Serum Neurofilament Light, Glial Fibrillary Acidic Protein and Tau Are Possible Serum Biomarkers for Activity of Brain Metastases and Gliomas

BACKGROUND: Primary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs. METHODS: Serum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data. RESULTS: fL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), P_{sNfL} = 0.03; ANOVA, P_{GFAp} = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004). CONCLUSION: sNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings

Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats

The increasing use of silver nanoparticles (AgNPs) in consumer products is concerning. We examined the potential toxic effects when inhaled in Brown-Norway (BN) rats with a pre-inflammatory state compared to Sprague-Dawley (SD) rats.We determined the effect of AgNPs generated from a spark generator (mass concentration: 600-800 μg/mm(3); mean diameter: 13-16 nm; total lung doses: 8 [Low] and 26-28 [High] μg) inhaled by the nasal route in both rat strains. Rats were sacrificed at day 1 and day 7 after exposure and measurement of lung function.In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at 24 h at the high dose, with concomitant eosinophilia in BN rats. While BAL inflammatory cells were mostly normalised by Day 7, lung inflammation scores remained increased although not the tissue eosinophil scores. Total protein levels were elevated at both lung doses in both strains. There was an increase in BAL IL-1β, KC, IL-17, CCL2 and CCL3 levels in both strains at Day 1, mostly at high dose. Phospholipid levels were increased at the high dose in SD rats at Day 1 and 7, while in BN rats, this was only seen at Day 1; surfactant protein D levels decreased at day 7 at the high dose in SD rats, but was increased at Day 1 at the low dose in BN rats. There was a transient increase in central airway resistance and in tissue elastance in BN rats at Day 1 but not in SD rats. Positive silver-staining was seen particularly in lung tissue macrophages in a dose and time-dependent response in both strains, maximal by day 7. Lung silver levels were relatively higher in BN rat and present at day 7 in both strains.Presence of cellular inflammation and increasing silver-positive macrophages in lungs at day 7, associated with significant levels of lung silver indicate that lung toxicity is persistent even with the absence of airway luminal inflammation at that time-point. The higher levels and persistence of lung silver in BN rats may be due to the pre-existing inflammatory state of the lungs

Moisture-driven shift in the climate sensitivity of white spruce xylem anatomical traits is coupled to large-scale oscillation patterns across northern treeline in northwest North America

Tree growth at northern treelines is generally temperature-limited due to cold and short growing seasons. However, temperature-induced drought stress was repeatedly reported for certain regions of the boreal forest in northwestern North America, provoked by a significant increase in temperature and possibly reinforced by a regime shift of the pacific decadal oscillation (PDO). The aim of this study is to better understand physiological growth reactions of white spruce, a dominant species of the North American boreal forest, to PDO regime shifts using quantitative wood anatomy and traditional tree-ring width (TRW) analysis. We investigated white spruce growth at latitudinal treeline across a >1,000\ua0km gradient in northwestern North America. Functionally important xylem anatomical traits (lumen area, cell-wall thickness, cell number) and TRW were correlated with the drought-sensitive standardized precipitation-evapotranspiration index of the growing season. Correlations were computed separately for complete phases of the PDO in the 20th century, representing alternating warm/dry (1925-1946), cool/wet (1947-1976) and again warm/dry (1977-1998) climate regimes. Xylem anatomical traits revealed water-limiting conditions in both warm/dry PDO regimes, while no or spatially contrasting associations were found for the cool/wet regime, indicating a moisture-driven shift in growth-limiting factors between PDO periods. TRW reflected only the last shift of 1976/1977, suggesting different climate thresholds and a higher sensitivity to moisture availability of xylem anatomical traits compared to TRW. This high sensitivity of xylem anatomical traits permits to identify first signs of moisture-driven growth in treeline white spruce at an early stage, suggesting quantitative wood anatomy being a powerful tool to study climate change effects in the northwestern North American treeline ecotone. Projected temperature increase might challenge growth performance of white spruce as a key component of the North American boreal forest biome in the future, when drier conditions are likely to occur with higher frequency and intensity

