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Metalated intact and deprotonated histidyl glycine and glycyl histidine dipeptides were investigated in the gas phase by using infrared multiple photon dissociation (IRMPD) spectroscopy with light from a free-electron laser (FEL). The dipeptides M2+(GlyHis), M2+(HisGly), [M(GlyHis-H)]+, and [M(HisGly-H)]+, where M = Zn and Cd, were probed to elucidate how the His position along the peptide chain and ligand charge state might influence the structures observed in the gas phase. Simulated annealing calculations were performed to determine energetically low-lying conformers and isomers of these structures. Quantum chemical calculations were used to optimize the structures at the B3LYP level of theory using the 6-311+G(d,p) and def2-TZVP basis sets for zinc and cadmium complexes, respectively. IRMPD and calculated linear absorption spectra were compared to evaluate which structures are present. Relative energies of the various species were evaluated using single-point energy calculations for low-lying structures at the B3LYP, B3LYP-GD3BJ, ωB97XD, and MP2(full) levels using the 6-311+G(2d,2p) and def2-TZVPP basis sets. For all species, structures for both metals mirror each other, and those that reproduce the experimental spectrum were determined to be iminol structures for the intact ligands or iminol-like structures for the deprotonated ligands. Additionally, when the spectra of the deprotonated dipeptides are compared to the intact dipeptides, the change in the spectra is correlated to the group that is deprotonated.

Mitophagy preserves overall mitochondrial fitness by selectively targeting damaged mitochondria for degradation. The regulatory mechanisms that prevent PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin (PINK1/Parkin)-dependent mitophagy and other selective autophagy pathways from overreacting while ensuring swift progression once initiated are largely elusive. Here, we demonstrate how the TBK1 (TANK-binding kinase 1) adaptors NAP1 (NAK-associated protein 1) and SINTBAD (similar to NAP1 TBK1 adaptor) restrict the initiation of OPTN (optineurin)-driven mitophagy by competing with OPTN for TBK1. Conversely, they promote the progression of nuclear dot protein 52 (NDP52)-driven mitophagy by recruiting TBK1 to NDP52 and stabilizing its interaction with FIP200. Notably, OPTN emerges as the primary recruiter of TBK1 during mitophagy initiation, which in return boosts NDP52-mediated mitophagy. Our results thus define NAP1 and SINTBAD as cargo receptor rheostats, elevating the threshold for mitophagy initiation by OPTN while promoting the progression of the pathway once set in motion by supporting NDP52. These findings shed light on the cellular strategy to prevent pathway hyperactivity while still ensuring efficient progression.

The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli. We stimulated healthy peripheral blood mononuclear cells with pretransplant and posttransplant serum of kidney transplant patients and immunosuppressive drugs in an in vitro trained immunity assay and measured tumor necrosis factor and interleukin 6 cytokine levels in the supernatant as a readout for trained immunity. We show that the serum of kidney transplant recipients collected 1 week after transplantation can suppress trained immunity. Importantly, we found that kidney transplant recipients whose serum most strongly suppressed trained immunity rarely experienced graft loss. This suppressive effect of posttransplant serum is likely mediated by previously unreported effects of immunosuppressive drugs. Our findings provide mechanistic insights into the role of innate immunity in kidney allograft survival, uncovering trained immunity as a potential therapeutic target for improving graft survival.

Confinement of clathrate hydrate enables an energy efficient, cyclic and carbon neutral storage concept in which CO2, generated by E-methane conversion, replaces E-methane by direct exchange.

Freezing of Gait (FoG) is a common symptom of Parkinson’s disease (PD), manifesting as a brief, episodic absence, or marked reduction in walking, despite a patient’s intention to move. Clinical assessment of FoG events from manual observations by experts is both time-consuming and highly subjective. Therefore, machine learning-based FoG identification methods would be desirable. In this article, we address this task as a fine-grained human action recognition problem based on vision inputs. A novel deep learning architecture, namely, higher order polynomial transformer (HP-Transformer), is proposed to incorporate pose and appearance feature sequences to formulate fine-grained FoG patterns. In particular, a higher order self-attention mechanism is proposed based on higher order polynomials. To this end, linear, bilinear, and trilinear transformers are formulated in pursuit of discriminative fine-grained representations. These representations are treated as multiple streams and further fused by a cross-order fusion strategy for FoG detection. Comprehensive experiments on a large in-house dataset collected during clinical assessments demonstrate the effectiveness of the proposed method, and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92 is achieved for detecting FoG.

