Secretory vesicle transport velocity in living cells depends on the myosin-V lever arm length

Myosins are molecular motors that exert force against actin filaments. One widely conserved myosin class, the myosin-Vs, recruits organelles to polarized sites in animal and fungal cells. However, it has been unclear whether myosin-Vs actively transport organelles, and whether the recently challenged lever arm model developed for muscle myosin applies to myosin-Vs. Here we demonstrate in living, intact yeast that secretory vesicles move rapidly toward their site of exocytosis. The maximal speed varies linearly over a wide range of lever arm lengths genetically engineered into the myosin-V heavy chain encoded by the MYO2 gene. Thus, secretory vesicle polarization is achieved through active transport by a myosin-V, and the motor mechanism is consistent with the lever arm model

Primary Intestinal Lymphoma in Crohn's Disease: Minute Tumor with a Fatal Outcome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75263/1/j.1572-0241.1992.tb02897.x.pd

Efficient and perfect state transfer in quantum chains

We present a communication protocol for chains of permanently coupled qubits which achieves perfect quantum state transfer and which is efficient with respect to the number chains employed in the scheme. The system consists of $M$ uncoupled identical quantum chains. Local control (gates, measurements) is only allowed at the sending/receiving end of the chains. Under a quite general hypothesis on the interaction Hamiltonian of the qubits a theorem is proved which shows that the receiver is able to asymptotically recover the messages by repetitive monitoring of his qubits.Comment: 6 pages, 2 figures; new material adde

A Precision Measurement of Nuclear Muon Capture on 3He

The muon capture rate in the reaction mu- 3He -> nu + 3H has been measured at PSI using a modular high pressure ionization chamber. The rate corresponding to statistical hyperfine population of the mu-3He atom is (1496.0 +- 4.0) s^-1. This result confirms the PCAC prediction for the pseudoscalar form factors of the 3He-3H system and the nucleon.Comment: 13 pages, 6 PostScript figure

Combination vinorelbine and capecitabine for metastatic breast cancer using a non-body surface area dosing scheme

Purpose : This study sought to determine the maximum tolerated dose of flat-dosed vinorelbine in combination with capecitabine in patients with metastatic breast cancer. At the time of study initiation, it was anticipated that vinorelbine would be developed as an oral capsule. A flat dosing scheme of both drugs was used to facilitate development of the oral regimen, and because neither drug’s clearance is associated with body surface area (BSA), pharmacokinetic and pharmacogenetic endpoints were explored. Experimental Design : Capecitabine was administered orally at 3,000 mg/day on days 1–14. The starting dose of vinorelbine was 20 mg intravenously on days 1 and 8 of a 21-day cycle. The vinorelbine dose was escalated until dose limiting toxicity (DLT). Vinorelbine pharmacokinetics were measured after the first dose. Patients underwent genotype analysis for polymorphisms in the CYP3A5 gene, and the erythromycin breath test (ERMBT), a phenotypic test of CYP3A enzyme activity. Results : Twenty five eligible patients were enrolled. Hematologic DLT was seen at the 50 and 45 mg vinorelbine doses; thus the recommended dose is 40 mg on days 1 and 8. Response rate was 30%, and disease stabilization rate was 64% (all dose levels included). Vinorelbine clearance was not associated with ERMBT, BSA, or age. CYP3A5 genotype in this small sample did not have an obvious relationship to clearance or toxicity. Conclusions : A non-BSA based dosing scheme of capecitabine and vinorelbine is safe and efficacious. BSA did not affect vinorelbine clearance. We recommend future studies with capecitabine and/or vinorelbine to compare the safety and efficacy of flat dosed versus BSA-dosed treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46933/1/280_2005_Article_132.pd

Straight and Divergent Pathways to Cognitive State: Seven Decades of Follow-Up in the British 1946 Birth Cohort

BACKGROUND: Using the British 1946 birth cohort we previously estimated life course paths to the Addenbrooke's Cognitive Examination (ACE-III). OBJECTIVE: We now compared those whose ACE-III scores were expected, worse and better than predicted from the path model on a range of independent variables including clinical ratings of cognitive impairment and neuroimaging measures. METHODS: Predicted ACE-III scores were categorized into three groups: those with Expected (between -1.5 and 1.5 standard deviation; SD); Worse (1.5 SD) scores. Differences in the independent variables were then tested between these three groups. RESULTS: Compared with the Expected group, those in the Worse group showed independent evidence of progressive cognitive impairment: faster memory decline, more self-reported memory difficulties, more functional difficulties, greater likelihood of being independently rated by experienced specialist clinicians as having a progressive cognitive impairment, and a cortical thinning pattern suggestive of preclinical Alzheimer's disease. Those in the Better group showed slower verbal memory decline and absence of independently rated progressive cognitive impairment compared to the Expected group, but no differences in any of the other independent variables including the neuroimaging variables. CONCLUSION: The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective

