Best practices in heterotrophic high-cell-density microalgal processes: achievements, potential and possible limitations

Microalgae of numerous heterotrophic genera (obligate or facultative) exhibit considerable metabolic versatility and flexibility but are currently underexploited in the biotechnological manufacturing of known plant-derived compounds, novel high-value biomolecules or enriched biomass. Highly efficient production of microalgal biomass without the need for light is now feasible in inexpensive, well-defined mineral medium, typically supplemented with glucose. Cell densities of more than 100g l−1 cell dry weight have been achieved with Chlorella, Crypthecodinium and Galdieria species while controlling the addition of organic sources of carbon and energy in fedbatch mode. The ability of microalgae to adapt their metabolism to varying culture conditions provides opportunities to modify, control and thereby maximise the formation of targeted compounds with non-recombinant microalgae. This review outlines the critical aspects of cultivation technology and current best practices in the heterotrophic high-cell-density cultivation of microalgae. The primary topics include (1) the characteristics of microalgae that make them suitable for heterotrophic cultivation, (2) the appropriate chemical composition of mineral growth media, (3) the different strategies for fedbatch cultivations and (4) the principles behind the customisation of biomass composition. The review confirms that, although fundamental knowledge is now available, the development of efficient, economically feasible large-scale bioprocesses remains an obstacle to the commercialisation of this promising technolog

Pions in the Pionless Effective Field Theory

We show that processes involving pions that remain very near their mass-shell can be reliably computed in the pionless effective field theory, with the pion integrated in as a heavy field. As an application, we compute the pion-deuteron scattering amplitude near threshold to next-to-leading order in the momentum expansion. This amplitude is formally dominated by an infrared logarithm of the form log(gamma/mpi), where gamma is the deuteron binding momentum, and mpi is the mass of the pion. The coefficient of this logarithm is determined by the S-wave pion-nucleon scattering lengths.Comment: 10 pages LaTeX, 4 eps fig

Best practices in heterotrophic high-cell-density microalgal processes: achievements, potential and possible limitations

Microalgae of numerous heterotrophic genera (obligate or facultative) exhibit considerable metabolic versatility and flexibility but are currently underexploited in the biotechnological manufacturing of known plant-derived compounds, novel high-value biomolecules or enriched biomass. Highly efficient production of microalgal biomass without the need for light is now feasible in inexpensive, well-defined mineral medium, typically supplemented with glucose. Cell densities of more than 100 g l−1 cell dry weight have been achieved with Chlorella, Crypthecodinium and Galdieria species while controlling the addition of organic sources of carbon and energy in fedbatch mode. The ability of microalgae to adapt their metabolism to varying culture conditions provides opportunities to modify, control and thereby maximise the formation of targeted compounds with non-recombinant microalgae. This review outlines the critical aspects of cultivation technology and current best practices in the heterotrophic high-cell-density cultivation of microalgae. The primary topics include (1) the characteristics of microalgae that make them suitable for heterotrophic cultivation, (2) the appropriate chemical composition of mineral growth media, (3) the different strategies for fedbatch cultivations and (4) the principles behind the customisation of biomass composition. The review confirms that, although fundamental knowledge is now available, the development of efficient, economically feasible large-scale bioprocesses remains an obstacle to the commercialisation of this promising technology

Examining the effects of the HIV‐1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain

Abstract Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro‐acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV‐associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co‐exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV‐1 Tat transgenic mouse model by using infrared‐matrix‐assisted laser desorption electrospray ionization mass spectrometry imaging (IR‐MALDESI MSI). Morphine exposure uniquely decreased antiretroviral concentrations in anterior cerebral (primary motor and somatosensory) cortices, corpus collosum (anterior forceps), caudoputamen, nucleus accumbens, and posterior regions including the hippocampus, corpus callosum (main body), cerebral cortex (somatosensory and auditory cortices), thalamus, and hypothalamus. Interestingly, male mice experienced greater morphine‐associated decreases in antiretroviral concentrations than females. The study also assessed whether changes in antiretroviral concentrations were linked with inflammation in astroglia, assessed through the measurement of astroglial activation using glial fibrillary acidic protein (GFAP) as a marker. Alterations in antiretroviral concentrations co‐registering with areas of astroglial activation exhibited sex‐specific treatment differences. This study highlights the intricate interplay between HIV, opioids, and antiretroviral drugs within the CNS, elucidating distinct regional and sex variations in responsiveness. Our findings emphasize the identification of vulnerabilities within the neural landscape and underscore the necessity of carefully monitoring opioid use to maintain the efficacy of antiretroviral therapies

Search for nonresonant new physics signals in high-mass dilepton events produced in association with b-tagged jets in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for nonresonant new physics phenomena in high-mass dilepton events produced in association with b-tagged jets is performed using proton-proton collision data collected in 2016$-$2018 by the CMS experiment at the CERN LHC, at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138 fb$^{-1}$. The analysis considers two effective field theory models with dimension-six operators; involving four-fermion contact interactions between two leptons ($\ell\ell$, electrons or muons) and b or s quarks (bb$\ell\ell$ and bs$\ell\ell$). Two lepton flavor combinations (ee and $μμ$) are required and events are classified as having 0, 1, and $\geq$2 b-tagged jets in the final state. No significant excess is observed over the standard model backgrounds. Upper limits are set on the production cross section of the new physics signals. These translate into lower limits on the energy scale $Λ$ of 6.9 to 9.0 TeV in the bb$\ell\ell$ model, depending on model parameters, and on the ratio of energy scale and effective coupling, $Λ/g_*$, of 2.0 to 2.6 TeV in the bs$\ell\ell$ model. The latter represent the most stringent limits on this model to date. Lepton flavor universality is also tested by comparing the dielectron and dimuon mass spectra for different b-tagged jet multiplicities. No significant deviation from the standard model expectation of unity is observed

Determination of the spin and parity of all-charm tetraquarks

International audienceThe traditional quark model accounts for the existence of baryons, such as protons and neutrons, which consist of three quarks, as well as mesons, composed of a quark-antiquark pair. Only recently has substantial evidence started to accumulate for exotic states composed of four or five quarks and antiquarks. The exact nature of their internal structure remains uncertain. This paper reports the first measurement of quantum numbers of the recently discovered family of three all-charm tetraquarks, using data collected by the CMS experiment at the Large Hadron Collider from 2016 to 2018. The angular analysis techniques developed for the discovery and characterization of the Higgs boson have been applied to the new exotic states. The quantum numbers for parity $P$ and charge conjugation $C$ symmetries are found to be +1. The spin $J$ of these exotic states is consistent with 2$\hbar$, while 0$\hbar$ and 1$\hbar$ are excluded at 95% and 99% confidence level, respectively. The $J^{PC}=2^{++}$ assignment implies particular configurations of constituent spins and orbital angular momenta, which constrain the possible internal structure of these tetraquarks