4,369 research outputs found
Structural Comparison of Allogeneic and Syngeneic T Cell Receptor–Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing Vβ Interactions
The crystal structures of the 2C/H-2Kbm3–dEV8 allogeneic complex at 2.4 Å and H-2Kbm3–dEV8 at 2.15 Å, when compared with their syngeneic counterparts, elucidate structural changes that induce an alloresponse. The Asp77Ser mutation that imbues H-2Kbm3–dEV8 with its alloreactive properties is located beneath the peptide and does not directly contact the T cell receptor (TCR). However, the buried mutation induces local rearrangement of the peptide itself to preserve hydrogen bonding interactions between the peptide and the α1 77 residue. The COOH terminus of the peptide main chain is tugged toward the α1-helix such that its presentation to the TCR is altered. These changes increase the stability of the allogeneic peptide-major histocompatibility complex (pMHC) complex and increase complementarity in the TCR–pMHC interface, placing greater emphasis on recognition of the pMHC by the TCR β-chain, evinced by an increase in shape complementarity, buried surface area, and number of TCR–pMHC contacting residues. A nearly fourfold increase in the number of β-chain–pMHC contacts is accompanied by a concomitant 64% increase in β-chain–pMHC shape complementarity. Thus, the allogeneic mutation causes the same peptide to be presented differently, temporally and spatially, by the allogeneic and syngeneic MHCs
Experimental evidence for 56Ni-core breaking from the low-spin structure of the N=Z nucleus 58Cu
Low-spin states in the odd-odd N=Z nucleus 58Cu were investigated with the
58Ni(p,n gamma)58Cu fusion evaporation reaction at the FN-tandem accelerator in
Cologne. Seventeen low spin states below 3.6 MeV and 17 new transitions were
observed. Ten multipole mixing ratios and 17 gamma-branching ratios were
determined for the first time. New detailed spectroscopic information on the
2+,2 state, the Isobaric Analogue State (IAS) of the 2+,1,T=1 state of 58Ni,
makes 58Cu the heaviest odd-odd N=Z nucleus with known B(E2;2+,T=1 --> 0+,T=1)
value. The 4^+ state at 2.751 MeV, observed here for the first time, is
identified as the IAS of the 4+,1,T=1 state in 58Ni. The new data are compared
to full pf-shell model calculations with the novel GXPF1 residual interaction
and to calculations within a pf5/2 configurational space with a residual
surface delta interaction. The role of the 56Ni core excitations for the
low-spin structure in 58Cu is discussed.Comment: 15 pages, 7 figures, submitted to Phys. Rev.
Projected shell model study of odd-odd f-p-g shell proton-rich nuclei
A systematic study of 2-quasiparticle bands of the proton-rich odd-odd nuclei
in the mass A ~ 70-80 region is performed using the projected shell model
approach. The study includes Br-, Rb-, and Y-isotopes with N = Z+2, and Z+4. We
describe the energy spectra and electromagnetic transition strengths in terms
of the configuration mixing of the angular-momentum projected
multi-quasiparticle states. Signature splitting and signature inversion in the
rotational bands are discussed and are shown to be well described. A
preliminary study of the odd-odd N = Z nucleus, 74Rb using the concept of
spontaneous symmetry breaking is also presented.Comment: 14 pages, 7 figures, final version accepted by Phys. Rev.
Muscle co‐activation across activities of daily living in individuals with knee osteoarthritis
Core-coupled states and split proton-neutron quasi-particle multiplets in 122-126Ag
Neutron-rich silver isotopes were populated in the fragmentation of a 136Xe
beam and the relativistic fission of 238U. The fragments were mass analyzed
with the GSI Fragment separator and subsequently implanted into a passive
stopper. Isomeric transitions were detected by 105 HPGe detectors. Eight
isomeric states were observed in 122-126Ag nuclei. The level schemes of
122,123,125Ag were revised and extended with isomeric transitions being
observed for the first time. The excited states in the odd-mass silver isotopes
are interpreted as core-coupled states. The isomeric states in the even-mass
silver isotopes are discussed in the framework of the proton-neutron split
multiplets. The results of shell-model calculations, performed for the most
neutron-rich silver nuclei are compared to the experimental data
Can integrated care help in meeting the challenges posed on our health care systems by COVID-19? Some preliminary lessons learned from the european VIGOUR project
The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOUR
TCRep 3D: An Automated In Silico Approach to Study the Structural Properties of TCR Repertoires
TCRep 3D is an automated systematic approach for TCR-peptide-MHC class I structure prediction, based on homology and ab initio modeling. It has been considerably generalized from former studies to be applicable to large repertoires of TCR. First, the location of the complementary determining regions of the target sequences are automatically identified by a sequence alignment strategy against a database of TCR Vα and Vβ chains. A structure-based alignment ensures automated identification of CDR3 loops. The CDR are then modeled in the environment of the complex, in an ab initio approach based on a simulated annealing protocol. During this step, dihedral restraints are applied to drive the CDR1 and CDR2 loops towards their canonical conformations, described by Al-Lazikani et. al. We developed a new automated algorithm that determines additional restraints to iteratively converge towards TCR conformations making frequent hydrogen bonds with the pMHC. We demonstrated that our approach outperforms popular scoring methods (Anolea, Dope and Modeller) in predicting relevant CDR conformations. Finally, this modeling approach has been successfully applied to experimentally determined sequences of TCR that recognize the NY-ESO-1 cancer testis antigen. This analysis revealed a mechanism of selection of TCR through the presence of a single conserved amino acid in all CDR3β sequences. The important structural modifications predicted in silico and the associated dramatic loss of experimental binding affinity upon mutation of this amino acid show the good correspondence between the predicted structures and their biological activities. To our knowledge, this is the first systematic approach that was developed for large TCR repertoire structural modeling
UBVRI Light Curves of 44 Type Ia Supernovae
We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from
1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence
Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The
data set comprises 2190 observations and is the largest homogeneously observed
and reduced sample of SN Ia to date, nearly doubling the number of
well-observed, nearby SN Ia with published multicolor CCD light curves. The
large sample of U-band photometry is a unique addition, with important
connections to SN Ia observed at high redshift. The decline rate of SN Ia
U-band light curves correlates well with the decline rate in other bands, as
does the U-B color at maximum light. However, the U-band peak magnitudes show
an increased dispersion relative to other bands even after accounting for
extinction and decline rate, amounting to an additional ~40% intrinsic scatter
compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication
in the Astronomical Journal. Version with high-res figures and electronic
data at http://astron.berkeley.edu/~saurabh/cfa2snIa
Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.
A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
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