An elementary proof of Sylvester’s double sums for subresultants

In 1853 Sylvester stated and proved an elegant formula that expresses the polynomial subresultants in terms of the roots of the input polynomials. Sylvester’s formula was also recently proved by Lascoux and Pragacz using multi-Schur functions and divided differences. In this paper, we provide an elementary proof that uses only basic properties of matrix multiplication and Vandermonde determinants.     

Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure

The synthesis and the biological evaluation of a series of novel pyrroloquinoxaline derivatives are described. In binding studies several compounds proved to be potent and selective 5-HT3 receptor ligands. The most active pyrroloquinoxalines, 11d and 11e, showed a subnanomolar affinity for 5-HT3 receptor and were able to functionally discriminate the central and peripheral 5-HT3 receptor, being agonists and antagonists, respectively. In functional studies ([14C]-guanidinium accumulation test in NG 108-15 cells, in vitro) most of the synthesized compounds showed clear-cut 5-HT3 agonist properties. In in vivo studies on the von Bezold-Jarisch reflex test (a peripheral interaction model) the behavior of the tested compounds ranged from agonist to antagonist, while clear agonist properties were obtained with 12a on cortical acetylcholine release in freely moving rats. Pharmacokinetic studies with 11e and 12c indicate that the compounds easily cross the blood-brain barrier (BBB) after systemic administration with a brain/plasma ratio of 17.5 and 37.5, respectively. Thus compounds 11e and 12c represent the most potent central 5-HT3 agonists identified to date that are able to cross the blood-brain barrier.     

Maternal serum screening for trisomy 18 in the first trimester of pregnancy

It is widely accepted that thrombocytopenia associated with liver cirrhosis is caused by increased platelet destruction in the enlarged spleen, but this issue has not yet been analysed sufficiently in terms of platelet production. Thrombopoietin is produced mainly in the liver and strongly promotes platelet production. We studied serum thrombopoietin and the levels of its mRNA in liver tissue of cirrhotic patients and also in a rat model of liver cirrhosis. Furthermore, to clarify the influence of the spleen, we investigated thrombopoietin mRNA in splenectomized rats. The serum thrombopoietin level in humans with liver cirrhosis was not significantly reduced instead of thrombocytopenia. The expression of thrombopoietin mRNA in liver tissue decreased with the progression of liver cirrhosis in both patients and the rat model and no compensatory expression was observed in other organs or non-parenchymal cells. The level of thrombopoietin mRNA did not differ significantly in splenectomized cirrhotic rats before or after administration of dimethylnitrosamine, but was lower than that in splenectomized rats without cirrhosis. We conclude that thrombocytopenia in liver cirrhosis is caused not only by platelet destruction but also by decreased platelet production, perhaps due to reduction of thrombopoietin mRNA in the liver.     

A Web‐based Open‐source Geoinformation Tool for Regional Water Resources Assessment

Water Resources Management - To reduce the impact of droughts and increase the resilience of regional water systems, various competing demands, such as hydropower, supply, irrigation and river...     

Hull-form stochastic optimization via computational-cost reduction methods

In this paper, analytical functions for the estimation of the temperature-dependent behaviors of poorly and highly dispersed graphene oxide reinforced nanocomposite (GORNC) materials are studied in the framework of a machine learning-based approach. The validity of the presented models is shown comparing the results achieved from this modeling with those reported in the open literature. Also, the application of the obtained functions in solving the thermal buckling problem of beams constructed from such nanocomposites is demonstrated based on an energy-based method incorporated with a shear deformable beam hypothesis. The verification of the results indicates that the presented mechanical model can approximate the buckling behaviors of nanocomposite beams with remarkable precision. It can be realized from the results that the temperature plays an indispensable role in the determination of the buckling load which can be endured by the nanocomposite structure.

     

Valuation of online social networks taking into account users’ interconnectedness

Online social networks have been gaining increasing economic importance in light of the rising number of their users. Numerous recent acquisitions priced at enormous amounts have illustrated this development and revealed the need for adequate business valuation models. The value of an online social network is largely determined by the value of its users, the relationships between these users, and the resulting network effects. Therefore, the interconnectedness of a user within the network has to be considered explicitly to get a reasonable estimate for its economic value. Established standard business valuation models, however, do not account for these aspects sufficiently. Thus, we propose an economic model for the valuation of online social networks, which takes into account the users’ interconnectedness within the network. Furthermore, we analyze different centrality measures, which can be used to quantify users’ interconnectedness in online social networks and propose a measure which is based on the PageRank-algorithm. Finally, the practical application of the model is illustrated by an example of the European online social network XING.com.     

Sensitivity analysis for simulation-based decision making: Application to a hospital emergency service design

An increasing concern of decision makers when dealing with system design is preparation for a wide range of potentially uncertain operating conditions. This paper provides a novel multiobjective approach for simulation-driven decision making that accounts for not only the conventional average system performance indices, but also (i) upper-tail, or extreme, values of these indices, and (ii) measures of their sensitivity to uncertainty in model parameters. The proposed approach is applied to a hospital emergency department service design case study wherein different design alternatives are compared using total time-in-system performance metric under multiple uncertain operating conditions.     

Curcumin Prevents Cerebellar Hypoplasia and Restores the Behavior in Hyperbilirubinemic Gunn Rat by a Pleiotropic Effect on the Molecular Effectors of Brain Damage

Bilirubin toxicity to the central nervous system (CNS) is responsible for severe and permanent neurologic damage, resulting in hearing loss, cognitive, and movement impairment. Timely and effective management of severe neonatal hyperbilirubinemia by phototherapy or exchange transfusion is crucial for avoiding permanent neurological consequences, but these therapies are not always possible, particularly in low-income countries. To explore alternative options, we investigated a pharmaceutical approach focused on protecting the CNS from pigment toxicity, independently from serum bilirubin level. To this goal, we tested the ability of curcumin, a nutraceutical already used with relevant results in animal models as well as in clinics in other diseases, in the Gunn rat, the spontaneous model of neonatal hyperbilirubinemia. Curcumin treatment fully abolished the landmark cerebellar hypoplasia of Gunn rat, restoring the histological features, and reverting the behavioral abnormalities present in the hyperbilirubinemic rat. The protection was mediated by a multi-target action on the main bilirubin-induced pathological mechanism ongoing CNS damage (inflammation, redox imbalance, and glutamate neurotoxicity). If confirmed by independent studies, the result suggests the potential of curcumin as an alternative/complementary approach to bilirubin-induced brain damage in the clinical scenario.     

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Cushing’s Syndrome Effects on the Thyroid

The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.