900 research outputs found
MHC-linked and un-linked class I genes in the wallaby
Background: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and
non-classical genes that are found in all vertebrates and involved in diverse immune functions. However,
there is a fundamental difference between the organization of class I genes in mammals and non-mammals.
Non-mammals have a single classical gene responsible for antigen presentation, which is linked to the
antigen processing genes, including TAP. This organization allows co-evolution of advantageous class Ia/
TAP haplotypes. In contrast, mammals have multiple classical genes within the MHC, which are separated
from the antigen processing genes by class III genes. It has been hypothesized that separation of classical
class I genes from antigen processing genes in mammals allowed them to duplicate. We investigated this
hypothesis by characterizing the class I genes of the tammar wallaby, a model marsupial that has a novel
MHC organization, with class I genes located within the MHC and 10 other chromosomal locations.
Results: Sequence analysis of 14 BACs containing 15 class I genes revealed that nine class I genes, including
one to three classical class I, are not linked to the MHC but are scattered throughout the genome.
Kangaroo Endogenous Retroviruses (KERVs) were identified flanking the MHC un-linked class I. The
wallaby MHC contains four non-classical class I, interspersed with antigen processing genes. Clear
orthologs of non-classical class I are conserved in distant marsupial lineages.
Conclusion: We demonstrate that classical class I genes are not linked to antigen processing genes in the
wallaby and provide evidence that retroviral elements were involved in their movement. The presence of
retroviral elements most likely facilitated the formation of recombination hotspots and subsequent
diversification of class I genes. The classical class I have moved away from antigen processing genes in
eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this
loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of
pathogens. The discovery of non-classical orthologs between distantly related marsupial species is unusual
for the rapidly evolving class I genes and may indicate an important marsupial specific function
Gate fidelity fluctuations and quantum process invariants
We characterize the quantum gate fidelity in a state-independent manner by
giving an explicit expression for its variance. The method we provide can be
extended to calculate all higher order moments of the gate fidelity. Using
these results we obtain a simple expression for the variance of a single qubit
system and deduce the asymptotic behavior for large-dimensional quantum
systems. Applications of these results to quantum chaos and randomized
benchmarking are discussed.Comment: 13 pages, no figures, published versio
The tammar wallaby major histocompatibility complex shows evidence of past genomic instability
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The major histocompatibility complex (MHC) is a group of genes with a variety of roles in the innate and adaptive immune responses. MHC genes form a genetically linked cluster in eutherian mammals, an organization that is thought to confer functional and evolutionary advantages to the immune system. The tammar wallaby (Macropus eugenii), an Australian marsupial, provides a unique model for understanding MHC gene evolution, as many of its antigen presenting genes are not linked to the MHC, but are scattered around the genome. Results Here we describe the 'core' tammar wallaby MHC region on chromosome 2q by ordering and sequencing 33 BAC clones, covering over 4.5 MB and containing 129 genes. When compared to the MHC region of the South American opossum, eutherian mammals and non-mammals, the wallaby MHC has a novel gene organization. The wallaby has undergone an expansion of MHC class II genes, which are separated into two clusters by the class III genes. The antigen processing genes have undergone duplication, resulting in two copies of TAP1 and three copies of TAP2. Notably, Kangaroo Endogenous Retroviral Elements are present within the region and may have contributed to the genomic instability. Conclusions The wallaby MHC has been extensively remodeled since the American and Australian marsupials last shared a common ancestor. The instability is characterized by the movement of antigen presenting genes away from the core MHC, most likely via the presence and activity of retroviral elements. We propose that the movement of class II genes away from the ancestral class II region has allowed this gene family to expand and diversify in the wallaby. The duplication of TAP genes in the wallaby MHC makes this species a unique model organism for studying the relationship between MHC gene organization and function.Peer Reviewe
Voltage-activated currents in somatic muscle of the nematode parasite Ascaris suum
