A new approach to estimate the Shannon entropy of a long-range correlated sequence is proposed. The entropy is written as the sum of two terms corresponding respectively to power-law (ordered) and ...exponentially (disordered) distributed blocks (clusters). The approach is illustrated on the 24 human chromosome sequences by taking the nucleotide composition as the relevant information to be encoded/decoded. Interestingly, the nucleotide composition of the ordered clusters is found, on the average, comparable to the one of the whole analyzed sequence, while that of the disordered clusters fluctuates. From the information theory standpoint, this means that the power-law correlated clusters carry the same information of the whole analysed sequence. Furthermore, the fluctuations of the nucleotide composition of the disordered clusters are linked to relevant biological properties, such as segmental duplications and gene density.
Pairing gaps in neutron matter need to be computed in a wide range of densities to address open questions in neutron-star phenomenology. Traditionally, the Bardeen-Cooper-Schrieffer approach has been ...used to compute gaps from bare nucleon-nucleon interactions. Here we incorporate the influence of short-and long-range correlations in the pairing gaps. Short-range correlations are treated, including the appropriate fragmentation of single-particle states, and substantially suppress the gaps. Long-range correlations dress the pairing interaction via density and spin modes and provide a relatively small correction. We use different interactions, some with three-body forces, as a starting point to control for any systematic effects. Results are relevant for neutron-star cooling scenarios, in particular in view of the recent observational data on Cassiopeia A.
Summary
We evaluated mortality in a cohort of hip fracture patients and implemented a risk prediction score named ASAgeCoGeCC with excellent discrimination. It allowed to separate patients in 3 ...different risk groups with distinct mortality rates. Recognition of the heterogeneity of patients with femoral fractures may have relevant implications for their management.
Introduction
Usage of risk prediction models to estimate postoperative mortality risk for hip fracture patients represents a useful tool to give insight in the prognosis and assist in clinical decision-making. The aim of this study was to identify a predictive model able to determine the possible presence of distinct subgroups of hip fracture patients by risk classes in the mid-term.
Methods
Three hundred twenty-three hip fracture patients were evaluated, and mortality rates at 30 days, 1, 2, and 4 years were calculated. A multivariate logistic regression analysis using mortality 4 years after fracture as a dependent variable found ASA score, age, cognitive status, gender, and Charlson Comorbidities Index (CCI) as significant risk factors. Using these items, a score named ASAgeCoGeCC was implemented and compared with CCI and Nottingham Hip Fracture Score (NHFS) by a receiver operating characteristic (ROC) curve.
Results
The area under the ROC curve for ASAgeCoGeCC was always greater than that of CCI and NHFS and ranged between 0.804 and 0.820 suggesting an excellent discrimination. The ASAgeCoGeCC logistic model showed also a good calibration. Patients were divided in 3 groups: a low risk group, an intermediate risk group with an odds ratio for 4-year mortality of 5.6 (95% CI 2.9–10.6), and a high risk group with an odds ratio 21.6 (95% CI 10.6–44).
Conclusion
The ASAgeCoGeCC Score is a predictive tool for mortality after hip fracture with good calibration and excellent discrimination properties. It is the first scoring system stratifying hip fracture patients’ mortality at 4 years from fracture.
Background and purpose: α4 and β2 nicotinic acetylcholine (ACh) receptor subunits expressed heterologously in Xenopus oocytes assemble into a mixed population of (α4)2(β2)3 and (α4)3(β2)2 receptors. ...In order to express these receptors separately in heterologous systems, we have engineered pentameric concatenated (α4)2(β2)3 and (α4)3(β2)2 receptors.
Experimental approach: α4 and β2 subunits were concatenated by synthetic linkers into pentameric constructs to produce either (α4)2(β2)3 or (α4)3(β2)2 receptors. Using two‐electrode voltage‐clamp techniques, we examined the ability of the concatenated constructs to produce functional expression in Xenopus oocytes. Functional constructs were further characterized in respect to agonists, competitive antagonists, Ca2+ permeability, sensitivity to modulation by Zn2+ and sensitivity to up‐regulation by chaperone protein 14‐3‐3.
