164 research outputs found
Covariant actions and propagators for all spins, masses, and dimensions
The explicit covariant actions and propagators are given for fields
describing particles of all spins and masses, in any spacetime dimension.
Massive particles are realized as "dimensionally reduced" massless particles.
To obtain compact expressions for the propagators, it was useful to introduce
an auxiliary vector coordinate and consider "hyperfields" that are
functions of space and . The actions and propagators serve
as a basic starting point for concrete high spin computations amenable to
dimensional regularization, provided that gauge invariant interactions are
introduced.Comment: 37 page
Consistent actions for massive particles interacting with electromagnetism and gravity
Consistent interactions with electromagnetism and gravity for mass
particles of any spin are obtained. This is done by finding interactions which
preserve the covariantized massive gauge symmetry present in recently
constructed massive particle actions. This gauge principle is sufficient for
finding consistent completions of minimal as well as non-minimal couplings of
any type. For spins , consistency requires infinitely many
interaction terms in the action, including arbitrarily high order derivatives
of electromagnetic and gravitational curvatures, with correspondingly high
powers of . These interactions may be formally resummed and expressed in
terms of non-local operators. The inherent non-locality is a manifestation of
the known causality problems present in interacting massive particles with spin
.Comment: v1, 29 pages; v2, 30 pages: interactions linear in matter fields
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Properties of infinite product amplitudes: Veneziano, Virasoro, and Coon
We detail the properties of the Veneziano, Virasoro, and Coon amplitudes.
These tree-level four-point scattering amplitudes may be written as infinite
products with an infinite set of simple poles. Our approach for the Coon
amplitude uses the mathematical theory of -analysis. We interpret the Coon
amplitude as a -deformation of the Veneziano amplitude for all
and discover a new transcendental structure in its low-energy expansion. We
show that there is no analogous -deformation of the Virasoro amplitude.Comment: v1, 23 page
Generalized Veneziano and Virasoro amplitudes
We analyze so-called generalized Veneziano and generalized Virasoro
amplitudes. Under some physical assumptions, we find that their spectra must
satisfy an over-determined set of non-linear recursion relations. The recursion
relation for the generalized Veneziano amplitudes can be solved analytically
and yields a two-parameter family which includes the Veneziano amplitude, the
one-parameter family of Coon amplitudes, and a larger two-parameter family of
amplitudes with an infinite tower of spins at each mass level. In the
generalized Virasoro case, the only consistent solution is the string spectrum.Comment: v1, 22 page
A Screen for Endocytic Motifs
Sorting signals for cargo selection into coated vesicles are usually in the form of short linear motifs. Three motifs for clathrin-mediated endocytosis have been identified: YXXΦ, [D/E]XXXL[L/I] and FXNPXY. To search for new endocytic motifs, we made a library of CD8 chimeras with random sequences in their cytoplasmic tails, and used a novel fluorescence-activated cell sorting (FACS)-based assay to select for endocytosed constructs. Out of the five tails that were most efficiently internalized, only one was found to contain a conventional motif. Two contain dileucine-like sequences that appear to be variations on the [D/E]XXXL[L/I] motif. Another contains a novel internalization signal, YXXXΦN, which is able to function in cells expressing a mutant µ2 that cannot bind YXXΦ, indicating that it is not a variation on the YXXΦ motif. Similar sequences are present in endogenous proteins, including a functional YXXXΦN (in addition to a classical YXXΦ) in cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Thus, the repertoire of endocytic motifs is more extensive than the three well-characterized sorting signals
HIV-1 Matrix Dependent Membrane Targeting Is Regulated by Gag mRNA Trafficking
Retroviral Gag polyproteins are necessary and sufficient for virus budding. Productive HIV-1 Gag assembly takes place at the plasma membrane. However, little is known about the mechanisms by which thousands of Gag molecules are targeted to the plasma membrane. Using a bimolecular fluorescence complementation (BiFC) assay, we recently reported that the cellular sites and efficiency of HIV-1 Gag assembly depend on the precise pathway of Gag mRNA export from the nucleus, known to be mediated by Rev. Here we describe an assembly deficiency in human cells for HIV Gag whose expression depends on hepatitis B virus (HBV) post-transcriptional regulatory element (PRE) mediated-mRNA nuclear export. PRE-dependent HIV Gag expressed well in human cells, but assembled with slower kinetics, accumulated intracellularly, and failed to associate with a lipid raft compartment where the wild-type Rev-dependent HIV-1 Gag efficiently assembles. Surprisingly, assembly and budding of PRE-dependent HIV Gag in human cells could be rescued in trans by co-expression of Rev-dependent Gag that provides correct membrane targeting signals, or in cis by replacing HIV matrix (MA) with other membrane targeting domains. Taken together, our results demonstrate deficient membrane targeting of PRE-dependent HIV-1 Gag and suggest that HIV MA function is regulated by the trafficking pathway of the encoding mRNA
