Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

First Digit Distribution of Hadron Full Width

A phenomenological law, called Benford's law, states that the occurrence of the first digit, i.e., $1,2,...,9$, of numbers from many real world sources is not uniformly distributed, but instead favors smaller ones according to a logarithmic distribution. We investigate, for the first time, the first digit distribution of the full widths of mesons and baryons in the well defined science domain of particle physics systematically, and find that they agree excellently with the Benford distribution. We also discuss several general properties of Benford's law, i.e., the law is scale-invariant, base-invariant, and power-invariant. This means that the lifetimes of hadrons follow also Benford's law.Comment: 8 latex pages, 4 figures, final version in journal publicatio

Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results

We consider one of the most important problems in directional statistics, namely the problem of testing the null hypothesis that the spike direction $\theta$ of a Fisher-von Mises-Langevin distribution on the $p$-dimensional unit hypersphere is equal to a given direction $\theta_0$. After a reduction through invariance arguments, we derive local asymptotic normality (LAN) results in a general high-dimensional framework where the dimension $p_n$ goes to infinity at an arbitrary rate with the sample size $n$, and where the concentration $\kappa_n$ behaves in a completely free way with $n$, which offers a spectrum of problems ranging from arbitrarily easy to arbitrarily challenging ones. We identify various asymptotic regimes, depending on the convergence/divergence properties of $(\kappa_n)$, that yield different contiguity rates and different limiting experiments. In each regime, we derive Le Cam optimal tests under specified $\kappa_n$ and we compute, from the Le Cam third lemma, asymptotic powers of the classical Watson test under contiguous alternatives. We further establish LAN results with respect to both spike direction and concentration, which allows us to discuss optimality also under unspecified $\kappa_n$. To investigate the non-null behavior of the Watson test outside the parametric framework above, we derive its local asymptotic powers through martingale CLTs in the broader, semiparametric, model of rotationally symmetric distributions. A Monte Carlo study shows that the finite-sample behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure

Insulin adsorption to catheter materials used for intensive insulin therapy in critically ill patients: Polyethylene versus polyurethane - possible cause of variation in glucose control?

Introduction: Restoring and maintaining normoglycemia by intensified insulin therapy in critically ill patients is a matter of ongoing debate since the risk of hypoglycemia may outweigh positive effects on morbidity and mortality. In this context, adsorption of insulin to different catheter materials may contribute to instability of glucose control. We studied the adsorption of insulin to different tubing materials in vitro and the effects on glycemic control in vivo. Materials and Methods: In vitro experiments: A syringe pump was filled with 50 IU insulin diluted to 50 ml saline. A flow of 2 ml/h was perfused through polyethylene (PET) or polyurethane (PUR) tubing. Insulin concentrations were measured at the end of the tube for 24 hours using Bradford's protein assay. In vivo study: In a randomized double-blinded cross-over design, 10 intensive care patients received insulin via PET and PUR tubes for 24 hours each, targeting blood glucose levels of 80-150 mg/dl. We measured blood glucose levels, the insulin dose required to maintain target levels, and serum insulin and C-peptide levels. Results: In vitro experiments: After the start of the insulin infusion, only 20% (median, IQR 20-27) (PET) and 22% (IQR 16-27) (PUR) of the prepared insulin concentration were measured at the end of the 2 meter tubing. Using PET, after one hour infusion the concentration increased to 34% (IQR 29-36) and did not increase significantly during the next 24 hours (39% (IQR 39-40)). Using PUR, higher concentrations were detected than for PET at every measurement from 1 hour (82% (IQR 70-86)) to 24 hours (79% (IQR 64-87)). In vivo study: Glycemic control was effective and not different between groups. Significantly higher volumes of insulin solution had to be infused with PET compared to PUR (median PET 70.0 (IQR 56-82) ml vs. PUR 42 (IQR 31-63) ml; p=0.0015). Serum insulin concentrations did not decrease significantly one hour after changing to PET or PUR tubing. Conclusion: Polyurethane tubing systems allow application of insulin with significantly lower adsorption rates than polyethylene tubing systems. As a consequence, less insulin solution has to be infused to patients for effective blood glucose control. Tubing material of the insulin infusion may be crucial for safe and effective glycemic control in critically ill patients

Mimicking Mills’ syndrome: progressive spastic hemiparesis on upper motor neuron dominant amyotrophic lateral sclerosis

Mills’ syndrome is an idiopathic, slowly progressive, spastic hemiparetic variant of primary lateral sclerosis (PLS). Despite this classic definition, this syndrome has recently been suggested to be present on all the variants of motor neuron disease (MND) spectrum (ALS, PLS or UMNdALS). Authors presented a 63 years old male with history of gradually progressive right-side hemiparesis associated with dysarthria and dysphagia. Neurologic examination revealed intact cognition, weak bilateral orofacial muscles, marked right-side spasticity with hyperreflexia and mild sensory deficit, progressing to right-upper extremity atrophy upon follow-up. Relevant blood and CSF examinations were within normal limits. MRI of brain and cervical spine were unremarkable. electromyography (EMG), nerve conduction velocity (NCV), facial motor and blinks studies initially revealed no evidence of lower motor neuron involvement. Based on the revised El escorial criteria, patient was diagnosed as upper motor neuron dominant amyotrophic lateral sclerosis (UMNdALS) mimicking the classic PLS-Mills’ hemiparetic variant

Novel solvates M(BH4)3S(CH3)2 and properties of halide-free M(BH4)3 (M = Y or Gd)

Rare earth metal borohydrides have been proposed as materials for solid-state hydrogen storage because of their reasonably low temperature of decomposition. New synthesis methods, which provide halide-free yttrium and gadolinium borohydride, are presented using dimethyl sulfide and new solvates as intermediates. The solvates M(BH4)3S(CH3)2 (M = Y or Gd) are transformed to a-Y(BH4)3 or Gd(BH4)3 at ~140 °C as verified by thermal analysis. The monoclinic structure of Y(BH4)3S(CH3)2, space group P21/c, a = 5.52621(8), b = 22.3255(3), c = 8.0626(1) Å and ß = 100.408(1)°, is solved from synchrotron radiation powder X-ray diffraction data and consists of buckled layers of slightly distorted octahedrons of yttrium atoms coordinated to five borohydride groups and one dimethyl sulfide group. Significant hydrogen loss is observed from Y(BH4)3 below 300 °C and rehydrogenation at 300 °C and p(H2) = 1550 bar does not result in the reformation of Y(BH4)3, but instead yields YH3. Moreover, composites systems Y(BH4)3–LiBH4 1 : 1 and Y(BH4)3–LiCl 1 : 1 prepared from as-synthesised Y(BH4)3 are shown to melt at 190 and 220 °C, respectively

Quantum Communication with Phantom Photons

We show that quantum information may be transferred between atoms in different locations by using ``phantom photons'': the atoms are coupled through electromagnetic fields, but the corresponding field modes do not have to be fully populated. In the case where atoms are placed inside optical cavities, errors in quantum information processing due to photon absorption inside the cavity are diminished in this way. This effect persists up to intercavity distances of about a meter for the current levels of cavity losses, and may be useful for distributed quantum computing.Comment: 6 pages RevTex, 4 eps figures included. Revised calculation with more details about mode structure calculation and the introduction of losse

All-electron GW calculation based on the LAPW method: application to wurtzite ZnO

We present a new, all-electron implementation of the GW approximation and apply it to wurtzite ZnO. Eigenfunctions computed in the local-density approximation (LDA) by the full-potential linearized augmented-plane-wave (LAPW) or the linearized muffin-tin-orbital (LMTO) method supply the input for generating the Green function G and the screened Coulomb interaction W. A mixed basis is used for the expansion of W, consisting of plane waves in the interstitial region and augmented-wavefunction products in the augmentation-sphere regions. The frequency-dependence of the dielectric function is computed within the random-phase approximation (RPA), without a plasmon-pole approximation. The Zn 3d orbitals are treated as valence states within the LDA; both core and valence states are included in the self-energy calculation. The calculated bandgap is smaller than experiment by about 1eV, in contrast to previously reported GW results. Self-energy corrections are orbital-dependent, and push down the deep O 2s and Zn 3d levels by about 1eV relative to the LDA. The d level shifts closer to experiment but the size of shift is underestimated, suggesting that the RPA overscreens localized states.Comment: 10 pages, 3 figures, submitted to Phys. Rev.