Studies of the Decay B+- -> D_CP K+-

We report studies of the decay B+- -> D_CP K+-, where D_CP denotes neutral D mesons that decay to CP eigenstates. The analysis is based on a 29.1/fb data sample of collected at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+ e- storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes involving D_CP are determined to be B(B- -> D_1 K-)/B(B- -> D_1 pi-)=0.125 +- 0.036 +- 0.010 and B(B- -> D_2 K-)/B(B- -> D_2 pi-)=0.119 +- 0.028 +- 0.006, where indices 1 and 2 represent the CP=+1 and CP=-1 eigenstates of the D0 - anti D0 system, respectively. We also extract the partial rate asymmetries for B+- -> D_CP K+-, finding A_1 = 0.29 +- 0.26 +- 0.05 and A_2 = -0.22 +- 0.24 +- 0.04.Comment: 10 pages, 2 figures, submitted to Physical Review Letter

Preparation and Evaluation of Poly(Ethylene Glycol)–Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

A series of monomethoxy poly(ethylene glycol)–poly(lactide) (mPEG–PLA) diblock copolymers were designed according to polymer–drug compatibility and synthesized, and mPEG–PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug

Conserved Mosquito/Parasite Interactions Affect Development of Plasmodium falciparum in Africa

In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists

Search for D-0-D-0(-) mixing in D-0 -> K+pi(-) decays and measurement of the doubly-Cabibbo-suppressed decay rate

We have searched for mixing in the Ddegrees-(D) over cap (0) D-0 system by measuring the decay-time distribution of D0 ! K(+)pi(-) decays. The analysis uses 90 fb(-1) of data collected by the Belle detector at the KEKB e(+) e(-) collider. We fit the decay-time distribution for the mixing parameters x(1) and y(1) and also for the parameter R-D, which is the ratio of the rate for the doubly-Cabibbo-suppressed decay D-0--> K(+)pi(-) to that for the Cabibbo-favored decay D-0 --> K- pi(+). We do these fits both assuming CP conservation and allowing for CP violation. We use a frequentist method to obtain a 95% C. L. region in the x(J2)- y(l) plane. Assuming no mixing, we measure R-D=(0: 381 +/- 0: 017 (+) (0.008)(-0.016))%

PET and SPECT Imaging in Hyperkinetic Movement Disorders

Movement disorders can be classified in hypokinetic (e.g., Parkinson's disease, PD) and hyperkinetic disorders (e.g., dystonia, chorea, tremor, tics, myoclonus, and restless legs syndrome). In this chapter, we will discuss results from positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging studies in patients with tremor, tics, myoclonus, and restless legs syndrome. Most studies in patients with tremor included patients with essential tremor (ET): a bilateral, largely symmetric, postural or kinetic tremor mainly involving the upper limbs and sometimes the head. Other studies evaluated patients with orthostatic tremor (OT): an unusually high frequent tremor in the legs that mainly occurs when patients are standing still. Increased regional cerebral blood flow (rCBF) and increased glucose metabolism have been found in the cerebellum, sensorimotor cortex, and thalamus in both patients with ET and OT compared to controls. Both PET and SPECT studies have evaluated the dopamine system in patients with ET and OT. Most imaging studies in patients with ET showed no, or only subtle loss of striatal tracer binding to the dopamine transporter indicating that ET is not characterized by nigrostriatal cell loss. The serotonin and/or gamma-aminobutyric acid (GABA) systems may play a role in the pathophysiology of ET. PET and SPECT imaging of the dopamine and serotonin system in patients with OT showed no abnormalities. Tics, the clinical hallmark of Gilles de la Tourette syndrome (TS), are relatively brief and intermittent involuntary movements (motor tic) and sounds (phonic tic). The essential features of tics are that (1) they can be temporarily suppressed; after suppression a rebound usually occurs with a flurry of tics; (2) the patient experiences an urge to tic, and (3) the tic is followed by a short moment of relief. Using 18F-FDG PET, it was shown that TS is a network disorder where multiple brain areas are active or inactive at the same time. The exact composition of this network is yet to be determined. Using rCBF PET and SPECT many brain regions were found to be abnormal, however, tics mostly correlated with hypoperfusion of the caudate nucleus and cingulate cortex. Both dopamine and serotonin are likely to play a role in the pathophysiology of TS. It is hypothesized that TS is characterized by low serotonin levels that modulate increased phasic dopamine release. Myoclonus is defined as a brief muscle jerk and occurs in many neurologic and non-neurologic disorders. Imaging with PET and SPECT in patients with myoclonus mainly showed abnormalities consistent with the underlying disorder. We described PET and SPECT imaging results in patients in which myoclonus was a prominent symptom. Hypoperfusion and/or hypometabolism of the frontoparietal cortex was found in patients with negative epileptic myoclonus, Alzheimer's disease, corticobasal degeneration, Creutzfeldt-Jakob disease, fatal familiar insomnia, and posthypoxic myoclonus. Other findings that were frequently reported were decreased rCBF and/or glucose metabolism in the cerebellum and thalamus and abnormalities in the dopamine system. Restless legs syndrome (RLS) is defined as an urge to move the legs accompanied with an unpleasant sensation in the legs or in another body part that is especially present during the evening and night and that can be accompanied by periodic limb movements in sleep (PLMS). Imaging studies in these patients have mainly focused on the dopamine system. Most PET studies found decreased tracer binding to the dopamine transporter, although this was not found in SPECT studies. Both PET and SPECT studies showed conflicting results regarding dopamine D2/3 receptor binding: both increased and decreased tracer binding was reported. Furthermore, it is likely that the serotonin and opioid systems also play a role in the pathophysiology of RLS.</p