Aim:To compare the microbial communities inside hemodialysis catheters from symptomatic and asymptomatic patients to determine their differences.Materials & methods:Catheters (n = 41) were removed from patients in the Saskatchewan Health Authority over an 18-month period. The catheter section inside the body was flushed and the contents were evaluated using culture-dependent and culture-independent analysis.Results:All catheters were colonized by bacteria, with considerable overlap between groups based on microbial communities and the individual species detected. More Gram-negative species were detected by sequencing, whereas predominantly Gram-positive strains were cultured. Antibiotic resistance and biofilm formation was widespread and not correlated with either catheter group.Conclusion:Common pathogens were detected in each set of catheters, therefore predicting infections based on the microbiology is difficult.

Purpose:To evaluate the visual outcomes and complications with a polytetrafluoroethylene (Gore-Tex)-fixated intraocular lens (IOL) (Akreos AO60, Bausch + Lomb). Methods:Eyes with inadequate capsule support for in-the-bag IOL implantation had pars plana vitrectomy (PPV) and IOL placement at a single center. The main outcome measures were the postoperative visual acuity (VA) and complication rates. Results:During the study, 783 surgeries were performed. The mean visual acuity gain was 28.5 Early Treatment Diabetic Retinopathy Study letters (P< .01), with a mean time to best VA of 3.05 months. Statistical hypotony (intraocular pressure <6.5 mm Hg) was present in 214 cases (27.3%), and clinical features of hypotony were present in 46 cases. Five percent of the complications were directly related to the IOL. There were 3 cases of IOL opacification, 2 with silicone oil endotamponade and 1 with perfluoropropane endotamponade. Conclusions:PPV with Akreos IOL implantation was an effective technique for secondary IOL placement. Complications directly related to the IOL were uncommon.

Les commotions cérébrales dans le sport représentent un défi majeur avec des implications importantes pour la santé des athlètes. Cet article présente des cas cliniques variés de commotions cérébrales dans le sport, offrant un aperçu des situations auxquelles les professionnels de santé sont confrontés. Le premier cas présente Alice, une joueuse de football de 18 ans, qui souffre de symptômes postcommotionnels après une collision. Les outils SCAT6® sont utilisés pour confirmer sa commotion et les recommandations incluent le repos relatif et une reprise progressive des activités cognitives et sportives. Le deuxième cas décrit Arthur, un demi-centre de handball de 20 ans, qui, après un choc violent, veut retourner au jeu malgré des symptômes initiaux importants. Il est évalué avec SCAT6® et ne peut pas reprendre le jeu immédiatement. Le troisième cas concerne Léo, un jeune joueur de hockey de 10 ans, dont les symptômes persistent une semaine après l’accident. Le SCOAT6 est utilisé pour son évaluation, et ses activités scolaires et sportives sont adaptées pour éviter toute exacerbation. Enfin, le quatrième cas présente Louise, une skieuse alpine de 24 ans, ayant subi plusieurs commotions cérébrales avec des répercussions croissantes sur sa santé et sa carrière sportive. Elle est évaluée avec SCOAT6 et doit suspendre son sport jusqu’à la disparition des symptômes. Ces cas soulèvent des questions critiques pour les professionnels de la santé : quels outils utiliser pour évaluer les commotions, quelles recommandations donner pour le retour au sport et à l’école, et comment gérer les facteurs aggravants ? En se basant sur ces situations réelles, l’article vise à enrichir les connaissances et les pratiques des médecins et des professionnels de santé, en mettant en lumière l’importance d’une évaluation rigoureuse et des recommandations adaptées.

La fiche synthèse pour l’utilisation des outils SCAT6® et SCOAT6 aide les cliniciens à comprendre et utiliser ces outils recommandés par la 6econférence de consensus sur les commotions cérébrales de 2022. Les commotions cérébrales, blessures courantes mais graves, nécessitent une prise en charge rapide. Le SCAT6® (Sport Concussion Assessment Tool) et le SCOAT6 (Sport Concussion Office Assessment Tool) fournissent des directives claires pour l’évaluation immédiate sur le terrain, le suivi à court terme et la gestion à long terme des commotions cérébrales. Cette fiche décrit l’utilisation de ces outils pour différentes situations cliniques, de l’évaluation initiale à la prise en charge post-commotionnelle, incluant des suggestions thérapeutiques adaptées.

