Search

We report calibrated microwave transmission and reflection measurements of a qubit sample holder at millikelvin temperatures. The methodology we present extends our previous work on one-port cryogenic short–open–load (SOL) calibration to a two-port SOLT measurement by implementing an unknown thru (T) standard. We report the resulting calibrated transmission and reflection at millikelvin temperatures through a printed circuit board that is installed into the sample holder. Finally, we consider a cascade of components at the end of a qubit drive line that includes (1) a cryogenic attenuator, (2) a coaxial cable, and (3) a qubit sample holder. Using experimentally determined parameters for return losses for all three components, we calculate the negligible state-preparation error in the frequency band of 5–7 GHz due to control pulse distortions arising from reflection at the coaxial launches. Taken together, our results highlight the utility of calibrated cryogenic scattering parameter measurements for the validation of qubit packaging and the wiring in its immediate vicinity. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is commonly associated with dental caries and the ability to form biofilms is essential for its pathogenicity. We recently identified the Pgf glycosylation machinery of S. mutans, responsible for the post-translational modification of the surface-associated adhesins Cnm and WapA. Since the four-gene pgf operon (pgfS-pgfM1-pgfE-pgfM2) is part of the S. mutans core genome, we hypothesized that the scope of the Pgf system goes beyond Cnm and WapA glycosylation. In silico analyses and tunicamycin sensitivity assays suggested a functional overlap between the Pgf machinery and the rhamnose-glucose polysaccharide synthesis pathway. Phenotypic characterization of pgf mutants (ΔpgfS, ΔpgfE, ΔpgfM1, ΔpgfM2, and Δpgf) revealed that the Pgf system is important for biofilm formation, surface charge, membrane stability, and survival in human saliva. Moreover, deletion of the entire pgf operon (Δpgf strain) resulted in significantly impaired colonization in a rat oral colonization model. Using Cnm as a model, we showed that Cnm is heavily modified with N-acetyl hexosamines but it becomes heavily phosphorylated with the inactivation of the PgfS glycosyltransferase, suggesting a crosstalk between these two post-translational modification mechanisms. Our results revealed that the Pgf machinery contributes to multiple aspects of S. mutans pathobiology that may go beyond Cnm and WapA glycosylation., (© 2023 John Wiley & Sons Ltd.)

A novel cascade reaction initiated by an enantioselective aminocatalysed 1,3-dipolar [6+4] cycloaddition between catalytically generated trienamines and 3-oxidopyridinium betaines is presented. The [6+4] cycloadduct spontaneously undergoes an intramolecular enamine-mediated aldol, hydrolysis, and E1cb sequence, which ultimately affords a chiral hexahydroazulene framework. In this process, three new C-C bonds and three new stereocenters are formed, enabled by a formal unfolding of the pyridine moiety from the dipolar reagent. The hexahydroazulenes are formed with excellent diastereo-, regio- and periselectivity (>20 : 1), up to 96 % ee, and yields up to 52 %. Synthetic elaborations of this scaffold were performed, providing access to a variety of functionalised hydroazulene compounds, of which some were found to display biological activity in U-2OS osteosarcoma cells in cell painting assays., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Diatoms captivate both biologists and engineers with their remarkable mechanical properties and lightweight design principles inherent in their shells. Recent studies have indicated that diatom frustules possess optimized shapes that align with vibrational modes, suggesting an inherent adaptation to vibratory loads. The mode shape adaptation method is known to significantly alter eigenfrequencies of 1D and 2D structures to prevent undesired vibration amplitudes. Leveraging this insight, the diatom-inspired approach to deform structures according to mode shapes was extended to different complex 3D structures, demonstrating a significant enhancement in eigenfrequencies with distinct mode shapes. Through extensive parameter studies, frequency increases exceeding 200% were obtained, showcasing the method's effectiveness. In the second study part, the studied method was integrated into a user-friendly, low-code software facilitating swift and automated structural adjustments for eigenfrequency optimization. The created software tools, encompassing various components, were successfully tested on the example structures demonstrating the versatility and practicality of implementing biomimetic strategies in engineering designs. Thus, the present investigation does not only highlight the noteworthiness of the structural adaptation method inspired by diatoms in maximizing eigenfrequencies, but also originate software tools permitting different users to easily apply the method to distinct structures that have to be optimized, e.g., lightweight structures in the mobility or aerospace industry that are susceptible toward vibrations.

