Shape complementarity is an important component of molecular recognition, and the ability to precisely adjust the shape of a binding scaffold to match a target of interest would greatly facilitate ...the creation of high-affinity protein reagents and therapeutics. Here we describe a general approach to control the shape of the binding surface on repeat-protein scaffolds and apply it to leucine-rich-repeat proteins. First, self-compatible building-block modules are designed that, when polymerized, generate surfaces with unique but constant curvatures. Second, a set of junction modules that connect the different building blocks are designed. Finally, new proteins with custom-designed shapes are generated by appropriately combining building-block and junction modules. Crystal structures of the designs illustrate the power of the approach in controlling repeat-protein curvature.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Significance To our knowledge, no other nano-based vaccine delivery platform has directly assessed the effects of nanoparticle charge on pulmonary vaccination without affecting other physio/chemical ...particle characteristics and/or antigen loading. The Particle Replication in Non-Wetting Templates nanoparticle fabrication process is unique in that it allows for isolation of charge as the sole variable in these studies while maintaining all other physical and chemical parameters constant. We find that positively charged nanoparticles induce robust mucosal and systemic antibody responses following pulmonary administration, whereas negatively charged nanoparticles fail to do so. Therefore, our studies underscore the importance of considering nanoparticle charge as a critical design parameter when generating pulmonary-based vaccines and may have implications for particulate vaccination through other routes of administration.
Pulmonary immunization enhances local humoral and cell-mediated mucosal protection, which are critical for vaccination against lung-specific pathogens such as influenza or tuberculosis. A variety of nanoparticle (NP) formulations have been tested preclinically for pulmonary vaccine development, yet the role of NP surface charge on downstream immune responses remains poorly understood. We used the Particle Replication in Non-Wetting Templates (PRINT) process to synthesize hydrogel NPs that varied only in surface charge and otherwise maintained constant size, shape, and antigen loading. Pulmonary immunization with ovalbumin (OVA)-conjugated cationic NPs led to enhanced systemic and lung antibody titers compared with anionic NPs. Increased antibody production correlated with robust germinal center B-cell expansion and increased activated CD4 ⁺ T-cell populations in lung draining lymph nodes. Ex vivo treatment of dendritic cells (DCs) with OVA-conjugated cationic NPs induced robust antigen-specific T-cell proliferation with ∼100-fold more potency than soluble OVA alone. Enhanced T-cell expansion correlated with increased expression of surface MHCII, T-cell coactivating receptors, and key cytokines/chemokine expression by DCs treated with cationic NPs, which were not observed with anionic NPs or soluble OVA. Together, these studies highlight the importance of NP surface charge when designing pulmonary vaccines, and our findings support the notion that cationic NP platforms engender potent humoral and mucosal immune responses.
Aim
In this review, the author focused on anticraving therapy for alcohol use disorder (AUD) defined by DMS‐5. A comprehensive review was carried out on the available published papers on anticraving ...drugs for treating AUD patients.
Methods
The author described all drugs with anticraving benefits for treating AUD patients approved by the Food and Drug Administration of the United States (US FDA) and European Medicines Agency of the European Union. Then, the commonly prescribed anticraving drugs and those under development were also described.
Results
The US FDA‐approved anticraving drugs included acamprosate and naltrexone, and those approved by European Medicines Agency were gamma‐hydroxybutyrate and nalmefene. The author also highlighted topiramate, gabapentin, ondansetron, LY196044, ifenprodil, varenicline, ABT‐436, mifepristone, citicoline, and baclofen. The putative mechanisms of action of and the use in clinical practice of those anticraving drugs were also described.
Conclusion
Although slowly developing, the field of anticraving drugs is getting into shape as a promising entity of a pharmaceutical class of drugs. Then, the author addressed on the underused issues of those recommended, and suggested anticraving drugs by the practice guideline of the American Psychiatric Association. The author urges that clinicians should be more “adventurous” in prescribing those promising drugs because benefits of those anticraving drugs are far‐outweighing the possible side effects of anticraving drugs, or the harms of untreated AUD itself.
In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. ...Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future.
Steam reforming, partial oxidation, and oxidative steam reforming of ethanol over Ir/CeO2 catalysts were studied to elucidate the reaction pathway and determine catalytic stability. ...Temperature-programmed desorption and surface reaction revealed that ethoxy species were immediately formed on ethanol adsorption at room temperature, and were mainly further oxidized to acetate and carbonate species that finally decomposed into CH4/CO and CO2, respectively. Under reaction conditions, acetaldehyde was the primary product below 673 K, which decomposed mainly to methane and carbon monoxide at higher temperatures, whereas methane reforming and the water-gas shift were the major reactions above 773 K. The Ir/CeO2 catalyst demonstrated rather high stability for the reactions at 823 and 923 K with no apparent deactivation for 60 h on stream; the mean size of Ir particles was stable at around 2-3 nm, but the ceria particles sintered significantly from 6-8 to 14-27 nm. CeO2 likely prevented the highly dispersed Ir particles from sintering and inhibited coke deposition through strong Ir-CeO2 interactions. PUBLICATION ABSTRACT
The Jülich-Bonn dynamical coupled-channel approach is extended to include
K
Σ
photoproduction off the proton. Differential cross section and (double) polarization data for
K
+
Σ
0
and
K
0
Σ
+
are ...analysed simultaneously with the pion- and photon-induced production of
π
N
,
η
N
,
K
Λ
, and
K
Σ
final states, totaling almost 72,000 data points for center-of-mass energies
W
<
2.4
GeV. Based on the fit results the spectrum of
N
∗
and
Δ
resonances is extracted in terms of pole positions and residues. We discuss the impact of the
γ
p
→
K
Σ
channels in detail and investigate the influence of recent polarization data for
η
p
photoproduction.
