86 research outputs found
The effects of common structural variants on 3D chromatin structure
BACKGROUND: Three-dimensional spatial organization of chromosomes is defined by highly self-interacting regions 0.1-1 Mb in size termed Topological Associating Domains (TADs). Genetic factors that explain dynamic variation in TAD structure are not understood. We hypothesize that common structural variation (SV) in the human population can disrupt regulatory sequences and thereby influence TAD formation. To determine the effects of SVs on 3D chromatin organization, we performed chromosome conformation capture sequencing (Hi-C) of lymphoblastoid cell lines from 19 subjects for which SVs had been previously characterized in the 1000 genomes project. We tested the effects of common deletion polymorphisms on TAD structure by linear regression analysis of nearby quantitative chromatin interactions (contacts) within 240 kb of the deletion, and we specifically tested the hypothesis that deletions at TAD boundaries (TBs) could result in large-scale alterations in chromatin conformation. RESULTS: Large (> 10 kb) deletions had significant effects on long-range chromatin interactions. Deletions were associated with increased contacts that span the deleted region and this effect was driven by large deletions that were not located within a TAD boundary (nonTB). Some deletions at TBs, including a 80 kb deletion of the genes CFHR1 and CFHR3, had detectable effects on chromatin contacts. However for TB deletions overall, we did not detect a pattern of effects that was consistent in magnitude or direction. Large inversions in the population had a distinguishable signature characterized by a rearrangement of contacts that span its breakpoints. CONCLUSIONS: Our study demonstrates that common SVs in the population impact long-range chromatin structure, and deletions and inversions have distinct signatures. However, the effects that we observe are subtle and variable between loci. Genome-wide analysis of chromatin conformation in large cohorts will be needed to quantify the influence of common SVs on chromatin structure
Hermite Coherent States for Quadratic Refractive Index Optical Media
Producción CientÃficaLadder and shift operators are determined for the set of Hermite–Gaussian modes associated with an optical medium with quadratic refractive index profile. These operators allow to establish irreducible representations of the su(1, 1) and su(2) algebras. Glauber coherent states, as well as su(1, 1) and su(2) generalized coherent states, were constructed as solutions of differential equations admitting separation of variables. The dynamics of these coherent states along the optical axis is also evaluated.MINECO grant MTM2014-57129-C2-1-P and Junta de Castilla y Leon grant VA057U16
Geometric approach to nonlinear coherent states using the Higgs model for harmonic oscillator
In this paper, we investigate the relation between the curvature of the
physical space and the deformation function of the deformed oscillator algebra
using non-linear coherent states approach. For this purpose, we study
two-dimensional harmonic oscillators on the flat surface and on a sphere by
applying the Higgs modell. With the use of their algebras, we show that the
two-dimensional oscillator algebra on a surface can be considered as a deformed
one-dimensional oscillator algebra where the effect of the curvature of the
surface is appeared as a deformation function. We also show that the curvature
of the physical space plays the role of deformation parameter. Then we
construct the associated coherent states on the flat surface and on a sphere
and compare their quantum statistical properties, including quadrature
squeezing and antibunching effect.Comment: 12 pages, 7 figs. To be appeared in J. Phys.
Barut-Girardello coherent states for u(p,q) and sp(N,R) and their macroscopic superpositions
The Barut-Girardello coherent states (BG CS) representation is extended to
the noncompact algebras u(p,q) and sp(N,R) in (reducible) quadratic boson
realizations. The sp(N,R) BG CS take the form of multimode ordinary
Schr\"odinger cat states. Macroscopic superpositions of 2^{n-1} sp(N,R) CS (2^n
canonical CS, n=1,2,...) are pointed out which are overcomplete in the N-mode
Hilbert space and the relation between the canonical CS and the u(p,q) BG-type
CS representations is established. The sets of u(p,q) and sp(N,R) BG CS and
their discrete superpositions contain many states studied in quantum optics
(even and odd N-mode CS, pair CS) and provide an approach to quadrature
squeezing, alternative to that of intelligent states. New subsets of weakly and
strongly nonclassical states are pointed out and their statistical properties
(first- and second-order squeezing, photon number distributions) are discussed.