Evidence for the effectiveness of physical activity (PA) in the treatment of depression prevails for outpatients with mild and moderate symptom levels. For inpatient treatment of severe depression, evidence-based effectiveness exists only for structured and supervised group PA interventions. The Step Away from Depression (SAD) study investigated the effectiveness of an individual pedometer intervention (PI) combined with an activity diary added to inpatient treatment as usual (TAU). In this multicenter randomized controlled trial, 192 patients were randomized to TAU or TAU plus PI. The two primary outcomes at discharge were depression-blindly rated with the Montgomery-Åsberg Depression Rating Scale (MADRS)-and average number of daily steps measured by accelerometers. Secondary outcomes were self-rated depression and PA, anxiety, remission and response rates. Multivariate analysis of variance (MANOVA) revealed no significant difference between both groups for depression and daily steps. Mean MADRS scores at baseline were 29.5 (SD = 8.3) for PI + TAU and 28.8 (SD = 8.1) for TAU and 16.4 (SD = 10.3) and 17.2 (SD = 9.9) at discharge, respectively. Daily steps rose from 6285 (SD = 2321) for PI + TAU and 6182 (SD = 2290) for TAU to 7248 (SD = 2939) and 7325 (SD = 3357). No differences emerged between groups in secondary outcomes. For severely depressed inpatients, a PI without supervision or further psychological interventions is not effective. Monitoring, social reinforcement and motivational strategies should be incorporated in PA interventions for this population to reach effectiveness., (© 2023. The Author(s).)

Diatoms have delicate and complex shells showing different lightweight design principles that have already been applied to technical products improving the mechanical properties. In addition, diatom inspired structures are expected to significantly affect the vibration characteristics, i.e., the eigenfrequencies. Directed eigenfrequency shifts are of great interest for many technical applications to prevent undesired high vibration amplitudes. Therefore, numerous complex diatom inspired dome structures primarily based on combs, ribs, and bulging patterns were constructed and their eigenfrequencies were numerically studied. Different structural patterns were identified to significantly affect eigenfrequencies. The results were compared to dome structures equipped with rib patterns in combination with a common structural optimization tool. The study indicates that a combination of (1) selecting diatom inspired structural patterns that strongly affect eigenfrequencies, and (2) adapting them to the boundary conditions of the technical problem is an efficient method to design diatom inspired lightweight solutions with high eigenfrequencies.

Cells in living organisms are dynamic compartments that continuously respond to changes in their environment to maintain physiological homeostasis. While basal autophagy exists in cells to aid in the regular turnover of intracellular material, autophagy is also a critical cellular response to stress, such as nutritional depletion. Conversely, the deregulation of autophagy is linked to several diseases, such as cancer, and hence, autophagy constitutes a potential therapeutic target. Image analysis to follow autophagy in cells, especially on high-content screens, has proven to be a bottleneck. Machine learning (ML) algorithms have recently emerged as crucial in analyzing images to efficiently extract information, thus contributing to a better understanding of the questions at hand. This paper presents CELLULAR, an open dataset consisting of images of cells expressing the autophagy reporter mRFP-EGFP-Atg8a with cell-specific segmentation masks. Each cell is annotated into either basal autophagy, activated autophagy, or unknown. Furthermore, we introduce some preliminary experiments using the dataset that can be used as a baseline for future research., (© 2023. The Author(s).)