In this study, the detonation diffraction and re-initiation processes around a single cuboid were studied experimentally. Experiments were performed in a 6-m-long duct with a cross section of 112 mm ...× 112 mm filled with stoichiometric methane–oxygen mixtures at initial pressures between 10 and 30 kPa. A cuboid was placed in the duct to form two perpendicular passages between the cuboid and the walls. Soot foils fixed on the side wall and bottom wall were used to characterize the cellular structure evolution process, from which the diffraction and re-initiation behavior of a detonation could be analyzed. The effects of the spacing between the cuboid and the top wall (
δ
) and the spacing between the cuboid and the side wall (
σ
) on diffraction and re-initiation were investigated systematically. It is shown that the diffraction and re-initiation of a detonation were influenced significantly by introducing a perpendicular channel. Compared with the unidirectional scenario, the boundary between the diffraction wave and the re-initiation region was not so sharp. Depending on the channel scale and mixtures sensitivity (or cell size,
λ
), two re-initiation modes could be observed. For more sensitive mixtures (
δ
/
λ
>
2
or
σ
/
λ
>
2
), an overdriven detonation occurs first. The overdriven detonation propagates toward the edge, generating a secondary overdriven detonation near the wall through detonation reflection. The new one propagates forward and decays to a steady-state detonation. On the other hand, only one overdriven detonation occurs for less sensitive mixtures. For a given channel width, it was demonstrated that the diffraction area could be narrowed as the perpendicular channel width was increased. The inverse feedback mechanism between the two perpendicular diffraction waves was analyzed.
Summary
Background
The cingulate cortex is the main area in the brain involved in pruritus processing and is deactivated after scratching. Lichen simplex chronicus (LSC) is a common pruritic skin ...disorder characterized by skin lichenification following excessive scratching. Psychological factors may contribute to both the development and persistence of LSC.
Objectives
To estimate the hazard ratio (HR) of LSC in people with anxiety disorders compared with the general population.
Methods
In this nationwide population‐based retrospective cohort study we identified a total of 69 386 people, who formed the anxiety cohort, by using the Taiwan National Health Insurance Research Database from 2000 to 2009. The comparison cohort was composed of randomly selected people frequency matched for age (within 5‐year intervals), sex and index date (the date of anxiety diagnosis) based on a 1 : 2 ratio. The risk of LSC was estimated as HRs and 95% confidence intervals (CIs) using the Cox proportional hazards model.
Results
After adjusting for age, sex and LSC‐associated comorbidities, the people with anxiety had a 1·41‐fold greater risk of developing LSC compared with the people in the comparison cohort (HR 1·41, 95% CI 1·30–1·52, P < 0·0001). In particular, individuals with obsessive–compulsive disorder had a significantly increased risk of developing LSC (HR 1·72, 95% CI 1·03–2·88, P = 0·0395).
Conclusions
This study demonstrates that having an anxiety disorder is associated with an increased risk of LSC. Psychological factors were found to contribute to LSC. We recommend combining the management of LSC and psychological disorders to achieve favourable outcomes.
What's already known about this topic?
Lichen simplex chronicus (LSC) is a common skin disorder characterized by skin lichenification following excessive scratching.
LSC is not a life‐threatening disease, but it can result in psychosocial problems and impair quality of life through sleep disturbance and sexual dysfunction.
What does this study add?
This study demonstrates that people with anxiety, especially those aged < 40 years, are at an increased risk of having LSC. Psychological factors were found to contribute to LSC.
We recommend combining the management of LSC and psychological disorders to achieve favourable outcomes.
We have successfully fabricated well-ordered silicon nanowire (SiNW) arrays of smooth surface by using a low-cost and facile Ag-assisted chemical etching technique. We have experimentally found that ...the reflectance can be significantly suppressed (<1%) over a wide solar spectrum (300-1000 nm) in the as-grown samples. Also, based on our bundled model, we have used rigorous coupled-wave analysis to simulate the reflectance in SiNW arrays, and found that the calculated results are in good agreement with the experimental data. From a further simulation study on the light absorption in SiNW arrays, we have obtained a photocurrent enhancement of up to 425% per unit volume of material as compared to crystalline Si, implying that effective light trapping can be realized in the as-grown samples. In addition, we have demonstrated experimentally and theoretically that the as-grown samples have an omnidirectional high-efficiency antireflection property.
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