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Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative use in healthcare, antivirals have been clinically approved to treat only 10 of the more than 200 known pathogenic human viruses. Additionally, many virus functions are intimately coupled with host cellular processes, which presents challenges in antiviral development due to the limited number of clear targets per virus, necessitating extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. We hypothesize that a viral attachment blocking chimera (VirABloC) composed of a viral binder and a bulky scaffold that sterically blocks interactions between a viral particle and a host cell may be suitable for the development of antivirals that are agnostic to the extravirion epitope that is being bound. We test this hypothesis by modifying a nanobody that specifically recognizes a nonessential epitope presented on the extravirion surface of pseudorabies virus strain 486 with a 3-dimensional wireframe DNA origami structure ∼100 nm in diameter. The nanobody switches from having no inhibitory properties to 4.2 ± 0.9 nM IC50when conjugated with the DNA origami scaffold. Mechanistic studies support that inhibition is mediated by the noncovalent attachment of the DNA origami scaffold to the virus particle, which obstructs the attachment of the viruses onto host cells. These results support the potential of VirABloC as a generalizable approach to developing antivirals.

Using the Theory of Scattering in Restricted Geometries developed by A. Lupu-Sax as a starting point, we present a comprehensive multi-channel theory of atom-atom scattering in tight atom waveguides.

Glycoside hydrolases (GHs) are critical to cycling of plant biomass in the environment, digestion of complex polysaccharides by the human gut microbiome, and industrial activities such as deployment of cellulosic biofuels. High-throughput sequencing methods show tremendous sequence diversity among GHs, yet relatively few examples from the over 150,000 unique domain arrangements containing GHs have been functionally characterized. Here, we show how cell-free expression, bioconjugate chemistry, and surface-based mass spectrometry can be used to study glycoside hydrolase reactions with plant biomass. Detection of soluble products is achieved by coupling a unique chemical probe to the reducing end of oligosaccharides in a stable oxime linkage, while the use of 13C-labeled monosaccharide standards (xylose and glucose) allows quantitation of the derivatized glycans. We apply this oxime-based nanostructure-initiator mass spectrometry (NIMS) method to characterize the functional diversity of GHs secreted by Clostridium thermocellum, a model cellulolytic organism. New reaction specificities are identified, and differences in rates and yields of individual enzymes are demonstrated in reactions with biomass substrates. Numerical analyses of time series data suggests that synergistic combinations of mono- and multifunctional GHs can decrease the complexity of enzymes needed for the hydrolysis of plant biomass during the production of biofuels.

New photoassociation data on the 0u+levels of Rb2below the 5S+5P1/2limit are combined with older data (Cline et al1994 Phys. Rev. Lett.73632) in a fit to potentials and spin-orbit functions. The P1/2data exhibit oscillations in the B(v) values due to coupling between the two 0u+series, as modelled accurately by a coupled potentials approach. The fitted value for the C3dispersion parameter from the combined data agrees well with the value derived from the pure long-range 0g?state.

A path model of genetic and environmental transmission was fitted to general and specific cognitive abilities (verbal, spatial, visual memory, and perceptual speed) data from biological, adoptive, and control parents and their children at ages 3 and 4. Using a maximum-likelihood estimation procedure. the significance of genetic influence, passive genotype-environment correlation, parental influence on the child's environment, assortative mating, and selective placement was assessed. As predicted, the parameter estimate for genetic influence (a function of the heritabilities of the character during early childhood and adulthood and their genetic correlation) is significant for general cognitive ability at both 3 and 4. Moreover, estimates of the genetic parameter are significant for spatial ability at both 3 and 4 years of age, for verbal ability at 3, and for perceptual speed at 4. Thus, there is at least some continuity between early childhood and adulthood as well as some genetic differentiation for specif cognitive abilities.

We present previously unpublished data on the A1Π, e3Σ−, d3Δi, a′ 3Σ+, and a3Π states of CS from uv emission and absorption transitions to the X1Σ+ground state. Term values obtained from d3Δi← a3Π ir emission bands are also included. Rotational analyses are presented for about 50 new fine-structure components in some 30 new vibrational levels, together with extended data and analyses for many of the previously observed levels. The data now availabe for these five electronic states more than triples that previously published. Vibrational numbering for the e, d, and a′ states is established by data for minor isotopes. In a Hund's case a-b basis, off-diagonal spin-orbit elements (incipient case c effects) produce extensive coupling among these levels, not only for perturbation crossings but also between levels widely separated in energy. A systematic deperturbation requires two stages, which are iterated. Term values computed from the spectral lines are used to fit parameters of Hamiltonian matrices for groups of nearby, coupled levels. Additional shifts are computed by second-order perturbation theory from the electronic interactions deduced from vibronic coupling elements. The resultant parameters satisfy certain tests for self-consistency; they conform to low-order polynomials in v + 12, and vibrational overlap factors from wave-functions computed with RKR potential curves are proportional to the vibronic coupling elements, to within experimental error in most cases. To obtain this self-consistency, we have computed and applied normally neglected centrifugal distortion effects in the off-diagonal coupling elements and in the second-order perturbation sums. We also present and interpret the diagonal spin-orbit fine structure in the aand dstates, including the centrifugal distortion parameters, AD, for the latter, and values for several fitted second-order elements. Possible assignments for three additional perturbations of the A1Π state and one faint band are discussed in view of 1Δ, 1Σ−, and 5Π states that are also expected to occur in the region studied. Tentative parameters for the D1Δ state are obtained from one possible set of assignments.