Background: This article is based on a study analysing survivors' testimonies (n = 870) about child sexual abuse (CSA) within the family. The context of the study is the Independent Inquiry into Child Sexual Abuse in Germany (IICSA). The Inquiry's work is based on the concept of witnessing and supporting mainly survivors of CSA to share their stories. Since 2016 the Inquiry has collected more than 2000 written and oral reports., Objective: The article explores the challenges of working through and coming to terms with past and present aspects of child sexual abuse (CSA) in the private space of the family. The main focus here is on findings from the statistical analysis on perpetrators and bystanders., Participants and Setting: The study involved an evaluation of 870 reports by survivors and third parties., Methods: Descriptive analysis was carried out on mentions of perpetrators, strategies of perpretators, climate in the family, bystanders in the family., Results: Significantly more female than male survivors have contacted the Inquiry. The youngest people who approached the Inquiry were adolescents and young adults between 16 and 21 years of age. The oldest people were between 76 and 80 years old (for reasons of secure pseudonymisation, spans of five years are given). The results pointed to insights about male and female perpetrators and the situation of the affected children in the family. In 47 % of the mentions of perpetrators, fathers and stepfathers were named, in 9 % it was the mother or stepmother, and in 11 % biological siblings were named. There is a proportion of cases in which more than one perpetrator is mentioned., Conclusions: One aim was to identify common characteristics in the actions of perpetrators within families as well as insights into the structures in families that promote child sexual abuse. The discussion shed light on the importance of the third party and the possibilities for the perpetrators to shape the environment of the family as a whole. Witnessing by survivors is an important epistemological, ethical, and political instrument for creating knowledge., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Streptococcus mutans is a key pathogen associated with dental caries and is often implicated in infective endocarditis. This organism forms robust biofilms on tooth surfaces and can use collagen-binding proteins (CBPs) to efficiently colonize collagenous substrates, including dentin and heart valves. One of the best characterized CBPs of S. mutans is Cnm, which contributes to adhesion and invasion of oral epithelial and heart endothelial cells. These virulence properties were subsequently linked to post-translational modification (PTM) of the Cnm threonine-rich repeat region by the Pgf glycosylation machinery, which consists of 4 enzymes: PgfS, PgfM1, PgfE, and PgfM2. Inactivation of the S. mutans pgf genes leads to decreased collagen binding, reduced invasion of human coronary artery endothelial cells, and attenuated virulence in the Galleria mellonella invertebrate model. The present study aimed to better understand Cnm glycosylation and characterize the predicted 4-epimerase, PgfE. Using a truncated Cnm variant containing only 2 threonine-rich repeats, mass spectrometric analysis revealed extensive glycosylation with HexNAc2. Compositional analysis, complemented with lectin blotting, identified the HexNAc2 moieties as GlcNAc and GalNAc. Comparison of PgfE with the other S. mutans 4-epimerase GalE through structural modeling, nuclear magnetic resonance, and capillary electrophoresis demonstrated that GalE is a UDP-Glc-4-epimerase, while PgfE is a GlcNAc-4-epimerase. While PgfE exclusively participates in protein O-glycosylation, we found that GalE affects galactose metabolism and cell division. This study further emphasizes the importance of O-linked protein glycosylation and carbohydrate metabolism in S. mutans and identifies the PTM modifications of the key CBP, Cnm., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Blinding is challenging in randomised controlled trials of physical, psychological, and self-management therapies for pain, mainly because of their complex and participatory nature. To develop standards for the design, implementation, and reporting of control interventions in efficacy and mechanistic trials, a systematic overview of currently used sham interventions and other blinding methods was required. Twelve databases were searched for placebo or sham-controlled randomised clinical trials of physical, psychological, and self-management treatments in a clinical pain population. Screening and data extraction were performed in duplicate, and trial features, description of control methods, and their similarity to the active intervention under investigation were extracted (protocol registration ID: CRD42020206590). The review included 198 unique control interventions, published between 2008 and December 2021. Most trials studied people with chronic pain, and more than half were manual therapy trials. The described control interventions ranged from clearly modelled based on the active treatment to largely dissimilar control interventions. Similarity between control and active interventions was more frequent for certain aspects (eg, duration and frequency of treatments) than others (eg, physical treatment procedures and patient sensory experiences). We also provide an overview of additional, potentially useful methods to enhance blinding, as well as the reporting of processes involved in developing control interventions. A comprehensive picture of prevalent blinding methods is provided, including a detailed assessment of the resemblance between active and control interventions. These findings can inform future developments of control interventions in efficacy and mechanistic trials and best-practice recommendations., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: A triple storage (TS) set allows for pathogen inactivation (PI) treatment of triple-dose apheresis platelet products with amotosalen + UVA. We evaluated the quality and metabolic parameters of platelet concentrates (PCs) pathogen inactivated and stored for 7 days., Materials and Methods: Twelve triple-dose products collected with two different apheresis platforms were treated with amotosalen+UVA. Products were split into three single-dose units. Testing was made pretreatment, after splitting, at days 5 and 7 of storage., Results: Single-dose PI PCs had a mean platelet content of 2.89 ± 0.35 x 10 11 . From baseline to day 7, pH remained stable (7.1 ± 0.1 vs. 7.0 ± 0.1), pO 2 increased (11.3 ± 2.4 vs. 18.3 ± 3.5 kPa) as did LDH (201 ± 119 vs. 324 ± 203 U/L) and lactate (3.6 ± 1.7 vs. 12.1 ± 1.5 mmol/L) (all p < 0.01); pCO 2 decreased (4.1 ± 0.8 vs. 1.5 ± 0.7 mmHg; p < 0.01) and so did bicarbonate (6.6 ± 1.1 vs. 2.5 ± 1.4 mmol/L), glucose (5.6 ± 1.2 vs. 0.4 ± 0.4 mmol/L) and ATP (3.4 ± 0.9 vs. 2.5 ± 1.4 nmol/10 8 platelets) (all p < 0.05)., Conclusion: Triple-dose PCs processed with the TS sets fulfilled the quality requirements and displayed metabolic changes of expected extent during 7-day storage., (© 2022 The Authors. Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

