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Abstract Precision of scanning tunneling microscopy (STM) enables control of matter at scales of single atoms. However, transition from atomic-scale manipulation strategies to practical devices encounters fundamental problems in protection of the designer structures formed atop the surface. In this context, STM manipulation of subsurface structures on technologically relevant materials is encouraging. Here, we propose a material platform and protocols for precise manipulation of a buried graphene interface. We show that an electric field from the STM tip reversibly controls breaking and restoring of covalent bonds between the graphene buffer layer and the SiC substrate. The process involves charge redistribution at the atomically sharp interface plane under the epitaxial graphene layer(s). This buried manipulation platform is laterally defined by unit cells from the corresponding (6×6)SiC moiré lattice of the epitaxial graphene. Local and reversible electric-field-induced patterning of graphene heterostructures from the bottom interface creates an alternative architecture concept for their applications.

Primary follicular lymphoma of the prostate is rare. This case report and literature review literature describes a 74-year old male patient who presented with worsening urinary symptoms, and imaging showing prostatomegaly compressing and displacing the rectum. He ultimately underwent a Millen retropubic prostatectomy for a prostate of 692 cc. The histology and immunohistochemistry confirmed the diagnosis as follicular lymphoma. His lymphoma underwent high-grade transformation with leptomeningeal involvement.

IDH-wild type (wt) glioblastoma (GB) accounts for approximately 90% of all GB and has a poor outcome. Surgery and adjuvant therapy with temozolomide and radiotherapy is the main therapeutic approach. Unfortunately, after relapse and progression, which occurs in most cases, there are very limited therapeutic options available. BRAF which plays a role in the oncogenesis of several malignant tumors, is also involved in a small proportion of IDH-wt GB. Previous successes with anti-B-Raf targeted therapy in tumors with V600E BRAF mutation like melanoma, combined with the poor prognosis and paucity of therapeutic options for GB patients is leading to a growing interest in the potential efficacy of this approach. This review is thus focused on dissecting the state of the art and future perspectives on BRAF pathway inhibition in IDH-wt GB. Overall, clinical efficacy is mostly described within case reports and umbrella trials, with promising but still insufficient results to draw more definitive conclusions. Further studies are needed to better define the molecular and phenotypic features that predict for a favorable response to treatment. In addition, limitations of B-Raf-inhibitors, in monotherapy or in combination with other therapeutic partners, to penetrate the blood-brain barrier and the development of acquired resistance mechanisms responsible for tumor progression need to be addressed.

Wild blueberries in Maine, USA are facing threats from our changing climate. While summer climate variations have been affecting this important commercial crop directly, significant climate variations in other seasons also can be potentially detrimental to blueberry production. Therefore, we analyzed annual and seasonal climate trends (temperature, rainfall, snow cover) over the past 41 years (1980–2020) for seven Maine counties (Piscataquis, Washington, Hancock, Knox, Lincoln, Kennebec, York) with large wild blueberry areas. We found that, across all blueberry production fields (or “barrens”), historical temperatures increased significantly (p < 0.05) in the fall and winter followed by summer, but not in the spring. Additionally, precipitation increased slightly (0.5–1.2 mm/year) in the winter and fall, whereas no changes were found in the spring and summer. Furthermore, we found that historical temperatures were lower in Piscataquis (north-central) and Washington (north-east) counties, whereas in south-western counties (Hancock to York) experienced a relatively warmer climate. The rate of increasing temperature was comparatively slower in the warmer barrens located towards the south-west (Hancock to York). Moreover, the growing season lengthened towards the fall season consistently in all locations, whereas lengthening towards the spring was inconsistent. These findings inform the wild blueberry growers in different locations of Maine about the seasonal shifts occurring for their crop. This knowledge may assist with land management planning in order for the growers to prepare for future impacts.

This literature review covers the solubility and processability of fluoropolymer polyvinylidine fluoride (PVDF). Fluoropolymers consist of a carbon backbone chain with multiple connected C–F bonds; they are typically nonreactive and nontoxic and have good thermal stability. Their processing, recycling and reuse are rapidly becoming more important to the circular economy as fluoropolymers find widespread application in diverse sectors including construction, automotive engineering and electronics. The partially fluorinated polymer PVDF is in strong demand in all of these areas; in addition to its desirable inertness, which is typical of most fluoropolymers, it also has a high dielectric constant and can be ferroelectric in some of its crystal phases. However, processing and reusing PVDF is a challenging task, and this is partly due to its limited solubility. This review begins with a discussion on the useful properties and applications of PVDF, followed by a discussion on the known solvents and diluents of PVDF and how it can be formed into membranes. Finally, we explore the limitations of PVDF’s chemical and thermal stability, with a discussion on conditions under which it can degrade. Our aim is to provide a condensed overview that will be of use to both chemists and engineers who need to work with PVDF.

Much of the pathogenic success of Phytophthora infestans, the potato and tomato late blight agent, relies on its ability to generate from mycelia large amounts of sporangia, which release zoospores that encyst and form infection structures. To better understand these stages, Affymetrix GeneChips based on 15,650 unigenes were designed and used to profile the life cycle. Approximately half of P. infestans genes were found to exhibit significant differential expression between developmental transitions, with approximately 1/10 being stage-specific and most changes occurring during zoosporogenesis. Quantitative reverse-transcription polymerase chain reaction assays confirmed the robustness of the array results and showed that similar patterns of differential expression were obtained regardless of whether hyphae were from laboratory media or infected tomato. Differentially expressed genes encode potential cellular regulators, especially protein kinases; metabolic enzymes such as those involved in glycolysis, gluconeogenesis, or the biosynthesis of amino acids or lipids; regulators of DNA synthesis; structural proteins, including predicted flagellar proteins; and pathogenicity factors, including cell-wall-degrading enzymes, RXLR effector proteins, and enzymes protecting against plant defense responses. Curiously, some stage-specific transcripts do not appear to encode functional proteins. These findings reveal many new aspects of oomycete biology, as well as potential targets for crop protection chemicals.

