Sulfate Removal from Reject Brined in Inland Desalination with Zero Liquid Discharge

Sulfate is one of the most problematic ions present in reject brine in desalination systems due to its high potential of scale formation and membrane fouling; making it an obstacle in the application of zero liquid discharge. The ultra-high lime with aluminum process (UHLA) has shown to effectively remove sulfate. This research involves the study of sulfate removal from the nano-filtration unit in the zero liquid discharge system for inland desalination via a two-stage process using a calcium source to remove sulfate in the first stage and implementing the UHLA process in the second stage. The kinetics, equilibrium characteristics, and effects of different parameters on sulfate removal were studied. Kinetics of sulfate removal was studied on both stages of the process. The observation of fast kinetics in both stages indicated that removal kinetics is not a limitation for the application of the process. Equilibrium characteristics of the UHLA process were performed which revealed efficient sulfate removal at practical ranges of lime and aluminum doses. The effect of pH on sulfate removal in the process was studied. Results showed that sulfate removal in Stage 1 was independent of the pH of the solution while effective sulfate removal in Stage 2 was found to be above a pH of 11. The effect of initial sulfate concentrations on sulfate removal in Stage 1 was investigated and sulfate removal was mainly controlled by calcium sulfate solubility. The effect of initial chloride concentrations on sulfate removal in Stage 2 was evaluated and the results indicated that chloride has negligible effect on the removal of sulfate. Experiments concerning the effect of the recycle of calcium sulfate solids in Stage 1 showed an increase of the reaction rate. In contrast, the recycle of Stage 2 dry solids into Stage 2 revealed no effect on sulfate removal. An equilibrium model was developed to explain the equilibrium characteristics of Stage 2. It was found that a valid explanation for the chemistry of sulfate removal in Stage 2 was the formation of a solid solution consisting of ettringite and monosulfate. XRD analysis confirmed the formation of these solids

Pharmacological targeting of AKAP-directed compartmentalized cAMP signalling

The second messenger cyclic adenosine monophosphate (cAMP) can bind and activate protein kinase A (PKA). The cAMP/PKA system is ubiquitous and involved in a wide array of biological processes and therefore requires tight spatial and temporal regulation. Important components of the safeguard system are the A-kinase anchoring proteins (AKAPs), a heterogeneous family of scaffolding proteins defined by its ability to directly bind PKA. AKAPs tether PKA to specific subcellular compartments, and they bind further interaction partners to create local signalling hubs. The recent discovery of new AKAPs and advances in the field that shed light on the relevance of these hubs for human disease highlight unique opportunities for pharmacological modulation. This review exemplifies how interference with signalling, particularly cAMP signalling, at such hubs can reshape signalling responses and discusses how this could lead to novel pharmacological concepts for the treatment of disease with an unmet medical need such as cardiovascular disease and cancer

Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee’s up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary

Synthesis of Nitrogenated Heterocycles by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)haloimines

Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (MICINN; grant no. CONSOLIDER INGENIO 2010, CSD2007-00006, CTQ2007-65218 and CTQ2011-24151) and the Generalitat Valenciana (PROMETEO/2009/039 and FEDER). O.P. thanks the Spanish Ministerio de Educación for a predoctoral fellowship (grant no. AP-2008-00989)

Understanding the potential role of whole genome sequencing (WGS) in managing patients with gonorrhoea: A systematic review of WGS use on human pathogens in individual patient care

Objectives: The utility of whole genome sequencing (WGS) to inform sexually transmitted infection (STI) patient management is unclear. Timely WGS data might support clinical management of STIs by characterising epidemiological links and antimicrobial resistance profiles. We conducted a systematic review of clinical application of WGS to any human pathogen that may be transposable to gonorrhoea. Methods: We searched six databases for articles published between 01/01/2010–06/02/2023 that reported on real/near real-time human pathogen WGS to inform clinical intervention. All article types from all settings were included. Findings were analysed using narrative synthesis. Results: We identified 12,179 articles, of which eight reported applications to inform tuberculosis (n = 7) and gonorrhoea (n = 1) clinical patient management. WGS data were successfully used as an adjunct to clinical and epidemiological data to enhance contact-tracing (n = 2), inform antimicrobial therapy (n = 5) and identify cross-contamination (n = 1). WGS identified gonorrhoea transmission chains that were not established via partner notification. Future applications could include insights into pathogen exposure detected within sexual networks for targeted patient management. Conclusions: While there was some evidence of WGS use to provide individualised tuberculosis and gonorrhoea treatment, the eight identified studies contained few participants. Future research should focus on testing WGS intervention effectiveness and examining ethical considerations of STI WGS use

The A-kinase anchoring protein (AKAP) glycogen synthase kinase 3β interaction protein (GSKIP) regulates β-catenin through its interactions with both protein kinase A (PKA) and GSK3β

