Combining the most suitable energetic tetrazole and triazole moieties: synthesis and characterization of 5-(1-hydroxy-3-nitro-1,2,4-triazol-5-yl)-1-hydroxy-tetrazole and its nitrogen-rich ionic derivatives

With the synthesis of 5-(1-hydroxy-3-nitro-1,2,4-triazol-5-yl)-1-hydroxy-tetrazole (1) we can report the first successful production of a combined bis-heterocyclic system composed of 1-hydroxy-tetrazole and 1-hydroxy-1,2,4-triazole. The straightforward synthesis modifies the cyano group of the nitro-triazole starting material within four steps to the tetrazol-1-ol and finally oxidizes the triazole selectively to the 1-hydroxy-triazole, resulting in compound 1, which is a hybrid molecule of the two in energetic materials chemistry established bis-heterocyclic motifs 1,1'-dihydroxy-3,3'-dinitro-bis-1,2,4-triazole and 1,1'-dihydroxy-5,5'-bistetrazoIe. In order to tune and improve the performance parameters, several nitrogen rich bases were used to obtain the respective ionic derivatives. All compounds were characterized using muItinudear NMR and IR spectroscopy, differential thermal analysis (DTA) and elemental analysis. Several compounds could be further analyzed using X-ray diffraction measurements. The heats of formation for all investigated compounds were determined and the detonation properties (EXPLO5 V6.05.02) were calculated. These data, as well as the sensitivity values, were compared to related substances

Does point of care prothrombin time measurement reduce the transfusion of fresh frozen plasma in patients undergoing major surgery? The POC-OP randomized-controlled trial

<p>Abstract</p> <p>Background</p> <p>Bleeding is a frequent complication during surgery. The intraoperative administration of blood products, including packed red blood cells, platelets and fresh frozen plasma (FFP), is often live saving. Complications of blood transfusions contribute considerably to perioperative costs and blood product resources are limited. Consequently, strategies to optimize the decision to transfuse are needed.</p> <p>Bleeding during surgery is a dynamic process and may result in major blood loss and coagulopathy due to dilution and consumption. The indication for transfusion should be based on reliable coagulation studies. While hemoglobin levels and platelet counts are available within 15 minutes, standard coagulation studies require one hour. Therefore, the decision to administer FFP has to be made in the absence of any data. Point of care testing of prothrombin time ensures that one major parameter of coagulation is available in the operation theatre within minutes. It is fast, easy to perform, inexpensive and may enable physicians to rationally determine the need for FFP.</p> <p>Methods/Design</p> <p>The objective of the POC-OP trial is to determine the effectiveness of point of care prothrombin time testing to reduce the administration of FFP. It is a patient and assessor blind, single center randomized controlled parallel group trial in 220 patients aged between 18 and 90 years undergoing major surgery (any type, except cardiac surgery and liver transplantation) with an estimated blood loss during surgery exceeding 20% of the calculated total blood volume or a requirement of FFP according to the judgment of the physicians in charge. Patients are randomized to usual care plus point of care prothrombin time testing or usual care alone without point of care testing. The primary outcome is the relative risk to receive any FFP perioperatively. The inclusion of 110 patients per group will yield more than 80% power to detect a clinically relevant relative risk of 0.60 to receive FFP of the experimental as compared with the control group.</p> <p>Discussion</p> <p>Point of care prothrombin time testing in the operation theatre may reduce the administration of FFP considerably, which in turn may decrease costs and complications usually associated with the administration of blood products.</p> <p>Trial registration</p> <p>NCT00656396</p

An update on dissolved methane distribution in the subtropical North Atlantic Ocean

Methane (CH4) is a potent greenhouse gas and plays a significant role in recent increasing global temperatures. The oceans are a natural source of methane contributing to atmospheric methane concentrations, yet our understanding of the oceanic methane cycle is poorly constrained. Accumulating evidence indicates that a significant part of oceanic CH4 is produced in oxygenated surface waters as a by-product of phytoplanktonic activity. This study focused on the subtropical North Atlantic Ocean (26∘ N, 80′ W and 26∘ N, 18′ W) where the distribution of dissolved CH4 concentrations and associated air–sea fluxes during winter 2020 were investigated. Water samples from 64 stations were collected from the upper water column up to depths of 400 m. The upper oxic mixed layer was oversaturated in dissolved CH4 with concentrations ranging 3–7 nmol L−1, with the highest concentrations of 7–10 nmol L−1 found to the east of the transect, consistent with other subtropical regions of the world's oceans. The high anomalies of dissolved CH4 were found to be associated with phosphate-depleted waters and regions where the abundance of the ubiquitous picocyanobacteria Synechococcus and Prochlorococcus were elevated. Although other phytoplanktonic phyla cannot be excluded, this suggests that cyanobacteria contribute to the release of CH4 in this region. The calculation of air–sea fluxes further confirmed the subtropical North Atlantic Ocean as a source of CH4. This study provides evidence to corroborate the key role that picocyanobacteria play in helping to explain the oversaturation of CH4 found in surface mixed layer of the open ocean, otherwise known as the “ocean methane paradox”

A DNA-Encoded Chemical Library Incorporating Elements of Natural Macrocycles

Abstract Here we show a seven-step chemical synthesis of a DNA-encoded macrocycle library (DEML) on DNA. Inspired by polyketide and mixed peptide-polyketide natural products, the library was designed to incorporate rich backbone diversity. Achieving this diversity, however, comes at the cost of the custom synthesis of bifunctional building block libraries. This study outlines the importance of careful retrosynthetic design in DNA-encoded libraries, while revealing areas where new DNA synthetic methods are needed

