Towards an Iterative Algorithm for the Optimal Boundary Coverage of a 3D Environment

This paper presents a new optimal algorithm for locating a set of sensors in 3D able to see the boundaries of a polyhedral environment. Our approach is iterative and is based on a lower bound on the sensors' number and on a restriction of the original problem requiring each face to be observed in its entirety by at least one sensor. The lower bound allows evaluating the quality of the solution obtained at each step, and halting the algorithm if the solution is satisfactory. The algorithm asymptotically converges to the optimal solution of the unrestricted problem if the faces are subdivided into smaller part

Cancer-associated fibroblasts—heroes or villains?

Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, more recently, ablation, and it is now widely appreciated that CAFs form a group of highly heterogeneous cells with no single overarching marker. Studies have demonstrated that the CAF population contains different subtypes based on the expression of marker proteins with the capacity to promote or inhibit cancer, with their biological role as accomplices or adversaries dependent on many factors, including the cancer stage. So, while CAFs have been endlessly shown to promote the growth, survival and spread of tumours via improvements in functionality and an altered secretome, they are also capable of retarding tumorigenesis via largely unknown mechanisms. It is important to reconcile these disparate results so that the functions of, or factors produced by, tumour-promoting subtypes can be specifically targeted to improve cancer patient outcomes. This review will dissect out CAF complexity and CAF-directed cancer treatment strategies in order to provide a case for future, rational therapies.Krystyna A. Gieniec, Lisa M. Butler, Daniel L. Worthley and Susan L. Wood

Personality characteristics are independently associated with prospective memory in the laboratory, and in daily life, among older adults

Prospective memory (PM) can deteriorate with age and adversely influence health behaviours. Research suggests that personality is related to PM in healthy young adults, but we know little about the role of personality in the PM amongst older adults. Community-dwelling older adults (N=152) completed the NEO Five-Factor Inventory-3 and PM measures. After adjusting for demographics and general cognition, higher neuroticism and lower levels of openness were independently associated with lower objectively-measured time- and event-based PM. Lower conscientiousness was the only personality predictor of self-reported everyday PM failures. Findings indicate that personality plays a role in PM functioning in the laboratory and daily life

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire–Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3–5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC = 0.899 ± 0.001). The EPS-26 outperformed the PQ-B (AUC = 0.834 ± 0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway

Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels

Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment

Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodiumdependent phosphate cotransporter, has been proposed as a cause of PAM.Weshow that epithelial deletion ofNpt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers.Microliths introduced by adoptive transfer into the lungs of wild-typemice produce markedmacrophagerich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic wholelung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAMmouse model as a preclinical platform for the development of biomarkers and therapeutic strategies

Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype

Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor

Structural and dynamical properties of superfluid helium: a density functional approach

We present a novel density functional for liquid 4He, properly accounting for the static response function and the phonon-roton dispersion in the uniform liquid. The functional is used to study both structural and dynamical properties of superfluid helium in various geometries. The equilibrium properties of the free surface, droplets and films at zero temperature are calculated. Our predictions agree closely to the results of ab initio Monte Carlo calculations, when available. The introduction of a phenomenological velocity dependent interaction, which accounts for backflow effects, is discussed. The spectrum of the elementary excitations of the free surface and films is studied.Comment: 37 pages, REVTeX 3.0, figures on request at [email protected]

Gaussian Tunneling Model of c-Axis Twist Josephson Junctions

We calculate the critical current density $J^J_c$ for c-axis Josephson tunneling between identical high temperature superconductors twisted an angle $\phi_0$ about the c-axis. We model the tunneling matrix element squared as a Gaussian in the change of wavevector q parallel to the junction, $<|t({\bf q})|^2>\propto\exp(-{\bf q}^2a^2/2\pi^2\sigma^2)$. The $J^J_c(\phi_0)/J^J_c(0)$ obtained for the s- and extended-s-wave order parameters (OP's) are consistent with the Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ data of Li {\it et al.}, but only for strongly incoherent tunneling, $\sigma^2\ge0.25$. A $d_{x^2-y^2}$-wave OP is always inconsistent with the data. In addition, we show that the apparent conventional sum rule violation observed by Basov et al. might be understandable in terms of incoherent c-axis tunneling, provided that the OP is not $d_{x^2-y^2}$-wave.Comment: 6 pages, 6 figure