4,484 research outputs found
Exploiting Polyhedral Symmetries in Social Choice
A large amount of literature in social choice theory deals with quantifying
the probability of certain election outcomes. One way of computing the
probability of a specific voting situation under the Impartial Anonymous
Culture assumption is via counting integral points in polyhedra. Here, Ehrhart
theory can help, but unfortunately the dimension and complexity of the involved
polyhedra grows rapidly with the number of candidates. However, if we exploit
available polyhedral symmetries, some computations become possible that
previously were infeasible. We show this in three well known examples:
Condorcet's paradox, Condorcet efficiency of plurality voting and in Plurality
voting vs Plurality Runoff.Comment: 14 pages; with minor improvements; to be published in Social Choice
and Welfar
Functional Analysis of the Chemokine Receptor CCR3 on Airway Epithelial Cells
The function of chemokine receptors on structural cells is only partially known. We previously reported the expression of a functional CCR3 receptor on airway epithelial cells (EC). We speculated that CCR3 might drive wound repair and expression of inflammatory genes in epithelium. The human airway EC lines BEAS-2B, 16-HBE, and primary bronchial EC were used to test the effect of in vitro challenge with the CCR3 ligands CCL11/eotaxin, CCL24/eotaxin-2, or CCL26/eotaxin-3 on 1) wound repair, using an established wound model; 2) cell proliferation and chemotaxis, using specific fluorometric assays; and 3) gene expression, using pathway-specific arrays for inflammatory and profibrotic cytokines, chemokines, and chemokine receptor genes. Agonist specificity was tested by cell pretreatment with an AstraZeneca CCR3 antagonist (10(-8) - 10(-6) M). CCL24 challenge significantly accelerated epithelial wound closure, with similar effects exerted by CCL11 and CCL26. This effect was time dependent, submaximal at 1 nM, and comparable in potency to epidermal growth factor. CCL24 induced a concentration-dependent increase in EC proliferation and chemotaxis, with significant effects observed at 10 nM. The AstraZeneca compound selectively inhibited these CCL24-mediated responses. CCL11 induced the up-regulation of several profibrogenic molecules such as fibroblast growth factor 1 and 5 and of several CC and CXC chemokines. Epithelial immunostaining for CCR3 was stronger in bronchial biopsies of asthmatics displaying marked inflammatory changes than in nondiseased samples. Epithelial CCR3 participates in key functions for wound repair, amplifies the expression of profibrogenic and chemokine transcripts, and appears up-regulated in inflamed asthmatic airways
Gaseous Galaxy Halos
Galactic halo gas traces inflowing star formation fuel and feedback from a
galaxy's disk and is therefore crucial to our understanding of galaxy
evolution. In this review, we summarize the multi-wavelength observational
properties and origin models of Galactic and low redshift spiral galaxy halo
gas. Galactic halos contain multiphase gas flows that are dominated in mass by
the ionized component and extend to large radii. The densest, coldest halo gas
observed in neutral hydrogen (HI) is generally closest to the disk (< 20 kpc),
and absorption line results indicate warm and warm-hot diffuse halo gas is
present throughout a galaxy's halo. The hot halo gas detected is not a
significant fraction of a galaxy's baryons. The disk-halo interface is where
the multiphase flows are integrated into the star forming disk, and there is
evidence for both feedback and fueling at this interface from the temperature
and kinematic gradient of the gas and HI structures. The origin and fate of
halo gas is considered in the context of cosmological and idealized local
simulations. Accretion along cosmic filaments occurs in both a hot (> 10^5.5 K)
and cold mode in simulations, with the compressed material close to the disk
the coldest and densest, in agreement with observations. There is evidence in
halo gas observations for radiative and mechanical feedback mechanisms,
including escaping photons from the disk, supernova-driven winds, and a
galactic fountain. Satellite accretion also leaves behind abundant halo gas.