An analytical theory for the interaction potential between surfaces (e.g., colloids) in polyelectrolyte solutions is derived. A superposition of a Debye–Hückel interaction potential and a damped oscillatory interaction potential, commonly employed to fit measured colloidal interactions, follows naturally from our theory. Using appropriate expressions for the structure factor of the bulk polyelectrolyte solution in the dilute, semidilute and concentrated regimes explicit expressions for the wavelength and decay length of the oscillatory part of the interaction potential were derived. Quantitative agreement between experimental measurements and our theory is found in the dilute and semidilute concentration regimes. In the concentrated regime, the theory predicts very weak oscillations and a large attractive region due to the electrostatically induced depletion interactions, in agreement with simulations.

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.

To determine the pathophysiologic and prognostic meaning of patient self-reported sodium intake in heart failure (HF) with preserved ejection fraction (HFpEF).

Rescoring of peptide–spectrum matches (PSMs) has emerged as a standard procedure for the analysis of tandem mass spectrometry data. This emphasizes the need for software maintenance and continuous improvement for such algorithms. We introduce MS2Rescore 3.0, a versatile, modular, and user-friendly platform designed to increase peptide identifications. Researchers can install MS2Rescore across various platforms with minimal effort and benefit from a graphical user interface, a modular Python API, and extensive documentation. To showcase this new version, we connected MS2Rescore 3.0 with MS Amanda 3.0, a new release of the well-established search engine, addressing previous limitations on automatic rescoring. Among new features, MS Amanda now contains additional output columns that can be used for rescoring. The full potential of rescoring is best revealed when applied on challenging data sets. We therefore evaluated the performance of these two tools on publicly available single-cell data sets, where the number of PSMs was substantially increased, thereby demonstrating that MS2Rescore offers a powerful solution to boost peptide identifications. MS2Rescore’s modular design and user-friendly interface make data-driven rescoring easily accessible, even for inexperienced users. We therefore expect the MS2Rescore to be a valuable tool for the wider proteomics community. MS2Rescore is available at https://github.com/compomics/ms2rescore.

Data-independent acquisition (DIA) has become a well-established method for MS-based proteomics. However, the list of options to analyze this type of data is quite extensive, and the use of spectral libraries has become an important factor in DIA data analysis. More specifically the use of in silico predicted libraries is gaining more interest. By working with a differential spike-in of human standard proteins (UPS2) in a constant yeast tryptic digest background, we evaluated the sensitivity, precision, and accuracy of the use of in silico predicted libraries in data DIA data analysis workflows compared to more established workflows. Three commonly used DIA software tools, DIA-NN, EncyclopeDIA, and Spectronaut, were each tested in spectral library mode and spectral library-free mode. In spectral library mode, we used independent spectral library prediction tools PROSIT and MS2PIP together with DeepLC, next to classical data-dependent acquisition (DDA)-based spectral libraries. In total, we benchmarked 12 computational workflows for DIA. Our comparison showed that DIA-NN reached the highest sensitivity while maintaining a good compromise on the reproducibility and accuracy levels in either library-free mode or using in silico predicted libraries pointing to a general benefit in using in silico predicted libraries.

Ni-rich layered oxides LiNi1–x–yMnxCoyO2(NMC811, x= 0.1 and y= 0.1) are considered promising cathode materials in lithium-ion batteries (LiBs) due to their high energy density. However, those suffer a severe capacity loss upon cycling at high delithiated states. The loss of performance over time can be retarded by Zr doping. Herein, a small amount of Zr is added to NMC811 material via two alternative pathways: during the formation of the transition metal (TM) hydroxide precursor at the co-precipitation step (0.1%-Zr-cp) and during the lithiation at the solid-state synthesis step (0.1%-Zr-ss). In this work, the crystallographic Zr uptake in both 0.1%-Zr-ss and 0.1%-Zr-cp is determined and quantified through synchrotron X-ray diffraction and X-ray absorption spectroscopy. We prove that the inclusion of Zr in the TM site for 0.1%-Zr-cp leads to an improvement of both specific capacity (156 vs 149 mAh/g) and capacity retention (85 vs 82%) upon 100 cycles compared to 0.1%-Zr-ss where the Zr does not diffuse into the active material and forms only an extra phase separated from the NMC811 particles.

The article highlights the dynamic and engaging atmosphere created by Opera Revue, a group revitalizing the Toronto music scene with their unique opera performances in casual settings. Topics include the casual and welcoming ambiance of Opera Revue's performances, the group's founding and key members, and the diverse audience they attract.

