A molecule containing a nitroamine redox center (2′-amino-4-ethynylphenyl-4′-ethynylphenyl-5′-nitro-1-benzenethiol) was used in the active self-assembled monolayer in an electronic device. ...Current-voltage measurements of the device exhibited negative differential resistance and an on-off peak-to-valley ratio in excess of 1000:1.
Whole-genome sequencing (WGS) is a powerful method for revealing the diversity and complexity of the somatic mutation burden of tumours. Here, we investigated the utility of tumour and matched ...germline WGS for understanding aetiology and treatment opportunities for high-risk individuals with familial breast cancer.
We carried out WGS on 78 paired germline and tumour DNA samples from individuals carrying pathogenic variants in BRCA1 (n=26) or BRCA2 (n=22) or from non-carriers (non-BRCA1/2; n=30).
Matched germline/tumour WGS and somatic mutational signature analysis revealed patients with unreported, dual pathogenic germline variants in cancer risk genes (BRCA1/BRCA2; BRCA1/MUTYH). The strategy identified that 100% of tumours from BRCA1 carriers and 91% of tumours from BRCA2 carriers exhibited biallelic inactivation of the respective gene, together with somatic mutational signatures suggestive of a functional deficiency in homologous recombination. A set of non-BRCA1/2 tumours also had somatic signatures indicative of BRCA-deficiency, including tumours with BRCA1 promoter methylation, and tumours from carriers of a PALB2 pathogenic germline variant and a BRCA2 variant of uncertain significance. A subset of 13 non-BRCA1/2 tumours from early onset cases were BRCA-proficient, yet displayed complex clustered structural rearrangements associated with the amplification of oncogenes and pathogenic germline variants in TP53, ATM and CHEK2.
Our study highlights the role that WGS of matched germline/tumour DNA and the somatic mutational signatures can play in the discovery of pathogenic germline variants and for providing supporting evidence for variant pathogenicity. WGS-derived signatures were more robust than germline status and other genomic predictors of homologous recombination deficiency, thus impacting the selection of platinum-based or PARP inhibitor therapy. In this first examination of non-BRCA1/2 tumours by WGS, we illustrate the considerable heterogeneity of these tumour genomes and highlight that complex genomic rearrangements may drive tumourigenesis in a subset of cases.
The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor ...cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.
The tip asymmetry of a bevel-tip needle results in the needle naturally bending when it is inserted into soft tissue. This enables robotic needle steering, which can be used in medical procedures to ...reach subsurface targets inaccessible by straight-line trajectories. However, accurate path planning and control of needle steering require models of needle-tissue interaction. Previous kinematic models required empirical observations of each needle and tissue combination in order to fit model parameters. This study describes a mechanics-based model of robotic needle steering, which can be used to predict needle behavior and optimize system design based on fundamental mechanical and geometrical properties of the needle and tissue. We first present an analytical model for the loads developed at the tip, based on the geometry of the bevel edge and material properties of soft-tissue simulants (gels). We then present a mechanics-based model that calculates the deflection of a bevel-tipped needle inserted through a soft elastic medium. The model design is guided by microscopic observations of needle-gel interactions. The energy-based formulation incorporates tissue-specific parameters, and the geometry and material properties of the needle. Simulation results follow similar trends (deflection and radius of curvature) to those observed in experimental studies of robotic needle insertion.
Changes in extreme weather, such as tropical cyclones, are one of the most serious ways society experiences the impact of climate change. Advance forecasted conditional attribution statements, using ...a numerical model, were made about the anthropogenic climate change influence on an individual tropical cyclone, Hurricane Florence. Mean total overland rainfall amounts associated with the forecasted storm's core were increased by 4.9 ± 4.6% with local maximum amounts experiencing increases of 3.8 ± 5.7% due to climate change. A slight increase in the forecasted storm size of 1 to 2% was also attributed. This work reviews our forecasted attribution statement with the benefit of hindsight, demonstrating credibility of advance attribution statements for tropical cyclones.
Background
About half of adult irritable bowel syndrome (IBS) patients report symptoms with eating and disordered eating habits. However, little is known about eating in adolescent IBS patients, a ...common age at which eating disorders develop. The aim of the study was to investigate if adolescents with IBS are more likely than healthy controls (HCs) to experience eating‐associated symptoms (EAS), report disordered eating patterns, and show differences in diet composition.
Methods
A total of 99 adolescents between 15 and 21 years‐of‐age participated (n = 48 IBS; n = 51 HCs). All subjects completed three 24‐h dietary recalls and questionnaires on EAS and disordered eating.
