A new MM algorithm for constrained estimation in the proportional hazards model

The constrained estimation in Cox’s model for the right-censored survival data is studied and the asymptotic properties of the constrained estimators are derived by using the Lagrangian method based on Karush–Kuhn–Tucker conditions. A novel minorization–maximization (MM) algorithm is developed for calculating the maximum likelihood estimates of the regression coefficients subject to box or linear inequality restrictions in the proportional hazards model. The first M-step of the proposed MM algorithm is to construct a surrogate function with a diagonal Hessian matrix, which can be reached by utilizing the convexity of the exponential function and the negative logarithm function. The second M-step is to maximize the surrogate function with a diagonal Hessian matrix subject to box constraints, which is equivalent to separately maximizing several one-dimensional concave functions with a lower bound and an upper bound constraint, resulting in an explicit solution via a median function. The ascent property of the proposed MM algorithm under constraints is theoretically justified. Standard error estimation is also presented via a non-parametric bootstrap approach. Simulation studies are performed to compare the estimations with and without constraints. Two real data sets are used to illustrate the proposed methods.postprin

Migration of carbon nanotubes from liquid phase to vapor phase in the refrigerant-based nanofluid pool boiling

The migration characteristics of carbon nanotubes from liquid phase to vapor phase in the refrigerant-based nanofluid pool boiling were investigated experimentally. Four types of carbon nanotubes with the outside diameters from 15 to 80 nm and the lengths from 1.5 to 10 μm were used in the experiments. The refrigerants include R113, R141b and n-pentane. The oil concentration is from 0 to 10 wt.%, the heat flux is from 10 to 100 kW·m-2, and the initial liquid-level height is from 1.3 to 3.4 cm. The experimental results indicate that the migration ratio of carbon nanotube increases with the increase of the outside diameter or the length of carbon nanotube. For the fixed type of carbon nanotube, the migration ratio decreases with the increase of the oil concentration or the heat flux, and increases with the increase of the initial liquid-level height. The migration ratio of carbon nanotube increases with the decrease of dynamic viscosity of refrigerant or the increase of liquid phase density of refrigerant. A model for predicting the migration ratio of carbon nanotubes in the refrigerant-based nanofluid pool boiling is proposed, and the predictions agree with 92% of the experimental data within a deviation of ±20%

Influences of refrigerant-based nanofluid composition and heating condition on the migration of nanoparticles during pool boiling. Part II: Model development and validation

The objective of this study is to propose a model for predicting the migration characteristics of nanoparticles during the refrigerant-based nanofluid pool boiling. In establishing the present model, the departure and rising processes of bubble, as well as the movement of nanoparticles in the liquid-phase are firstly simulated; then the capture of nanoparticles by bubble and the escape of nanoparticles from the liquid-vapor interface are simulated; finally, the migration ratio of nanoparticles is obtained by flotation theory combining the analysis on the boiling process. The proposed model can predict the influences of nanoparticle type, nanoparticle size, refrigerant type, mass fraction of lubricating oil, heat flux and initial liquid-level height on the migration of nanoparticles. The migration ratio of nanoparticles predicted by the model can agree with 90% of the experimental data of within a deviation of +/- 20%, and the mean deviation is 12.1%. (C) 2011 Elsevier Ltd and IIR. All rights reserved

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic ß-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in ß-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 ß-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18 hours promotes metabolic reprogramming of ß-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1a) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in ß-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated ß-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression

A Submodular Approach for Reference Recommendation

© 2020, Springer Nature Singapore Pte Ltd. Choosing appropriate references for a given topic is an important, yet challenging task. The pool of potential candidates is typically very large, in the order of tens of thousands, and growing by the day. For this reason, this paper proposes an approach for automatically providing a reference list for a given manuscript. The approach is based on an original submodular inference function which balances relevance, coverage and diversity in the reference list. Experiments are carried out using an ACL corpus as a source for the references and evaluated by MAP, MRR and precision-recall. The results show the remarkable comparative performance of the proposed approach

Self-adjustment mechanisms and their application for orthosis design

Medical orthoses aim at guiding anatomical joints along their natural trajectories while preventing pathological movements, especially in case of trauma or injuries. The motions that take place between bone surfaces have complex kinematics. These so-called arthrokinematic motions exhibit axes that move both in translation and rotation. Traditionally, orthoses are carefully adjusted and positioned such that their kinematics approximate the arthrokinematic movements as closely as possible in order to protect the joint. Adjustment procedures are typically long and tedious. We suggest in this paper another approach. We propose mechanisms having intrinsic self-aligning properties. They are designed such that their main axis self-adjusts with respect to the joint’s physiological axis during motion. When connected to a limb, their movement becomes homokinetic and they have the property of automatically minimizing internal stresses. The study is performed here in the planar case focusing on the most important component of the arthrokinematic motions of a knee joint

Hierarchical information clustering by means of topologically embedded graphs

We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry $S_4$ that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between $\lambda^{-2}$ and $\lambda^2$, with $\lambda\simeq0.2$. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE

Effects of simulated altitude (normobaric hypoxia) on cardiorespiratory parameters and circulating endothelial precursors in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Circulating Endothelial Precursors (PB-EPCs) are involved in the maintenance of the endothelial compartment being promptly mobilized after injuries of the vascular endothelium, but the effects of a brief normobaric hypoxia on PB-EPCs in healthy subjects are scarcely studied.</p> <p>Methods</p> <p>Clinical and molecular parameters were investigated in healthy subjects (n = 8) in basal conditions (T0) and after 1 h of normobaric hypoxia (T1), with Inspiratory Fraction of Oxygen set at 11.2% simulating 4850 mt of altitude. Blood samples were obtained at T0 and T1, as well as 7 days after hypoxia (T2).</p> <p>Results</p> <p>In all studied subjects we observed a prompt and significant increase in PB-EPCs, with a return to basal value at T2. The induction of hypoxia was confirmed by Alveolar Oxygen Partial Pressure (PAO₂) and Spot Oxygen Saturation decreases. Heart rate increased, but arterial pressure and respiratory response were unaffected. The change in PB-EPCs percent from T0 to T1 was inversely related to PAO₂at T1. Rapid (T1) increases in serum levels of hepatocyte growth factor and erythropoietin, as well as in cellular PB-EPCs-expression of Hypoxia Inducible Factor-1α were observed.</p> <p>Conclusion</p> <p>In conclusion, the endothelial compartment seems quite responsive to standardized brief hypoxia, possibly important for PB-EPCs activation and recruitment.</p