The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy

Background: Hypertrophic (HCM) and dilated (DCM) cardiomyopathies results from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings: We ablated Tnnt2 to produce heterozygous Tnnt2+/ mice, and crossbreeding produced homozygous null Tnnt2-/-embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/-/TGWT) or mutant (Tnnt2+/-/TGK210Δ) transgenes. Tnnt2+/-mice relative to wildtype had significantly reduced transcript (0.82 ± 0.06 [SD] vs. 1.00 ± 0.12 arbitrary units; p = 0.025), but not protein (1.01 ± 0.20 vs. 1.00 ± 0.13 arbitrary units; p = 0.44). Tnnt2+/-mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/-/ TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18 ± 4 vs. 29 ± 7%; p < 0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/-/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/-/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34 ± 0.08 vs. 5.58 ± 0.03 at sarcomere length 1.9 μm. p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2-/-embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions: Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal function of a mutant protein, which is associated with myocyte Ca2+ desensitization. The severity of DCM depends on the ratio of mutant to wildtype Tnnt2 transcript. cTnT is essential for sarcomere formation, but normal embryonic heart looping occurs without contractile activity. © 2008 Ahmad et al

Land subsidence susceptibility mapping in South Korea using machine learning algorithms

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. In this study, land subsidence susceptibility was assessed for a study area in South Korea by using four machine learning models including Bayesian Logistic Regression (BLR), Support Vector Machine (SVM), Logistic Model Tree (LMT) and Alternate Decision Tree (ADTree). Eight conditioning factors were distinguished as the most important affecting factors on land subsidence of Jeong-am area, including slope angle, distance to drift, drift density, geology, distance to lineament, lineament density, land use and rock-mass rating (RMR) were applied to modelling. About 24 previously occurred land subsidence were surveyed and used as training dataset (70% of data) and validation dataset (30% of data) in the modelling process. Each studied model generated a land subsidence susceptibility map (LSSM). The maps were verified using several appropriate tools including statistical indices, the area under the receiver operating characteristic (AUROC) and success rate (SR) and prediction rate (PR) curves. The results of this study indicated that the BLR model produced LSSM with higher acceptable accuracy and reliability compared to the other applied models, even though the other models also had reasonable results

A hybrid computational intelligence approach to groundwater spring potential mapping

© 2019 by the authors. This study proposes a hybrid computational intelligence model that is a combination of alternating decision tree (ADTree) classifier and AdaBoost (AB) ensemble, namely "AB-ADTree", for groundwater spring potential mapping (GSPM) at the Chilgazi watershed in the Kurdistan province, Iran. Although ADTree and its ensembles have been widely used for environmental and ecological modeling, they have rarely been applied to GSPM. To that end, a groundwater spring inventory map and thirteen conditioning factors tested by the chi-square attribute evaluation (CSAE) technique were used to generate training and testing datasets for constructing and validating the proposed model. The performance of the proposed model was evaluated using statistical-index-based measures, such as positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity accuracy, root mean square error (RMSE), and the area under the receiver operating characteristic (ROC) curve (AUROC). The proposed hybrid model was also compared with five state-of-the-art benchmark soft computing models, including singleADTree, support vector machine (SVM), stochastic gradient descent (SGD), logistic model tree (LMT), logistic regression (LR), and random forest (RF). Results indicate that the proposed hybrid model significantly improved the predictive capability of the ADTree-based classifier (AUROC = 0.789). In addition, it was found that the hybrid model, AB-ADTree, (AUROC = 0.815), had the highest goodness-of-fit and prediction accuracy, followed by the LMT (AUROC = 0.803), RF (AUC = 0.803), SGD, and SVM (AUROC = 0.790) models. Indeed, this model is a powerful and robust technique for mapping of groundwater spring potential in the study area. Therefore, the proposed model is a promising tool to help planners, decision makers, managers, and governments in the management and planning of groundwater resources

