Continuous flow synthesis of heterocycles: A recent update on the flow synthesis of indoles

Indole derivatives are among the most useful and interesting heterocycles employed in drug discovery and medicinal chemistry. In addition, flow chemistry and flow technology are changing the synthetic paradigm in the field of modern synthesis. In this review, the role of flow technology in the preparation of indole derivatives is showcased. Selected examples have been described with the aim to provide readers with an overview on the tactics and technologies used for targeting indole scaffolds

Multidimensional hydrodynamic simulations of the hydrogen injection flash

The injection of hydrogen into the convection shell powered by helium burning during the core helium flash is commonly encountered during the evolution of metal-free and extremely metal-poor low-mass stars. With specifically designed multidimensional hydrodynamic simulations, we aim to prove that an entropy barrier is no obstacle for the growth of the helium-burning shell convection zone in the helium core of a metal-rich Pop I star, i.e. convection can penetrate into the hydrogen-rich layers for these stars, too. We further study whether this is also possible in one-dimensional stellar evolutionary calculations. Our hydrodynamical simulations show that the helium-burning shell convection zone in the helium core moves across the entropy barrier and reaches the hydrogen-rich layers. This leads to mixing of protons into the hotter layers of the core and to a rapid increase of the nuclear energy production at the upper edge of the helium-burning convection shell - the hydrogen injection flash. As a result a second convection zone appears in the hydrogen-rich layers. Contrary to 1D models, the entropy barrier separating the two convective shells from each other is largely permeable to chemical transport when allowing for multidimensional flow, and consequently, hydrogen is continuously mixed deep into the helium core. We find it difficult to achieve such a behavior in one-dimensional stellar evolutionary calculations.Comment: 8 pages, 8 figures - accepted for publication in Astronomy and Astrophysics. Animations related to the manuscript can be downloaded from http://www-astro.ulb.ac.be/~mocak/index.php/Main/AnimationsHeFlas

Along strike preorogenic thickness variation and onlapping geometries control on thrust wedge evolution: insight from sandbox analogue modelling

Abstract: Thickness variation of sedimentary sequences is largely viewed as a controlling factor on the evolution of orogenic wedges; among the different structural and stratigraphic features generating thickness variation, we focused our analysis on the onlapping geometries, using laboratory sandbox experiments. The aim was trying to describe how a common sedimentary configuration could influence thrusts geometry and mode of accretion. Model results showed that onlapping geometries in pretectonic sediments cause a great complexity, dominated by curvilinear thrusts, back thrust and out-ofsequence thrusts. They also influence mode of accretion, generating diachronous thrusting along strike, reactivation and under-thrusting alternating to simple piggy-back sequence. Our modeling results are compared with natural examples from the Apennines, the southern Pyrenees, the Pindos (Greece) and the West Spitsbergen (Greenland) fold and thrust belts, among many others, where strain localization and diachronic thrusting affecting thrust propagation in correspondence to complex geometries both in the pre-orogenic stratigraphy and in the upper crust

Temporal Auditory Processing And Phonological Awareness In Children With Benign Epilepsy With Centrotemporal Spikes.

The aim of this research was to analyze temporal auditory processing and phonological awareness in school-age children with benign childhood epilepsy with centrotemporal spikes (BECTS). Patient group (GI) consisted of 13 children diagnosed with BECTS. Control group (GII) consisted of 17 healthy children. After neurological and peripheral audiological assessment, children underwent a behavioral auditory evaluation and phonological awareness assessment. The procedures applied were: Gaps-in-Noise test (GIN), Duration Pattern test, and Phonological Awareness test (PCF). Results were compared between the groups and a correlation analysis was performed between temporal tasks and phonological awareness performance. GII performed significantly better than the children with BECTS (GI) in both GIN and Duration Pattern test (P < 0.001). GI performed significantly worse in all of the 4 categories of phonological awareness assessed: syllabic (P = 0.001), phonemic (P = 0.006), rhyme (P = 0.015) and alliteration (P = 0.010). Statistical analysis showed a significant positive correlation between the phonological awareness assessment and Duration Pattern test (P < 0.001). From the analysis of the results, it was concluded that children with BECTS may have difficulties in temporal resolution, temporal ordering, and phonological awareness skills. A correlation was observed between auditory temporal processing and phonological awareness in the suited sample.201525634

