362 research outputs found
A Note on N=2 Superstrings
In this note we investigate the generalised critical superstrings in
spacetime signature. We calculate the four-point functions for the
tachyon operators of these theories. In contrast to the usual superstring
in spacetime, the four-point functions do not vanish. The exchanged
particles of the four-point function are included in the physical spectrum of
the corresponding theory and have vanishing fermion charge.Comment: 8 pages, CTP TAMU-57/92, EFI-92-3
Optimal contact map alignment of protein–protein interfaces
The long-standing problem of constructing protein structure alignments is of central importance in computational biology. The main goal is to provide an alignment of residue correspondences, in order to identify homologous residues across chains. A critical next step of this is the alignment of protein complexes and their interfaces. Here, we introduce the program CMAPi, a two-dimensional dynamic programming algorithm that, given a pair of protein complexes, optimally aligns the contact maps of their interfaces: it produces polynomial-time near-optimal alignments in the case of multiple complexes. We demonstrate the efficacy of our algorithm on complexes from PPI families listed in the SCOPPI database and from highly divergent cytokine families. In comparison to existing techniques, CMAPi generates more accurate alignments of interacting residues within families of interacting proteins, especially for sequences with low similarity. While previous methods that use an all-atom based representation of the interface have been successful, CMAPi's use of a contact map representation allows it to be more tolerant to conformational changes and thus to align more of the interaction surface. These improved interface alignments should enhance homology modeling and threading methods for predicting PPIs by providing a basis for generating template profiles for sequence–structure alignment
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
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
Space-Time Supersymmetry of Extended Fermionic Strings in Dimensions
The fermionic string theory is revisited in light of its recently
proposed equivalence to the non-compact fermionic string model. The
issues of space-time Lorentz covariance and supersymmetry for the BRST
quantized strings living in uncompactified dimensions are
discussed. The equivalent local quantum supersymmetric field theory appears to
be the most transparent way to represent the space-time symmetries of the
extended fermionic strings and their interactions. Our considerations support
the Siegel's ideas about the presence of Lorentz symmetry as well as
at least one self-dual space-time supersymmetry in the theory of the
fermionic strings, though we do not have a compelling reason to argue about the
necessity of the {\it maximal} space-time supersymmetry. The world-sheet
arguments about the absence of all string massive modes in the physical
spectrum, and the vanishing of all string-loop amplitudes in the Polyakov
approach, are given on the basis of general consistency of the theory.Comment: 29 pages, LaTeX, ITP-UH-1/9
Twisting the N=2 String
The most general homogeneous monodromy conditions in string theory
are classified in terms of the conjugacy classes of the global symmetry group
. 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 (untwisted) and (\`a la Mathur
and Mukhi), as well as for being a parabolic element of . In
particular, the sixteen -twisted sectors of the 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
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
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
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
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