Micro Cathode Arc Thruster for PhoneSat: Development and Potential Applications

NASA Ames Research Center and the George Washington University are developing an electric propulsion subsystem that will be integrated into the PhoneSat bus. Experimental tests have shown a reliable performance by firing three different thrusters at various frequencies in vacuum conditions. The interface consists of a microcontroller that sends a trigger pulse to the Pulsed Plasma Unit that is responsible for the thruster operation. A Smartphone is utilized as the main user interface for the selection of commands that control the entire system. The propellant, which is the cathode itself, is a solid cylinder made of Titanium. This simplicity in the design avoids miniaturization and manufacturing problems. The characteristics of this thruster allow an array of CATs to perform attitude control and orbital correction maneuvers that will open the door for the implementation of an extensive collection of new mission concepts and space applications for CubeSats. NASA Ames is currently working on the integration of the system to fit the thrusters and the PPU inside a 1.5U CubeSat together with the PhoneSat bus. This satellite is intended to be deployed from the ISS in 2015 and test the functionality of the thrusters by spinning the satellite around its long axis and measure the rotational speed with the phone gyros. This test flight will raise the TRL of the propulsion system from 5 to 7 and will be a first test for further CubeSats with propulsion systems, a key subsystem for long duration or interplanetary small satellite missions

Trusting Intelligent Machines: Deepening Trust Within Socio-Technical Systems

Intelligent machines have reached capabilities that go beyond a level that a human being can fully comprehend without sufficiently detailed understanding of the underlying mechanisms. The choice of moves in the game Go (generated by Deep Mind?s Alpha Go Zero [1]) are an impressive example of an artificial intelligence system calculating results that even a human expert for the game can hardly retrace [2]. But this is, quite literally, a toy example. In reality, intelligent algorithms are encroaching more and more into our everyday lives, be it through algorithms that recommend products for us to buy, or whole systems such as driverless vehicles. We are delegating ever more aspects of our daily routines to machines, and this trend looks set to continue in the future. Indeed, continued economic growth is set to depend on it. The nature of human-computer interaction in the world that the digital transformation is creating will require (mutual) trust between humans and intelligent, or seemingly intelligent, machines. But what does it mean to trust an intelligent machine? How can trust be established between human societies and intelligent machines

Accelerating science: The usage of commercial clouds in ATLAS Distributed Computing

The ATLAS experiment at CERN is one of the largest scientific machines built to date and will have ever growing computing needs as the Large Hadron Collider collects an increasingly larger volume of data over the next 20 years. ATLAS is conducting R&D projects on Amazon Web Services and Google Cloud as complementary resources for distributed computing, focusing on some of the key features of commercial clouds: lightweight operation, elasticity and availability of multiple chip architectures. The proof of concept phases have concluded with the cloud-native, vendoragnostic integration with the experiment’s data and workload management frameworks. Google Cloud has been used to evaluate elastic batch computing, ramping up ephemeral clusters of up to O(100k) cores to process tasks requiring quick turnaround. Amazon Web Services has been exploited for the successful physics validation of the Athena simulation software on ARM processors. We have also set up an interactive facility for physics analysis allowing endusers to spin up private, on-demand clusters for parallel computing with up to 4 000 cores, or run GPU enabled notebooks and jobs for machine learning applications. The success of the proof of concept phases has led to the extension of the Google Cloud project, where ATLAS will study the total cost of ownership of a production cloud site during 15 months with 10k cores on average, fully integrated with distributed grid computing resources and continue the R&D projects

Severe malaria in children leads to a significant impairment of transitory otoacoustic emissions--a prospective multicenter cohort study.

BACKGROUND: Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malaria. An objective method to quickly evaluate the function of the inner ear are the otoacoustic emissions. Negative transient otoacoustic emissions are associated with a threshold shift of 20 dB and above. METHODS: This prospective multicenter study analyses otoacoustic emissions in patients with severe malaria up to the age of 10 years. In three study sites (Ghana, Gabon, Kenya) 144 patients with severe malaria and 108 control children were included. All malaria patients were treated with parental artesunate. RESULTS: In the control group, 92.6 % (n = 108, 95 % confidence interval 86.19-6.2 %) passed otoacoustic emission screening. In malaria patients, 58.5 % (n = 94, malaria vs controls p < 0.001, 95 % confidence interval 48.4-67.9 %) passed otoacoustic emission screening at the baseline measurement. The value increased to 65.2 % (n = 66, p < 0.001, 95 % confidence interval 53.1-75.5 %) at follow up 14-28 days after diagnosis of malaria. The study population was divided into severe non-cerebral malaria and severe malaria with neurological symptoms (cerebral malaria). Whereas otoacoustic emissions in severe malaria improved to a passing percentage of 72.9 % (n = 48, 95 % confidence interval 59-83.4 %) at follow-up, the patients with cerebral malaria showed a drop in the passing percentage to 33 % (n = 18) 3-7 days after diagnosis. This shows a significant impairment in the cerebral malaria group (p = 0.012 at days 3-7, 95 % confidence interval 16.3-56.3 %; p = 0.031 at day 14-28, 95 % confidence interval 24.5-66.3 %). CONCLUSION: The presented data show that 40 % of children have involvement of the inner ear early in severe malaria. In children, audiological screening after severe malaria infection is not currently recommended, but is worth investigating in larger studies

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe