A photoreceiver with an integrated X-band low-noise amplifier

The paper presents development results for a photodetector module with an integrated lownoise amplifier. The photodetector is based on a commercial indium-phosphide photodiode and a custom-designed adapter board and allows to use an optical carrier with wavelengths of 1.31 and 1.55 μm and performs optoelectronic conversion for electrical signals into 0–50 GHz range. The developed gallium arsenide low-noise amplifier is used to compensate photodiode conversion loss in the X-band frequency range. The photodetector module is intended for use as a microwave photonic link receiver, which provides a significant extension of the signal transmission range in comparison with classical types of transmission lines

CO2 accelerates Candida albicans biofilm formation and reveals novel approaches to their inhibition on airway management devices

C. albicans is the predominant human fungal pathogen worldwide and frequently colonises medical devices, such as voice prosthesis, as a biofilm. It is a dimorphic yeast that can switch between yeast and hyphal forms in response to environmental cues, a property that is essential during biofilm establishment and maturation. One such cue is elevation of CO2 levels, as observed in exhaled breath for example. However, despite the clear medical relevance the effects of high CO2 levels on C. albicans biofilm growth has not been investigated to date. Here, we show that 5% CO2 significantly enhances each stage of the C. albicans biofilm forming process; from attachment through maturation to dispersion, via stimulation of the Ras/cAMP/PKA signalling pathway. Transcriptome analysis of biofilm formation under elevated CO2 conditions revealed the activation of key biofilm formation pathways governed by the central biofilm regulators Efg1, Brg1, Bcr1 and Ndt80. Biofilms grown in under elevated CO2 conditions also exhibit increases in azole resistance, tolerance to nutritional immunity and enhanced glucose uptake capabilities. We thus characterise the mechanisms by which elevated CO2 promote C. albicans biofilm formation. We also investigate the possibility of re-purposing drugs that can target the CO2 activated metabolic enhancements observed in C. albicans biofilms. Using this approach we can significantly reduce multi-species biofilm formation in a high CO2 environment and demonstrate a significant extension of the lifespan of voice prostheses in a patient trial. Our research demonstrates a bench to bedside approach to tackle Candida albicans biofilm formation.

Morphology-Governed Performance of Multi-Dimensional Photocatalysts for Hydrogen Generation

In the past few decades, extensive studies have been performed to utilize the solar energy for photocatalytic water splitting; however, up to the present, the overall efficiencies reported in the literature are still unsatisfactory for commercialization. The crucial element of this challenging concept is the proper selection and design of photocatalytic material to enable significant extension of practical application perspectives. One of the important features in describing photocatalysts, although underestimated, is particle morphology. Accordingly, this review presents the advances achieved in the design of photocatalysts that are dedicated to hydrogen generation, with an emphasis on the particle morphology and its potential correlation with the overall reaction performance. The novel concept of this work—with the content presented in a clear and logical way—is based on the division into five parts according to dimensional arrangement groups of 0D, 1D, 2D, 3D, and combined systems. In this regard, it has been shown that the consideration of the discussed aspects, focusing on different types of particle morphology and their correlation with the system’s efficiency, could be a promising route for accelerating the development of photocatalytic materials oriented for solar-driven hydrogen generation. Finally, concluding remarks (additionally including the problems connected with experiments) and potential future directions of particle morphology-based design of photocatalysts for hydrogen production systems have been presented.

On the value of using 3D-shape and electrostatic similarities in deep generative methods

Multi-parameter optimization, the heart of drug design, is still an open challenge. Thus, improved methods for automated compounds design with multiple controlled properties are desired. Here, we present a significant extension to our previously described fragment-based reinforcement learning method (DeepFMPO) for the generation of novel molecules with optimal properties. As before, the generative process outputs optimized molecules similar to the input structures, now with the improved feature of replacing parts of these molecules with fragments of similar 3D-shape and electrostatics. By performing comparisons of 3D-fragments, we can simulate 3D properties while overcoming the notoriously difficult step of accurately describing bioactive conformations. The comparison of electrostatic potential and molecular shape is performed using the new ESP-Sim python package, allowing the calculation of state-of-the-art partial charges (e.g., RESP with B3LYP/6-31G**) obtained using the quantum chemistry program Psi4. The new improved method is demonstrated with a scaffold-hopping exercise identifying CDK2 bioisosteres. All code is open-source and freely available.

Set characterizations and convex extensions for geometric convex-hull proofs

In the present work, we consider Zuckerberg’s method for geometric convex-hull proofs introduced in Zuckerberg (Oper Res Lett 44(5):625–629, 2016). It has only been scarcely adopted in the literature so far, despite the great flexibility in designing algorithmic proofs for the completeness of polyhedral descriptions that it offers. We suspect that this is partly due to the rather heavy algebraic framework its original statement entails. This is why we present a much more lightweight and accessible approach to Zuckerberg’s proof technique, building on ideas from Gupte et al. (Discrete Optim 36:100569, 2020). We introduce the concept of set characterizations to replace the set-theoretic expressions needed in the original version and to facilitate the construction of algorithmic proof schemes. Along with this, we develop several different strategies to conduct Zuckerberg-type convex-hull proofs. Very importantly, we also show that our concept allows for a significant extension of Zuckerberg’s proof technique. While the original method was only applicable to 0/1-polytopes, our extended framework allows to treat arbitrary polyhedra and even general convex sets. We demonstrate this increase in expressive power by characterizing the convex hull of Boolean and bilinear functions over polytopal domains. All results are illustrated with indicative examples to underline the practical usefulness and wide applicability of our framework.