Key results: We found that pentameric concatamers with a subunit arrangement of β2_α4_β2_α4_β2 or β2_α4_β2_α4_α4 were stable and functional in Xenopus oocytes. By comparison, when α4 and β2 were concatenated with a subunit order of β2_β2_α4_β2_α4 or β2_α4_α4_β2_α4, functional expression in Xenopus oocytes was very low, even though the proteins were synthesized and stable. Both β2_α4_β2_α4_β2 and β2_α4_β2_α4_α4 concatamers recapitulated the ACh concentration response curve, the sensitivity to Zn2+ modulation, Ca2+ permeability and the sensitivity to up‐regulation by chaperone protein 14‐3‐3 of the corresponding non‐linked (α4)2(β2)3 and (α4)3(β2)2 receptors respectively. Using these concatamers, we found that most α4β2‐preferring compounds studied, including A85380, 5I‐A85380, cytisine, epibatidine, TC2559 and dihydro‐β‐erythroidine, demonstrate stoichiometry‐specific potencies and efficacies.
Conclusions and implications: We concluded that the α4β2 nicotinic ACh receptors produced with β2_α4_β2_α4_β2 or β2_α4_β2_α4_α4 pentameric constructs are valid models of non‐linked (α4)2(β2)3 and (α4)3(β2)2 receptors respectively.
Abstract Purpose The complications reported after sentinel lymph node biopsy (SLNB) for melanoma is highly variable in the worldwide literature; the overall complication rate varies between 1.8% and ...29.9%. With heterogeneous reporting of morbidity data, no ‘average’ complication rates of this procedure have been reported. This systematic review aims to determine the complications rates associated with SLNB. Methods A systematic review of English-language literature from 2000-2015, which reported morbidity information about SLNB for melanoma, was performed. The methodological quality of the included studies was performed using the methodological index for non-randomised studies (MINORS) instrument and Detsky score. Pooled proportions of specific post-operative complications were constructed using a random effects statistical model, and subgroups including lymph node basin and continent of origin of the study were compared. Results After application of inclusion and exclusion criteria, 21 articles progressed to the final analysis. 9047 patients were included. The overall complication rate was 11.3% (95% CI: 8.1-15.0). The incidence of infection was 2.9% (95% CI 1.5-4.6); seroma 5.1% (95% CI: 2.5-8.6); haematoma 0.5% (95% CI:0.3-0.9) lymphoedema 1.3% (95% CI: 0.5-2.6) and nerve injury 0.3% (95% CI:0.1-0.6). There was no statistically significant difference in morbidity between the sites of SLNB or between continents. Discussion This study provides information about the incidence of complications after SLNB. It can be used to counsel patients about the procedure and it sets a benchmark against which surgeons can audit their practice.
Abstract
Functional classification of proteins from sequences alone has become a critical bottleneck in understanding the myriad of protein sequences that accumulate in our databases. The great ...diversity of homologous sequences hides, in many cases, a variety of functional activities that cannot be anticipated. Their identification appears critical for a fundamental understanding of the evolution of living organisms and for biotechnological applications. ProfileView is a sequence-based computational method, designed to functionally classify sets of homologous sequences. It relies on two main ideas: the use of multiple profile models whose construction explores evolutionary information in available databases, and a novel definition of a representation space in which to analyze sequences with multiple profile models combined together. ProfileView classifies protein families by enriching known functional groups with new sequences and discovering new groups and subgroups. We validate ProfileView on seven classes of widespread proteins involved in the interaction with nucleic acids, amino acids and small molecules, and in a large variety of functions and enzymatic reactions. ProfileView agrees with the large set of functional data collected for these proteins from the literature regarding the organization into functional subgroups and residues that characterize the functions. In addition, ProfileView resolves undefined functional classifications and extracts the molecular determinants underlying protein functional diversity, showing its potential to select sequences towards accurate experimental design and discovery of novel biological functions. On protein families with complex domain architecture, ProfileView functional classification reconciles domain combinations, unlike phylogenetic reconstruction. ProfileView proves to outperform the functional classification approach PANTHER, the two k-mer-based methods CUPP and eCAMI and a neural network approach based on Restricted Boltzmann Machines. It overcomes time complexity limitations of the latter.
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