Maritime Autonomous Surface Ships (MASS) do require shifting from human information processing to automation functions. While supporting the sensory processing of human navigation by automated ...information acquisition from different sensors is an already established (and even in many cases mandatory) technology with a set of framing standards and information exchanges, defining a common data set for a perceived environment model is currently neglected which hinders modularization of MASS technology development. Beginning with an introduction into the navigational process as well as information processing, this paper subsequently proposes an initial minimum data set for different aspects of ship navigation.
Highlights ►EMT is associated with reproducible changes in mitogenic signaling pathways. ►EMT-associated “mitogenic switching” may facilitate the acquisition of tumor resistance to targeted ...therapeutics. ►Effectively treating cancer may require simultaneously targeting both pre- and post-EMT tumor cells.
Although rice resistance plays an important role in controlling the brown planthopper (BPH), Nilaparvata lugens, not all varieties have the same level of protection against BPH infestation. ...Understanding the molecular interactions in rice defense response is an important tool to help to reveal unexplained processes that underlie rice resistance to BPH. A proteomics approach was used to explore how wild type IR64 and near-isogenic rice mutants with gain and loss of resistance to BPH respond during infestation. A total of 65 proteins were found markedly altered in wild type IR64 during BPH infestation. Fifty-two proteins associated with 11 functional categories were identified using mass spectrometry. Protein abundance was less altered at 2 and 14 days after infestation (DAI) (T1, T2, respectively), whereas higher protein levels were observed at 28 DAI (T3). This trend diminished at 34 DAI (T4). Comparative analysis of IR64 with mutants showed 22 proteins that may be potentially associated with rice resistance to the brown planthopper (BPH). Ten proteins were altered in susceptible mutant (D1131) whereas abundance of 12 proteins including S-like RNase, Glyoxalase I, EFTu1 and Salt stress root protein "RS1" was differentially changed in resistant mutant (D518). S-like RNase was found in greater quantities in D518 after BPH infestation but remained unchanged in IR64 and decreased in D1131. Taken together, this study shows a noticeable level of protein abundance in the resistant mutant D518 compared to the susceptible mutant D1131 that may be involved in rendering enhanced level of resistance against BPH.
While rapamycin and the "rapalogs" Everolimus and Temsirolimus have been approved for clinical use in the treatment of a number of forms of cancer, they have not met overarching success. Some tumors ...are largely refractory to rapamycin treatment, with some even undergoing an increase in growth rates. However the mechanisms by which this occurs are largely unknown. The results presented here reveal novel cell-signaling mechanisms that may lead to this resistance. The absence of TGFβ signaling results in resistance to rapamycin. Additionally, we observed that treatment of some cancer cell lines with rapamycin and its analogs not only potentiates mitogenic signaling and proliferation induced by HGF, but also stimulates the pro-survival kinase Akt. Together, the data show that the effectiveness of rapamycin treatment can be influenced by a number of factors and bring to light potential biomarkers for the prediction of responsiveness to treatment, and suggest combination therapies to optimize rapalog anticancer efficacy.
Vessel groundings pose a major risk for maritime safety, constituting 20 percent of all incidents in the last decade. Frequent dredging and bottom mapping are resource intensive solutions currently ...employed, but these services cannot be maintained with the necessary frequency in all critical areas. While ships are carrying echo sounders to acquire precise and current under keel clearance data, it does not allow the vessel to react to possible deviations from the map data. Within the RoboVaaS project, a service is designed, implemented and tested in simulation. This service consists of one or more small MASS travelling ahead of a merchant vessel, collecting bathymetric data with enough lead time for the merchant vessel to react to possible threats, e.g. by course correction. This service is tested in compliance with the IMO HCD guideline in a quick approach and safe environment using a ship handling simulator. The simulator is augmented by a display system based on an ECDIS map and displaying the bathymetric data in three different scenarios. These scenarios are tested with nautical officers to collect feedback for service design and implementation with trained personnel and show the effectiveness of the chosen human machine interface.