Machine learning is increasingly introduced into medical fields, yet there is limited evidence for its benefit over more commonly used statistical methods in epidemiological studies. We introduce an unsupervised machine learning framework for longitudinal features and evaluate it using sexual behaviour data from the last 20 years from over 3'700 participants in the Swiss HIV Cohort Study (SHCS). We use hierarchical clustering to find subgroups of men who have sex with men in the SHCS with similar sexual behaviour up to May 2017, and apply regression to test whether these clusters enhance predictions of sexual behaviour or sexually transmitted diseases (STIs) after May 2017 beyond what can be predicted with conventional parameters. We find that behavioural clusters enhance model performance according to likelihood ratio test, Akaike information criterion and area under the receiver operator characteristic curve for all outcomes studied, and according to Bayesian information criterion for five out of ten outcomes, with particularly good performance for predicting future sexual behaviour and recurrent STIs. We thus assess a methodology that can be used as an alternative means for creating exposure categories from longitudinal data in epidemiological models, and can contribute to the understanding of time-varying risk factors., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DLB reports honoraria and travel grants outside of the submitted work from Gilead, ViiV and Merck. HFG, outside of this study, reports grants from Swiss HIV Cohort Study, grants from Swiss National Science Foundation, during the conduct of the study; grants from Swiss HIV Cohort Study, grants from Swiss National Science Foundation, grants from NIH, grants from Gilead unrestricted research grant, personal fees from Advisor/consultant for Merck, ViiV healthcare and Gilead sciences and member of DSMB for Merck, grants from Yvonne Jacob Foundation. KEAD’s institution has received research funding unrelated to this publication from Gilead and sponsorship to specialist meetings from MSD. AR reports fees for sitting on advisory boards from Merck Sharp & Dohme and Gilead Sciences; travel grants from Gilead Sciences, Pfizer, and AbbVie; and a research grant from Gilead Sciences, outside of the submitted work. All fees were paid to AR’s institution and not to AR personally., (Copyright: © 2022 Andresen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The regulated uptake and consumption of d-amino acids by bacteria remain largely unexplored, despite the physiological importance of these compounds. Unlike other characterized bacteria, such as Escherichia coli, which utilizes only l-Asp, Acinetobacter baylyi ADP1 can consume both d-Asp and l-Asp as the sole carbon or nitrogen source. As described here, two LysR-type transcriptional regulators (LTTRs), DarR and AalR, control d- and l-Asp metabolism in strain ADP1. Heterologous expression of A. baylyi proteins enabled E. coli to use d-Asp as the carbon source when either of two transporters (AspT or AspY) and a racemase (RacD) were coexpressed. A third transporter, designated AspS, was also discovered to transport Asp in ADP1. DarR and/or AalR controlled the transcription of aspT , aspY , racD , and aspA (which encodes aspartate ammonia lyase). Conserved residues in the N-terminal DNA-binding domains of both regulators likely enable them to recognize the same DNA consensus sequence (ATGC-N 7 -GCAT) in several operator-promoter regions. In strains lacking AalR, suppressor mutations revealed a role for the ClpAP protease in Asp metabolism. In the absence of the ClpA component of this protease, DarR can compensate for the loss of AalR. ADP1 consumed l- and d-Asn and l-Glu, but not d-Glu, as the sole carbon or nitrogen source using interrelated pathways. IMPORTANCE A regulatory scheme was revealed in which AalR responds to l-Asp and DarR responds to d-Asp, a molecule with critical signaling functions in many organisms. The RacD-mediated interconversion of these isomers causes overlap in transcriptional control in A. baylyi. Our studies improve understanding of transport and regulation and lay the foundation for determining how regulators distinguish l- and d-enantiomers. These studies are relevant for biotechnology applications, and they highlight the importance of d-amino acids as natural bacterial growth substrates.