This satellite gas interacts with the existing halo medium, and much of this
gas will become part of the diffuse halo before it can reach the disk. The
accretion rate from cold and warm halo gas is generally below a galaxy disk's
star formation rate, but gas at the disk-halo interface and stellar feedback
may be important additional fuel sources.Comment: 50 pages, 9 figures (1 in 3D, view with a current version of Adobe),
to appear in ARA&A, 50, 49
Diminished temperature and vegetation seasonality over northern high latitudes
Global temperature is increasing, especially over northern lands (>50°âN), owing to positive feedbacks1. As this increase is most pronounced in winter, temperature seasonality (ST)âconventionally defined as the difference between summer and winter temperaturesâis diminishing over time2, a phenomenon that is analogous to its equatorward decline at an annual scale. The initiation, termination and performance of vegetation photosynthetic activity are tied to threshold temperatures3. Trends in the timing of these thresholds and cumulative temperatures above them may alter vegetation productivity, or modify vegetation seasonality (SV), over time. The relationship between ST and SV is critically examined here with newly improved ground and satellite data sets. The observed diminishment of ST and SV is equivalent to 4° and 7° (5° and 6°) latitudinal shift equatorward during the past 30 years in the Arctic (boreal) region. Analysis of simulations from 17 state-of-the-art climate models4 indicates an additional STdiminishment equivalent to a 20° equatorward shift could occur this century. How SV will change in response to such large projected ST declines and the impact this will have on ecosystem services5 are not well understood. Hence the need for continued monitoring6 of northern lands as their seasonal temperature profiles evolve to resemble thosefurther south.Lopullinen vertaisarvioitu kĂ€sikirjoitu
A functional methylome map of ulcerative colitis
The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation
Applying blockchain to improve the integrity of the software development process
Software development is a complex endeavor that encompasses application and implementation layers with functional (refers to
what is done) and non-functional (how is done) aspects. The efforts to
scale agile software development practices are not wholly able to address
issues such as integrity, which is a crucial non-functional aspect of the
software development process. However, if we consider most software failures are Byzantine failures (i.e., where components may fail and there is
imperfect information on which a component has failed.) that might impair the operation but do not completely disable the production line. In
this paper, we assume software practitioners who cause defects as Byzantine participants and claim that most software failures can be mitigated
by viewing software development as the Byzantine Generals Problem.
Consequently, we propose a test-driven incentive mechanism based on
a blockchain concept to orchestrate the software development process
where production is controlled by a similar infrastructure based on the
working principles of blockchain. We discuss the model that integrates
blockchain with the software development process, and provide some recommendations for future work to address the issues while orchestrating
software productio
Chromophobe renal cell carcinoma with prolonged response to targeted therapy: a case report
Abstract Introduction Chromophobe renal cell carcinoma is universally accepted as a distinct subtype of renal cell carcinoma. There are conflicting reports on prognosis, and few data on response to treatment exist. Currently, we do not have any effective treatment for the metastatic disease apart from surgical procedures. Current strategies are based on results obtained in the context of clear cell-type renal cell carcinoma. Separate trials for rare histologies seem unfeasible and are unlikely to be performed. For these cases, clinical observations are an important part for advancing therapeutic insight. In recent years, novel tyrosine kinase inhibitors have been shown to have significant clinical benefit in advanced renal cell carcinoma. Case presentation We present the case of a 43-year-old Caucasian man with advanced chromophobe renal cell carcinoma treated with the tyrosine kinase inhibitor sunitinib and subsequently with sorafenib and the mammalian target of the rapamycin inhibitor everolimus, achieving a prolonged response and significant clinical benefit. We report an unexpectedly high efficacy of everolimus as a third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. Conclusions Up to now, no published data from randomized clinical studies have addressed the question of efficacy of everolimus as a third-line treatment after failure of tyrosine kinase inhibitors. To the best of our knowledge, this case is the first report of chromophobe renal cell carcinoma treated successfully with sequential tyrosine kinase and mammalian target of rapamycin inhibitor therapy. Notably, the time on treatment with sunitinib exceeded four years. The case presented here implies that everolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.</p
The co-administration of quetiapine or placebo to cognitive-behavior therapy in treatment refractory depression: A preliminary trial
Level of suicidal intent predicts overall mortality and suicide after attempted suicide: a 12-year follow-up study
BACKGROUND: The aim of this study was to comprehensively examine clinical risk factors, including suicide intent and hopelessness, for suicide and risk of death from all causes after attempted suicide over a 12-year follow-up period. METHODS: A systematic sample of 224 patients from consecutive cases of attempted suicide referred to health care in four Finnish cities between 1 January and 31 July 1990 was interviewed. RESULTS: After 12 years of follow-up 22% of these patients had died, 8% by committing suicide. The only statistically significant risk factor for eventual suicide was high scores on Beck's Suicidal Intention Scale. Male gender, older age, physical illness or disability and high scores on Beck's Suicidal Intention Scale predicted death overall. CONCLUSIONS: Following attempted suicide, high intention to kill oneself is a significant risk factor for both death from all causes and suicide
Intra-Organ Variation in Age-Related Mutation Accumulation in the Mouse
Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen) or hydrogen peroxide (a clastogen). The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra-organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its consequences on aging and disease
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