A comparison of forward and backward pp pair knockout in 3He(e,e'pp)n

Measuring nucleon-nucleon Short Range Correlations (SRC) has been a goal of the nuclear physics community for many years. They are an important part of the nuclear wavefunction, accounting for almost all of the high-momentum strength. They are closely related to the EMC effect. While their overall probability has been measured, measuring their momentum distributions is more difficult. In order to determine the best configuration for studying SRC momentum distributions, we measured the $^3$He$(e,e'pp)n$ reaction, looking at events with high momentum protons ($p_p > 0.35$ GeV/c) and a low momentum neutron ($p_n< 0.2$ GeV/c). We examined two angular configurations: either both protons emitted forward or one proton emitted forward and one backward (with respect to the momentum transfer, $\vec q$). The measured relative momentum distribution of the events with one forward and one backward proton was much closer to the calculated initial-state $pp$ relative momentum distribution, indicating that this is the preferred configuration for measuring SRC.Comment: 8 pages, 9 figures, submitted to Phys Rev C. Version 2 incorporates minor corrections in response to referee comment

Measurement of the nuclear multiplicity ratio for Ks0K^0_s hadronization at CLAS

The influence of cold nuclear matter on lepto-production of hadrons in semi-inclusive deep inelastic scattering is measured using the CLAS detector in Hall B at Jefferson Lab and a 5.014 GeV electron beam. We report the $K_s^0$ multiplicity ratios for targets of C, Fe, and Pb relative to deuterium as a function of the fractional virtual photon energy $z$ transferred to the $K_s^0$ and the transverse momentum squared $p_{T}^2$ of the $K_s^0$. We find that the multiplicity ratios for $K^0_s$ are reduced in the nuclear medium at high $z$ and low $p_{T}^2$, with a trend for the $K^0_s$ transverse momentum to be broadened in the nucleus for large $p_{T}^2$.Comment: Submitted to Phys. Lett.

Measurement of Exclusive π0\pi^0 Electroproduction Structure Functions and their Relationship to Transversity GPDs

Exclusive $\pi^0$ electroproduction at a beam energy of 5.75 GeV has been measured with the Jefferson Lab CLAS spectrometer. Differential cross sections were measured at more than 1800 kinematic values in $Q^2$, $x_B$, $t$, and $\phi_\pi$, in the $Q^2$ range from 1.0 to 4.6 GeV$^2$,\ $-t$ up to 2 GeV$^2$, and $x_B$ from 0.1 to 0.58. Structure functions $\sigma_T +\epsilon \sigma_L, \sigma_{TT}$ and $\sigma_{LT}$ were extracted as functions of $t$ for each of 17 combinations of $Q^2$ and $x_B$. The data were compared directly with two handbag-based calculations including both longitudinal and transversity GPDs. Inclusion of only longitudinal GPDs very strongly underestimates $\sigma_T +\epsilon \sigma_L$ and fails to account for $\sigma_{TT}$ and $\sigma_{LT}$, while inclusion of transversity GPDs brings the calculations into substantially better agreement with the data. There is very strong sensitivity to the relative contributions of nucleon helicity flip and helicity non-flip processes. The results confirm that exclusive $\pi^0$ electroproduction offers direct experimental access to the transversity GPDs.Comment: 6 pages, 2 figure

Near-threshold Photoproduction of Phi Mesons from Deuterium

We report the first measurement of the differential cross section on $\phi$-meson photoproduction from deuterium near the production threshold for a proton using the CLAS detector and a tagged-photon beam in Hall B at Jefferson Lab. The measurement was carried out by a triple coincidence detection of a proton, $K^+$ and $K^-$ near the theoretical production threshold of 1.57 GeV. The extracted differential cross sections $\frac{d\sigma}{dt}$ for the initial photon energy from 1.65-1.75 GeV are consistent with predictions based on a quasifree mechanism. This experiment establishes a baseline for a future experimental search for an exotic $\phi$-N bound state from heavier nuclear targets utilizing subthreshold/near-threshold production of $\phi$ mesons