Challenging the Astral mass analyzer to quantify up to 5,300 proteins per single cell at unseen accuracy to uncover cellular heterogeneity.

Despite significant advancements in sample preparation, instrumentation and data analysis, single-cell proteomics is currently limited by proteomic depth and quantitative performance. Here we demonstrate highly improved depth of proteome coverage as well as accuracy and precision for quantification of ultra-low input amounts. Using a tailored library, we identify up to 7,400 protein groups from as little as 250 pg of HeLa cell peptides at a throughput of 50 samples per day.

Low-voltage-tunable electromechanical photonic directional coupler in silicon nitride for telecom wavelengths.

Silicon nitride is a low-loss photonic integrated circuit (PIC) platform. However, silicon nitride also shows small nonlinear optical properties and is dielectric, which makes the implementation of programmability challenging. Typically, the thermo-optic effect is used for this, but modulators based on this effect are often slow and cross talk-limited.

Does adding parent education and workforce training to Head Start promote or interfere with children's development?

This study explores the effects of the two-generation program CareerAdvance-which combines education and training for parents in healthcare with Head Start for children-on children's academic, language, mathematics, and inhibitory control followed for 3 years. The sample (collected in Tulsa, Oklahoma from 2011 to 2018) includes 147 children in the CareerAdvance group and 139 children in a matched comparison group (n = 286; 40% Black, 17%, White, 10% Hispanic, 33% Mixed Race, or Other Race; M = 3.6 years old; 47% female).

K48- and K63-linked ubiquitin chain interactome reveals branch- and length-specific ubiquitin interactors.

The ubiquitin (Ub) code denotes the complex Ub architectures, including Ub chains of different lengths, linkage types, and linkage combinations, which enable ubiquitination to control a wide range of protein fates. Although many linkage-specific interactors have been described, how interactors are able to decode more complex architectures is not fully understood. We conducted a Ub interactor screen, in humans and yeast, using Ub chains of varying lengths, as well as homotypic and heterotypic branched chains of the two most abundant linkage types-lysine 48-linked (K48) and lysine 63-linked (K63) Ub.

EU-LIFE charter of independent life science research institutes.

The diverse range of organizations contributing to the global research ecosystem is believed to enhance the overall quality and resilience of its output. Mid-sized autonomous research institutes, distinct from universities, play a crucial role in this landscape. They often lead the way in new research fields and experimental methods, including those in social and organizational domains, which are vital for driving innovation.

Effects of estrogen on spatial navigation and memory.

Rationale: Animal studies suggest that the so-called "female" hormone estrogen enhances spatial navigation and memory. This contradicts the observation that males generally out-perform females in spatial navigation and tasks involving spatial memory. A closer look at the vast number of studies actually reveals that performance differences are not so clear.

Improving the education and wellbeing of student parents.

Student parents, who make up approximately four million US undergraduates, are highly motivated to succeed in school but often face barriers to educational success due to logistical and financial constraints as well as mental health stressors. This randomized control trial examined the effectiveness of an education program centered in an adult workforce agency that was specifically designed to meet the needs of student parents and their families. Family-centered supportive services included coordinated parent-child schedules and childcare in addition to peer cohorts led by coaches, tuition-free courses, and additional financial assistance.

Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium.

Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo.

Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values.

3DSC - a dataset of superconductors including crystal structures.

Data-driven methods, in particular machine learning, can help to speed up the discovery of new materials by finding hidden patterns in existing data and using them to identify promising candidate materials. In the case of superconductors, the use of data science tools is to date slowed down by a lack of accessible data. In this work, we present a new and publicly available superconductivity dataset ('3DSC'), featuring the critical temperature T of superconducting materials additionally to tested non-superconductors.

Efficient determination of the accessible conformation space of multi-domain complexes based on EPR PELDOR data.

Many proteins can adopt multiple conformations which are important for their function. This is also true for proteins and domains that are covalently linked to each other. One important example is ubiquitin, which can form chains of different conformations depending on which of its lysine side chains is used to form an isopeptide bond with the C-terminus of another ubiquitin molecule.

Time-dependent memory transformation in hippocampus and neocortex is semantic in nature.

Memories undergo a time-dependent neural reorganization, which is assumed to be accompanied by a transformation from detailed to more gist-like memory. However, the nature of this transformation and its underlying neural mechanisms are largely unknown. Here, we report that the time-dependent transformation of memory is semantic in nature, while we find no credible evidence for a perceptual transformation.

