Spectral determinations for discrete sources with EGRET

The ability of the EGRET (Energetic Gamma-Ray Experimental Telescope) to determine the spectral parameters of point sources in 14-day exposures, as planned for the initial survey phase of the GRO (Gamma Ray Observatory) mission, is explored by numerical simulation. Results are given for both galactic and extragalactic objects as a function of source strength and for representative levels of diffuse background emission

Fast scan control for deflection type mass spectrometers

A high speed scan device is reported that allows most any scanning sector mass spectrometer to measure preselected gases at a very high sampling rate. The device generates a rapidly changing staircase output which is applied to the accelerator of the spectrometer and it also generates defocusing pulses that are applied to one of the deflecting plates of the spectrometer which when shorted to ground deflects the ion beam away from the collector. A defocusing pulse occurs each time there is a change in the staircase output

Nonthermal X-Ray Emission from G266.2-1.2 (RX J0852.0-4622)

The newly discovered supernova remnant G266.2-1.2 (RX J0852.0-4622), along the line of sight to the Vela SNR, was observed with ASCA for 120 ks. We find that the X-ray spectrum is featureless, and well described by a power law, extending to three the class of shell-type SNRs dominated by nonthermal X-ray emission. Although the presence of the Vela SNR compromises our ability to accurately determine the column density, the GIS data appear to indicate absorption considerably in excess of that for Vela itself, indicating that G266.2-1.2 may be several times more distant. An unresolved central source may be an associated neutron star, though difficulties with this interpretation persist.Comment: 4 pages, 5 figures, uses aipproc.sty & epsfig.sty. To appear in "Young Supernova Remnants" (11th Annual Astrophysics Conference in Maryland), S. S. Holt & U. Hwang (eds), AIP, New York (2001

Choice of Study Populations for Vaccines

The natural history of cytomegalovirus (CMV) infection is complex. Individuals may experience primary infection, reactivation of latent infection, or reinfection with a new strain despite natural immunity. The ability of this virus to continue to replicate despite substantial immune responses is attributable to the many immune evasion genes encoded within its genome. Given this complex natural history and immunology, the design of clinical trials of CMV vaccines may require components not usually found in trials of vaccines designed to protect against viruses that cause only acute infections. In this article, we focus on specific aspects of clinical trial design that could be adopted to address the complexities of CMV infections. We consider women of childbearing age, toddlers, recipients of solid organ transplantation, and stem cell transplant patients, emphasizing the parallels between women and solid organ transplantation that could allow vaccines to be developed in parallel in both these patient groups. We emphasize the potential for studies of passive immunity to inform the selection of immunogens as candidates for active immunization and vice versa. We also illustrate how application of whole-genomic sequencing could document whether vaccines protect against reactivation or reinfection of CMV or both

Enhanced dielectrophoresis of nanocolloids by dimer formation

We investigate the dielectrophoretic motion of charge-neutral, polarizable nanocolloids through molecular dynamics simulations. Comparison to analytical results derived for continuum systems shows that the discrete charge distributions on the nanocolloids have a significant impact on their coupling to the external field. Aggregation of nanocolloids leads to enhanced dielectrophoretic transport, provided that increase in the dipole moment upon aggregation can overcome the related increase in friction. The dimer orientation and the exact structure of the nanocolloid charge distribution are shown to be important in the enhanced transport

Modeling reactivity to biological macromolecules with a deep multitask network

Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural networkthe XenoSite reactivity modelusing literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule-level, the model’s performances significantly outperformed reactivity indices derived from quantum simulations that are reported in the literature. Moreover, we developed and applied a selectivity score to assess preferential reactions with the macromolecules as opposed to the common screening traps. For the entire data set of 2803 molecules, this approach yielded totals of 257 (9.2%) and 227 (8.1%) molecules predicted to be reactive only with DNA and protein, respectively, and hence those that would be missed by standard reactivity screening experiments. Site of reactivity data is an underutilized resource that can be used to not only predict if molecules are reactive, but also show where they might be modified to reduce toxicity while retaining efficacy. The XenoSite reactivity model is available at http://swami.wustl.edu/xenosite/p/reactivity

Theory of the Three Dimensional Quantum Hall Effect in Graphite

We predict the existence of a three dimensional quantum Hall effect plateau in a graphite crystal subject to a magnetic field. The plateau has a Hall conductivity quantized at $\frac{4e^2}{\hbar} \frac{1}{c_0}$ with $c_0$ the c-axis lattice constant. We analyze the three-dimensional Hofstadter problem of a realistic tight-binding Hamiltonian for graphite, find the gaps in the spectrum, and estimate the critical value of the magnetic field above which the Hall plateau appears. When the Fermi level is in the bulk Landau gap, Hall transport occurs through the appearance of chiral surface states. We estimate the magnetic field necessary for the appearance of the three dimensional quantum Hall Effect to be $15.4$T for electron carriers and $7.0$T for hole carriers.Comment: Several new references adde

Dirac's Footsteps and Supersymmetry

One hundred years after its creator's birth, the Dirac equation stands as the cornerstone of XXth Century physics. But it is much more, as it carries the seeds of supersymmetry. Dirac also invented the light-cone, or "front form" dynamics, which plays a crucial role in string theory and in elucidating the finiteness of N=4 Yang-Mills theory. The light-cone structure of eleven-dimensional supergravity (N=8 supergravity in four dimensions) suggests a group-theoretical interpretation of its divergences. We speculate they could be compensated by an infinite number of triplets of massless higher spin fields, each obeying a Dirac-like equation associated with the coset $F_4/SO(9)$. The divergences are proportional to the trace over a non-compact structure containing the compact form of $F_4$. Its nature is still unknown, but it could show the way to $M$-theory.Comment: Invited Talk at Dirac's Centennial Symposium, Tallahasse, Florida, Dec 200