Combining radial and continuous flow synthesis to optimize and scale-up the production of medicines

Current drug production in batch cannot adapt rapidly to market demands,} evidenced by recent shortages in many markets globally of essential medicines. Flow chemistry is a valuable tool for on-demand production of active pharmaceutical ingredients (APIs). Here{,} we reveal a new concept to develop and produce APIs{,} where an automated synthesizer that works with discrete volumes of solutions is employed at the discovery stage to identify the optimal synthetic route and conditions before a commercially available continuous flow system is used for scale-up. This concept is illustrated by the synthesis of nifedipine and paracetamol{,} in short supply in Germany during the COVID-19 pandemic{, and the local anesthetic lidocaine

Study of impact on helicopter blade

This article presents a study of damage in structures that are similar to helicopter blade sections, subjected to an impact. These complex composite structures were impacted by a steel ball of 125 g at impact speed ranging from 30 to 130 m/s. This led to properly highlight the kinematics of the impact and to define the sequence of the damage’s mechanisms. An explicit FE model is also presented. The damage modelling of the roving is performed through a scale change. It allows a good representation of observed experimental behaviour. As the mesh density is low, it can be used for the modelling of a real structure

Oneiric stress and safety and security at work: the discovery of a new universal symbol

Cox and Griffiths define as psychosocial risks at work “those aspects of the planning, organization and management of work, which, along with their environmental and social contexts, may affect mental and physical health of the employees, directly or indirectly producing stress”. Therefore, a more effective approach to occupational safety and security should include integrated risk management through the identification of any work stress related problem. The purpose of this paper is to analyze the possible correlation of risk at work with the modification of sleep, and inside it, the specific function of dream activity

Deconstruction of the Corso Grosseto viaduct and setup of a testing site for full scale load tests

BRIDGE|50 is a research project recently launched in Italy in the context of the Torino-Ceres construction works jointly with Politecnico di Milano, Politecnico di Torino, public authorities and private companies. The aim of the BRIDGE|50 research project is to investigate the residual structural performance of the Corso Grosseto 50-year-old prestressed concrete bridge through an experimental campaign. The dismantling and demolition procedures of Corso Grosseto viaduct are presented in this paper, including the setup of the field laboratory where several deck beams and pier caps will be tested up to collapse

Triptans and troponin: a case report

This case report describes for the first time acute coronary syndrome in a 67-year old patient after oral intake of naratriptan for migraine. So far in the literature, only sumatriptan, zolmitriptan and frovatriptan have been described to cause acute coronary syndromes

Intraligand charge transfer enables visible-light-mediated nickel-catalyzed cross-coupling reactions

We demonstrate that several visible-light mediated carbon–heteroatom cross-couplings can be carried out using a photoactive NiII precatalyst that forms in situ from a nickel salt and a bipyridine ligand decorated with two carbazole groups (Ni(Czbpy)Cl2). The activation of this precatalyst towards cross-couplings follows a hitherto undisclosed mechanism that is different from previously reported light-responsive nickel complexes that were reported to undergo metal-to-ligand charge transfer. Theoretic and spectroscopic investigations revealed that irradiation of Ni(Czbpy)Cl2 with visible-light causes an initial intraligand charge transfer event that triggers productive catalysis. Ligand polymerization affords a porous, recyclable organic polymer for heterogeneous nickel catalysis of cross-couplings. The heterogeneous catalyst shows stable performance in a packed-bed flow reactor during a week of continuous operation

Value of long-term streamflow forecasts to reservoir operations for water supply in snow-dominated river catchments

We present a forecast-based adaptive management framework for water supply reservoirs and evaluate the contribution of long-term inflow forecasts to reservoir operations. Our framework is developed for snow-dominated river basins that demonstrate large gaps in forecast skill between seasonal and inter-annual time horizons. We quantify and bound the contribution of seasonal and inter-annual forecast components to optimal, adaptive reservoir operation. The framework uses an Ensemble Streamflow Prediction (ESP) approach to generate retrospective, one-year-long streamflow forecasts based on the Variable Infiltration Capacity (VIC) hydrology model. We determine the optimal sequence of daily release decisions using the Model Predictive Control (MPC) optimization scheme. We then assess the forecast value by comparing system performance based on the ESP forecasts with the performances based on climatology and perfect forecasts. We distinguish among the relative contributions of the seasonal component of the forecast versus the inter-annual component by evaluating system performance based on hybrid forecasts, which are designed to isolate the two contributions. As an illustration, we first apply the forecast-based adaptive management framework to a specific case study, i.e., Oroville Reservoir in California, and we then modify the characteristics of the reservoir and the demand to demonstrate the transferability of the findings to other reservoir systems. Results from numerical experiments show that, on average, the overall ESP value in informing reservoir operation is 35% less than the perfect forecast value and the inter-annual component of the ESP forecast contributes 20–60% of the total forecast value.</p

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

OBJECT: Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. METHODS: The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. RESULTS: The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. CONCLUSIONS: Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT)

Enzymatic processing of protein-based fibers

Wool and silk are major protein fiber materials used by the textile industry. Fiber protein structure-function relationships are briefly described here, and the major enzymatic processing routes for textiles and other novel applications are deeply reviewed. Fiber biomodification is described here with various classes of enzymes such as protease, transglutaminase, tyrosinase, and laccase. It is expected that the reader will get a perspective on the research done as a basis for new applications in other areas such as cosmetics and pharma.This work was financially supported by the National Natural Science Foundation of China (21274055,51373071, 31201134 and 31470509), the Program for New Century Excellent Talents in University (NCET-12-0883), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1135), the Jiangsu Provincial Natural Science Foundation of China (BK2012112), and the Fundamental Research Funds for the Central Universities (JUSRP51312B)