Expressive Stream Reasoning with Laser

An increasing number of use cases require a timely extraction of non-trivial knowledge from semantically annotated data streams, especially on the Web and for the Internet of Things (IoT). Often, this extraction requires expressive reasoning, which is challenging to compute on large streams. We propose Laser, a new reasoner that supports a pragmatic, non-trivial fragment of the logic LARS which extends Answer Set Programming (ASP) for streams. At its core, Laser implements a novel evaluation procedure which annotates formulae to avoid the re-computation of duplicates at multiple time points. This procedure, combined with a judicious implementation of the LARS operators, is responsible for significantly better runtimes than the ones of other state-of-the-art systems like C-SPARQL and CQELS, or an implementation of LARS which runs on the ASP solver Clingo. This enables the application of expressive logic-based reasoning to large streams and opens the door to a wider range of stream reasoning use cases.Comment: 19 pages, 5 figures. Extended version of accepted paper at ISWC 201

New development: Directly elected mayors in Italy: creating a strong leader doesn’t mean creating strong leadership

More than 20 years after their introduction, directly elected mayors are key players in Italian urban governance. This article explains the main effects of this reform on local government systems and provides lessons for other countries considering directly elected mayors

Overview of the design of the ITER heating neutral beam injectors

The heating neutral beam injectors (HNBs) of ITER are designed to deliver 16.7MWof 1 MeVD0 or 0.87 MeVH0 to the ITER plasma for up to 3600 s. They will be the most powerful neutral beam\uf0a0(NB) injectors ever, delivering higher energy NBs to the plasma in a tokamak for longer than any previous systems have done. The design of the HNBs is based on the acceleration and neutralisation of negative ions as the efficiency of conversion of accelerated positive ions is so low at the required energy that a realistic design is not possible, whereas the neutralisation ofH 12 andD 12 remains acceptable ( 4856%). The design of a long pulse negative ion based injector is inherently more complicated than that of short pulse positive ion based injectors because: \u2022 negative ions are harder to create so that they can be extracted and accelerated from the ion source; \u2022 electrons can be co-extracted from the ion source along with the negative ions, and their acceleration must be minimised to maintain an acceptable overall accelerator efficiency; \u2022 negative ions are easily lost by collisions with the background gas in the accelerator; \u2022 electrons created in the extractor and accelerator can impinge on the extraction and acceleration grids, leading to high power loads on the grids; \u2022 positive ions are created in the accelerator by ionisation of the background gas by the accelerated negative ions and the positive ions are back-accelerated into the ion source creating a massive power load to the ion source; \u2022 electrons that are co-accelerated with the negative ions can exit the accelerator and deposit power on various downstream beamline components. The design of the ITER HNBs is further complicated because ITER is a nuclear installation which will generate very large fluxes of neutrons and gamma rays. Consequently all the injector components have to survive in that harsh environment. Additionally the beamline components and theNBcell, where the beams are housed, will be activated and all maintenance will have to be performed remotely. This paper describes the design of theHNBinjectors, but not the associated power supplies, cooling system, cryogenic system etc, or the high voltage bushingwhich separates the vacuum of the beamline fromthehighpressureSF6 of the high voltage (1MV) transmission line, through which the power, gas and coolingwater are supplied to the beam source. Also themagnetic field reduction system is not described

Increased tumor necrosis factor alpha-converting enzyme activity induces insulin resistance and hepatosteatosis in mice

Tumor necrosis factor alpha-converting enzyme (TACE, also known as ADAM17) was recently involved in the pathogenesis of insulin resistance. We observed that TACE activity was significantly higher in livers of mice fed a high-fat diet (HFD) for 1 month, and this activity was increased in liver > white adipose tissue > muscle after 5 months compared with chow control. In mouse hepatocytes, C(2)C(12) myocytes, and 3T3F442A adipocytes, TACE activity was triggered by palmitic acid, lipolysaccharide, high glucose, and high insulin. TACE overexpression significantly impaired insulin-dependent phosphorylation of AKT, GSK3, and FoxO1 in mouse hepatocytes. To test the role of TACE activation in vivo, we used tissue inhibitor of metalloproteinase 3 (Timp3) null mice, because Timp3 is the specific inhibitor of TACE and Timp3(-/-) mice have higher TACE activity compared with wild-type (WT) mice. Timp3(-/-) mice fed a HFD for 5 months are glucose-intolerant and insulin-resistant; they showed macrovesicular steatosis and ballooning degeneration compared with WT mice, which presented only microvesicular steatosis. Shotgun proteomics analysis revealed that Timp3(-/-) liver showed a significant differential expression of 38 proteins, including lower levels of adenosine kinase, methionine adenosysltransferase I/III, and glycine N-methyltransferase and higher levels of liver fatty acid-binding protein 1. These changes in protein levels were also observed in hepatocytes infected with adenovirus encoding TACE. All these proteins play a role in fatty acid uptake, triglyceride synthesis, and methionine metabolism, providing a molecular explanation for the increased hepatosteatosis observed in Timp3(-/-) compared with WT mice. Conclusion: We have identified novel mechanisms, governed by the TACE-Timp3 interaction, involved in the determination of insulin resistance and liver steatosis during overfeeding in mice

Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines

The effect of the glutathione transferase P1-1 (GSTP1-1) targeting has been investigated in both sensitive (U-2OS) and cisplatin-resistant (U-2OS/CDDP4μg) human osteosarcoma cell lines. Despite the different enzyme’s content, inhibition of GSTP1-1 by 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) causes the activation of c-Jun N-terminal kinase (JNK) and apoptosis in both cell lines. However, different time courses of JNK activation and cell responses are observed. Whereas in the U-2OS/CDDP4μg cell line drug treatment results in an early increase of caspase activity and secondary necrosis, in the U-2OS cells it mainly causes cell cycle arrest followed by apoptosis. Thereafter, we detailed the action mechanism of NBDHEX in the U-2OS cell line. We report evidence of the interaction between GSTP1-1 and the TNF receptor associated factor 2 (TRAF2) and we demonstrate that NBDHEX is able to dissociate the GSTP1-1:TRAF2 complex. This restores the TRAF2:ASK1 signaling, thereby leading to the simultaneous and prolonged activation of JNK and p38. These mitogen-activated protein kinases (MAPKs) mediate different effects: JNK is crucial for apoptosis, whereas p38 causes an increase in the p21 level and a concomitant cell cycle arrest. Our study shows that GSTP1-1 plays an important regulatory role in TRAF signaling of osteosarcoma and discloses new features of the action mechanism of NBDHEX that suggest potentially practical consequences of these finding

p63 isoforms regulate metabolism of cancer stem cells

p63 is an important regulator of epithelial development expressed in different variants containing (TA) or lacking (\u394N) the N-terminal transactivation domain. The different isoforms regulate stem-cell renewal and differentiation as well as cell senescence. Several studies indicate that p63 isoforms also play a role in cancer development; however, very little is known about the role played by p63 in regulating the cancer stem phenotype. Here we investigate the cellular signals regulated by TAp63 and \u394Np63 in a model of epithelial cancer stem cells. To this end, we used colon cancer stem cells, overexpressing either TAp63 or \u394Np63 isoforms, to carry out a proteomic study by chemical-labeling approach coupled to network analysis. Our results indicate that p63 is implicated in a wide range of biological processes, including metabolism. This was further investigated by a targeted strategy at both protein and metabolite levels. The overall data show that TAp63 overexpressing cells are more glycolytic-active than \u394Np63 cells, indicating that the two isoforms may regulate the key steps of glycolysis in an opposite manner. The mass-spectrometry proteomics data of the study have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository with data set identifiers PXD000769 and PXD000768

Amyloid persistence in decellularized liver: biochemical and histopathological characterization

Systemic amyloidoses are a group of debilitating and often fatal diseases in which fibrillar protein aggregates are deposited in the extracellular spaces of a range of tissues. The molecular basis of amyloid formation and tissue localization is still unclear. Although it is likely that the extracellular matrix (ECM) plays an important role in amyloid deposition, this interaction is largely unexplored, mostly because current analytical approaches may alter the delicate and complicated three-dimensional architecture of both ECM and amyloid. We describe here a decellularization procedure for the amyloidotic mouse liver which allows high-resolution visualization of the interactions between amyloid and the constitutive fibers of the extracellular matrix. The primary structure of the fibrillar proteins remains intact and the amyloid fibrils retain their amyloid enhancing factor activity

Critical energy landscape of linear soft spheres

We show that soft spheres interacting with a linear ramp potential when overcompressed beyond the jamming point fall in an amorphous solid phase which is critical, mechanically marginally stable and share many features with the jamming point itself. In the whole phase, the relevant local minima of the potential energy landscape display an isostatic contact network of perfectly touching spheres whose statistics is controlled by an infinite lengthscale. Excitations around such energy minima are non-linear, system spanning, and characterized by a set of non-trivial critical exponents. We perform numerical simulations to measure their values and show that, while they coincide, within numerical precision, with the critical exponents appearing at jamming, the nature of the corresponding excitations is richer. Therefore, linear soft spheres appear as a novel class of finite dimensional systems that self-organize into new, critical, marginally stable, states

Fear of Birth Defects Is a Major Barrier to Soil-Transmitted Helminth Treatment (STH) for Pregnant Women in the Philippines

The World Health Organization recommends anthelminthic treatment for pregnant women after the first trimester in soil-transmitted helminth (STH) endemic regions to prevent adverse maternal-fetal consequences. Although studies have shown the high prevalence of infection in the Philippines, no research has evaluated deworming practices. We hypothesized that pregnant women are not receiving deworming treatment and we aimed to identify barriers to World Health Organization guideline implementation. We conducted key informant interviews with local Department of Health (DOH) administrators, focus group discussions with nurses, midwives, and health care workers, and knowledge, attitudes, and practices surveys with women of reproductive age to elicit perspectives about deworming during pregnancy. Key informant interviews revealed that healthcare workers were not deworming pregnant women due to inadequate drug supply, infrastructure and personnel as well as fear of teratogenicity. Focus group discussions showed that healthcare workers similarly had not implemented guidelines due to infrastructure challenges and concerns for fetal malformations. The majority of local women believed that STH treatment causes side effects (74.8%) as well as maternal harm (67.3%) and fetal harm (77.9%). Women who were willing to take anthelminthics while pregnant had significantly greater knowledge as demonstrated by higher Treatment Scores (mean rank 146.92 versus 103.1, z = −4.40, p<0.001) and higher Birth Defect Scores (mean rank 128.09 versus 108.65, z = −2.43, p = 0.015). This study concludes that World Health Organization guidelines are not being implemented in the Philippines. Infrastructure, specific protocols, and education for providers and patients regarding anthelminthic treatment are necessary for the successful prevention of STH morbidity and mortality among pregnant women