Effects of post-subduction processes on continental lithosphere

Subduction is a key driver of plate tectonics on Earth1. A range of observations indicate that the termination of subduction leads to diverse and unexplained tectonic and geological activity, including anomalous magmatism, exhumation and topographic subsidence, followed by rapid uplift. However, the mechanism driving this complex surface response remains enigmatic. A prime example of recent subduction termination can be found in northern Borneo (Malaysia), where subduction ceased in the late Miocene2 and was followed by a puzzling tectonic response3,4,5,6,7,8 that cannot be reconciled with our current understanding of post-subduction tectonics. Here, we use new passive-seismic data to image, in unprecedented detail, a sub-vertical lithospheric drip that developed as a Rayleigh-Taylor gravitational instability9 from the root of a volcanic arc. We use thermo-mechanical simulations to reconcile these images with time-dependent dynamical processes within the crust and underlying mantle following subduction termination. Our model predictions illustrate how significant extension from a downwelling lithospheric drip can thin the crust in an adjacent orogenic belt, facilitating lower crustal melting and possible exhumation of subcontinental material. Our study provides a new paradigm for core-complex formation in other areas of recent subduction termination.

Osteoarthritis Induces Gender Related Changes in the Knee Range of Motion

In time, osteoarthritis (OA) generates the misalignment of the affected joint structures. However, due to the nature of bipedal gait, OA in the lower limb can also cause pathological gait patterns, which can generate instability and falls, with great consequence, especially in the aged population. With goniometry used to evaluate the range of motion of joints (ROM), we wanted to evaluate how gender impacts gait dynamics in OA patients. For this study we have compared 106 OA patients (male=32, female=74) to age matched controls. All participants had their right leg as dominant. Video recording of normal gait was analysed with a digital goniometry tool phone application, and the knee’s ROM was measured in midstance and midswing of the gait. During midstance, significant extension and flexion of the knee excursion have been observed in both males and females. During midswing, knee OA presents more differences, whereas subjects with hip and knee OA present changes on the dominant knee. Midstance changes suggest that the knee’s joint degenerative changes can be linked to hip OA secondary changes. Midswing changes in lower limb OA suggest a connection to the activities of daily life. Gender differences generated by OA must furthermore be studied in both lower limbs so that the best therapeutic approach can be chosen.

Sociability and Polite Improvement in Addison’s Periodicals

Addison argued in his periodical essays that the distinctive sociability of the coffee house was especially, if not uniquely, polite, rational, and civic, and as such, an important metaphor and location for Addison’s social reform. Addison developed his conception of coffee-house sociability in dialogue with Richard Steele, but while Steele argued that emulation of virtuous behaviour in neighbourly communities was sufficient guarantor of the polite and rational reformation of public culture, Addison repeatedly toyed with a more regulated model in which an arbiter or censor moderated coffee-house behaviour. In The Spectator, Addison had identified women readers as an important commercial and ideological opportunity. While women of the polite and middling classes bore the weight of Addison’s reformist expectations, such women were excluded from the public sociability of the coffee house. In recognition of this impasse, Addison and Steele addressed a series of essays to the tea table, a form of sociability in which women and female manners were dominant. These essays develop an innovative construction of tea-table sociability located in a fluid zone between public sociability and private domesticity, centred around tea consumption, polite conversation, and reading essays from The Spectator. The tea table was, accordingly, a significant extension and revision of their theory of public sociability.

Dialysis-related carpal tunnel syndrome in the past 40 years

Purpose and method Patients on hemodialysis develop carpal tunnel syndrome (CTS) due to an accumulation of dialysis-related β2 microglobulin (β2m) amyloid (DRA). In Japan, dialysis technology has progressed remarkably in the past 40 years and has increased the time until patients require surgery for CTS. However, unclear is whether the time from the start of hemodialysis to the first surgery for CTS is associated with β2m clearance by the different hemodialysis techniques. Therefore, we retrospectively evaluated β2m clearance, serum β2m levels, and the change in the length of this period in patients across 4 periods according to the year that first surgery for CTS was performed: period 1, 1982–1989; period 2, 1990–1999; period 3, 2000–2009; and period 4, 2010–2019. Result A total of 222 patients who met the selection criteria were included. Mean β2m clearance was −1.8 ± 16.7% in period 1, and improved to 65.4 ± 8.6% in period 3. Accordingly, the serum β2m value after hemodialysis decreased significantly. The time from the start of hemodialysis to the first surgery for CTS was 12.4 ± 2.9 years in period 1 but increased to 21.8 ± 6.3 years in period 3. In multivariable linear regression analysis, the significant factors contributing to β2m clearance were periods 2, 3, and 4. In particular, the relation between removal of β2m and the extension of the dialysis vintage in period 1 and 2 was remarkable compared with periods 3 and 4. Conclusion Our findings indicate that improvement of β2m clearance via advances in dialysis technology might result in a significant extension in the time between starting HD and the first surgery for CTS.

Conjugates for use in peptide therapeutics: a systematic review and meta-analysis

While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (# CRD42020222579 ). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.