Continuous flow biocatalysis Britton, Joshua; Majumdar, Sudipta; Weiss, Gregory A
Chemical Society reviews,
07/2018, Volume:
47, Issue:
15
Journal Article
Peer reviewed
Open access
The continuous flow synthesis of active pharmaceutical ingredients, value-added chemicals, and materials has grown tremendously over the past ten years. This revolution in chemical manufacturing has ...resulted from innovations in both new methodology and technology. This field, however, has been predominantly focused on synthetic organic chemistry, and the use of biocatalysts in continuous flow systems is only now becoming popular. Although immobilized enzymes and whole cells in batch systems are common, their continuous flow counterparts have grown rapidly over the past two years. With continuous flow systems offering improved mixing, mass transfer, thermal control, pressurized processing, decreased variation, automation, process analytical technology, and in-line purification, the combination of biocatalysis and flow chemistry opens powerful new process windows. This Review explores continuous flow biocatalysts with emphasis on new technology, enzymes, whole cells, co-factor recycling, and immobilization methods for the synthesis of pharmaceuticals, value-added chemicals, and materials.
Merging the power of proteins and continuous flow for improved chemical synthesis.
Triplet excited state chemistry has enabled a range of important organic transformations by accessing reaction pathways inaccessible to photoredox chemistry. Such photoreactions are triggered by ...triplet photosensitizers, which absorb visible-light photons and transfer the energy to the substrate or to a co-catalyst through triplet–triplet energy transfer (TT EnT). The most popular triplet photosensitizers, metal complexes and organic chromophores, have proven useful in a range of pericyclic reactions, bond dissociations, and isomerizations, but they have several characteristics related to their chemical and electronic structure that limit their selectivity, energy efficiency, and sustainability. This Perspective describes some ways that colloidal quantum dots (QDs) address the limitations of molecular photocatalysts for TT EnT-driven organic transformations. These sub-5-nm particles have the large catalytic surface area and electronic/optical tunability of homogeneous catalysts, and the easy separation and surface templating effects of heterogeneous catalysts. Their optical and electronic properties, small singlet–triplet energy splitting, narrow emission line widths, and high photostability enhance their performance as triplet photosensitizers. This Perspective describes these advantages in the context of published and ongoing investigations of TT EnT-driven reactions, and then highlights the advantages and challenges associated with using related emerging materials, specifically lead halide perovskite QDs and quasi-2D nanoplatelets, as photocatalysts for triplet excited state chemistry.
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IJS, KILJ, NUK, PNG, UL, UM
Alternative splicing has critical roles in normal development and can promote growth and survival in cancer. Aberrant splicing, the production of noncanonical and cancer-specific mRNA transcripts, ...can lead to loss-of-function in tumor suppressors or activation of oncogenes and cancer pathways. Emerging data suggest that aberrant splicing products and loss of canonically spliced variants correlate with stage and progression in malignancy. Here, we review the splicing landscape of TP53, BARD1 and AR to illuminate roles for alternative splicing in cancer. We also examine the intersection between alternative splicing pathways and novel therapeutic approaches.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There is a rapidly growing interest in psychological well-being (PWB) as outcome of interventions. Ryff developed theory-based indicators of PWB that are consistent with a eudaimonic perspective of ...happiness. Numerous interventions have been developed with the aim to increase PWB. However, the effects on PWB measured as coherent outcome have not been examined across studies yet. This meta-analysis of randomized controlled trials of behavioral interventions aims to answer the question whether it is possible to enhance PWB.
A systematic literature search was performed in PsycINFO, Cochrane and Web of Science. To be included, studies had to be randomized controlled trials of behavioral interventions with psychological well-being as primary or secondary outcome measure, measured with either Ryff's Psychological Well-Being Scales or the Mental Health Continuum-Short Form. The meta-analysis was performed using a random effects model. From the 2,298 articles found, 27 met the inclusion criteria. The included studies involved 3,579 participants.
We found a moderate effect (Cohen's d = 0.44; z = 5.62; p < .001). Heterogeneity between the studies was large (Q (26) = 134.12; p < .001; I2 = 80.62). At follow-up after two to ten months, a small but still significant effect size of 0.22 was found. There was no clear indication of publication bias. Interventions were more effective in clinical groups and when they were delivered individually. Effects were larger in studies of lower quality.
It appears to be possible to improve PWB with behavioral interventions. The results are promising for the further development and implementation of interventions to promote PWB. Delivering interventions face-to-face seems to be the most promising option. We recommend to keep including clinical groups in the research of psychological well-being. Heterogeneity is a limitation of the study and there is need for more high-quality studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melanoma is among the most sensitive of malignancies to immune modulation. Although multiple trials conducted over decades with vaccines, cytokines, and cell therapies demonstrated meaningful ...responses in a small subset of patients with metastatic disease, a true increase in overall survival (OS) within a randomized phase III trial was not observed until the development of anti-CTLA-4 (ipilimumab). Further improvements in OS for metastatic disease were observed with the anti-PD-1-based therapies (nivolumab, pembrolizumab) as single agents or combined with ipilimumab. A lower bound for expected 5-year survival for metastatic melanoma is currently approximately 35% and could be as high as 50% for the nivolumab/ipilimumab combination among patients who would meet criteria for clinical trials. Moreover, a substantial fraction of long-term survivors will likely remain progression-free without continued treatment. The hope and major challenge for the future is to understand the immunobiology of tumors with primary or acquired resistance to anti-PD-1 or anti-PD-1/anti-CTLA-4 and to develop effective immune therapies tailored to individual patient subsets not achieving long-term clinical benefit. Additional goals include optimal integration of immune therapy with nonimmune therapies, the development and validation of predictive biomarkers in the metastatic setting, improved prognostic and predictive biomarkers for the adjuvant setting, understanding mechanisms of and decreasing toxicity, and optimizing the duration of therapy.
