Specificity of the ribosomal A site for aminoacyl-tRNAs

Although some experiments suggest that the ribosome displays specificity for the identity of the esterified amino acid of its aminoacyl-tRNA substrate, a study measuring dissociation rates of several misacylated tRNAs containing the GAC anticodon from the A site showed little indication for such specificity. In this article, an expanded set of misacylated tRNAs and two 2′-deoxynucleotide-substituted mRNAs are used to demonstrate the presence of a lower threshold in koff values for aa-tRNA binding to the A site. When a tRNA binds sufficiently well to reach this threshold, additional stabilizing effects due to the esterified amino acid or changes in tRNA sequence are not observed. However, specificity for different amino acid side chains and the tRNA body is observed when tRNA binding is sufficiently weaker than this threshold. We propose that uniform aa-tRNA binding to the A site may be a consequence of a conformational change in the ribosome, induced by the presence of the appropriate combination of contributions from the anticodon, amino acid and tRNA body

Pre-clinical evaluation of antiproteases as potential candidates for HIV-1 pre-exposure prophylaxis

Previous studies on highly HIV-1-exposed, yet persistently seronegative women from the Punwami Sex Worker cohort in Kenya, have shed light on putative protective mechanisms, suggesting that mucosal immunological factors, such as antiproteases, could be mediating resistance to HIV-1 transmission in the female reproductive tract. Nine protease inhibitors were selected for this study: serpin B4, serpin A1, serpin A3, serpin C1, cystatin A, cystatin B, serpin B13, serpin B1 and α-2-macroglobulin-like-protein 1. We assessed in a pilot study, the activity of these antiproteases with cellular assays and an ex vivo HIV-1 challenge model of human ecto-cervical tissue explants. Preliminary findings with both models, cellular and tissue explants, established an order of inhibitory potency for the mucosal proteins as candidates for pre-exposure prophylaxis when mimicking pre-coital use. Combination of all antiproteases considered in this study was more active than any of the individual mucosal proteins. Furthermore, the migration of cells out of ecto-cervical explants was blocked indicating potential prevention of viral dissemination following amplification of the founder population. These findings constitute the base for further development of these mucosal protease inhibitors for prevention strategies

Boundary Layer Transition and Trip Effectiveness on an Apollo Capsule in the JAXA High Enthalpy Shock Tunnel (HIEST) Facility

Computational assessments were performed to size boundary layer trips for a scaled Apollo capsule model in the High Enthalpy Shock Tunnel (HIEST) facility at the JAXA Kakuda Space Center in Japan. For stagnation conditions between 2 MJ/kg and 20 MJ/kg and between 10 MPa and 60 MPa, the appropriate trips were determined to be between 0.2 mm and 1.3 mm high, which provided kappa/delta values on the heatshield from 0.15 to 2.25. The tripped configuration consisted of an insert with a series of diamond shaped trips along the heatshield downstream of the stagnation point. Surface heat flux measurements were obtained on a capsule with a 250 mm diameter, 6.4% scale model, and pressure measurements were taken at axial stations along the nozzle walls. At low enthalpy conditions, the computational predictions agree favorably to the test data along the heatshield centerline. However, agreement becomes less favorable as the enthalpy increases conditions. The measured surface heat flux on the heatshield from the HIEST facility was under-predicted by the computations in these cases. Both smooth and tripped configurations were tested for comparison, and a post-test computational analysis showed that kappa/delta values based on the as-measured stagnation conditions ranged between 0.5 and 1.2. Tripped configurations for both 0.6 mm and 0.8 mm trip heights were able to effectively trip the flow to fully turbulent for a range of freestream conditions

Development of extracellular matrix supported 3D culture of renal cancer cells and renal cancer stem cells

Novel experimental conditions of cancer cell line culture have evolved throughout the recent years, with significantly growing interest in xeno-free, serum-free and three-dimensional culture variants. The choice of proper culture media may enable to mimic tumor microenvironment and promotion of cancer stem cells proliferation. To assess whether stem-like phenotype inducing media may be applied in renal cancer stem cell research, we performed a widespread screening of 13 cell culture media dedicated for mesenchymal cells, stem cells as well as mesenchymal stem cells. We have also screened extracellular matrix compounds and selected optimal RCC 3D—ECM supported culture model. Our results revealed that 786-O as well as HKCSCs cell line cultures in xeno-free media (NutriStem/StemXvivo) and laminin coated plates provide a useful tool in RCC cancer biology research and at the same time enable effective drug toxicity screening. We propose bio-mimic 3D RCC cell culture model with specific low-serum and xeno-free media that promote RCC cell viability and stem-like phenotype according to the tested genes encoding stemness factors including E-cadherin, N-cadherin, HIF1, HIF2, VEGF, SOX2, PAX2 and NESTIN

Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left frontal lobe hemorrhage who developed right face and hand epilepsia partialis continua followed by refractory focal clonic seizures; a 51-year-old male with history of traumatic intracranial hemorrhage who exhibited left-sided epilepsia partialis continua; and a 75-year-old female with history of breast cancer who manifested nonconvulsive status epilepticus and refractory focal clonic seizures. All patients continued experiencing RS/SE despite first- and second-line therapy, and one patient continued to experience RS/SE despite third-line therapy. Failure to abort RS/SE with conventional therapy motivated us to administer intravenous dexamethasone. A 10-mg load was given (except in one patient) followed by 4.0- 5.2 mg q6h. All clinical and electrographic seizures stopped 3-4 days after starting dexamethasone. When dexamethasone was discontinued 1-3 days after seizures stopped, all patients remained seizure-free on 2-3 AEDs. The cessation of RS/SE when dexamethasone was added to conventional antiseizure therapy suggests that inflammatory processes are involved in the pathogenesis of RS/SE

