measured.Comment: 10 page

Heavy Baryon Production and Decay

The branching ratio B(Lambda_c -> p K- pi+) normalizes the production and decay of charmed and bottom baryons. At present, this crucial branching ratio is extracted dominantly from B.bar -> baryons analyses. This note questions several of the underlying assumptions and predicts sizable B.bar -> D(*) N N'.bar X transitions, which were traditionally neglected. It predicts B(Lambda_c -> p K- pi+) to be significantly larger (0.07 +/- 0.02) than the world average. Some consequences are briefly mentioned. Several techniques to measure B(Lambda_c -> p K- pi+) are outlined with existing or soon available data samples. By equating two recent CLEO results, an appendix obtains B(D0 -> K- pi+)= 0.035 +/- 0.002, which is somewhat smaller than the current world average.Comment: 27 pages, 4 eps figures, revte

Lorecivivint, a Novel Intraarticular CDC‐like Kinase 2 and Dual‐Specificity Tyrosine Phosphorylation‐Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162805/2/art41315_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162805/1/art41315.pd

Constraints on R-parity violating supersymmetry from leptonic and semileptonic tau, B_d and B_s decays

We put constraints on several products of R-parity violating lambda lambda' and lambda' lambda' type couplings from leptonic and semileptonic tau, B_d and B_s decays. Most of them are one to two orders of magnitude better than the existing bounds, and almost free from theoretical uncertainties. A significant improvement of these bounds can be made in high luminosity tau-charm or B factories.Comment: 14 pages, latex. A few references added, two typos corrected. Version to be published in Physical Review

B→ϕπB\to \phi \pi and B0→ϕϕB^0 \to \phi\phi in the Standard Model and new bounds on R parity violation

We study the pure penguin decays $B \to \phi\pi$ and $B^0 \to \phi\phi$. Using QCD factorization, we find ${\cal B}(B^\pm \to\phi\pi^{\pm} )=2.0^{+0.3}_{-0.1}\times 10^{-8}$. For the pure penguin annihilation process $B^0 \to \phi\phi$, analyzed here for the first time, ${\cal B}(B^0 \to\phi\phi)=2.1^{+1.6}_{-0.3}\times 10^{-9}$. The smallness of these decays in the Standard Model makes them sensitive probes for new physics. From the upper limit of $B\to \phi\pi$,we find constraints on R parity violating couplings, $| \lambda{''}_{i23}\lambda{''}_{i21}|<6\times10^{-5}$, $| \lambda'_{i23}\lambda'_{i21}|<4\times10^{-4}$ and $| \lambda'_{i32}\lambda'_{i12}|<4\times10^{-4}$ for $i=1,2,3$. Our new bounds on $|\lambda{''}_{i23}\lambda{''}_{i21}|$ are one order of magnitude stronger than before. Within the available upper bounds for $| \lambda{''}_{i23}\lambda{''}_{i21}|$, $|\lambda'_{i23}\lambda'_{i21}|$ and $|\lambda'_{i32}\lambda'_{i12}|$, we find that ${\cal B}(B\to\phi\phi)$ could be enhanced to $10^{-8}\sim 10^{-7}$. Experimental searches for these decays are strongly urged.Comment: 5 pages, 3 figures embede

Analysis of Neutral Higgs-Boson Contributions to the Decays B_s -> l^+l^- and B -> K l^+l^-

We report on a calculation of Higgs-boson contributions to the decays B_s -> l^+l^- and B -> K l^+l^- (l=e, mu) which are governed by the effective Hamiltonian describing b -> s l^+ l^-. Compact formulae for the Wilson coefficients are provided in the context of the type-II two-Higgs-doublet model (2HDM) and supersymmetry (SUSY) with minimal flavour violation, focusing on the case of large tan(beta). We derive, in a model-independent way, constraints on Higgs-boson-mediated interactions, using present experimental results on rare B decays including b -> s gamma, B_s -> mu^+ mu^-, and B -> K^(*) mu^+ mu^-. In particular, we assess the impact of possible scalar and pseudoscalar interactions transcending the standard model (SM) on the branching ratio of B_s -> mu^+ mu^- and the forward-backward (FB) asymmetry of mu^- in B -> K mu^+ mu^- decay. We find that the average FB asymmetry, which is unobservably small within the SM, and therefore a potentially valuable tool to search for new physics, is predicted to be no greater than 4% for a nominal branching ratio of about 6x10^{-7}. Moreover, striking effects on the decay spectrum of B -> K mu^+ mu^- are already ruled out by experimental data on the B_s -> mu^+ mu^- branching fraction. In addition, we study the constraints on the parameter space of the 2HDM and SUSY with minimal flavour violation. While the type-II 2HDM does not give any sizable contributions to the above decay modes, we find that SUSY contributions obeying the constraint on b -> s gamma can affect significantly the branching ratio of B_s -> mu^+ mu^-. We also comment on previous calculations contained in the literature.Comment: 29 pages, REVTeX, 8 figures. Minor corrections in Eqs. (5.4), (5.11) and (6.3) of the published versio