Message-Passing Methods for Complex Contagions

Message-passing methods provide a powerful approach for calculating the expected size of cascades either on random networks (e.g., drawn from a configuration-model ensemble or its generalizations) asymptotically as the number $N$ of nodes becomes infinite or on specific finite-size networks. We review the message-passing approach and show how to derive it for configuration-model networks using the methods of (Dhar et al., 1997) and (Gleeson, 2008). Using this approach, we explain for such networks how to determine an analytical expression for a "cascade condition", which determines whether a global cascade will occur. We extend this approach to the message-passing methods for specific finite-size networks (Shrestha and Moore, 2014; Lokhov et al., 2015), and we derive a generalized cascade condition. Throughout this chapter, we illustrate these ideas using the Watts threshold model.Comment: 14 pages, 3 figure

Modulational Instability in Nonlinearity-Managed Optical Media

We investigate analytically, numerically, and experimentally the modulational instability in a layered, cubically-nonlinear (Kerr) optical medium that consists of alternating layers of glass and air. We model this setting using a nonlinear Schr\"odinger (NLS) equation with a piecewise constant nonlinearity coefficient and conduct a theoretical analysis of its linear stability, obtaining a Kronig-Penney equation whose forbidden bands correspond to the modulationally unstable regimes. We find very good {\it quantitative} agreement between the theoretical analysis of the Kronig-Penney equation, numerical simulations of the NLS equation, and the experimental results for the modulational instability. Because of the periodicity in the evolution variable arising from the layered medium, we find multiple instability regions rather than just the one that would occur in uniform media.Comment: 13 pages, 12 figures (several with multiple parts); some important changes from the page proof stage implemented in this preprint versio

Effect of Tuned Parameters on a LSA MCQ Answering Model

This paper presents the current state of a work in progress, whose objective is to better understand the effects of factors that significantly influence the performance of Latent Semantic Analysis (LSA). A difficult task, which consists in answering (French) biology Multiple Choice Questions, is used to test the semantic properties of the truncated singular space and to study the relative influence of main parameters. A dedicated software has been designed to fine tune the LSA semantic space for the Multiple Choice Questions task. With optimal parameters, the performances of our simple model are quite surprisingly equal or superior to those of 7th and 8th grades students. This indicates that semantic spaces were quite good despite their low dimensions and the small sizes of training data sets. Besides, we present an original entropy global weighting of answers' terms of each question of the Multiple Choice Questions which was necessary to achieve the model's success.Comment: 9 page

Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development

Cluster Performance reconsidered: Structure, Linkages and Paths in the German Biotechnology Industry, 1996-2003

This paper addresses the evolution of biotechnology clusters in Germany between 1996 and 2003, paying particular attention to their respective composition in terms of venture capital, basic science institutions and biotechnology firms. Drawing upon the significance of co-location of "money and ideas", the literature stressing the importance of a cluster's openness and external linkages, and the path dependency debate, the paper aims to analyse how certain cluster characteristics correspond with its overall performance. After identifying different cluster types, we investigate their internal and external interconnectivity in comparative manner and draw on changes in cluster composition. Our results indicate that the structure, i.e. to which group the cluster belongs, and the openness towards external knowledge flows deliver merely unsystematic indications with regard to a cluster's overall success. Its ability to change composition towards a more balanced ratio of science and capital over time, on the other hand, turns out as a key explanatory factor. Hence, the dynamic perspective proves effective illuminating cluster growth and performance, where our explorative findings provide a promising avenue for further evolutionary research

Isotretinoin Use and the Risk of Inflammatory Bowel Disease: A Case–Control Study

Isotretinoin is commonly prescribed for the treatment of severe acne. Though cases of inflammatory bowel disease (IBD) have been reported in isotretinoin users, a causal association remains unproven

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin