Persistence of dissolved organic matter explained by molecular changes during its passage through soil

Dissolved organic matter affects fundamental biogeochemical processes in the soil such as nutrient cycling and organic matter storage. The current paradigm is that processing of dissolved organic matter converges to recalcitrant molecules (those that resist degradation) of low molecular mass and high molecular diversity through biotic and abiotic processes. Here we demonstrate that the molecular composition and properties of dissolved organic matter continuously change during soil passage and propose that this reflects a continual shifting of its sources. Using ultrahigh-resolution mass spectrometry and nuclear magnetic resonance spectroscopy, we studied the molecular changes of dissolved organic matter from the soil surface to 60 cm depth in 20 temperate grassland communities in soil type Eutric Fluvisol. Applying a semi-quantitative approach, we observed that plant-derived molecules were first broken down into molecules containing a large proportion of low-molecular-mass compounds. These low-molecular-mass compounds became less abundant during soil passage, whereas larger molecules, depleted in plant-related ligno-cellulosic structures, became more abundant. These findings indicate that the small plant-derived molecules were preferentially consumed by microorganisms and transformed into larger microbial-derived molecules. This suggests that dissolved organic matter is not intrinsically recalcitrant but instead persists in soil as a result of simultaneous consumption, transformation and formation

Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin

The approval of histone deacetylase inhibitors for treatment of lymphoma subtypes has positioned histone modifications as potential targets for the development of new classes of anticancer drugs. Histones also undergo phosphorylation events, and Haspin is a protein kinase the only known target of which is phosphorylation of histone H3 at Thr3 residue (H3T3ph), which is necessary for mitosis progression. Mitotic kinases can be blocked by small drugs and several clinical trials are underway with these agents. As occurs with Aurora kinase inhibitors, Haspin might be an optimal candidate for the pharmacological development of these compounds. A high-throughput screening for Haspin inhibitors identified the CHR-6494 compound as being one promising such agent. We demonstrate that CHR-6494 reduces H3T3ph levels in a dose-dependent manner and causes a mitotic catastrophe characterized by metaphase misalignment, spindle abnormalities and centrosome amplification. From the cellular standpoint, the identified small-molecule Haspin inhibitor causes arrest in G2/M and subsequently apoptosis. Importantly, ex vivo assays also demonstrate its anti-angiogenetic features; in vivo, it shows antitumor potential in xenografted nude mice without any observed toxicity. Thus, CHR-6494 is a first-in-class Haspin inhibitor with a wide spectrum of anticancer effects that merits further preclinical research as a new member of the family of mitotic kinase inhibitors

A novel canine histiocytic sarcoma cell line:initial characterization and utilization for drug screening studies

Abstract Background Histiocytic sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine histiocytic sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. Methods The histiocytic sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Results Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. Conclusions In the present study we demonstrated that a novel canine histiocytic sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans

A novel canine histiocytic sarcoma cell line:initial characterization and utilization for drug screening studies

In order to be responsible stewards of other people’s data, cloud providers must be accountable for their data handling practices. The potential long provider chains in cloud computing introduces additional accountability challenges, and this paper examines requirements which must be fulfilled to achieve an accountability-based approach.acceptedVersio

Developing digital health technologies for frontotemporal degeneration

Frontotemporal degeneration (FTD) is a rare neurodegenerative disease in which patients can present with cognitive, behavioral, motor, and speech impairment. Currently, there are no approved therapies available to slow or halt disease progression. Detection and monitoring of patient symptoms is challenging for this heterogeneous disease and has negatively impacted progress in FTD clinical trials. Rapid technological advancements can promote the development of digital health technologies (DHTs) capable of capturing even the most subtle clinical impairments. DHTs are computing platforms being designed to measure meaningful aspects of disease onset and progression. Here we present some of the numerous tools currently being developed to measure changes in the functional domains that become impaired in FTD, challenges faced by developers, and a proposed roadmap for developing fit-for-purpose DHTs that will aid in the development of effective therapies for FTD. HIGHLIGHTS: DHTs are being developed to assess FTD onset and progression. Tool developers must overcome numerous challenges in creating effective applications. Guidance to tool developers aims to benefit FTD drug development and patient care

Umweltschutz und Arbeitsschutz zwischen Eigenstaendigkeit und Gemeinsamkeit vom Programm zur Praxis

SIGLEIAB-91-8040..-80 BB 678 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Towards an Accurate Solution of Wireless Network Design Problems

The optimal design of wireless networks has been widely studied in the literature and many optimization models have been proposed over the years. However, most models directly include the signal-to-interference ratios representing service coverage conditions. This leads to mixed-integer linear programs with constraint matrices containing tiny coefficients that vary widely in their order of magnitude. These formulations are known to be challenging even for state-of-the-art solvers: the standard numerical precision supported by these solvers is usually not sufficient to reliably guarantee feasible solutions. Service coverage errors are thus commonly present. Though these numerical issues are known and become evident even for small-sized instances, just a very limited number of papers has tried to tackle them, by mainly investigating alternative non-compact formulations in which the sources of numerical instabilities are eliminated. In this work, we explore a new approach by investigating how recent advances in exact solution algorithms for linear and mixed-integer programs over the rational numbers can be applied to analyze and tackle the numerical difficulties arising in wireless network design models.Comment: This is the authors' final version of the paper published in: R. Cerulli, S. Fujishige, A.R. Mahjoub (Eds.), Combinatorial Optimization - 4th International Symposium, ISCO 2016, LNCS 9849, pp. 135-147, 2016, DOI: 10.1007/978-3-319-45587-7_12. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-45587-7_1