For specific values of the angle parameters and small amplitude of the
canonical CS components these states approaches multimode Fock states with one,
two or three bosons/photons. It is shown that eigenstates of a squared
non-Hermitian operator A^2 (generalized cat states) can exhibit squeezing of
the quadratures of A.Comment: 29 pages, LaTex, 5 figures. Improvements in text, corrections in some
formulas. To appear in J. Phys. A, v. 3
Quasi-Elastic Scattering in the Inclusive (He, t) Reaction
The triton energy spectra of the charge-exchange C(He,t) reaction
at 2 GeV beam energy are analyzed in the quasi-elastic nucleon knock-out
region. Considering that this region is mainly populated by the charge-exchange
of a proton in He with a neutron in the target nucleus and the final proton
going in the continuum, the cross-sections are written in the distorted-wave
impulse approximation. The t-matrix for the elementary exchange process is
constructed in the DWBA, using one pion- plus rho-exchange potential for the
spin-isospin nucleon- nucleon potential. This t-matrix reproduces the
experimental data on the elementary pn np process. The calculated
cross-sections for the C(He,t) reaction at to triton
emission angle are compared with the corresponding experimental data, and are
found in reasonable overall accord.Comment: 19 pages, latex, 11 postscript figures available at
[email protected], submitted to Phy.Rev.
The Construction of Some Important Classes of Generalized Coherent states: The Nonlinear Coherent States Method
Considering some important classes of generalized coherent states known in
literature, we demonstrated that all of them can be created via conventional
fashion, i.e. the "lowering operator eigen-state" and the "displacement
operator" techniques using the {\it "nonlinear coherent states"} approach. As a
result we obtained a {\it "unified method"} to construct a large class of
coherent states which already have been introduced by different prescriptions.Comment: 17pages, The section 7 in last version is revised, Some references
are adde
Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Background:
The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).
Methods:
This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.
Results:
Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes.
Conclusions:
The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies
Detailed Kinetics of the Direct Allo-Response in Human Liver Transplant Recipients: New Insights from an Optimized Assay
Conventional assays for quantification of allo-reactive T-cell precursor frequencies (PF) are relatively insensitive. We present a robust assay for quantification of PF of T-cells with direct donor-specificity, and establish the kinetics of circulating donor-specific T cells after liver transplantation (LTx). B cells from donor splenocytes were differentiated into professional antigen-presenting cells by CD40-engagement (CD40-B cells). CFSE-labelled PBMC from LTx-recipients obtained before and at several time points after LTx, were stimulated with donor-derived or 3rd party CD40-B cells. PF of donor-specific T cells were calculated from CFSE-dilution patterns, and intracellular IFN-γ was determined after re-stimulation with CD40-B cells. Compared to splenocytes, stimulations with CD40-B cells resulted in 3 to 5-fold higher responding T-cell PF. Memory and naïve T-cell subsets responded equally to allogeneic CD40-B cell stimulation. Donor-specific CD4+ and CD8+ T-cell PF ranged from 0.5 to 19% (median: 5.2%). One week after LTx, PF of circulating donor-specific CD4+ and CD8+ T cells increased significantly, while only a minor increase in numbers of T cells reacting to 3rd party allo-antigens was observed. One year after LTx numbers of CD4+ and CD8+ T cells reacting to donor antigens, as well as those reacting to 3rd party allo-antigens, were slightly lower compared to pre-transplant values. Moreover, CD4+ and CD8+ T cells responding to donor-derived, as well as those reacting to 3rd party CD40-B cells, produced less IFN-γ. In conclusion, our alternative approach enables detection of allo-reactive human T cells at high frequencies, and after application we conclude that donor-specific T-cell PF increase immediately after LTx. However, no evidence for a specific loss of circulating T-cells recognizing donor allo-antigens via the direct pathway up to 1 year after LTx was obtained, underscoring the relative insensitiveness of previous assays
Yeast : the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast
Among the most important factors influencing beer quality is the presence of well-adjusted amounts of higher alcohols and esters. Thus, a heavy body of literature focuses on these substances and on the parameters influencing their production by the brewing yeast. Additionally, the complex metabolic pathways involved in their synthesis require special attention. More than a century of data, mainly in genetic and proteomic fields, has built up enough information to describe in detail each step in the pathway for the synthesis of higher alcohols and their esters, but there is still place for more. Higher alcohols are formed either by anabolism or catabolism (Ehrlich pathway) of amino acids. Esters are formed by enzymatic condensation of organic acids and alcohols. The current paper reviews the up-to-date knowledge in the pathways involving the synthesis of higher alcohols and esters by brewing yeasts. Fermentation parameters affecting yeast response during biosynthesis of these aromatic substances are also fully reviewed.Eduardo Pires gratefully acknowledges the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for the PhD fellowship support (SFRH/BD/61777/2009). The financial contributions of the EU FP7 project Ecoefficient Biodegradable Composite Advanced Packaging (EcoBioCAP, grant agreement no. 265669) as well as of the Grant Agency of the Czech Republic (project GACR P503/12/1424) are also gratefully acknowledged. The authors thank the Ministry of Education, Youth and Sports of the Czech Republic (MSM 6046137305) for their financial support
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