Modulation of microglial activation by adenosine A2a receptor in animal models of perinatal brain injury

Neuroinflammation has a key role in the pathogenesis of perinatal brain injury. Caffeine, a nonspecific antagonist of adenosine receptors (ARs), is widely used to treat apnea of prematurity and has been linked to a decrease in the incidence of cerebral palsy in premature infants. The mechanisms explaining its neuroprotective effect have not yet been elucidated. The objective of this study was to characterize the expression of adenosine and ARs in two neonatal rat models of neuroinflammation and to determine the effect of A2aR blockade on microglial activation assessed through inflammatory cytokine gene expression. We have used two rat models of microglial activation: the gestational low protein diet (LPD) model, associated with chronic brain injury, and postnatal ibotenate intracerebral injections, responsible for acute excitotoxicity injury. Adenosine blood levels have been measured by Tandem Mass Spectrometry. The expression of ARs in vivo was assessed using qPCR and immunohistochemistry. In vivo models have been replicated in vitro on primary microglial cell cultures exposed to A2aR agonist CGS-21680 or antagonist SCH-58261. The effects of these treatments have been assessed on the M1/M2 cytokine expressions measured by RT-qPCR. LPD during pregnancy was associated with higher adenosine levels in pups at postnatal day 1 and 4. A2aR mRNA expression was significantly increased in both cortex and magnetically sorted microglial cells from LPD animals compared to controls. CD73 expression, responsible for extracellular production of brain adenosine, was significantly increased in LPD cortex and sorted microglia cells. Moreover, CD73 protein level was increased in ibotenate treated animals. In vitro experiments confirmed that LPD or control microglial cells exposed to ibotenate display an increased expression, at both protein and molecular levels, of A2aR and M1 markers (IL-1\u3b2, IL-6, iNOS, TNF\u3b1). This pro-inflammatory profile was significantly reduced by SCH-58261, which reduces M1 markers in both LPD and ibotenate-exposed cells, with no effect on control cells. In the same experimental conditions, a partial increased of M1 cytokines was observed in response to A2aR agonist CGS-21680. These results support the involvement of adenosine and particularly of its receptor A2aR in the regulation of microglia in two different animal models of neuroinflammation

New Relativistic Effects in the Dynamics of Nonlinear Hydrodynamical Waves

In Newtonian and relativistic hydrodynamics the Riemann problem consists of calculating the evolution of a fluid which is initially characterized by two states having different values of uniform rest-mass density, pressure and velocity. When the fluid is allowed to relax, one of three possible wave-patterns is produced, corresponding to the propagation in opposite directions of two nonlinear hydrodynamical waves. New effects emerge in a special relativistic Riemann problem when velocities tangential to the initial discontinuity surface are present. We show that a smooth transition from one wave-pattern to another can be produced by varying the initial tangential velocities while otherwise maintaining the initial states unmodified. These special relativistic effects are produced by the coupling through the relativistic Lorentz factors and do not have a Newtonian counterpart.Comment: 4 pages, 5 figure

Management of self-inflicted orchiectomy in psychiatric patient. Case report and non-systematic review of the literature.

INTRODUCTION: Self-inflicted orchidectomy and auto-castration, also known as "Eshmun complex" is a rare phenomenon. The aim of our study it to present the management of a patient who performed a self orchiectomy and propose a non-systematic review of literature about self-orchiectomy. MATERIAL AND METHOD: A 27-years old male Patient with psychiatric disorder was admitted to our ward to have been cutted his scrotum with scissors and cut away his left testicle causing active bleeding from the left spermatic artery. The patient underwent emergency surgery with clamping of the spermatic cord and hemostasis of the wound. RESULTS: After surgery the clinical condition of the patient remained good during whole hospitalization. Urgent psychiatric evaluation was performed in order to administer proper therapy for acute management. To best of our knowledge, only 11 cases of self-orchidectomy are reported in literature and all of them except 1 case, underwent surgical exploration. CONCLUSIONS: Self-orchidectomy is an extremely rare phenomenon, often associated with psychiatric disorders, compounded by the use of drugs. In our opinion, emergency surgery should be the first choice of treatment, offering diagnostic and hemostatic purpose in a single act, aimed to prevent acute and postacute complications

Paving the way toward autonomous shipping development for European Waters – The AUTOSHIP project