Bearing capacity charts of soft soil reinforced by deep mixing

A series of preliminary design charts were developed to predict the bearing capacity of fully and partially penetrated deep mixing (DM) of soft soil. The charts were produced by a new numerical analysis tool based on discontinuity layout optimisation (DLO) in which a previously proposed homogenisation method was used to define the improvement area. To measure the applicability of implementation of the homogenisation method in the DLO, a series of validation processes was performed against several previous studies under uniform soil strength. A new empirical solution was developed from the DLO method using the homogenisation method for the bearing capacity of soft ground under uniform soil strength, improved by the fully penetrated DM method. Results produced by the DLO approach were compared with existing analytical solutions and better agreement was found from the present model. The charts consider variation in improvement area ratio, column length and strength, and foundation width for the fully and partially penetrated DM cases. The simulations were related to real field cases in which the strength characteristics of soft soil increase with depth. An example is given to demonstrate use of the charts

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Biphasic effect of extracellular ATP on human and rat airways is due to multiple P2 purinoceptor activation

BACKGROUND: Extracellular ATP may modulate airway responsiveness. Studies on ATP-induced contraction and [Ca(2+)](i )signalling in airway smooth muscle are rather controversial and discrepancies exist regarding both ATP effects and signalling pathways. We compared the effect of extracellular ATP on rat trachea and extrapulmonary bronchi (EPB) and both human and rat intrapulmonary bronchi (IPB), and investigated the implicated signalling pathways. METHODS: Isometric contraction was measured on rat trachea, EPB and IPB isolated rings and human IPB isolated rings. [Ca(2+)](i )was monitored fluorimetrically using indo 1 in freshly isolated and cultured tracheal myocytes. Statistical comparisons were done with ANOVA or Student's t tests for quantitative variables and χ(2 )tests for qualitative variables. Results were considered significant at P < 0.05. RESULTS: In rat airways, extracellular ATP (10(-6)–10(-3 )M) induced an epithelium-independent and concentration-dependent contraction, which amplitude increased from trachea to IPB. The response was transient and returned to baseline within minutes. Similar responses were obtained with the non-hydrolysable ATP analogous ATP-γ-S. Successive stimulations at 15 min-intervals decreased the contractile response. In human IPB, the contraction was similar to that of rat IPB but the time needed for the return to baseline was longer. In isolated myocytes, ATP induced a concentration-dependent [Ca(2+)](i )response. The contractile response was not reduced by thapsigargin and RB2, a P2Y receptor inhibitor, except in rat and human IPB. By contrast, removal of external Ca(2+), external Na(+ )and treatment with D600 decreased the ATP-induced response. The contraction induced by α-β-methylene ATP, a P2X agonist, was similar to that induced by ATP, except in IPB where it was lower. Indomethacin and H-89, a PKA inhibitor, delayed the return to baseline in extrapulmonary airways. CONCLUSION: Extracellular ATP induces a transient contractile response in human and rat airways, mainly due to P2X receptors and extracellular Ca(2+ )influx in addition with, in IPB, P2Y receptors stimulation and Ca(2+ )release from intracellular Ca(2+ )stores. Extracellular Ca(2+ )influx occurs through L-type voltage-dependent channels activated by external Na(+ )entrance through P2X receptors. The transience of the response cannot be attributed to ATP degradation but to purinoceptor desensitization and, in extrapulmonary airways, prostaglandin-dependent PKA activation

The ability of analysts’ recommendations to predict optimistic and pessimistic forecasts

Previous researches show that buy (growth) companies conduct income increasing earnings management in order to meet forecasts and generate positive forecast Errors (FEs). This behavior however, is not inherent in sell (non-growth) companies. Using the aforementioned background, this research hypothesizes that since sell companies are pressured to avoid income increasing earnings management, they are capable, and in fact more inclined, to pursue income decreasing Forecast Management (FM) with the purpose of generating positive FEs. Using a sample of 6553 firm-years of companies that are listed in the NYSE between the years 2005–2010, the study determines that sell companies conduct income decreasing FM to generate positive FEs. However, the frequency of positive FEs of sell companies does not exceed that of buy companies. Using the efficiency perspective, the study suggests that even though buy and sell companies have immense motivation in avoiding negative FEs, they exploit different but efficient strategies, respectively, in order to meet forecasts. Furthermore, the findings illuminated the complexities behind informative and opportunistic forecasts that falls under the efficiency versus opportunistic theories in literature

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98