Computing the Exponential of Large Block-Triangular Block-Toeplitz Matrices Encountered in Fluid Queues

The Erlangian approximation of Markovian fluid queues leads to the problem of computing the matrix exponential of a subgenerator having a block-triangular, block-Toeplitz structure. To this end, we propose some algorithms which exploit the Toeplitz structure and the properties of generators. Such algorithms allow to compute the exponential of very large matrices, which would otherwise be untreatable with standard methods. We also prove interesting decay properties of the exponential of a generator having a block-triangular, block-Toeplitz structure

The Effect of Simple Melodic Lines on Aesthetic Experience: Brain Response to Structural Manipulations

This fMRI study investigates the effect of melody on aesthetic experience in listeners na\uefve to formal musical knowledge. Using simple melodic lines, whose syntactic structure was manipulated, we created systematic acoustic dissonance. Two stimulus categories were created: canonical (syntactically \u201ccorrect,\u201d in the Western culture) and modified (made of an altered version of the canonical melodies). The stimuli were presented under two tasks: listening and aesthetic judgment. Data were analyzed as a function of stimulus structure (canonical and modified) and stimulus aesthetics, as appraised by each participant during scanning. The critical contrast modified versus canonical stimuli produced enhanced activation of deep temporal regions, including the parahippocampus, suggesting that melody manipulation induced feelings of unpleasantness in the listeners. This was supported by our behavioral data indicating decreased aesthetic preference for the modified melodies. Medial temporal activation could also have been evoked by stimulus structural novelty determining increased memory load for the modified stimuli. The analysis of melodies judged as beautiful revealed that aesthetic judgment of simple melodies relied on a fine-structural analysis of the stimuli subserved by a left frontal activation and, possibly, on meaning attribution at the charge of right superior temporal sulcus for increasingly pleasurable stimuli

Остеоартроз, артериальная гипертензия и ожирение: проблема коморбидности

Представлены данные современных исследований отечественных и зарубежных ученых, касающиеся распространенности сочетанной патологии − остеоартроза с артериальной гипертензией и ожирением.Наведено дані сучасних досліджень вітчизняних і зарубіжних вчених щодо поширеності поєднаної патології − остеоартрозу з артеріальною гіпертензією та ожирінням.The data of contemporary investigations of Ukrainian and foreign scientists about the prevalence of combined pathology (osteoarthrosis with arterial hypertension and obesity) are presented

Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase

Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the bla[subscript NDM] gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.Kinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr

Long-term clinical outcomes in critical limb ischemia--A retrospective study of 181 patients

Critical limb ischemia (CLI) is the most severe manifestation of the peripheral arterial disease. To date, several prognostic factors have been identified but the data of long-term follow-up in real life setting are scarce. The aim of our study is to describe a large group of CLI patients and identify possible prognostic factors, in a long-term follow-up

Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients

Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ

Recognition in emergency department of septic patients at higher risk of death: Beware of patients without fever

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed

PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor

Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [35S]GTPγS functional assay, only a few derivatives lacked detectable activity, so were tested in the same functional assay in the presence of CP55940. Among these, compounds 11 and 18 proved to be functional NAMs at CB1Rs, dampening the orthosteric agonist-induced receptor functionality by approximately 30%. The structural features presented in this work provide new CB1R-allosteric modulators (with a profile similar to the reference compound PSNCBAM-1) and an extension of the structure-activity relationships for this type of molecule at CB1Rs