The legacy of cover crops on the soil habitat and ecosystem services in a heavy clay, minimum tillage rotation

Abstract Cover crops are grown as potential ways to improve soil fertility, soil structure, and biodiversity, while reducing weed/pest burdens. Yet, increased costs (in both time and fuel), farmer knowledge requirements, and yield uncertainty (green bridge effect and variable crop establishment) have led to hesitation among farmers. This study was conducted at the field scale (covering an area of nearly 20 hectares) to determine whether different cover crop mixtures affected soil properties and ecosystem services on a heavy clay soil. Measurements of soil chemistry, physics, biology, weed abundance, and subsequent crop performance were taken within a minimum tillage management system, across three cover crop mixtures (commonly sold to UK farmers). The cover crop mixtures included oats (Avena sativa), radish (Raphanus sativus), phacelia (Phacelia tanacetifolia), vetch (Vicia sativa), legumes, buckwheat (Fagopyrum esculentum) and a bare stubble control followed by a spring oat crop. Soil physics (penetrometer and bulk density) and chemistry (N, P, K, Mg, Ca, and organic matter) varied little across treatments, although there was significantly lower Mg in the cover crop including legumes and an increase in NO3 within this treatment. Soil biology and botanical composition were also assessed, monitoring earthworm and mesofauna abundance; and sown and unsown (weed) biomass. Epigeic earthworms were found to have significantly larger abundance in cover crop mixtures with radish present, although other meso- and macrofauna did not differ. Significant weed suppression was found during both the cover crop growing period and as a legacy in the subsequent crop, leading to significant yield increases and economic benefits in some treatments. Our study confirms that cover crops are providing benefits, even on heavy clay soils, including improvements in nutrient leaching risk reduction, weed suppression, and crop yield, coupled with wider ecosystem benefits. We therefore consider cover crops to have a role in sustainable management of arable rotations

Collateral effect of COVID-19 on orthopedic and trauma surgery

Objectives: The purpose of this study was to assess the impact of the COVID-19 pandemic on orthopedic and trauma surgery in private practices and hospitals in Germany. Design: In this cross-sectional study, an online-based anonymous survey was conducted from April 2th to April 16th 2020. Setting: The survey was conducted among 15.0000 of 18.000 orthopedic and trauma surgeons in Germany, both in private practices and hospitals. Participants: All members of the German Society of Orthopedic and Trauma Surgery (DGOU) and the Professional Association for Orthopedic and Trauma Surgery (BVOU). were invited by e-mail to participate in the survey. Main outcome measures: Out of 50 questions 42 were designed to enquire a certain dimension of the pandemic impact and contribute to one of six indices, namely “Preparedness”, “Resources”, “Reduction”, “Informedness”, “Concern”, and “Depletion”. Data was analyzed in multiple stepwise regression, aiming to identify those factors that independently influenced the indices. Results: 858 orthopedic and trauma surgeons participated in the survey throughout Germany. In the multiple regression analysis, being employed at a hospital was identified as an independent positive predictor in the indices for “Preparedness”, “Resources”, and “Informedness” and an independent negative predictor regarding “Depletion”. Self-employment was found to be an independent positive predictor of the financial index “Depletion”. Female surgeons were identified as an independent variable for a higher level of “Concern”. Conclusions: The study confirms a distinct impact of the COVID-19 pandemic on orthopedic and trauma surgery in Germany. The containment measures are largely considered appropriate despite severe financial constraints. A substantial lack of personal protective equipment (PPE) is reported. The multiple regression analysis shows that self-employed surgeons are more affected by this shortage as well as by the financial consequences than surgeons working in hospitals. What are the new findings: The COVID-19 pandemic has a profound impact on orthopedic and trauma surgery as an unrelated specialty. Self-employed surgeons are affected especially by a shortage of PPE and financial consequences. How might it impact on clinical practice in the near future: Political and financial support can now be applied more focused to subgroups in the field of orthopedics and trauma surgery with an increased demand for support. A special emphasis should be set on the support of self-employed surgeons which are a more affected by the shortage of PPE and financial consequences than surgeons working in hospital

Stability of the nonlinear dynamics of an optically injected VCSEL

Automated protocols have been developed to characterize time series data in terms of stability. These techniques are applied to the output power time series of an optically injected vertical cavity surface emitting laser (VCSEL) subject to varying injection strength and optical frequency detuning between master and slave lasers. Dynamic maps, generated from high resolution, computer controlled experiments, identify regions of dynamic instability in the parameter space. © 2012 Optical Society of America

Conversion of electrical energy from one form to another, and its management through multichip module structures

The design and fabrication of a highly integrated, intelligent integral horsepower, three-phase induction motor drive based on multichip module (MCM) technology is described. A conventional three-phase induction motor is transformed into a stand-alone variable-speed drive by way of MCM technology. This solid-state controller-known as a multichip power module (MCPM)-uses known good die (KGD) to obtain minimal footprint, volume, and mass, while maximizing efficiency, reliability, and manufacturability. This is done by integrating the low-power control and high-power sections onto a single substrate. In accordance with one embodiment of the present invention, an integrated circuit assembly formed on a single substrate is capable of transforming and controlling AC power input to DC power output responsive to input signals. In accordance with another embodiment, an integrated circuit assembly on a single substrate is capable of receiving direct current power and controlling it and transforming it to alternating current power in single phase or multiphase form having variable magnitude and/or variable frequency. In accordance with a further embodiment, an integrated circuit assembly on a single substrate is capable of receiving alternating current power and controlling it and transforming it to alternating current power in single phase or multiphase form having variable magnitude and/or variable frequency