Baryon Current Matrix Elements in a Light-Front Framework

Current matrix elements and observables for electro- and photo-excitation of baryons from the nucleon are studied in a light-front framework. Relativistic effects are estimated by comparison to a nonrelativistic model, where we use simple basis states to represent the baryon wavefunctions. Sizeable relativistic effects are found for certain transitions, for example, to radial excitations such as that conventionally used to describe to the Roper resonance. A systematic study shows that the violation of rotational covariance of the baryon transition matrix elements stemming from the use of one-body currents is generally small.Comment: 32 pages, LaTeX, 10 postscript figures, uses epsf.sty; figures uuencoded with uufiles (or available by request in .ps or hardcopy form

The position and the residues of the delta resonance pole in pion photoproduction

We have analyzed the $M_{1+}^{(3/2)}$ and $E_{1+}^{(3/2)}$ multipole amplitudes of pion photoproduction in the framework of fixed-$t$ dispersion relations. Applying the speed plot technique to our results for these multipoles, we have determined the position and the residues of the $\Delta$ (1232) resonance pole. The pole is found at total $c.m.$ energy $W = (1211 - 50i)$ MeV on the second Riemann sheet, and the ratio of the electric and magnetic residues is $R_{\Delta} = - 0.035 - 0.046 i$, resulting in an E2/M1 ratio for the "dressed" delta resonance of $- 3.5 \%$.Comment: 16 pages LATEX including 5 postscript figures in a self-extracting uufile archiv

Crystal structure of the anthrax lethal factor

Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62772/1/414229a0.pd

Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

Twisting the N=2 String

The most general homogeneous monodromy conditions in $N{=}2$ string theory are classified in terms of the conjugacy classes of the global symmetry group $U(1,1)\otimes{\bf Z}_2$. For classes which generate a discrete subgroup \G, the corresponding target space backgrounds {\bf C}^{1,1}/\G include half spaces, complex orbifolds and tori. We propose a generalization of the intercept formula to matrix-valued twists, but find massless physical states only for $\Gamma{=}{\bf 1}$ (untwisted) and $\Gamma{=}{\bf Z}_2$ (\`a la Mathur and Mukhi), as well as for $\Gamma$ being a parabolic element of $U(1,1)$. In particular, the sixteen ${\bf Z}_2$-twisted sectors of the $N{=}2$ string are investigated, and the corresponding ground states are identified via bosonization and BRST cohomology. We find enough room for an extended multiplet of `spacetime' supersymmetry, with the number of supersymmetries being dependent on global `spacetime' topology. However, world-sheet locality for the chiral vertex operators does not permit interactions among all massless `spacetime' fermions.Comment: 42 pages, LaTeX, no figures, 120 kb, ITP-UH-24/93, DESY 93-191 (abstract and introduction clarified, minor corrections added

Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

Evaluation of Suppressed Mite Reproduction (SMR) Reveals Potential for Varroa Resistance in European Honey Bees (Apis melliferaL.)

Simple Summary The miteVarroa destructorrepresents a great threat to honey bees and the beekeeping industry. The opportunity to select and breed honey bees that are naturally able to fight the mite stands a sustainable solution. This can be achieved by evaluation of the failure of mite reproduction (SMR, suppressed mite reproduction). We conducted a large European experiment to assess the SMR trait in different populations of honey bees spread over 13 different countries, and representing different honey bee populations. The first goal was to standardize and validate the SMR evaluation method, and then to compare the SMR trait between the different populations. Our results indicate that it is necessary to examine at least 35 brood cells infested by a single mite to reliably estimate the SMR score of any given colony. Several colonies from our dataset display high SMR scores, indicating that this trait is present within the European honey bee populations. No major differences could be identified between countries for a given population, or between populations in different countries. This study shows the potential to increase selection efforts to breedV. destructorhoney bee resistant populations. In the fight against theVarroa destructormite, selective breeding of honey bee (Apis melliferaL.) populations that are resistant to the parasitic mite stands as a sustainable solution. Selection initiatives indicate that using the suppressed mite reproduction (SMR) trait as a selection criterion is a suitable tool to breed such resistant bee populations. We conducted a large European experiment to evaluate the SMR trait in different populations of honey bees spread over 13 different countries, and representing different honey bee genotypes with their local mite parasites. The first goal was to standardize and validate the SMR evaluation method, and then to compare the SMR trait between the different populations. Simulation results indicate that it is necessary to examine at least 35 single-infested cells to reliably estimate the SMR score of any given colony. Several colonies from our dataset display high SMR scores indicating that this trait is present within the European honey bee populations. The trait is highly variable between colonies and some countries, but no major differences could be identified between countries for a given genotype, or between genotypes in different countries. This study shows the potential to increase selective breeding efforts ofV. destructorresistant populations

Causal Modeling Using Network Ensemble Simulations of Genetic and Gene Expression Data Predicts Genes Involved in Rheumatoid Arthritis

Tumor necrosis factor α (TNF-α) is a key regulator of inflammation and rheumatoid arthritis (RA). TNF-α blocker therapies can be very effective for a substantial number of patients, but fail to work in one third of patients who show no or minimal response. It is therefore necessary to discover new molecular intervention points involved in TNF-α blocker treatment of rheumatoid arthritis patients. We describe a data analysis strategy for predicting gene expression measures that are critical for rheumatoid arthritis using a combination of comprehensive genotyping, whole blood gene expression profiles and the component clinical measures of the arthritis Disease Activity Score 28 (DAS28) score. Two separate network ensembles, each comprised of 1024 networks, were built from molecular measures from subjects before and 14 weeks after treatment with TNF-α blocker. The network ensemble built from pre-treated data captures TNF-α dependent mechanistic information, while the ensemble built from data collected under TNF-α blocker treatment captures TNF-α independent mechanisms. In silico simulations of targeted, personalized perturbations of gene expression measures from both network ensembles identify transcripts in three broad categories. Firstly, 22 transcripts are identified to have new roles in modulating the DAS28 score; secondly, there are 6 transcripts that could be alternative targets to TNF-α blocker therapies, including CD86 - a component of the signaling axis targeted by Abatacept (CTLA4-Ig), and finally, 59 transcripts that are predicted to modulate the count of tender or swollen joints but not sufficiently enough to have a significant impact on DAS28

Building bridges between industry and academia: what is the profile of an industrial doctorate student?

info:eu-repo/semantics/acceptedVersio