Background: A year has passed since COVID-19 began disrupting systems. Although children are not considered a risk population for the virus, there is accumulating knowledge regarding children's escalating risk for maltreatment during the pandemic., Objective: The current study is part of a larger initiative using an international platform to examine child maltreatment (CM) reports and child protective service (CPS) responses in various countries. The first data collection, which included a comparison between eight countries after the pandemic's first wave (March-June 2020), illustrated a worrisome picture regarding children's wellbeing. The current study presents the second wave of data across 12 regions via population data (Australia [New South Wales], Brazil, United States [California, Pennsylvania], Colombia, England, Germany, Israel, Japan, Canada [Ontario, Quebec], South Africa)., Method: Regional information was gathered, including demographics, economic situation, and CPS responses to COVID-19. A descriptive analysis was conducted to provide an overview of the phenomenon., Results: Across all of the countries, COVID-19 had a substantial negative impact on the operation of CPSs and the children and families they serve by disrupting in-person services. One year into the COVID-19 pandemic, new reports of CM varied across the regions. 1 In some, the impact of COVID-19 on CPS was low to moderate, while in others, more significant changes created multiple challenges for CPS services., Conclusions: COVID-19 created a barrier for CPS to access and protect children. The dramatic variance between the regions demonstrated how social, economic and structural contexts impact both CM reports and CPS responses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cryoprecipitate is a plasma-derived blood product, enriched for fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Due to infectious risk, the use of cryoprecipitate in Central Europe diminished over the last decades. However, after the introduction of various pathogen-reduction technologies for plasma, cryoprecipitate production in blood centers is a feasible alternative to pharmaceutical fibrinogen concentrate with a high safety profile. In our study, we evaluated the feasibility of the production of twenty-four cryoprecipitate units from pools of two units of apheresis plasma pathogen reduced using amotosalen and ultraviolet light A (UVA) (INTERCEPT ® Blood System). The aim was to assess the compliance of the pathogen-reduced cryoprecipitate with the European Directorate for the Quality of Medicines (EDQM) guidelines and the stability of coagulation factors after frozen (≤-25 °C) storage and five-day liquid storage at ambient temperature post-thawing. All pathogen-reduced cryoprecipitate units fulfilled the European requirements for fibrinogen, factor VIII and von Willebrand factor content post-preparation. After five days of liquid storage, content of these factors exceeded the minimum values in the European requirements and the content of other factors was sufficient. Our method of production of cryoprecipitate using pathogen-reduced apheresis plasma in a jumbo bag is feasible and efficient.

Human intelectin-1 (hIntL-1) is a secreted glycoprotein capable of binding exocyclic 1,2-diols within surface glycans of human pathogens such as Streptococcus pneumoniae, Vibrio cholerae, and Helicobacter pylori. For the latter, lectin binding was shown to cause bacterial agglutination and increased phagocytosis, suggesting a role for hIntL-1 in pathogen surveillance. In this study, we investigated the interactions between hIntL-1 and S. pneumoniae, the leading cause of bacterial pneumonia. We show that hIntL-1 also agglutinates S. pneumoniae serotype 43, which displays an exocyclic 1,2-diol moiety in its capsular polysaccharide but is unable to kill in a complement-dependent manner or to promote bacterial killing by peripheral blood mononuclear cells. In contrast, hIntL-1 not only significantly increases serotype-specific S. pneumoniae killing by neutrophils but also enhances the attachment of these bacteria to A549 lung epithelial cells. Taken together, our results suggest that hIntL-1 participates in host surveillance through microbe sequestration and enhanced targeting to neutrophils.