A Markov model for inferring flows in directed contact networks

Directed contact networks (DCNs) are a particularly flexible and convenient class of temporal networks, useful for modeling and analyzing the transfer of discrete quantities in communications, transportation, epidemiology, etc. Transfers modeled by contacts typically underlie flows that associate multiple contacts based on their spatiotemporal relationships. To infer these flows, we introduce a simple inhomogeneous Markov model associated to a DCN and show how it can be effectively used for data reduction and anomaly detection through an example of kernel-level information transfers within a computer.Comment: 12 page

Hybridizing Cartesian Genetic Programming and Harmony Search for Adaptive Feature Construction in Supervised Learning Problems

The advent of the so-called Big Data paradigm has motivated a flurry of research aimed at enhancing machine learning models by following very di- verse approaches. In this context this work focuses on the automatic con- struction of features in supervised learning problems, which differs from the conventional selection of features in that new characteristics with enhanced predictive power are inferred from the original dataset. In particular this manuscript proposes a new iterative feature construction approach based on a self-learning meta-heuristic algorithm (Harmony Search) and a solution encoding strategy (correspondingly, Cartesian Genetic Programming) suited to represent combinations of features by means of constant-length solution vectors. The proposed feature construction algorithm, coined as Adaptive Cartesian Harmony Search (ACHS), incorporates modifications that allow exploiting the estimated predictive importance of intermediate solutions and, ultimately, attaining better convergence rate in its iterative learning proce- dure. The performance of the proposed ACHS scheme is assessed and com- pared to that rendered by the state of the art in a toy example and three practical use cases from the literature. The excellent performance figures obtained in these problems shed light on the widespread applicability of the proposed scheme to supervised learning with legacy datasets composed by already refined characteristics

TFAW survey II: 6 Newly Validated Planets and 13 Planet Candidates from K2

Searching for Earth-sized planets in data from Kepler's extended mission (K2) is a niche that still remains to be fully exploited. The TFAW survey is an ongoing project that aims to re-analyze all light curves in K2 C1-C8 and C12-C18 campaigns with a wavelet-based detrending and denoising method, and the period search algorithm TLS to search for new transit candidates not detected in previous works. We have analyzed a first subset of 24 candidate planetary systems around relatively faint host stars (10.9 < $K_{p}$ < 15.4) to allow for follow-up speckle imaging observations. Using VESPA and TRICERATOPS, we statistically validate six candidates orbiting four unique host stars by obtaining false-positive probabilities smaller than 1% with both methods. We also present 13 vetted planet candidates that might benefit from other, more precise follow-up observations. All of these planets are sub-Neptune-sized, with two validated planets and three candidates with sub-Earth sizes, and have orbital periods between 0.81 and 23.98 days. Some interesting systems include two ultra-short-period planets, three multi-planetary systems, three sub-Neptunes that appear to be within the small planet Radius Gap, and two validated and one candidate sub-Earths (EPIC 210706310, EPIC 210768568, and EPIC 246078343) orbiting metal-poor stars.Comment: Submitted to Monthly Notices of the Royal Astronomical Society. 25 pages, 14 figure

The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity

The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5(+) malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5(+)-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Patients in cohort 4 received increased intensity pre-conditioning (cyclophosphamide and fludarabine), systemic IL2 support and CAR T cells. No objective clinical responses were observed. CAR T cell engraftment in patients within cohort 4 was significantly higher. However, engraftment was short-lived with a rapid decline of systemic CAR T cells within 14 days. Patients in cohort 4 had transient, acute respiratory toxicity which, in combination with lack of prolonged CAR T cell persistence, resulted in the premature closure of the trial. Elevated levels of systemic IFNγ and IL-6 implied that the CEACAM5-specific T cells had undergone immune activation in vivo but only in patients receiving high-intensity pre-conditioning. Expression of CEACAM5 on lung epithelium may have resulted in this transient toxicity. Raised levels of serum cytokines including IL-6 in these patients implicate cytokine release as one of several potential factors exacerbating the observed respiratory toxicity. Whilst improved CAR designs and T cell production methods could improve the systemic persistence and activity, methods to control CAR T 'on-target, off-tissue' toxicity are required to enable a clinical impact of this approach in solid malignancies

Can peer learning support doctoral education? Evidence from an ethnography of a research team

This paper focuses on peer learning as a process to develop PhD students’ disciplinary and scholarly skills. PhD students’ experience is not usually framed in terms of peer learning, because peer learning is more often studied and applied at the undergraduate level. This contribution builds on an ethnography of a research team to show the potential of peer learning over the course of the doctorate. A socio-constructivist conceptualisation of learning, inspired by activity theory, guides the analysis. The contribution of this paper is threefold. First, it proposes an original definition of learning that highlights process and practice, and shows how to work with it. Second, it demonstrates how peer learning unfolds in the interplay between structured and emergent types of interactions. Third, it provides scholars with insights into the conditions facilitating peer learning and stimulates debate around the initiatives that institutions can put in place to support PhD students