The A-kinase anchoring protein (AKAP) GSK3beta interaction protein (GSKIP) is a cytosolic scaffolding protein binding protein kinase A (PKA) and glycogen synthase kinase 3beta (GSK3beta). Here we show that both the AKAP function of GSKIP, i.e. its direct interaction with PKA, and its direct interaction with GSK3beta are required for the regulation of beta-catenin and thus Wnt signaling. A cytoplasmic destruction complex targets beta-catenin for degradation and thus prevents Wnt signaling. Wnt signals cause beta-catenin accumulation and translocation into the nucleus, where it induces Wnt target gene expression. GSKIP facilitates control of the beta-catenin stabilizing phosphorylation at Ser-675 by PKA. Its interaction with GSK3beta facilitates control of the destabilizing phosphorylation of beta-catenin at Ser-33/Ser-37/Thr-41. The influence of GSKIP on beta-catenin is explained by its scavenger function; it recruits the kinases away from the destruction complex without forming a complex with beta-catenin. The regulation of beta-catenin by GSKIP is specific for this AKAP as AKAP220, which also binds PKA and GSK3beta, did not affect Wnt signaling. We find that the binding domain of AKAP220 for GSK3beta is a conserved GSK3beta interaction domain (GID), which is also present in GSKIP. Our findings highlight an essential compartmentalization of both PKA and GSK3beta by GSKIP, and ascribe a function to a cytosolic AKAP-PKA interaction as a regulatory factor in the control of canonical Wnt signaling. Wnt signaling controls different biological processes, including embryonic development, cell cycle progression, glycogen metabolism, and immune regulation; deregulation is associated with diseases such as cancer, type 2 diabetes, inflammatory, and Alzheimer's and Parkinson's diseases

Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development

Doublecortin reinforces microtubules to promote growth cone advance in soft environments

Doublecortin (DCX) is a microtubule (MT)-associated protein in immature neurons. DCX is essential for early brain development,1 and DCX mutations account for nearly a quarter of all cases of lissencephaly-spectrum brain malformations2,3 that arise from a neuronal migration failure through the developing cortex.4 By analyzing pathogenic DCX missense mutations in non-neuronal cells, we show that disruption of MT binding is central to DCX pathology. In human-induced pluripotent stem cell (hiPSC)-derived cortical i3Neurons, genome edited to express DCX-mEmerald from the endogenous locus, DCX-MT interactions polarize very early during neuron morphogenesis. DCX interacts with MTs through two conserved DCX domains5,6 that bind between protofilaments and adjacent tubulin dimers,7 a site that changes conformation during guanosine triphosphate (GTP) hydrolysis.8 Consequently and consistent with our previous results,5 DCX specifically binds straight growth cone MTs and is excluded from the GTP/guanosine diphosphate (GDP)-inorganic phosphate (Pi) cap recognized by end-binding proteins (EBs). Comparing MT-bound DCX fluorescence to mEmerald-tagged nanocage standards, we measure approximately one hundred DCX molecules per micrometer growth cone MT. DCX is required for i3Neuron growth cone advance in soft microenvironments that mimic the viscoelasticity of brain tissue, and using high-resolution traction force microscopy, we find that growth cones produce comparatively small and transient traction forces. Given our finding that DCX stabilizes MTs in the growth cone periphery by inhibiting MT depolymerization, we propose that DCX contributes to growth cone biomechanics and reinforces the growth cone cytoskeleton to counteract actomyosin-generated contractile forces in soft physiological environments in which weak and transient adhesion-mediated traction may be insufficient for productive growth cone advance.</p

The microstructure and hardness of casting a solid brake disc after late graphitizing modification

The features of graphite formation in hypoeutectic and hypereutectic gray cast iron are considered. It is shown that this process in hypoeutectic gray cast irons is easier to control than in hypereutectic, because the formation of a predominantly rectilinear uniformly distributed graphite with a smaller size range and the presence of other distributions is achieved by an one-stage operation of ladle graphitization. The structure of graphite in hypereutectic gray cast irons is characterized by a large variety of its shapes, sizes and distributions, and it is also less technologically stable and controllable. Its characteristics can be approximated to the structure of hypoeutectic gray cast iron due to the obligatory second stage of graphitization. The microstructure and hardness of casting a solid brake disc after late graphitizing modification in a mold are investigated. The content of interdendritic distributions of graphite PGr8, PGr9 and short inclusions of graphite PGd45-90 (GOST 3443-87) was minimized due to the operation of the secondary (late) graphitizing modification. And Brinell hardness of the solid brake disc meets production requirements. © Published under licence by IOP Publishing Ltd.This work is carried out within a framework of the government order (No. FZRU-2020-0011) of the Ministry of Science and Higher Education of the Russian Federation