Dopamine regulates decision thresholds in human reinforcement learning in males.

Dopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation of response vigour. Here, we examine dopaminergic mechanisms underlying human reinforcement learning and action selection via a combined pharmacological neuroimaging approach in male human volunteers (n = 31, within-subjects; Placebo, 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist Haloperidol). We found little credible evidence for previously reported beneficial effects of L-dopa vs.

Mechanisms of substrate processing during ER-associated protein degradation.

Maintaining proteome integrity is essential for long-term viability of all organisms and is overseen by intrinsic quality control mechanisms. The secretory pathway of eukaryotes poses a challenge for such quality assurance as proteins destined for secretion enter the endoplasmic reticulum (ER) and become spatially segregated from the cytosolic machinery responsible for disposal of aberrant (misfolded or otherwise damaged) or superfluous polypeptides. The elegant solution provided by evolution is ER-membrane-bound ubiquitylation machinery that recognizes misfolded or surplus proteins or by-products of protein biosynthesis in the ER and delivers them to 26S proteasomes for degradation.

Effects of 24-hour oral estradiol-valerate administration on hormone levels in men and pre-menopausal women.

In order to translate the findings from the vast animal literature on the effect of 17β-estradiol (E2) on brain and behavior to humans, a placebo-controlled pharmacological enhancement of E2 levels for at least 24 h is necessary. However, an exogenous increase in E2 for such a prolonged period might affect the endogenous secretion of other (neuroactive) hormones. Such effects would be of relevance for the interpretation of the effects of this pharmacological regimen on cognition and its neural correlates as well as be of basic scientific interest.

Efficient adiabatic-coupler-based silicon nitride waveguide crossings for photonic quantum computing.

Optical integrated quantum computing protocols, in particular using the dual-rail encoding, require that waveguides cross each other to realize, e.g., SWAP or Toffoli gate operations.

Captive-reared Delta Smelt (Hypomesus transpacificus) exhibit high survival in natural conditions using in situ enclosures.

Conservation of endangered fishes commonly includes captive breeding, applied research, and management. Since 1996, a captive breeding program has existed for the federally threatened and California endangered Delta Smelt Hypomesus transpacificus, an osmerid fish endemic to the upper San Francisco Estuary. Although this program serves as a captive refuge population, with experimental releases being initiated to supplement the wild population, it was uncertain how individuals would survive, feed, and maintain condition outside hatchery conditions.

Haloperidol vs. placebo for the treatment of delirium in ICU patients: a pre-planned, secondary Bayesian analysis of the AID-ICU trial.

Purpose: The AID-ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID-ICU trial results.

Methods: We used adjusted Bayesian linear and logistic regression models with weakly informative priors to analyse all primary and secondary outcomes reported up to day 90, and with sensitivity analyses using other priors.

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies.

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles.

Generating human blastoids modeling blastocyst-stage embryos and implantation.

Human early development sets the stage for embryonic and adult life but remains difficult to investigate. A solution came from the ability of stem cells to organize into structures resembling preimplantation embryos-blastocysts-that we termed blastoids. This embryo model is available in unlimited numbers and could thus support scientific and medical advances.

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Incisional and parastomal hernias are frequent complications after abdominal surgery. Patients with relevant symptoms should be referred to the local surgical department for diagnosis and indication for surgery. Patients with giant and parastomal hernias are referred to one of the five Danish regional hernia centres.

Graph neural networks for materials science and chemistry.

Machine learning plays an increasingly important role in many areas of chemistry and materials science, being used to predict materials properties, accelerate simulations, design new structures, and predict synthesis routes of new materials. Graph neural networks (GNNs) are one of the fastest growing classes of machine learning models. They are of particular relevance for chemistry and materials science, as they directly work on a graph or structural representation of molecules and materials and therefore have full access to all relevant information required to characterize materials.

Getting to the Root of Branched Ubiquitin Chains: A Review of Current Methods and Functions.

Nearly 20 years since the first branched ubiquitin (Ub) chains were identified by mass spectrometry, our understanding of these chains and their function is still evolving. This is due to the limitations of classical Ub research techniques in identifying these chains and the vast complexity of potential branched chains. Considering only lysine or N-terminal methionine attachment sites, there are already 28 different possible branch points.