Key Results
IBS patients were more likely to report EASs than HC (91.7% vs 28%, p < 0.001). Eating‐associated symptoms were controlled by avoiding the offending food (97.7%), not eating any food even when hungry (43.2%), or vomiting after eating (13.6%). Compared to HC, IBS patients reported reduced daily intake of overall calories (1828 vs 2139; p < 0.05), fat (65.4 g vs 81.4 g, p < 0.05), and lactose (8.2 g vs 12.8 g, p < 0.01). No differences were found between IBS and HC in screening for disordered eating patterns or BMI, though IBS patients endorsed using potentially unhealthy eating behaviors in an attempt to control symptoms.
Conclusions & Inferences
Eating‐associated symptoms are very common in adolescents with IBS and associated with changes in eating behaviors and dietary composition. They do not appear to change BMI and risk for eating disorders. More research is needed to guide adolescents with IBS in making appropriate dietary changes to control EASs.
Adolescence is a common age at which disordered eating patterns develop, but little is known about eating habits in adolescents with IBS. This study found that more than 90% of BS patients age 15–21 reported eating‐associated symptoms and over 40% reported disordered eating patterns such as skipping meals and vomiting to avoid IBS symptoms. IBS patients also ate fewer calories, fat, and lactose than healthy adolescents, but were not at increased risk for disordered eating to lose weight.
We use high-resolution Hydro+N-Body cosmological simulations to compare the assembly and evolution of a small field dwarf (stellar mass ∼106−7 M⊙, total mass 1010 M⊙) in Λ-dominated cold dark matter ...(CDM) and 2 keV warm dark matter (WDM) cosmologies. We find that star formation (SF) in the WDM model is reduced and delayed by 1–2 Gyr relative to the CDM model, independently of the details of SF and feedback. Independent of the dark matter (DM) model, but proportionally to the SF efficiency, gas outflows lower the central mass density through ‘dynamical heating’, such that all realizations have circular velocities <20 km s−1 at 500 pc, in agreement with local kinematic constraints. As a result of dynamical heating, older stars are less centrally concentrated than younger stars, similar to stellar population gradients observed in nearby dwarf galaxies. Introducing an important diagnostic of SF and feedback models, we translate our simulations into artificial colour–magnitude diagrams and star formation histories (SFHs) in order to directly compare to available observations. The simulated galaxies formed most of their stars in many ∼10 Myr long bursts. The CDM galaxy has a global SFH, H i abundance and Fe/H and alpha-elements distribution well matched to current observations of dwarf galaxies. These results highlight the importance of directly including ‘baryon physics’ in simulations when (1) comparing predictions of galaxy formation models with the kinematics and number density of local dwarf galaxies and (2) differentiating between CDM and non-standard models with different DM or power spectra.
Direct ionization from low energy protons is shown to cause upsets in a 65-nm bulk CMOS SRAM, consistent with results reported for other deep submicron technologies. The experimental data are used to ...calibrate a Monte Carlo rate prediction model, which is used to evaluate the importance of this upset mechanism in typical space environments. For the ISS orbit and a geosynchronous (worst day) orbit, direct ionization from protons is a major contributor to the total error rate, but for a geosynchronous (solar min) orbit, the proton flux is too low to cause a significant number of events. The implications of these results for hardness assurance are discussed.
We describe and benchmark a new quantum charge-coupled device (QCCD) trapped-ion quantum computer based on a linear trap with periodic boundary conditions, which resembles a race track. The new ...system successfully incorporates several technologies crucial to future scalability—including electrode broadcasting, multilayer rf routing, and magneto-optical trap (MOT) loading—while maintaining, and in some cases exceeding, the gate fidelities of previous QCCD systems. The system is initially operated with 32 qubits, but future upgrades will allow for more. We benchmark the performance of primitive operations, including an average state preparation and measurement error of 1.6(1)×10^{-3}, an average single-qubit gate infidelity of 2.5(3)×10^{-5}, and an average two-qubit gate infidelity of 1.84(5)×10^{-3}. The system-level performance of the quantum processor is assessed with mirror benchmarking, linear cross-entropy benchmarking, a quantum volume measurement of QV=2^{16}, and the creation of 32-qubit entanglement in a GHZ state. We also tested application benchmarks, including Hamiltonian simulation, QAOA, error correction on a repetition code, and dynamics simulations using qubit reuse. We also discuss future upgrades to the new system aimed at adding more qubits and capabilities.
PDF