Plasma Membrane Is the Site of Productive HIV-1 Particle Assembly
Recently proposed models that have gained wide acceptance posit that HIV-1 virion morphogenesis is initiated by targeting the major structural protein (Gag) to late endosomal membranes. Thereafter, late endosome-based secretory pathways are thought to deliver Gag or assembled virions to the plasma membrane (PM) and extracellular milieu. We present several findings that are inconsistent with this model. Specifically, we demonstrate that HIV-1 Gag is delivered to the PM, and virions are efficiently released into the extracellular medium, when late endosome motility is abolished. Furthermore, we show that HIV-1 virions are efficiently released when assembly is rationally targeted to the PM, but not when targeted to late endosomes. Recently synthesized Gag first accumulates and assembles at the PM, but a proportion is subsequently internalized via endocytosis or phagocytosis, thus accounting for observations of endosomal localization. We conclude that HIV-1 assembly is initiated and completed at the PM, and not at endosomal membranes
AP-2 complex-mediated endocytosis of Drosophila Crumbs regulates polarity via antagonizing Stardust
Maintenance of epithelial polarity depends on the correct localization and levels of polarity determinants. The evolutionarily conserved transmembrane protein Crumbs is crucial for the size and identity of the apical membrane, yet little is known about the molecular mechanisms controlling the amount of Crumbs at the surface. Here, we show that Crumbs levels on the apical membrane depend on a well-balanced state of endocytosis and stabilization. The adaptor protein 2 (AP-2) complex binds to a motif in the cytoplasmic tail of Crumbs that overlaps with the binding site of Stardust, a protein known to stabilize Crumbs on the surface. Preventing endocytosis by mutations in AP-2 causes expansion of the Crumbs-positive plasma membrane and polarity defects, which can be partially rescued by removing one copy of crumbs. Strikingly, knocking-down both AP-2 and Stardust retains Crumbs on the membrane. This study provides evidence for a molecular mechanism, based on stabilization and endocytosis, to adjust surface levels of Crumbs, which are essential for maintaining epithelial polarity
T Cell Polarization at the Virological Synapse
Cell-to-cell spread of HIV-1 between CD4+ T cells takes place at multimolecular structures called virological synapses. A defining feature of the virological synapse is polarization of viral assembly and budding at sites of T cell-T cell contact. Recent work is beginning to address how viral proteins are targeted to the virological synapse and the molecular mechanisms that regulate HIV-1 egress by cell-to-cell spread. This review discusses our current understanding of these processes and considers how T cell polarization during other forms of intercellular communication may provide insight into HIV-1 assembly and dissemination
Revisions to the International Neuroblastoma Response Criteria: A Consensus Statement From the National Cancer Institute Clinical Trials Planning Meeting
Purpose
More than two decades ago, an international working group established the International Neuroblastoma Response Criteria (INRC) to assess treatment response in children with neuroblastoma. However, this system requires modification to incorporate modern imaging techniques and new methods for quantifying bone marrow disease that were not previously widely available. The National Cancer Institute sponsored a clinical trials planning meeting in 2012 to update and refine response criteria for patients with neuroblastoma.
Methods
Multidisciplinary investigators from 13 countries reviewed data from published trials performed through cooperative groups, consortia, and single institutions. Data from both prospective and retrospective trials were used to refine the INRC. Monthly international conference calls were held from 2011 to 2015, and consensus was reached through review by working group leadership and the National Cancer Institute Clinical Trials Planning Meeting leadership council.
Results
Overall response in the revised INRC will integrate tumor response in the primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and iodine-123 (123I) –metaiodobenzylguanidine (MIBG) scans or [18F]fluorodeoxyglucose–positron emission tomography scans if the tumor is MIBG nonavid. 123I-MIBG scans, or [18F]fluorodeoxyglucose–positron emission tomography scans for MIBG-nonavid disease, replace technetium-99m diphosphonate bone scintigraphy for osteomedullary metastasis assessment. Bone marrow will be assessed by histology or immunohistochemistry and cytology or immunocytology. Bone marrow with ≤ 5% tumor involvement will be classified as minimal disease. Urinary catecholamine levels will not be included in response assessment. Overall response will be defined as complete response, partial response, minor response, stable disease, or progressive disease.
Conclusion
These revised criteria will provide a uniform assessment of disease response, improve the interpretability of clinical trial results, and facilitate collaborative trial designs
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