Quantum chemistry calculation aided design of chiral ionic liquid-based extraction system for amlodipine separation

Amlodipine is a widely used medication in treating hypertension, which is also known as a chiral compound. So far efforts have been made to obtain optically pure (S)-amlodipine because (R)-amlodipine has poor efficacy and is related to undesirable side effects. However, the available separation methods for amlodipine are still unsatisfactory. Recently, chiral separation has become a promising application of chiral ionic liquids (CILs), because the structural designability enables them adjustable separation efficiency for specific tasks. In this work, a high-efficient CIL-based liquid-liquid extraction system was developed for racemic amlodipine separation with the assistance of quantum chemistry calculations. Enantioselectivity up to 1.35 achieved by the novel system at 298.15 K is significantly higher than other available extraction systems. Moreover, the recycling of CIL can be easily realized by backward extraction of amlodipine, which is important for the industrial application of CILs

Computational Physics on Graphics Processing Units

The use of graphics processing units for scientific computations is an emerging strategy that can significantly speed up various different algorithms. In this review, we discuss advances made in the field of computational physics, focusing on classical molecular dynamics, and on quantum simulations for electronic structure calculations using the density functional theory, wave function techniques, and quantum field theory.Comment: Proceedings of the 11th International Conference, PARA 2012, Helsinki, Finland, June 10-13, 201

Real-time PCR detection of mixed Plasmodium ovale curtisi and wallikeri infections in human and mosquito hosts

Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) represent distinct non-recombining Plasmodium species that are increasing in prevalence in sub-Saharan Africa. Though they circulate sympatrically, co-infection within human and mosquito hosts has rarely been described. Separate 18S rRNA real-time PCR assays that detect Poc and Pow were modified to allow species determination in parallel under identical cycling conditions. The lower limit of detection was 0.6 plasmid copies/μL (95% CI 0.4–1.6) for Poc and 4.5 plasmid copies/μL (95% CI 2.7–18) for Pow, or 0.1 and 0.8 parasites/μL, respectively, assuming 6 copies of 18s rRNA per genome. However, the assays showed cross-reactivity at concentrations greater than 103 plasmid copies/μL (roughly 200 parasites/μL). Mock mixtures were used to establish criteria for classifying mixed Poc/Pow infections that prevented false-positive detection while maintaining sensitive detection of the minority ovale species down to 100 copies/μL (<1 parasite/μL). When the modified real-time PCR assays were applied to field-collected blood samples from Tanzania and Cameroon, species identification by real-time PCR was concordant with nested PCR in 19 samples, but additionally detected two mixed Poc/Pow infections where nested PCR detected a single Po species. When real-time PCR was applied to oocyst-positive Anopheles midguts saved from mosquitoes fed on P. ovale-infected persons, mixed Poc/Pow infections were detected in 11/14 (79%). Based on these results, 8/9 P. ovale carriers transmitted both P. ovale species to mosquitoes, though both Po species could only be detected in the blood of two carriers. The described real-time PCR approach can be used to identify the natural occurrence of mixed Poc/Pow infections in human and mosquito hosts and reveals that such co-infections and co-transmission are likely more common than appreciated

A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science

Monkeys and Humans Share a Common Computation for Face/Voice Integration

Speech production involves the movement of the mouth and other regions of the face resulting in visual motion cues. These visual cues enhance intelligibility and detection of auditory speech. As such, face-to-face speech is fundamentally a multisensory phenomenon. If speech is fundamentally multisensory, it should be reflected in the evolution of vocal communication: similar behavioral effects should be observed in other primates. Old World monkeys share with humans vocal production biomechanics and communicate face-to-face with vocalizations. It is unknown, however, if they, too, combine faces and voices to enhance their perception of vocalizations. We show that they do: monkeys combine faces and voices in noisy environments to enhance their detection of vocalizations. Their behavior parallels that of humans performing an identical task. We explored what common computational mechanism(s) could explain the pattern of results we observed across species. Standard explanations or models such as the principle of inverse effectiveness and a “race” model failed to account for their behavior patterns. Conversely, a “superposition model”, positing the linear summation of activity patterns in response to visual and auditory components of vocalizations, served as a straightforward but powerful explanatory mechanism for the observed behaviors in both species. As such, it represents a putative homologous mechanism for integrating faces and voices across primates

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data