Preliminary study of minimum performance approaches to automated Mars sample return missions Final report, 19 Oct. - 20 Nov. 1970

Alternative mission/system approaches to automated Mars surface sample return based on utilization of Titan 3 or Saturn Intermediate-20 launch vehicle

Controllability and universal three-qubit quantum computation with trapped electron states

We show how to control and perform universal three-qubit quantum computation with trapped electron quantum states. The three qubits are the electron spin, and the first two quantum states of the cyclotron and axial harmonic oscillators. We explicitly show how the universal gates can be performed. As an example of a non-trivial quantum algorithm, we outline the implementation of the Deutsch-Jozsa algorithm in this system.Comment: 4 pages, 1 figure. Typos corrected. The original publication is available at http://www.springerlink.co

A novel FRET-based screen in high-throughput format to identify inhibitors of malarial and human glucose transporters

The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose sensor. This allows assessment of the ability of small molecules to inhibit glucose uptake with high accuracy (Z′ factor of >0.8), thereby eliminating the need for radiolabeled substrates. Furthermore, we have adapted this assay to counterscreen PfHT hits against the human orthologues GLUT1, -2, -3, and -4. We report the identification of several hits after screening the Medicines for Malaria Venture (MMV) Malaria Box, a library of 400 compounds known to inhibit erythrocytic development of P. falciparum. Hit compounds were characterized by determining the half-maximal inhibitory concentration (IC(50)) for the uptake of radiolabeled glucose into isolated P. falciparum parasites. One of our hits, compound MMV009085, shows high potency and orthologue selectivity, thereby successfully validating our assay for antimalarial screening

ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update)

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023

Identification of druggable small molecule antagonists of the Plasmodium falciparum hexose transporter PfHT and assessment of ligand access to the glucose permeation pathway via FLAG-mediated protein engineering

Although the Plasmodium falciparum hexose transporter PfHT has emerged as a promising target for anti-malarial therapy, previously identified small-molecule inhibitors have lacked promising drug-like structural features necessary for development as clinical therapeutics. Taking advantage of emerging insight into structure/function relationships in homologous facilitative hexose transporters and our novel high throughput screening platform, we investigated the ability of compounds satisfying Lipinksi rules for drug likeness to directly interact and inhibit PfHT. The Maybridge HitFinder chemical library was interrogated by searching for compounds that reduce intracellular glucose by >40% at 10 μM. Testing of initial hits via measurement of 2-deoxyglucose (2-DG) uptake in PfHT over-expressing cell lines identified 6 structurally unique glucose transport inhibitors. WU-1 (3-(2,6-dichlorophenyl)-5-methyl-N-[2-(4-methylbenzenesulfonyl)ethyl]-1,2-oxazole-4-carboxamide) blocked 2-DG uptake (IC50 = 5.8 ± 0.6 μM) with minimal effect on the human orthologue class I (GLUTs 1–4), class II (GLUT8) and class III (GLUT5) facilitative glucose transporters. WU-1 showed comparable potency in blocking 2-DG uptake in freed parasites and inhibiting parasite growth, with an IC50 of 6.1 ± 0.8 μM and EC50 of 5.5 ± 0.6 μM, respectively. WU-1 also directly competed for N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) binding and inhibited the transport of D-glucose with an IC50 of 5.9 ± 0.8 μM in liposomes containing purified PfHT. Kinetic analysis revealed that WU-1 acts as a non-competitive inhibitor of zero-trans D-fructose uptake. Decreased potency for WU-1 and the known endofacial ligand cytochalasin B was observed when PfHT was engineered to contain an N-terminal FLAG tag. This modification resulted in a concomitant increase in affinity for 4,6-O-ethylidene-α-D-glucose, an exofacially directed transport antagonist, but did not alter the Km for 2-DG. Taken together, these data are consistent with a model in which WU-1 binds preferentially to the transporter in an inward open conformation and support the feasibility of developing potent and selective PfHT antagonists as a novel class of anti-malarial drugs.</div

Conductance of carbon nanotubes with disorder: A numerical study

We study the conductance of carbon nanotube wires in the presence of disorder, in the limit of phase coherent transport. For this purpose, we have developed a simple numerical procedure to compute transmission through carbon nanotubes and related structures. Two models of disorder are considered, weak uniform disorder and isolated strong scatterers. In the case of weak uniform disorder, our simulations show that the conductance is not significantly affected by disorder when the Fermi energy is close to the band center. Further, the transmission around the band center depends on the diameter of these zero bandgap wires. We also find that the calculated small bias conductance as a function of the Fermi energy exhibits a dip when the Fermi energy is close to the second subband minima. In the presence of strong isolated disorder, our calculations show a transmission gap at the band center, and the corresponding conductance is very small

Multiple Functionality in Nanotube Transistors

Calculations of quantum transport in a carbon nanotube transistor show that such a device offers unique functionality. It can operate as a ballistic field-effect transistor, with excellent characteristics even when scaled to 10 nm dimensions. At larger gate voltages, channel inversion leads to resonant tunneling through an electrostatically defined nanoscale quantum dot. Thus the transistor becomes a gated resonant tunelling device, with negative differential resistance at a tunable threshold. For the dimensions considered here, the device operates in the Coulomb blockade regime, even at room temperature.Comment: To appear in Phys. Rev. Let

The Standard Model of Electroweak Interactions

In this chapter, we summarize the structure of the standard EW theory and specify the couplings of the intermediate vector bosons W\ub1, Z and of the Higgs particle with the fermions and among themselves, as dictated by the gauge symmetry plus the observed matter content and the requirement of renormalizability

van der Waals interaction in nanotube bundles : consequences on vibrational modes

We have developed a pair-potential approach for the evaluation of van der Waals interaction between carbon nanotubes in bundles. Starting from a continuum model, we show that the intertube modes range from $5 cm^{-1}$ to $60 cm^{-1}$. Using a non-orthogonal tight-binding approximation for describing the covalent intra-tube bonding in addition, we confirme a slight chiral dependance of the breathing mode frequency and we found that this breathing mode frequency increase by $\sim$ 10 % if the nanotube lie inside a bundle as compared to the isolated tube.Comment: 5 pages, 2 figure

Bandgap Change of Carbon Nanotubes: Effect of Small Tensile and Torsional Strain

We use a simple picture based on the $\pi$ electron approximation to study the bandgap variation of carbon nanotubes with uniaxial and torsional strain. We find (i) that the magnitude of slope of bandgap versus strain has an almost universal behaviour that depends on the chiral angle, (ii) that the sign of slope depends on the value of $(n-m) \bmod 3$ and (iii) a novel change in sign of the slope of bandgap versus uniaxial strain arising from a change in the value of the quantum number corresponding to the minimum bandgap. Four orbital calculations are also presented to show that the $\pi$ orbital results are valid.Comment: Revised. Method explained in detai