1. Voltage-activated currents in cell bodies of the somatic muscle cells of Ascaris suum were studied using a two-microelectrode voltage-clamp technique. Cells recorded from had resting membrane potentials around -35 mV and had input conductances in the range 1-10 microS. 2. In cells bathed in artificial perienteric fluid, depolarizing steps from a holding potential of -35 mV elicited outward currents at a threshold of -15 mV. These currents had inwardly directed inflections on the rising phase, suggesting the presence of more than one current. Hyperpolarizing steps did not activate current. 3. Tetraethylammonium (TEA+, 69 mmol l-1) blocked the outward currents and allowed a voltage-dependent inactivating Ca2+ current to be observed. The peak current-voltage relationship was U-shaped with a threshold around -15 mV and peak at +5 mV. The reversal potential of the Ca2+ current was estimated by extrapolation to be +45 mV. 4. The permeability of the voltage-activated outward currents was studied by examining reversal potentials of tail currents. The reversal potentials were linearly dependent on the logarithm of the extracellular potassium concentration if extracellular [K+] was greater than 10 mmol l-1. The Na+/K+ permeability ratio of the currents was 0.04. 5. Inactivation, seen as a decline following the peak of the K+ current, was produced by maintained depolarization. The recovery from inactivation was complex and could be described by the sum of two exponentials with time constants of 0.67 s and 20.1 s. Steady-state inactivation of the K+ currents was observed at a range of holding potentials. Only a proportion (34%) of the total K+ current was inactivated by holding potentials more positive than -20 mV. 6. Extracellular application of 5 mmol l-1 4-aminopyridine (4-AP) selectively abolished an early fast component of the K+ current (the peak). The 4-AP-sensitive current decayed quickly with a time constant of around 10 ms; a Boltzmann fit to its activation curve had a half-maximal activation voltage of +14 mV and a 'slope' of 10.5 mV. The 4-AP-resistant current decayed with a time constant of around 1 s; a Boltzmann fit to its activation curve had a half-maximal activation voltage of +29 mV and a 'slope' of 12 mV. 7. Depolarization activates a Ca2+ current and two K+ currents: the K+ currents were separated into lower-threshold, fast-inactivating (Ia-like) and higher-threshold, slowly inactivating (Ik-like) currents
Quantum heuristic algorithm for traveling salesman problem
We propose a quantum heuristic algorithm to solve a traveling salesman
problem by generalizing Grover search. Sufficient conditions are derived to
greatly enhance the probability of finding the tours with extremal costs,
reaching almost to unity and they are shown characterized by statistical
properties of tour costs. In particular for a Gaussian distribution of the
tours along the cost we show that the quantum algorithm exhibits the quadratic
speedup of its classical counterpart, similarly to Grover search.Comment: Published versio
Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study
Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.
Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.
Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.
Trial registration number NCT01836692; Pre-result
Efficient and feasible state tomography of quantum many-body systems
We present a novel method to perform quantum state tomography for
many-particle systems which are particularly suitable for estimating states in
lattice systems such as of ultra-cold atoms in optical lattices. We show that
the need for measuring a tomographically complete set of observables can be
overcome by letting the state evolve under some suitably chosen random circuits
followed by the measurement of a single observable. We generalize known results
about the approximation of unitary 2-designs, i.e., certain classes of random
unitary matrices, by random quantum circuits and connect our findings to the
theory of quantum compressed sensing. We show that for ultra-cold atoms in
optical lattices established techniques like optical super-lattices, laser
speckles, and time-of-flight measurements are sufficient to perform fully
certified, assumption-free tomography. Combining our approach with tensor
network methods - in particular the theory of matrix-product states - we
identify situations where the effort of reconstruction is even constant in the
number of lattice sites, allowing in principle to perform tomography on
large-scale systems readily available in present experiments.Comment: 10 pages, 3 figures, minor corrections, discussion added, emphasizing
that no single-site addressing is needed at any stage of the scheme when
implemented in optical lattice system
Allopurinol and Nitric Oxide Activity in the Cerebral Circulation of Those With Diabetes: A randomized trial
OBJECTIVE—Type 2 diabetes increases risk of stroke, perhaps because of impaired cerebrovascular basal nitric oxide (NO) activity. We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol
Quantum state merging and negative information
We consider a quantum state shared between many distant locations, and define
a quantum information processing primitive, state merging, that optimally
merges the state into one location. As announced in [Horodecki, Oppenheim,
Winter, Nature 436, 673 (2005)], the optimal entanglement cost of this task is
the conditional entropy if classical communication is free. Since this quantity
can be negative, and the state merging rate measures partial quantum
information, we find that quantum information can be negative. The classical
communication rate also has a minimum rate: a certain quantum mutual
information. State merging enabled one to solve a number of open problems:
distributed quantum data compression, quantum coding with side information at
the decoder and sender, multi-party entanglement of assistance, and the
capacity of the quantum multiple access channel. It also provides an
operational proof of strong subadditivity. Here, we give precise definitions
and prove these results rigorously.Comment: 23 pages, 3 figure
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