Measurements of the D-sJ resonance properties

We report measurements of the properties of the D-sJ(+)(2317) and D-sJ(+)(2457) resonances produced in continuum e(+)e(-) annihilation near roots=10.6 GeV. The analysis is based on an 86.9 fb(-1) data sample collected with the Belle detector at KEKB. We determine the masses to be M(D-sJ(+)(2317))=2317.2+/-0.5(stat)+/-0.9(syst) MeV/c(2) and M(D-sJ(+)(2457))=2456.5+/-1.3(stat)+/-1.3(syst) MeV/c(2). We observe the radiative decay mode D-sJ(+)(2457)-->D(s)(+)gamma and the dipion decay mode D-sJ(+)(2457)-->D(s)(+)pi(+)pi(-) and determine their branching fractions. No corresponding decays are observed for the D-sJ(2317) state. These results are consistent with the spin-parity assignments of 0(+) for the D-sJ(2317) and 1(+) for the D-sJ(2457)

Improved measurements of branching fractions for B -> K pi and B -> pi pi decays

We report improved measurements of branching fractions for B -> K pi and B -> pi pi decays based on a data sample of 449 million B Bbar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB e^+e^- collider. We also calculate the ratios of partial widths for the decays B -> K pi and pi pi, namely R_c = 1.08 +- 0.06 +- 0.08 and R_n = 1.08 +-0.08 +0.09-0.08, where the first and second errors are statistical and systematical, respectively. These ratios are sensitive to enhanced electroweak penguin contributions from new physics; the new measurements are, however, consistent with Standard Model expectations.Comment: 6 pages, 1 figur

Observation of Ds+K- and evidence for D-s(+)pi(-) final states in neutral B decays

We report the first observation of a B meson decay that is not accessible by a direct spectator process. The channel (B) over bar (0)-->Ds+K- is found in a sample of 85x10(6) B (B) over bar events, collected with the Belle detector at KEKB, with a branching fraction B((B) over bar (0)-->Ds+K-)=(4.6(-1.1)(+1.2)+/-1.3)x10(-5). We also obtain evidence for the B-0-->D(s)(+)pi(-) decay with branching fraction B(B-0-->D(s)(+)pi(-))=(2.4(-0.8)(+1.0)+/-0.7)x10(-5). This value may be used to extract a model-dependent value of \V-ub\

Evidence for direct CP violation in B-0 -> K+pi(-) decays

We report evidence for direct CP violation in the decay B-0-->K(+)pi(-) with 253 fb(-1) of data collected with the Belle detector at the KEKB e(+)e(-) collider. Using 275x10(6) B(B) over bar pairs we observe a B-->K(+/-)pi(-/+) signal with 2140+/-53 events. The measured CP violating asymmetry is A(CP)(K(+)pi(-))=-0.101+/-0.025(stat)+/-0.005(syst), corresponding to a significance of 3.9sigma including systematics. We also search for CP violation in the decays B+-->K(+)pi(0) and B+-->pi(+)pi(0). The measured CP violating asymmetries are A(CP)(K(+)pi(0))=0.04+/-0.05(stat)+/-0.02(syst) and A(CP)(pi(+)pi(0))=-0.02+/-0.10(stat)+/-0.01(syst), corresponding to the intervals -0.05< A(CP)(K(+)pi(0))<0.13 and -0.18< A(CP)(pi(+)pi(0))<0.14 at 90% confidence level