In the past decade or so, small-pore zeolites have received greater attention than large- and medium-pore molecular sieves that have historically dominated the literature. This is primarily due to ...the commercialization of two major catalytic processes, NOx exhaust removal and methanol conversion to light olefins, that take advantage of the properties of these materials with smaller apertures. Small-pore zeolites possess pores that are constructed of eight tetrahedral atoms (Si4+ and Al3+), each time linked by a shared oxygen These eight-member ring pores (8MR) provide small molecules access to the intracrystalline void space, e.g., to NOx during car exhaust cleaning (NOx removal) or to methanol en route to its conversion into light olefins, while restricting larger molecule entrance and departure that is critical to overall catalyst performance. In total, there are forty-four structurally different small-pore zeolites. Forty-one of these zeolites can be synthesized, and the first synthetic zeolite (KFI, 1948) was in fact a small-pore material. Although the field of 8MR zeolite chemistry has expanded in many directions, the progress in synthesis is framework-specific, leaving insights and generalizations difficult to realize. This review first focuses on the relevant synthesis details of all 8MR zeolites and provides some generalized findings and related insights. Next, catalytic applications where 8MR zeolites either have been commercialized or have dominated investigations are presented, with the aim of providing structure–activity relationships. The review ends with a summary that discusses (i) both synthetic and catalytic progress, (ii) a list of opportunities in the 8MR zeolite field, and (iii) a brief future outlook.
Zeolites and zeolite-like materials are continually finding new applications. Because of the uniformity of these solids, the expression of macroscale materials properties that are controlled by the ...materials chemistry at the atomic/molecular scale are achievable. In this Perspective, I discuss the following areas of current interest in zeolites and zeolite-like materials that rely on manipulation of the materials chemistry for their preparation and provide new opportunities for application: (i) exploitation of organic structure-directing agents (SDAs) for new materials, (ii) the synthesis of zeolites without SDAs, (iii) the synthesis of very hydrophobic materials, (iv) conversions of two-dimensional (2D) to 3D materials and vice versa, (v) hierarchically organized materials, (vi) chiral materials, and (vii) direction of tetrahedral atoms to specific framework positions.
The science and medicine of human immunology Pulendran, Bali; Davis, Mark M
Science (American Association for the Advancement of Science),
09/2020, Letnik:
369, Številka:
6511
Journal Article
Recenzirano
Odprti dostop
Although the development of effective vaccines has saved countless lives from infectious diseases, the basic workings of the human immune system are complex and have required the development of ...animal models, such as inbred mice, to define mechanisms of immunity. More recently, new strategies and technologies have been developed to directly explore the human immune system with unprecedented precision. We discuss how these approaches are advancing our mechanistic understanding of human immunology and are facilitating the development of vaccines and therapeutics for infection, autoimmune diseases, and cancer.
Experimental therapeutics developed to exploit RNA interference (RNAi) are now in clinical studies. Here, the translation from concept to clinic for the first experimental therapeutic to provide ...targeted delivery of synthetic, small interfering RNA (siRNA) in humans is described. This targeted, nanoparticle formulation of siRNA, denoted as CALAA-01, consists of a cyclodextrin-containing polymer (CDP), a polythethylene glycol (PEG) steric stabilization agent, and human transferrin (Tf) as a targeting ligand for binding to transferrin receptors (TfR) that are typically upregulated on cancer cells. The four component formulation is self-assembled into nanoparticles in the pharmacy and administered intravenously (iv) to patients. The designed features of this experimental therapeutic are described, and their functions illustrated.
This paper explores the evolving renewable energy ‘prosumer’ phenomenon in the United Kingdom (UK). It identifies and evaluates how prosumer business models can exist beyond direct subsidy and the ...range of prosumer business model archetypes currently in operation. Through a series of in-depth interviews and document analysis, the paper identifies the key opportunities and challenges for these innovative energy business models. The analysis shows that recent developments in technology such as the diffusion of smart meters, li-ion batteries, peer-to-peer trading platforms and electric vehicles are opening up a range of new value propositions, which in turn are beginning to be exploited by a range of new business models. In many cases the regulatory, financing and institutional governance landscape of the UK lags behind, however, inhibiting these emerging business models. Moreover, these business models rely on managing a complex set of values for consumers that reach deeper into their lives than traditional tariffs. Thus, successful business models must manage this complexity if they are to be adopted by the disengaged majority. Energy policy and energy practitioners can leverage these emerging trends in service of a low carbon energy transition by adopting ‘ten principles’ of prosumerism; and six UK policy recommendations.
•Prosumers –who produce and consume renewable energy – are key actors in energy transitions.•Traditional prosumer business models are increasingly unviable without subsidies.•New business models should play an increasing role in this post subsidy environment.•These include microgrids; local energy companies; P2P, aggregators, ESCOs and V2G models.•We outline drivers and barriers for these models and propose ‘10 principles of prosumerism’.
Human immune system variation Brodin, Petter; Davis, Mark M
Nature reviews. Immunology,
01/2017, Letnik:
17, Številka:
1
Journal Article
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The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology ...analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.
The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. It is now conceivable that an antibody-dependent HIV vaccine might be possible, ...given the discovery of HIV broadly neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these antibodies are difficult to develop and have characteristics indicative of a high degree of affinity maturation in germinal centers (GCs). CD4+ T follicular helper (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal individuals a subpopulation of circulating memory PD-1+CXCR5+CD4+ T cells that are resting memory cells most related to bona fide GC Tfh cells by gene expression profile, cytokine profile, and functional properties. Importantly, the frequency of these cells correlated with the development of bnAbs against HIV in a large cohort of HIV+ individuals.
•PD-1+CXCR5+CD4+ T cells are a population of circulating memory Tfh cells•Optimal Tfh-cell-like function is restricted to PD-1+CXCR3−CXCR5+CD4+ T cells•PD-1+CXCR3−CXCR5+CD4+ T cells correlate with HIV broadly neutralizing antibodies
Poorly water-soluble drugs are a significant and ongoing issue for the pharmaceutical industry. An overview of recent developments for the preparation of spray-dried delivery systems is presented. ...Examples include amorphous solid dispersions, spray dried dispersions, microparticles, nanoparticles, surfactant systems and self-emulsifying drug delivery systems. Several aspects of formulation are considered, such as pre-screening, choosing excipient(s), the effect of polymer structure on performance, formulation optimisation, ternary dispersions, fixed-dose combinations, solvent selection and component miscibility. Process optimisation techniques including nozzle selection are discussed. Comparisons are drawn with other preparation techniques such as hot melt extrusion, freeze drying, milling, electro spinning and film casting. Novel analytical and dissolution techniques for the characterization of amorphous solid dispersions are included. Progress in understanding of amorphous supersaturation or recrystallisation from solution gathered from mechanistic studies is discussed. Aspects of powder flow and compression are considered in a section on downstream processing. Overall, spray drying has a bright future due to its versatility, efficiency and the driving force of poorly soluble drugs.
Schematic representation of amorphous solid dispersions (ASD), microparticles, nanoparticles, Fixed dose (ASD), Ternary ASD and Self-emulsifying drug delivery systems (SEDDS) prepared by spray drying. Active pharmaceutical ingredient (API) 1 and 2, surfactant and polymers 1 and 2 are illustrated in the legend. Display omitted
A meta-analysis of 62 experimental and 10 non-experimental studies was conducted to evaluate the positive-mood-enhances-creativity generalization. While the results demonstrate that positive mood ...enhances creativity, the strength of that effect is contingent upon the comparative or referent mood state (i.e., neutral or negative mood) as well as the type of creative task. Further, the pattern of effect sizes supports a curvilinear relationship between affective intensity and creative performance. In general, a contextual perspective of mood–creativity relations is supported.
We have developed a single-molecule imaging technique that uses quantum-dot-labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4+ T cell functional sensitivity. We found that ...naive T cells, T cell blasts, and memory T cells could all be triggered by a single pMHC to secrete tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) cytokines with a rate of ∼1,000, ∼10,000, and ∼10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. We also found that a single pMHC localized to the immunological synapse induced the slow formation of a long-lasting T cell receptor (TCR) cluster, consistent with a serial engagement mechanism. These data show that scaling up CD4+ T cell cytokine responses involves increasingly efficient T cell recruitment rather than greater cytokine production per cell.
•Naive, blasting, and memory T cells are equally sensitive to antigenic stimulation•A single pMHC triggers CD4+ T cell cytokine secretion•CD4+ T cell cytokine secretion displays a digital signaling pattern•A single pMHC induces the formation of a TCR cluster
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