Using aircraft measurements to determine the refractive index of Saharan dust during the DODO Experiments

Much uncertainty in the value of the imaginary part of the refractive index of mineral dust contributes to uncertainty in the radiative effect of mineral dust in the atmosphere. A synthesis of optical, chemical and physical in-situ aircraft measurements from the DODO experiments during February and August 2006 are used to calculate the refractive index mineral dust encountered over West Africa. Radiative transfer modeling and measurements of broadband shortwave irradiance at a range of altitudes are used to test and validate these calculations for a specific dust event on 23 August 2006 over Mauritania. Two techniques are used to determine the refractive index: firstly a method combining measurements of scattering, absorption, size distributions and Mie code simulations, and secondly a method using composition measured on filter samples to apportion the content of internally mixed quartz, calcite and iron oxide-clay aggregates, where the iron oxide is represented by either hematite or goethite and clay by either illite or kaolinite. The imaginary part of the refractive index at 550 nm (ni550) is found to range between 0.0001 i to 0.0046 i, and where filter samples are available, agreement between methods is found depending on mineral combination assumed. The refractive indices are also found to agree well with AERONET data where comparisons are possible. ni550 is found to vary with dust source, which is investigated with the NAME model for each case. The relationship between both size distribution and ni550 on the accumulation mode single scattering albedo at 550 nm (ω0550) are examined and size distribution is found to have no correlation to ω0550, while ni550 shows a strong linear relationship with ω0550. Radiative transfer modeling was performed with different models (Mie-derived refractive indices, but also filter sampling composition assuming both internal and external mixing). Our calculations indicate that Mie-derived values of ni550 and the externally mixed dust where the iron oxide-clay aggregate corresponds to the goethite-kaolinite combination result in the best agreement with irradiance measurements. The radiative effect of the dust is found to be very sensitive to the mineral combination (and hence refractive index) assumed, and to whether the dust is assumed to be internally or externally mixed

Myeloid-Derived Cells in Tumors: Effects of Radiation

The discrepancy between the in vitro and in vivo response to radiation is readily explained by the fact that tumors do not exist independently of the host organism; cancer cells grow in the context of a complex microenvironment composed of stromal cells, vasculature, and elements of the immune system. As the antitumor effect of radiotherapy depends in part on the immune system, and myeloid-derived cells in the tumor microenvironment modulate the immune response to tumors, it follows that understanding the effect of radiation on myeloid cells in the tumor is likely to be essential for comprehending the antitumor effects of radiotherapy. In this review, we describe the phenotype and function of these myeloid-derived cells, and stress the complexity of studying this important cell compartment owing to its intrinsic plasticity. With regard to the response to radiation of myeloid cells in the tumor, evidence has emerged demonstrating that it is both model and dose dependent. Deciphering the effects of myeloid-derived cells in tumors, particularly in irradiated tumors, is key for attempting to pharmacologically modulate their actions in the clinic as part of cancer therapy

Decomposition and factorisation of transients in Functional Graphs

Functional graphs (FGs) model the graph structures used to analyze the behavior of functions from a discrete set to itself. In turn, such functions are used to study real complex phenomena evolving in time. As the systems involved can be quite large, it is interesting to decompose and factorize them into several subgraphs acting together. Polynomial equations over functional graphs provide a formal way to represent this decomposition and factorization mechanism, and solving them validates or invalidates hypotheses on their decomposability. The current solution method breaks down a single equation into a series of \emph{basic} equations of the form $A\times X=B$ (with $A$, $X$, and $B$ being FGs) to identify the possible solutions. However, it is able to consider just FGs made of cycles only. This work proposes an algorithm for solving these basic equations for general connected FGs. By exploiting a connection with the cancellation problem, we prove that the upper bound to the number of solutions is closely related to the size of the cycle in the coefficient $A$ of the equation. The cancellation problem is also involved in the main algorithms provided by the paper. We introduce a polynomial-time semi-decision algorithm able to provide constraints that a potential solution will have to satisfy if it exists. Then, exploiting the ideas introduced in the first algorithm, we introduce a second exponential-time algorithm capable of finding all solutions by integrating several `hacks' that try to keep the exponential as tight as possible

L’inibizione tireotropinica da metformina non si associa a segni cardiologici di ipertiroidismo subclinico