A battery of cognitive tests was administered by telephone to 194 pairs of MZ and DZ twins: 112 pairs reared apart and 82 pairs reared together. The six measures, chosen to identify known intelligence and short-term memory factors, included two marker variables for crystallized intelligence (information and synonyms), two markers for fluid intelligence (analogies and figure logic), and two markers for short-term memory (forward and backward digit span). The data provide support for the feasibility of substituting telephone testing of abilities for more traditional assessment procedures.

We consider quantized motion of neutral atoms cooled below the recoil limit in a quadrupole magnetostatic trap. Because of Majorana transitions to untrapped levels near the point of zero field at the trap center, all quantum levels have a nonzero decay rate. The Schrödinger equation associated with the potential _gμB • S (S is the total atomic spin) takes the form of coupled equations in r when the spinor components are expanded in spherical harmonics. We integrate the multichannel problem numerically to obtain asymptotic phase shifts, resonance energies, and widths. For S = ½, the lowest levels have widths somewhat less than their spacing. Thus the trap quantum-level structure might possibly be observable if the atoms are sufficiently cold, namely, in the 0.1-_μK regime for most atoms and attainable trap field gradients. The width decreases rapidly with increasing M_J, the angular momentum about the symmetry axis. Spectroscopic linewidths of a few hertz are possible if there is enough population in the lowest levels with a few M_J quanta. The decay rate of the lowest levels, however, is probably too rapid for studying Bose-Einstein condensation in such a trap.

We have demonstrated the first reported use of quantum-beat spectroscopy for the precision measurement of energy-level splittings. We have measured the magnetic-field-level crossings of different hfs states of the OH free radical as well as the g factors, including the rotational and anisotropic contributions, of several states. We have constructed a Hamiltonian whose eigenvalues are in excellent agreement with our measurements. The hfs constants are b = 719.0 (1.2) MHz and c = 160.5 (0.9) MHz.

Addresses issues surrounding Marine graduates of the Naval Postgraduate School in Monterey, California, and their value to the United States Marine Corps. Overview of the NPS program; Promotability of an NPS graduate; Value and timing of the payback tour; What the NPS graduate brings to the fleet.

Discusses the related concepts of management decision-making that are applicable to the United States Marine Corps leadership doctrines. Muddling through and the need to make incremental decision based on the information at hand; Clear sense of direction of the commanding officer; Lessons from past experiences.

Adequate expression and function of Jak2 in hematopoietic progenitors is critical for normal myelopoiesis. The JAK2 46/1 (GGCC) haplotype, a congenital particularity, predisposes to myeloproliferative neoplasm (MPN) both independently and through mutation of the JAK2 gene. The JAK2 V617F mutation and acquired homozygous status for JAK2 V617F are frequent in MPN. JAK2 V617F homozygosity is currently explained acquisition of the JAK2 V617F mutation followed by mitotic homologous recombination (HR) of JAK2 occurred between wild-type and mutant alleles, leading to uniparental disomy (UPD) of chromosome 9p (9pUPD). Here we report the cases of 2 PV patients (Na1061 and Na1253) with acquired homozygous status for the JAK2 46/1 haplotype yet their granulocytes carried <20% JAK2 V617F.To determine whether HR of JAK2 can precede the V617F mutation in MPN.Granulocyte DNA and CD3+ lymphocyte DNA were examined in parallel with qPCR assays specific for the wild type and 46/1 haplotypes using rs12343867, a JAK2 intron 14 marker, as well as 4 other single nucleotide polymorphisms (SNP) on chromosome 9p. 9pUPD clonality and length were determined using SNP array studies.For both patients, lymphocytes were heterozygous for the 46/1 haplotype, confirming that granulocyte 46/1 homozygosity was acquired. Direct sequencing of the JAK2 and GNE genes and SNP array analyses revealed homologous recombination of part of the JAK2 gene (exons 6–19, patient Na1061) and of the complete 46/1 JAK2 haplotype (patient Na1253). Furthermore, for both patients, full length sequencing of JAK2 cDNA revealed no additional mutation. In both cases, HR of wild-type JAK2 was associated with growth advantage and high expression of recombined JAK2. For both patients, further SNP array analyses revealed partial 9pUPD concerning <30% cells, which correlated with %JAK2 V617F and was consistent with 9pUPD having occurred after JAK2 V617F (Figure 1).The distortion of SNP allelic differences was higher at the telomeric end than in the centromeric region of chr. 9p. This indicated 2 distinct partial 9pUPDs for Na1061 and 1 partial 9pUPD for Na1253.Homologous recombination involving wild type JAK2 can precede JAK2 mutation and 9pUPD in MPN. Thus multiple paths and diverse alterations of the JAK2 gene can lead to MPN in individuals carrying the JAK2 GGCC haplotype. We propose a new model with JAK2 HR as early event, followed or not by JAK2 mutation, or/and JAK2 mutation(s) facilitating subsequent recombination resulting in 9pUPD and JAK2 V617F homozygosity.No relevant conflicts of interest to declare.

Abstract 2805