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Incidence of the Beet Leafhopper-Transmitted Virescence Agent Phytoplasma in local Populations of the Beet Leafhopper, Circulifer tenellus, in Washington State

Phytoplasma diseases are increasingly becoming important in vegetable crops in the Pacific Northwest. Recently, growers in the Columbia Basin and Yakima Valley experienced serious outbreaks of potato purple top disease that caused significant yield loss and a reduction in tuber processing quality. It was determined that the beet leafhopper-transmitted virescence agent (BLTVA) phytoplasma was the causal agent of the disease in the area and that this pathogen was transmitted by the beet leafhopper, Circulifer tenellus Baker (Hemiptera: Cicadellidae). To provide the most effective management of phytoplasmas, timing of insecticide applications targeted against insects vectoring these pathogens should be correlated with both insect abundance and infectivity. Beet leafhoppers were collected from a potato field and nearby weeds in Washington throughout the 2005, 2006, and 2007 growing seasons and tested for BLTVA by PCR to determine the incidence of this phytoplasma in the insects. In addition, overwintering beet leafhoppers were collected throughout Columbia Basin and Yakima Valley and tested for BLTVA to investigate if these insects might constitute a source of inoculum for this phytoplasma from one season to the next. Results showed that 29.6% of overwintering leafhoppers collected near potato fields carried the phytoplasma. BLTVA-infected leafhoppers were also found in both potatoes and nearby weedy habitats throughout the growing season. PCR testing indicated that a large proportion of beet leafhoppers invading potatoes were infected with the phytoplasma, with an average of 20.8, 34.8, and 9.2% in 2005, 2006, and 2007, respectively. Similarly, BLTVA infection rate in leafhoppers collected from weeds in the vicinity of potatoes averaged 28.3, 24.5, and 5.6% in 2005, 2006, and 2007, respectively. Information from this study will help develop action thresholds for beet leafhopper control to reduce incidence of purple top disease in potatoes

The First Naked-eye Superflare Detected from Proxima Centauri

Proxima b is a terrestrial-mass planet in the habitable zone of Proxima Centauri. Proxima Centauri's high stellar activity, however, casts doubt on the habitability of Proxima b: sufficiently bright and frequent flares and any associated proton events may destroy the planet's ozone layer, allowing lethal levels of UV flux to reach its surface. In 2016 March, the Evryscope observed the first naked-eye-brightness superflare detected from Proxima Centauri. Proxima increased in optical flux by a factor of ∼68 during the superflare and released a bolometric energy of 1033.5 erg, ∼10× larger than any previously detected flare from Proxima. Over the last two years the Evryscope has recorded 23 other large Proxima flares ranging in bolometric energy from 1030.6 to 1032.4 erg; coupling those rates with the single superflare detection, we predict that at least five superflares occur each year. Simultaneous high-resolution High Accuracy Radial velocity Planet Searcher (HARPS) spectroscopy during the Evryscope superflare constrains the superflare's UV spectrum and any associated coronal mass ejections. We use these results and the Evryscope flare rates to model the photochemical effects of NOx atmospheric species generated by particle events from this extreme stellar activity, and show that the repeated flaring may be sufficient to reduce the ozone of an Earth-like atmosphere by 90% within five years; complete depletion may occur within several hundred kyr. The UV light produced by the Evryscope superflare would therefore have reached the surface with ∼100× the intensity required to kill simple UV-hardy microorganisms, suggesting that life would have to undergo extreme adaptations to survive in the surface areas of Proxima b exposed to these flares

Cerebral microinfarcts: the invisible lesions

The association between small but still visible lacunar infarcts and cognitive decline has been established by multiple population-based radiological and pathological studies. Microscopic examination of brain sections reveals even smaller but substantially more numerous microinfarcts, the focus of the current review. These lesions often result from small vessel pathologies such as arteriolosclerosis or cerebral amyloid angiopathy. They typically go undetected in clinical-radiological correlation studies that rely on conventional structural MRI, though the largest acute microinfarcts may be detectable by diffusion-weighted imaging. Given their high numbers and widespread distribution, microinfarcts may directly disrupt important cognitive networks and thus account for some of the neurologic dysfunction seen in association with lesions visible on conventional MRI such as lacunar infarcts and white matter hyperintensities. Standardized neuropathological assessment criteria and development of non-invasive means of detection during life would be major steps towards understanding the causes and consequences of the otherwise macroscopically invisible microinfarct