Recenti dati di letteratura hanno evidenziato come metformina determini una riduzione/soppressione dei livelli sierici di tireotro- pina (TSH), simulando un ipertiroidismo subclinico il cui signifi- cato clinico rimane a oggi ancora assai controverso. Sebbene l’ipertiroidismo subclinico sia nella maggioranza dei casi una condizione clinica asintomatica, è altrettanto noto come esso si associ a un aumentato rischio di aritmie (più frequentemente la fibrillazione atriale) e ad alterazioni morfo-funzionali cardiache determinando un aumento di morbilità e mortalità cardiovasco- lare. Scopo del presente studio è stato quello di valutare retrospetti- vamente le alterazioni di differenti indici elettrocardiografici in pazienti diabetici eutiroidei che, dopo aver intrapreso terapia con metformina, hanno sviluppato riduzione/soppressione dei valori di TSH comparando i dati con quelli ottenuti in pazienti con iper- tiroidismo subclinico secondario a patologie tiroidee o a terapia soppressiva con L-tiroxina. I parametri elettrocardiografici (frequenza cardiaca, durata del- l’onda P, indice di dispersione dell’onda P, QT max, QT min, indice di dispersione dell’intervallo QT) sono stati valutati in 23 pazienti diabetici in terapia con metformina prima e dopo 6 mesi dall’instaurarsi della soppressione del TSH e in 31 con- trolli con ipertiroidismo subclinico. Nessuna modifica significa- tiva è stata osservata tra i parametri elettrocardiografici rilevati prima e dopo la riduzione del TSH. Al contrario, significative dif- ferenze nella durata dell’onda P (102,9 ± 7,4 vs 92,1 ± 5,8 ms, p < 0,001), dell’indice di dispersione dell’onda P (13,1 ± 3,4 vs 7,1 ± 3,5 ms, p < 0,001), del QT max (399 ± 18 vs 388 ± 16 ms, p = 0,024), del QT min (341 ± 14 vs 350 ± 17 ms, p = 0,038) e di quello dell’intervallo QT (49,9 ± 9,6 vs 30,9 ± 9,2 ms, p < 0,001) sono state rilevate tra i controlli con iperti- roidismo subclinico e il gruppo di pazienti diabetici con valori ridotti/soppressi di TSH. I risultati del nostro studio evidenzierebbero come l’effetto di riduzione/soppressione del TSH osservato in alcuni pazienti dia- betici in terapia con metformina non si associ a marker periferi- ci cardiaci da eccesso di ormoni tiroidei. L’alterazione del profilo tiroideo metformina-indotto sembrerebbe non indicativo di iper- tiroidismo subclinico, suggerendo quindi che non sussiste la necessità di sottoporre a stretti controlli della funzione tiroidea i pazienti diabetici in terapia con metformin

Turing degrees of limit sets of cellular automata

Cellular automata are discrete dynamical systems and a model of computation. The limit set of a cellular automaton consists of the configurations having an infinite sequence of preimages. It is well known that these always contain a computable point and that any non-trivial property on them is undecidable. We go one step further in this article by giving a full characterization of the sets of Turing degrees of cellular automata: they are the same as the sets of Turing degrees of effectively closed sets containing a computable point

Pattern Recognition in Bioinformatics - 8th IAPR International Conference, PRIB 2013