The aim of this study is to provide a better understanding of performance degrading mechanisms occurring when a proton exchange membrane water electrolyzer (PEM-WE) is coupled with renewable ...energies, where times of operation and idle periods alternate. An accelerated stress test (AST) is proposed, mimicking a fluctuating power supply by operating the electrolyzer cell between high (3 A cm−2geo) and low current densities (0.1 A cm−2geo), alternating with idle periods during which no current is supplied and the cell rests at open circuit voltage (OCV). Polarization curves, periodically recorded during the OCV-AST, reveal an initial increase in activity (≈50 mV after 10 cycles) followed by a significant decrease in performance during prolonged OCV cycling due to an increasing high frequency resistance (HFR) (≈1.6-fold after 718 cycles). These performance changes can clearly be related to the OCV periods, since they are not observed in a reference experiment where the OCV period is replaced by a potential hold at 1.3 V. The origin of the phenomena, which are responsible for the initial performance gain as well as the subsequent decay are analyzed via detailed electrochemical and physical characterization of the MEAs, and an operating strategy to prevent performance degradation is proposed.
Stellar evolution codes, as all other numerical tools, need to be verified. One of the standard stellar objects that allow stringent tests of stellar evolution theory and models, are detached ...eclipsing binaries. We have used 19 such objects to test our stellar evolution code, in order to see whether standard methods and assumptions suffice to reproduce the observed global properties. In this paper we concentrate on three effects that contain a specific uncertainty: atomic diffusion as used for standard solar model calculations, overshooting from convective regions, and a simple model for the effect of stellar spots on stellar radius, which is one of the possible solutions for the radius problem of M dwarfs. We find that in general old systems need diffusion to allow for, or at least improve, an acceptable fit, and that systems with convective cores indeed need overshooting. Only one system (AI Phe) requires the absence of it for a successful fit. To match stellar radii for very low-mass stars, the spot model proved to be an effective approach, but depending on model details, requires a high percentage of the surface being covered by spots. We briefly discuss improvements needed to further reduce the freedom in modelling and to allow an even more restrictive test by using these objects.
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FMFMET, NUK, UL, UM, UPUK
Amplification of epidermal growth factor receptor (EGFR) and its active mutant EGFRvIII occurs frequently in glioblastoma (GBM). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted ...therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has only shown limited efficacy in patients. Here we discuss signaling pathways mediated by EGFR/EGFRvIII, current therapeutics, and novel strategies to target EGFR/EGFRvIII-amplified GBM.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This Perspective reviews strategies for tuning the surface chemistry of colloidal semiconductor nanocrystals (quantum dots, QDs) to function as photoredox catalysts or sensitizers of redox catalysts ...for organic transformations. These strategies include (i) tuning surface charge density to encourage high-affinity interactions between the QD and substrate (or co-catalyst) in the absence of a covalent linkage, (ii) maximizing the QD’s catalytic surface area through ligand exchange, (iii) using “hole shuttle” ligands to efficiently extract oxidative equivalents from the QD core, and (iv) controlling the concentration of protons on the QD surface to lower the kinetic barrier for proton-coupled electron-transfer reactions.
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IJS, KILJ, NUK, PNG, UL, UM
Unique among leukocytes, neutrophils follow daily cycles of release from and migration back into the bone marrow, where they are eliminated. Because removal of dying cells generates homeostatic ...signals, we explored whether neutrophil elimination triggers circadian events in the steady state. Here, we report that the homeostatic clearance of neutrophils provides cues that modulate the physiology of the bone marrow. We identify a population of CD62LLO CXCR4HI neutrophils that have “aged” in the circulation and are eliminated at the end of the resting period in mice. Aged neutrophils infiltrate the bone marrow and promote reductions in the size and function of the hematopoietic niche. Modulation of the niche depends on macrophages and activation of cholesterol-sensing nuclear receptors and is essential for the rhythmic egress of hematopoietic progenitors into the circulation. Our results unveil a process that synchronizes immune and hematopoietic rhythms and expand the ascribed functions of neutrophils beyond inflammation.
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•Neutrophils undergo a process of aging during their lifetime in circulation•Neutrophil clearance reduces the size and function of the hematopoietic niche•Macrophages and LXR receptors mediate changes in the niche•Neutrophil clearance triggers rhythmic release of progenitors during homeostasis
Aged neutrophils are cleared from the circulation by macrophages in the bone marrow, which in turn activate LXR receptors to promote the systemic egress of hematopoietic precursors from their niche in a circadian manner. Neutrophil clearance is, therefore, a homeostatic mechanism linking the immune and hemapoietic systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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