Electrosynthesis has much to offer to the synthetic organic chemist. But in order to be widely accepted as a routine procedure in an organic synthesis laboratory, electrosynthesis needs to be ...presented in a much more user-friendly way. The literature is largely based on electrolysis in a glass beaker or H-cells that often give poor performance for synthesis with a very slow rate of conversion and, often, low selectivity and reproducibility. Flow cells can lead to much improved performance. Electrolysis is participating in the trend toward continuous flow synthesis, and this has led to a number of innovations in flow cell design that make possible selective syntheses with high conversion of reactant to product with a single passage of the reactant solution through the cell. In addition, the needs of the synthetic organic chemist can often be met by flow cells operating with recycle of the reactant solution. These cells give a high rate of product formation while the reactant concentration is high, but they perform best at low conversion. Both approaches are considered in this review and the important features of each cell design are discussed. Throughout, the application of the cell designs is illustrated with syntheses that have been reported.
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IJS, KILJ, NUK, PNG, UL, UM
To maintain optimal fitness, a cell must balance the risk of inadequate energy reserve for response to a potentially fatal perturbation against the long-term cost of maintaining high concentrations ...of ATP to meet occasional spikes in demand. Here we apply a game theoretic approach to address the dynamics of energy production and expenditure in eukaryotic cells. Conventionally, glucose metabolism is viewed as a function of oxygen concentrations in which the more efficient oxidation of glucose to CO2 and H2O produces all or nearly all ATP except under hypoxic conditions when less efficient (2 ATP/ glucose vs. about 36ATP/glucose) anaerobic metabolism of glucose to lactic acid provides an emergency backup. We propose an alternative in which energy production is governed by the complex temporal and spatial dynamics of intracellular ATP demand. In the short term, a cell must provide energy for constant baseline needs but also maintain capacity to rapidly respond to fluxes in demand particularly due to external perturbations on the cell membrane. Similarly, longer-term dynamics require a trade-off between the cost of maintaining high metabolic capacity to meet uncommon spikes in demand versus the risk of unsuccessfully responding to threats or opportunities. Here we develop a model and computationally explore the cell's optimal mix of glycolytic and oxidative capacity. We find the Warburg effect, high glycolytic metabolism even under normoxic conditions, is represents a metabolic strategy that allow cancer cells to optimally meet energy demands posed by stochastic or fluctuating tumor environments.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oral microbiota contribute to health and disease, and their disruption may influence the course of oral diseases. Here, we used pyrosequencing to characterize the oral bacteriome and mycobiome of 12 ...HIV-infected patients and matched 12 uninfected controls. The number of bacterial and fungal genera in individuals ranged between 8-14 and 1-9, among uninfected and HIV-infected participants, respectively. The core oral bacteriome (COB) comprised 14 genera, of which 13 were common between the two groups. In contrast, the core oral mycobiome (COM) differed between HIV-infected and uninfected individuals, with Candida being the predominant fungus in both groups. Among Candida species, C. albicans was the most common (58% in uninfected and 83% in HIV-infected participants). Furthermore, 15 and 12 bacteria-fungi pairs were correlated significantly within uninfected and HIV-infected groups, respectively. Increase in Candida colonization was associated with a concomitant decrease in the abundance of Pichia, suggesting antagonism. We found that Pichia spent medium (PSM) inhibited growth of Candida, Aspergillus and Fusarium. Moreover, Pichia cells and PSM inhibited Candida biofilms (P = .002 and .02, respectively, compared to untreated controls). The mechanism by which Pichia inhibited Candida involved nutrient limitation, and modulation of growth and virulence factors. Finally, in an experimental murine model of oral candidiasis, we demonstrated that mice treated with PSM exhibited significantly lower infection score (P = .011) and fungal burden (P = .04) compared to untreated mice. Moreover, tongues of PSM-treated mice had few hyphae and intact epithelium, while vehicle- and nystatin-treated mice exhibited extensive fungal invasion of tissue with epithelial disruption. These results showed that PSM was efficacious against oral candidiasis in vitro and in vivo. The inhibitory activity of PSM was associated with secretory protein/s. Our findings provide the first evidence of interaction among members of the oral mycobiota, and identifies a potential novel antifungal.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, ...general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, ...general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure ...(radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.
A customized susceptible, exposed, infected, and recovered compartmental model is presented for describing the control of asymptomatic spread of COVID-19 infections on a residential, urban college ...campus embedded in a large urban community by using public health protocols, founded on surveillance testing, contact tracing, isolation, and quarantine. Analysis in the limit of low infection rates-a necessary condition for successful operation of the campus-yields expressions for controlling the infection and understanding the dynamics of infection spread. The number of expected cases on campus is proportional to the exogenous infection rate in the community and is decreased by more frequent testing and effective contact tracing. Simple expressions are presented for the dynamics of superspreader events and the impact of partial vaccination. The model results compare well with residential data from Boston University's undergraduate population for fall 2020.
ABSTRACT
We introduce the Assembly of high-ResoluTion Eagle-simulations of MIlky Way-type galaxieS (artemis) simulations, a new set of 42 zoomed-in, high-resolution (baryon particle mass of $\approx ...2\times 10^4 \, {\rm M}_{\odot }\, h^{-1}$), hydrodynamical simulations of galaxies residing in haloes of Milky Way mass, simulated with the eagle galaxy formation code with re-calibrated stellar feedback. In this study, we analyse the structure of stellar haloes, specifically the mass density, surface brightness, metallicity, colour, and age radial profiles, finding generally very good agreement with recent observations of local galaxies. The stellar density profiles are well fitted by broken power laws, with inner slopes of ≈−3, outer slopes of ≈−4, and break radii that are typically ≈20–40 kpc. The break radii generally mark the transition between in situ formation and accretion-driven formation of the halo. The metallicity, colour, and age profiles show mild large-scale gradients, particularly when spherically averaged or viewed along the major axes. Along the minor axes, however, the profiles are nearly flat, in agreement with observations. Overall, the structural properties can be understood by two factors: that in situ stars dominate the inner regions and that they reside in a spatially flattened distribution that is aligned with the disc. Observations targeting both the major and minor axes of galaxies are thus required to obtain a complete picture of stellar haloes.
Many effective drugs for metastatic and/or advanced-stage cancers have been developed over the past decade, although the evolution of resistance remains the major barrier to disease control or cure. ...In large, diverse populations such as the cells that compose metastatic cancers, the emergence of cells that are resistant or that can quickly develop resistance is virtually inevitable and most likely cannot be prevented. However, clinically significant resistance occurs only when the pre-existing resistant phenotypes are able to proliferate extensively, a process governed by eco-evolutionary dynamics. Attempts to disrupt the molecular mechanisms of resistance have generally been unsuccessful in clinical practice. In this Review, we focus on the Darwinian processes driving the eco-evolutionary dynamics of treatment-resistant cancer populations. We describe a variety of evolutionarily informed strategies designed to increase the probability of disease control or cure by anticipating and steering the evolutionary dynamics of acquired resistance.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, ...general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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