675 research outputs found
Proof Theory and Ordered Groups
Ordering theorems, characterizing when partial orders of a group extend to
total orders, are used to generate hypersequent calculi for varieties of
lattice-ordered groups (l-groups). These calculi are then used to provide new
proofs of theorems arising in the theory of ordered groups. More precisely: an
analytic calculus for abelian l-groups is generated using an ordering theorem
for abelian groups; a calculus is generated for l-groups and new decidability
proofs are obtained for the equational theory of this variety and extending
finite subsets of free groups to right orders; and a calculus for representable
l-groups is generated and a new proof is obtained that free groups are
orderable
Generic Modal Cut Elimination Applied to Conditional Logics
We develop a general criterion for cut elimination in sequent calculi for
propositional modal logics, which rests on absorption of cut, contraction,
weakening and inversion by the purely modal part of the rule system. Our
criterion applies also to a wide variety of logics outside the realm of normal
modal logic. We give extensive example instantiations of our framework to
various conditional logics. For these, we obtain fully internalised calculi
which are substantially simpler than those known in the literature, along with
leaner proofs of cut elimination and complexity. In one case, conditional logic
with modus ponens and conditional excluded middle, cut elimination and
complexity were explicitly stated as open in the literature
Practical Implementation of Attitude-Control Algorithms for an Underactuated Satellite
The challenging problem of controlling the attitude of satellites subject to actuator failures has been the subject of increased attention in recent years. The problem of controlling the attitude of a satellite on all three axes with two reaction wheels is addressed in this paper. This system is controllable in a zero-momentum mode. Three-axis attitude stability is proven by imposing a singular quaternion feedback law to the angular velocity trajectories.Two approaches are proposed and compared to achieve three-axis control: The first one does not require angular velocity measurements and is based on the assumption of a perfect zero momentum, while the second approach consists of tracking the desired angular velocity trajectories. The full-state feedback is a nonlinear singular controller. In-orbit tests of the first approach provide an unprecedented practical proof of three-axis stability with two control torques. The angular velocity tracking approach is shown to be less efficient using the nonlinear singular controller. However, when inverse optimization theory is applied to enhance the nonlinear singular controller, the angular velocity tracking approach is shown to be the most efficient. The resulting switched inverse optimal controller allows for a significant enhancement of settling time, for a prescribed level of the integrated torque
Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era
Abstract
Background
Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings.
Methods
We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding.
Results
Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4.
Conclusions
These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci.http://deepblue.lib.umich.edu/bitstream/2027.42/109537/1/12920_2013_Article_485.pd
The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations
C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy
Iron and copper sulfides in asteroid (162173) Ryugu: Formation conditions and a comparison to the CI and CY chondrites
JAXA's Hayabusa2 sample return mission visited the volatile‐rich carbonaceous (C‐type) asteroid (162173) Ryugu with the aim of ground‐truthing remote observations, returning a pristine sample from a C‐type asteroid, and strengthening links between asteroids and the meteorite collection. Here, we have conducted a systematic study of coarse (>10 μm) sulfide grains in Ryugu particles C0025‐01 and C0103‐02, the CI chondrites Orgueil and Ivuna, and the CY chondrites Y‐86029 (Stage III, heated to 500–750°C) and Y‐86720 (Stage IV, >750°C), using scanning electron microscopy (SEM) and electron probe microanalysis (EPMA). Sulfides are sensitive tracers of secondary alteration conditions, and we find that Ryugu and the CI chondrites share a distinct sulfide assemblage that includes the iron sulfides pyrrhotite and pentlandite, and the copper sulfide cubanite, that equilibrated during periods of low temperature (~25°C) aqueous alteration. Sulfides in the CY chondrites are compositionally distinct from Ryugu and the CI chondrites as a result of post‐hydration heating. However, the occurrence of Cu‐rich sulfides in Ryugu, the CIs, and the CYs suggests a genetic relationship between these samples
Combining Effects and Coeffects via Grading
This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Association for Computing Machinery. and are two general, complementary aspects of program behaviour. They roughly correspond to computations which change the execution context (effects) versus computations which make demands on the context (coeffects). Effectful features include partiality, non-determinism, input-output, state, and exceptions. Coeffectful features include resource demands, variable access, notions of linearity, and data input requirements.
The effectful or coeffectful behaviour of a program can be captured and described via type-based analyses, with fine grained information provided by monoidal effect annotations and semiring coeffects. Various recent work has proposed models for such typed calculi in terms of for effects and for coeffects.
Effects and coeffects have been studied separately so far, but in practice many computations are both effectful and coeffectful, e.g., possibly throwing exceptions but with resource requirements. To remedy this, we introduce a new general calculus with a combined . This can describe both the and that a program has on its context, as well as interactions between these effectful and coeffectful features of computation. The effect-coeffect system has a denotational model in terms of effect-graded monads and coeffect-graded comonads where interaction is expressed via the novel concept of . This graded semantics unifies the syntactic type theory with the denotational model. We show that our calculus can be instantiated to describe in a natural way various different kinds of interaction between a program and its evaluation context.Orchard was supported by EPSRC grant EP/M026124/1 and EP/K011715/1 (whilst previously at Imperial College London), Katsumata by JSPS KAKENHI grant JP15K00014, Uustalu by Estonian Min. of Educ. and Res. grant IUT33-13 and Estonian Sci. Found. grant 9475. Gaboardi’s work was done in part while at the University of Dundee, UK supported by EPSRC grant EP/M022358/1
Measured and projected beam backgrounds in the Belle II experiment at the SuperKEKB collider
The Belle II experiment at the SuperKEKB electron-positron collider aims to
collect an unprecedented data set of to study -violation
in the -meson system and to search for Physics beyond the Standard Model.
SuperKEKB is already the world's highest-luminosity collider. In order to
collect the planned data set within approximately one decade, the target is to
reach a peak luminosity of by further
increasing the beam currents and reducing the beam size at the interaction
point by squeezing the betatron function down to . To ensure detector longevity and maintain good reconstruction
performance, beam backgrounds must remain well controlled. We report on current
background rates in Belle II and compare these against simulation. We find that
a number of recent refinements have significantly improved the background
simulation accuracy. Finally, we estimate the safety margins going forward. We
predict that backgrounds should remain high but acceptable until a luminosity
of at least is reached for
. At this point, the most vulnerable Belle II
detectors, the Time-of-Propagation (TOP) particle identification system and the
Central Drift Chamber (CDC), have predicted background hit rates from
single-beam and luminosity backgrounds that add up to approximately half of the
maximum acceptable rates.Comment: 28 pages, 17 figures, 9 tables (revised
An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime
The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure.
We describe an impact experiment on Ryugu using Hayabusa2’s Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition
of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu’s surface age
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