New developments in maritime industry include the design and operation of autonomous ships. The AUTOSHIP project is one initiative promoting the use of autonomous ships in European waters focusing on two specific use cases, a Short Sea Shipping (SSS) cargo vessel and an Inland Waterways (IWW) barge. The AUTOSHIP objectives include thorough regulatory, societal, financial, safety and security analyses for the two investigated use cases as well as the development of a novel framework and methods for the design of autonomous vessels. This objective is achieved with the support of a number of activities, including supply chain, regulatory, risk and gaps analyses. Some results and findings from these activities are presented in this paper. The results demonstrate that the supply chain analysis is important to understand the complex relationships between different partners and phases for the effective design of maritime autonomous systems. Furthermore, a number of regulatory gaps needs to be addressed for the wider adoption of the AUTOSHIP use cases. There is a number of essential hazards associated with each of the two use cases; measures to mitigate these hazards are presented

The feasibility and applications of non-invasive cardiac monitoring in obese patients undergoing day-case surgery: Results of a prospective observational study

Aims: This prospective observational study evaluates the utility of non-invasive cardiac monitoring in obese patients in the day-surgery case, considering factors, such as Body Mass Index (BMI) and anaesthesia technique. Background: Obese patients are more likely to be admitted to hospital or to get hospitalized because they are more prone to concomitant diseases and obesity itself is not a contraindication to day surgery. Obese patients are a high-risk patient population that may particularly benefit from monitoring perioperative haemodynamic variations. Methods: In this observational study, we compared haemodynamic variations between overweight or obese and normal weight patients undergoing day-case surgery. We adopted NICOM® as a non-invasive cardiac output monitoring. Objective: The aim of the current study was to investigate the haemodynamic impact of BMI and anaesthesia technique during day-case surgery procedures. The other goal was to evaluate the feasibility and applications of non-invasive cardiac output monitoring among the obese population in day-surgery. Results: 74 patients were included in the study. 34 were overweight or obese (weight 84 ± 10 kg, height 160 ± 10 cm, BMI ≈ 30 kg/m2), 40 were normal weight (weight 63 ± 15 kg, height 160 ± 10 cm, BMI ≈ 22 kg/m2). Compared to normal-weight patients, obese patients show an increase in blood pressure with a return to baseline values at the end of surgery (p &lt; 0.05). The Cardiac Output (CO) shows a similar trend, whereas the heart rate is normal. A decrease in the Cardiac Index (CI) during the operation was noticed in both groups, the one in obese patients (p = 0.24) being greater. In the same way, the Stroke Volume Index (SVI) was lower in obese patients during surgery (p &lt; 0.05). In spinal anaesthesia, the Total Peripheral Resistance Index (TPRI) was not statistically different between the groups of study. As for the TPRI in obese patients, we reported values similar to the ones in non-obese patients in spinal anaesthesia. In local anesthesia, TPRI was higher in obese patients than in non-obese. Conclusion: Cardiovascular alterations in relation to obesity include an increase in blood pressure, CO and SV. An inadequate monitoring of haemodynamic parameters is a risk factor for perioperative complications. NICOM® provides a continuous, non-invasive haemodynamic measurement

An IoT-Aware Smart System Exploiting the Electromagnetic Behavior of UHF-RFID Tags to Improve Worker Safety in Outdoor Environments

Recently, different solutions leveraging Internet of Things (IoT) technologies have been adopted to avoid accidents in agricultural working environments. As an example, heavy vehicles, e.g., tractors or excavators, have been upgraded with remote controls. Nonetheless, the community continues to encourage discussions on safety issues. In this framework, a localization system installed on remote-controlled farm machines (RCFM) can help in preventing fatal accidents and reduce collision risks. This paper presents an innovative system that exploits passive UHF-RFID technology supported by commercial BLE Beacons for monitoring and preventing accidents that may occur when ground-workers in RCFM collaborate in outdoor agricultural working areas. To this aim, a modular architecture is proposed to locate workers, obstacles and machines and guarantees the security of RCFM movements by using specific notifications for ground-workers prompt interventions. Its main characteristics are presented with its main positioning features based on passive UHF-RFID technology. An experimental campaign discusses its performance and determines the best configuration of the UHF-RFID tags installed on workers and obstacles. Finally, system validation demonstrates the reliability of the main components and the usefulness of the proposed architecture for worker safety