International audienceIn the post-genomic era, a holistic understanding of biological systems and pro- cesses, in all their complexity, is critical in comprehending nature’s choreogra- phy of life. As a result, bioinformatics involving its two main disciplines, namely, the life sciences and the computational sciences, is fast becoming a very promis- ing multidisciplinary research field. With the ever-increasing application of large- scale high-throughput technologies, such as gene or protein microarrays and mass spectrometry methods, the enormous body of information is growing rapidly. Bioinformaticians are posed with a large number of difficult problems to solve, arising not only due to the complexities in acquiring the molecular information but also due to the size and nature of the generated data sets and/or the limi- tations of the algorithms required for analyzing these data. The recent advance- ments in computational and information-theoretic techniques are enabling us to conduct various in silico testing and screening of many lab-based experiments be- fore these are actually performed in vitro or in vivo. These in silico investigations are providing new insights for interpreting and establishing new direction for a deeper understanding. Among the various advanced computational methods cur- rently being applied to such studies, the pattern recognition techniques are mostly found to be at the core of the whole discovery process for apprehending the under- lying biological knowledge. Thus, we can safely surmise that the ongoing bioin- formatics revolution may, in future, inevitably play a major role in many aspects of medical practice and/or the discipline of life sciences.The aim of this conference on Pattern Recognition in Bioinformatics (PRIB) is to provide an opportunity to academics, researchers, scientists, and industry professionals to present their latest research in pattern recognition and compu- tational intelligence-based techniques applied to problems in bioinformatics and computational biology. It also provides them with an excellent forum to interact with each other and share experiences. The conference is organized jointly by the Nice Sophia Antipolis University, France, and IAPR (International Association for Pattern Recognition) Bioinformatics Technical Committee (TC-20).This volume presents the proceedings of the 8th IAPR International Confer- ence on Pattern Recognition in Bioinformatics (PRIB 2013), held in Nice, June 17–19, 2013. It includes 25 technical contributions that were selected by the In- ternational Program Committee from 43 submissions. Each of these rigorously reviewed papers was presented orally at PRIB 2013. The proceedings consists of five parts:Part I Bio-Molecular Networks and Pathway Analysis Part II Learning, Classification, and ClusteringPart III Data Mining and Knowledge DiscoveryPart IV Protein: Structure, Function, and Interaction Part V Motifs, Sites, and Sequences AnalysisPart I of the proceedings contains six chapters on “Bio-Molecular Networks and Pathway Analysis.” Rahman et al. propose a fast agglomerative cluster- ing method for protein complex discovery. A new criterion is introduced that combines an edge clustering coefficient and an edge clustering value, allowing us to decide when a node can be added to the current cluster. Maduranga et al. use the well-known random forest method to predict GRNs. The problem of in- ferring GRNs from (limited) time-series data is recast as a number of regression problems, and the random forest approach is used here to fit a model to this. Winterbach et al. evaluate how well topological signatures in protein interaction networks predict protein function. They compare several complex signatures and their own simple signature. They find that network topology is only a weak predictor of function and the simple signature performs on par with the more sophisticated ones. De Ridder et al. propose an approach for identifying putative cancer pathways. This approach relies on expression profiling tumors that are induced by retroviral insertional mutagenesis. This provides the opportunity to search for associations between tumor-initiating events (the viral insertion sites) and the consequent transcription changes, thus revealing putative regulatory in- teractions. An important advantage is that the selective pressure exerted by the tumor growth is exploited to yield a relatively small number of loci that are likely to be causal for tumor formation. Ochs et al. apply outlier statistics, gene set analysis, and top scoring pair methods to identify deregulated pathways in can- cer. Analysis of the results on pediatric acute myeloid leukemia data indicate the effectiveness of the proposed methodology. Pizzuti et al. present some variants of RNSC (restricted neighborhood search clustering) for prediction of protein com- plexes that are based on new score functions and evolutionary computation. It is shown via computational experiments that the proposed methods have better prediction accuracies (in F-measure) than the basic RNSC algorithm.Part II of the proceedings contains three chapters on “Learning, Classifica- tion, and Clustering.” Marchiori addresses a limitation of the RELIEF feature weighting algorithm that maximizes the sample margin over the entire training set, or the sum of the possibly competing feature weights. Her work proposes, instead, a conditional weighting algorithm (CCFW) and classifier (CCWNN) to improve feature weighting and classification. Mundra et al. propose a sample se- lection criterion using a modified logistic regression loss function and a backward elimination based gene ranking algorithm. On the basis of the classifier margin for sample points, points on or within the margin are more important than those outside, the sample selection criterion based on T-score is proposed. Li et al. describe a generalization of sparse matrix factorization (SMF) algorithms and showcase a few very concisely described applications in bioinformatics. The main merit of the work is the fact that a unified representation for SMF algorithms is proposed, as well as an optimization algorithm to solve this problem.Part III of the proceedings contains six chapters on “Data Mining and Knowl- edge Discovery.” Hsu et al. consider prediction of RNA secondary structure in the “triple helix” setting for which they argue existing methods are inade- quate. Their approach uses a Simple Tree Adjoining Grammar (STAG) coupledwith maximum likelihood estimation (MLE), implemented via an efficient dy- namic programming formulation. Higgs et al. present an algorithm for generating near-native protein models. It combines a fragment feature-based resampling algorithm with a local optimization method that performed best, for protein structure prediction (PSP), among a set of five optimization techniques. Com- putational experiments show that the use of local optimization is beneficial in terms of both RMSD and TM score. Spirov et al. discuss a method for trans- formation of variables, in order to normalize Drosophila oocyte images acquired via confocal microscopy. The paper describes an interesting problem, namely, the experimental determination of intrinsic Drosophila embryo coordinates, and proposes an approach using evolutionary computation by genetic algorithms. Rezaeian et al. propose a novel and flexible hierarchical framework to select dis- criminative genes and predict breast tumor subtypes simultaneously. Dai et al. tackle an important problem in drug-target interaction research and present an interesting application of machine learning methods to the analysis of drugs. Gritsenko et al. make an adaptation of their previously developed protocol for building and evaluating predictors, in order to introduce a framework that en- ables forward engineering in biology. An experimental test is performed in the biological field of codon optimization and the results obtained are comparable with those produced by the reference tool JCat.Part IV of the proceedings contains six chapters on “Protein: Structure, Func- tion, and Interaction.” Xiong et al. propose an active learning-based approach for protein function prediction. The novelty of the proposal is the use of a pre- processing phase that uses spectral clustering before selecting candidates for labeling with graph centrality metrics. Experimental results show that cluster- ing reveals a valid pre-processing step for the active learning method. Gehrmann et al. address the problem of integrating multiple sources of evidence to predict protein functions. The paper proposes to use a conditional random field (CRF) to represent protein functions as random variables to be predicted and different sources of evidence as conditioning variables. Inference and learning algorithms based on MCMC are described and the proposed method is applied to a yeast dataset. Dehzangi et al. describe a new approach to protein fold recognition, a problem that has been widely studied over the past decade. The main contribu- tion is the proposal of a new set of global protein features based on evolutionary consensus sequences and predicted secondary structure, and local features based on distributions and auto covariances of these features over segments. An RBF SVM using these features is applied to two benchmark datasets in an extensive comparison with a number of existing methods and is demonstrated to work well. Dehzangi et al. present a novel approach to using features extracted from the position specific scoring matrix (PSSM) to predict the structural class of a protein. The authors propose two new sets of features: a global one based on the consensus sequence of a PSSM and a local one that takes the auto-covariance in sequence segments into account. The features extracted are used to train an RBF SVM and are shown to lead to good results (better than other state-of-the-art algorithms) on two benchmarks. Chiu et al. discuss a new method for detecting associated sites in aligned sequence ensembles. The main idea is derived from the concept of granular computing, where information is extracted at different levels of granularity or resolution. The experimentation was focused on p53 and it has been demonstrated that the extracted association patterns are useful in discov- ering sites with some structural and functional properties of a protein molecule. Tung presents a new method for predicting the potential hepatocarcinogenicity of non-genotoxic chemicals. The proposed method based on chemical–protein interactions and interpretable decision tree is compared with other data-mining approaches and shows very good performances in both accuracy and simplicity of the found model.Part V of the proceedings contains four chapters on “Motifs, Sites, and Se- quences Analysis.” Pathak et al. present an algorithm that exploits structural information for reducing false positives in motifs prediction. They tested the validity of the algorithm using the minimotifs stored in the MnM database. Lacroix et al. present a workflow for the prediction of the effects of residue sub- stitution on protein stability. The workflow integrates eight algorithms that use delta-delta-G as a measure of stability. The workflow is designed to populate the online resource SPROUTS. A use case of the workflow is presented using the PDB entry 1enh. Malhotra et al. present an algorithm for inferring haplotypes of virus populations from k-mer counts obtained from next-generation sequencing (NGS) data. The algorithm takes as input read counts for a set of k-mers and produces as output a predicted number of haplotypes, their relative frequen- cies and, for reads covering SNPs, can assign reads to a haplotype. The novel feature of the algortihm is that it does not rely on having a reference genome. The authors report that it performs well on synthetic data compared with the existing algorithm ShoRAH, which relies on a reference genome. Comin et al. discuss and improve the Entropic Profile method introduced in the literature for detecting conservation in genome sequences. The authors propose a linear-time linear-space algorithm that captures the importance of given regions with re- spect to the whole genome, suitable for large genomes and for the discovery of motifs with unbounded length.Many have contributed directly or indirectly toward the organization and success of the PRIB 2013 conference. We would like to thank all the individ- uals and institutions, especially the authors for submitting the papers and the sponsors for generously providing financial support for the conference. We are very grateful to IAPR for the sponsorship. Our gratitude goes to the Nice Sophia Antipolis University, Nice, France, and IAPR (International Association for Pat- tern Recognition) Bioinformatics Technical Committee (TC-20) for supporting the conference in many ways.We would like to express our gratitude to all PRIB 2013 International Pro- gram Committee members for their objective and thorough reviews of the sub- mitted papers. We fully appreciate the PRIB 2013 Organizing Committee for their time, efforts, and excellent work. We would also like to thank the Nice Sophia Antipolis University for hosting the symposium and providing technical support. We sincerely thank the EDSTIC doctoral school for providing grants toa number of students attending the conference. We also thank “Region PACA” and the University of Salerno (Italy) for partially funding the invited speakers. Last, but not least, we wish to convey our sincere thanks to Springer forproviding excellent professional support in preparing this volume

Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients.

BackgroundWe previously reported the results of a multicentric prospective randomized trial of chemo-refractory metastatic breast cancer patients testing the efficacy of two doses of TGFβ blockade during radiotherapy. Despite a lack of objective responses to the combination, patients who received a higher dose of TGFβ blocking antibody fresolimumab had a better overall survival when compared to those assigned to lower dose (hazard ratio of 2.73, p = 0.039). They also demonstrated an improved peripheral blood mononuclear cell (PBMC) counts and increase in the CD8 central memory pool. We performed additional analysis on residual PBMC using single cell network profiling (SCNP).MethodsThe original trial randomized metastatic breast cancer patients to either 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, combined with radiotherapy to a metastatic site at week 1 and 7 (22.5 Gy given in 3 doses of 7.5 Gy). Trial immune monitoring results were previously reported. In 15 patients with available residual blood samples, additional functional studies were performed, and compared with data obtained in parallel from seven healthy female donors (HD): SCNP was applied to analyze T cell receptor (TCR) modulated signaling via CD3 and CD28 crosslinking and measurement of evoked phosphorylation of AKT and ERK in CD4 and CD8 T cell subsets defined by PD-1 expression.ResultsAt baseline, a significantly higher level of expression (p &lt; 0.05) of PD-L1 was identified in patient monocytes compared to HD. TCR modulation revealed dysfunction of circulating T-cells in patient baseline samples as compared to HD, and this was more pronounced in PD-1+ cells. Treatment with radiotherapy and fresolimumab did not resolve this dyfunctional signaling. However, in vitro PD-1 blockade enhanced TCR signaling in patient PD-1+ T cells and not in PD-1- T cells or in PD-1+ T cells from HD.ConclusionsFunctional T cell analysis suggests that baseline T cell functionality is hampered in metastatic breast cancer patients, at least in part mediated by the PD-1 signaling pathway. These preliminary data support the rationale for investigating the possible beneficial effects of adding PD-1 blockade to improve responses to TGFβ blockade and radiotherapy.Trial registrationNCT01401062

Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery.

Drug malabsorption is a potential concern after bariatric surgery. We present four case reports of hypothyroid patients who were well replaced with thyroxine tablets to euthyroid thyrotropin (TSH) levels prior to Roux-en-Y gastric bypass surgery. These patients developed elevated TSH levels after the surgery, the TSH responded reversibly to switching from treatment with oral tablets to a liquid formulation

Bilateral asymmetry of skin temperature is not related to bilateral asymmetry of crank torque during an incremental cycling exercise to exhaustion

© 2018 Trecroci et al. Although moderate relationships (|r|~0:5) were reported between skin temperature and performance-related variables (e.g., kinetic), it remains unclear whether skin temperature asymmetry reflects muscle force imbalance in cycling. Therefore, the aim of this study was to assess whether a relationship exists between kinetic and thermal asymmetry during a fatiguing exercise. Ten elite cyclists were enrolled and tested on a maximal incremental cycling test. Peak crank torques of both legs were obtained at the initial and final workload. Likewise, bilateral skin temperatures were recorded before and after exercise. Asymmetric indexes were also calculated for kinetic (AIK) and skin temperature (AIT) outcomes. The bilateral peak crank torques showed a larger difference at the final compared to the initial workload (p0:05). Additionally, trivial relationships were reported between AIK and AIT (-0:3<r<0:2) at the initial and final workload. The obtained results showed that changes in bilateral kinetic values did not reflect concurrent changes in bilateral skin temperatures. This finding emphasizes the difficulty of associating the asymmetry of skin temperature with those of muscle effort in elite cyclists. Lastly, our study also provided further insights on thermal skin responses during exhaustive cycling exercise in very highly-trained athletes