A symptom-based subgroup taxonomy for obsessive–compulsive disorder (OCD) was evaluated and refined. The Yale-Brown Obsessive–Compulsive Scale symptom checklist was scored and cluster analysis was ...conducted with a sample of OCD patients (
N=114). Results were compared to Calamari et al.’s (Behaviour Research and Therapy 37 (1999) 113) five subgroup model. Rules for determining the number of subgroups supported a more complex model. In between sample comparisons, a stable contamination subgroup was found in both a five and seven subgroup taxonomy. Between sample stability was not as strong for Harming, Obsessionals, Symmetry, and Certainty subgroups. Hoarding, as a distinctive subgroup, was unstable in separate samples. When the Calamari et al. sample and the present sample were combined (
N=220), we found a reliable Hoarding subgroup. More interpretable and stable models emerged with the combined samples suggesting that large clinical samples are needed to identify OCD subgroups. Greater support was found for a seven subgroup taxonomy based subgroup interpretability and validation measure differences. The potential utility of symptom-based subgroup models of OCD and alternative approaches are discussed. Identification of reliable and valid OCD subtypes may advance theory and treatment.
Acetyltransferase p300 (KAT3B) plays key roles in signaling cascades that support cancer cell survival and sustained proliferation. Thus, p300 represents a potential anticancer therapeutic target. To ...discover novel anticancer agents that target p300, we conducted a high-throughput screening campaign. A library of 622,079 compounds was assayed for cytotoxicity to the triple-negative breast cancer (TNBC) cell line MDA-MB-231 but not to the human mammary epithelial cells. The resulting compounds were tested in a biochemical assay for inhibiting the enzymatic activity of p300. One compound (L002, NSC764414) displayed an IC50 of 1.98 μmol/L against p300 in vitro, inhibited acetylation of histones and p53, and suppressed STAT3 activation in cell-based assays. L002 could be docked to the active site of the p300 catalytic domain. Biochemical tests of a series of related compounds revealed functional groups that may impact inhibitory potency of L002 against p300. Interestingly, these analogs showed inhibitory activities against the cellular paralog of p300 (CBP), p300/CBP-associated factor, and GCN5, but not to other acetyltransferases (KAT5, KAT6B, and KAT7), histone deacetylases, and histone methyltransferases. Among the NCI-60 panel of cancer cell lines, leukemia and lymphoma cell lines were extremely sensitive to L002, whereas it is toxic to only a limited number of cell lines derived from solid tumors. Notably, breast cancer cell lines, especially those derived from TNBC, were highly susceptible to L002. In vivo, it potently suppressed tumor growth and histone acetylation of MDA-MB-468 xenografts. Thus, these new acetyltransferase inhibitors are potential anticancer therapeutics.
Abstract Background, objectives The extent of microvascular obstruction (MVO) during myocardial infarction referred to as the “no-reflow phenomenon”, may determine myocardial damage. Our study aimed ...to investigate the incidence and the influencing factors of MVO in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous intervention (PCI). Patients, methods Using contrast-enhanced MRI, microvascular obstruction was defined as early hypoenhancement. Contrast defects were scored from 0 (no hypoenhancement) to 3 (strong hypoenhancement). 50 patients (56 ± 11 years) with STEMI underwent PCI. Contrast-enhanced MRI (6 ± 2 days after STEMI) and biochemical parameters were evaluated. Results Microvascular obstruction (score 1 to 3) was observed in 90% of the patients and major microvascular obstruction (score 2–3) in 54%. In univariate analysis, leukocytes and CRP levels were associated with MVO, whereas pre-infarction angina and prior medication by aspirin or calcium channel antagonist appeared protective. Microvascular obstruction intensity positively correlated with baseline inflammation status assessed by C-reactive protein and leukocytes (rho = 0.43 and rho = 0.44; p = 0.003), the peak of CK (rho = 0.56; p = 0.01) or Troponin I (rho = 0.59; p = 0.01) and negatively correlated with LVEF (rho = − 0.44; p = 0.002). Multivariate analysis identified the absence of pre-infarction angina as the only independent predictor for microvascular obstruction (odds ratio, 8.35, 95% confidence interval 1.27–54.71; p = 0.027). Conclusion MRI-detected microvascular obstruction has a high incidence in patients with STEMI treated by primary PCI and determines post-MI LVEF even in patients with post PCI TIMI 3 flow score. Pre-infarction angina appears to be an independent determinant of the extent of MVO detected by MRI.
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