Nanopore field-effect transistor (NP-FET) devices hold great promise as sensitive single-molecule sensors, which provide CMOS-based on-chip readout and are also highly amenable to parallelization. A plethora of applications will therefore benefit from NP-FET technology, such as large-scale molecular analysis (e.g., proteomics). Due to its potential for parallelization, the NP-FET looks particularly well-suited for the high-throughput readout of DNA-based barcodes. However, to date, no study exists that unravels the bit-rate capabilities of NP-FET devices. In this paper, we design DNA-based barcodes by labeling a piece of double-stranded DNA with dumbbell-like DNA structures. We explore the impact of both the size of the dumbbells and their spacing on achievable bit-rates. The conformational fluctuations of this DNA-origami, as observed by molecular dynamics (MD) simulation, are accounted for when selecting label sizes. An experimentally informed 3D continuum nanofluidic–nanoelectronic device model subsequently predicts both the ionic current and FET signals. We present a barcode design for a conceptually generic NP-FET, with a 14 nm diameter pore, operating in conditions corresponding to experiments. By adjusting the spacing between the labels to half the length of the pore, we show that a bit-rate of 78 kbit·s–1is achievable. This lies well beyond the state-of-the-art of ≈40 kbit·s–1, with significant headroom for further optimizations. We also highlight the advantages of NP-FET readout based on the larger signal size and sinusoidal signal shape.

ABSTRACTSearch engines match user queries with webpages. Search efficiency, increases when data-driven network effects attract more users and generate economies of scale and scope in data aggregation. Network effects enhance user welfare but also trigger antitrust concerns because they may “tip” the market towards a single dominant search engine – Google Search. The EU Digital Markets Act imposes an obligation on very large gatekeepers search engines to share their user data with smaller search engines to facilitate market entry and competition. The available empirical literature on search engine efficiency shows that asymmetric data sharing, from larger to smaller search engines, may increase competition but reduce user welfare because it fragments the user data pool that is crucial for efficiency, in particular for rare queries. Tension between competition and user welfare can be overcome by symmetric and mutual data sharing between all search engines, irrespective of market share.

Citrusfruits are among the most economically important crops in the world. In the global market, the Citrus peel is often considered a byproduct but substitutes an important phenotypic characteristic of the fruit and a valuable source of essential oils, flavonoids, carotenoids, and phenolic acids with variable concentrations. The Mediterranean basin is a particularly dense area of autochthonous genotypes of Citrusthat are known for being a source of healthy foods, which can be repertoires of valuable genes for molecular breeding with the focus on plant resistance and quality improvement. The scope of this study was to characterize and compare the main phenotypic parameters (i.e., peel thickness, fruit volume, and area) and levels of bioactive compounds in the peel of fruits from the local germplasm of Citrusin Greece, to assess their chemodiversity regarding their polyphenolic, volatile, and carotenoid profiles. A targeted liquid chromatographic approach revealed hesperidin, tangeretin, narirutin, eriocitrin, and quercetin glycosides as the major polyphenolic compounds identified in orange, lemon, and mandarin peels. The content of tangeretin and narirutin followed the tendency mandarin > orange > lemon. Eriocitrin was a predominant metabolite of lemon peel, following its identification in lower amounts in mandarin and at least in the orange peel. For these citrus-specific metabolites, high intra- but also interspecies chemodiversity was monitored. Significant diversity was found in the essential oil content, which varied between 1.2 and 3% in orange, 0.2 and 1.4% in mandarin, and 0.9 and 1.9% in lemon peel. Limonene was the predominant compound in all Citrusspecies peel essential oils, ranging between 88 and 93% among the orange, 64 and 93% in mandarin, and 55 and 63% in lemon cultivars. Carotenoid analysis revealed different compositions among the Citrusspecies and accessions studied, with β-cryptoxanthin being the most predominant metabolite. This large-scale metabolic investigation will enhance the knowledge of Citruspeel secondary metabolite chemodiversity supported by the ample availability of Citrusgenetic resources to further expand their exploitation in future breeding programs and potential applications in the global functional food and pharmaceutical industries.

During World War II, Canadian pilot Robert Leslie Spence and Australian gunner John Wood were shot down over Africa and had to trek over 500 kilometers through the African desert to find safety. They endured extreme heat and limited supplies before reaching British-occupied territory and being rescued by a British advance armoured division. Their story was published in a comic book called "Men against the Desert," which depicted them as heroes and was well-received by readers. Spence and Wood survived the war and lived fulfilling lives. [Extracted from the article]