1,228 research outputs found
Controlling crystallization and its absence: Proteins, colloids and patchy models
The ability to control the crystallization behaviour (including its absence)
of particles, be they biomolecules such as globular proteins, inorganic
colloids, nanoparticles, or metal atoms in an alloy, is of both fundamental and
technological importance. Much can be learnt from the exquisite control that
biological systems exert over the behaviour of proteins, where protein
crystallization and aggregation are generally suppressed, but where in
particular instances complex crystalline assemblies can be formed that have a
functional purpose. We also explore the insights that can be obtained from
computational modelling, focussing on the subtle interplay between the
interparticle interactions, the preferred local order and the resulting
crystallization kinetics. In particular, we highlight the role played by
``frustration'', where there is an incompatibility between the preferred local
order and the global crystalline order, using examples from atomic glass
formers and model anisotropic particles.Comment: 11 pages, 7 figure
A comparison of�alternative methods to�compute conditional genotype probabilities for�genetic evaluation with�finite locus models
An increased availability of genotypes at marker loci has prompted the
development of models that include the effect of individual genes.
Selection based on these models is known as marker-assisted selection
(MAS). MAS is known to be efficient especially for traits that have
low heritability and non-additive gene action. BLUP methodology under
non-additive gene action is not feasible for large inbred or crossbred
pedigrees. It is easy to incorporate non-additive gene action in a
finite locus model. Under such a model, the unobservable genotypic
values can be predicted using the conditional mean of the genotypic
values given the data. To compute this conditional mean, conditional
genotype probabilities must be computed. In this study these
probabilities were computed using iterative peeling, and three Markov
chain Monte Carlo (MCMC) methods — scalar Gibbs, blocking Gibbs, and
a sampler that combines the Elston Stewart algorithm with iterative
peeling (ESIP). The performance of these four methods was assessed
using simulated data. For pedigrees with loops, iterative peeling
fails to provide accurate genotype probability estimates for some
pedigree members. Also, computing time is exponentially related to the
number of loci in the model. For MCMC methods, a linear relationship
can be maintained by sampling genotypes one locus at a time. Out of
the three MCMC methods considered, ESIP, performed the best while
scalar Gibbs performed the worst
Geometric Quantization of Topological Gauge Theories
We study the symplectic quantization of Abelian gauge theories in
space-time dimensions with the introduction of a topological Chern-Simons term.Comment: 13 pages, plain TEX, IF/UFRJ/9
Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin
OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps
Cyclophilins in Ischemic Heart Disease: Differences Between Acute and Chronic Coronary Artery Disease Patients
Background: Cyclophilins (Cyps) are a family of peptidyl-prolyl cis/trans isomerases consistently involved in cardiovascular diseases through the inflammation pathway. This study aims to investigate the serum levels of Cyps (CypA, CypB, CypC and CypD) in patients with coronary artery disease (CAD) and the correlation with clinical characteristics and inflammation parameters. Methods: We developed an observational prospective study with a total of 125 subjects: 40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers, in whom serum levels of Cyps (CypA, CypB, CypC and CypD), interleukins and metalloproteinases were measured. Results: CypA levels increased significantly in CAD patients compared with control subjects, but no differences were noted between acute CAD (7.80 +/- 1.30 ng/mL) and chronic CAD (5.52 +/- 0.76 ng/mL) patients (P = 0.13). No differences in CypB and CypD levels were showed between CAD patients and controls and between acute CAD and chronic CAD patients. In relation with CypC, the levels in CAD patients were significantly higher compared to controls (32.42 +/- 3.71 pg/mL vs. 9.38 +/- 1.51 pg/mL, P 17.5 pg/mL cut-off point, and it was significantly associated with older age, hypertension, dyslipidemia and more extensive CAD in acute and chronic CAD groups. Conclusions: CypA and CypC levels are increased in CAD patients. High CypC serum levels could be a novel biomarker in CAD patients correlating with a more severe disease
Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial
234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours
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