To overview the gene content of the important pathogen Phytophthora infestans, large-scale cDNA and genomic sequencing was performed. A set of 75,757 high-quality expressed sequence tags (ESTs) from P. infestans was obtained from 20 cDNA libraries representing a broad range of growth conditions, stress responses, and developmental stages. These included libraries from P. infestans-potato and -tomato interactions, from which 963 pathogen ESTs were identified. To complement the ESTs, onefold coveragethe P. infestans genome was obtained and regions of coding potential identified. A unigene set of 18,256 sequences was derived from the EST and genomic data and characterized for potential functions, stage-specific patterns of expression, and codon bias. Cluster analysis of ESTs revealed major differences between the expressed gene content of mycelial and spore-related stages, and affinities between some growth conditions. Comparisons with databases of fungal pathogenicity genes revealed conserved elements of pathogenicity, such as class III pectate lyases, despite the considerable evolutionary distance between oomycetes and fungi. Thirty-seven genes encoding components of flagella also were identified. Several genes not anticipated to occur in oomycetes were detected, including chitin synthases, phosphagen kinases, and a bacterial-type FtsZ cell-division protein. The sequence data described are available in a searchable public database.

Abstract Observed links between parasites, such as ticks, and climate change have aroused concern for human health, wildlife population dynamics, and broader ecosystem effects. The one‐host life history of the winter tick (Dermacentor albipictus) links each annual cohort to environmental conditions during three specific time periods when they are predictably vulnerable: spring detachment from hosts, summer larval stage, and fall questing for hosts. We used mixed‐effects generalized linear models to investigate the drivers of tick loads carried by moose (Alces alces) relative to these time periods and across 750 moose, 10 years, and 16 study areas in the western United States. We tested for the effects of biotic factors (moose density, shared winter range, vegetation, migratory behavior) and weather conditions (temperature, snow, humidity) during each seasonal period when ticks are vulnerable and off‐host. We found that warm climatic regions, warm seasonal periods across multiple partitions of the annual tick life cycle, and warm years relative to long‐term averages each contributed to increased tick loads. We also found important effects of snow and other biotic factors such as host density and vegetation. Tick loads in the western United States were, on average, lower than those where tick‐related die‐offs in moose populations have occurred recently, but loads carried by some individuals may be sufficient to cause mortality. Lastly, we found interannual variation in tick loads to be most correlated with spring snowpack, suggesting this environmental component may have the highest potential to induce change in tick load dynamics in the immediate future of this region.

Abstract Background Optical coherence tomography (OCT) is an intravascular imaging modality for analysing coronary vessels. Image interpretation remains an obstacle for novice readers due to technical artefacts and uncertainty in tissue characterization. Despite an expanding clinical and research role for OCT, few training efforts exist, and there is an absence of a national standardized educational curriculum. We sought to determine whether an interactive, feedback-based OCT curriculum improved image interpretation among naive readers. Methods Naive OCT readers completed both a Standard curriculum, comprised of self-directed didactics and consensus statements, and an Augmented curriculum, which provided real-time digital feedback of feature identification and measurements. Modules were separated by a minimum one-week washout period. After each module, and blinded to the exam answers, subjects completed an identical expert-designed 413-item exam to assess technical knowledge and ability to identify and measure vessel features. Performances were compared using Exact Wilcoxon signed-rank tests. Results Among the 7 included subjects were 3 medical students, 3 internal medicine residents, and 1 cardiovascular medicine fellow with no prior OCT experience. The technical knowledge score (maximum 13) was significantly higher with the Augmented compared with the Standard curriculum (median 11 vs. 7, p = 0.03). After undergoing the Augmented curriculum, all 7 subjects were able to identify features of plaque rupture (Standard curriculum: 5/7 subjects, p = 0.5) and macrophages (Standard curriculum: 6/7 subjects, p = 0.99), differentiate the components between red and white thrombus (Standard curriculum: 6/7 subjects, p = 0.99), and characterize lipid plaque by attenuation, signal, homogeneity, and borders (Standard curriculum: 5/7 subjects, p = 0.5). Performances on the remaining exam portions did not differ between curricula. Conclusions The need for standardized, effective training in OCT image interpretation is increasingly essential as the intravascular imaging modality becomes widely utilized among interventional cardiologists and trainees. A novel interactive OCT curriculum enhanced naive readers’ technical knowledge and may supplement traditional self-learning in refining analytic skills.

A variety of genetic mutations affect cell proliferation during organism development, leading to structural birth defects. However, the mechanisms by which these alterations influence the development of the face remain unclear. Cell proliferation and its relation to shape variation can be studied using Light-Sheet Microscopy (LSM) imaging across a range of developmental time points using mouse models. The aim of this work was to develop and evaluate accurate automatic methods based on convolutional neural networks (CNNs) for: (i) tissue segmentation (neural ectoderm and mesenchyme), (ii) cell segmentation in nuclear-stained images, and (iii) segmentation of proliferating cells in phospho-Histone H3 (pHH3)-stained LSM images of mouse embryos. For training and evaluation of the CNN models, 155 to 176 slices from 10 mouse embryo LSM images with corresponding manual segmentations were available depending on the segmentation task. Three U-net CNN models were trained optimizing their loss functions, among other hyper-parameters, depending on the segmentation task. The tissue segmentation achieved a macro-average F-score of 0.84, whereas the inter-observer value was 0.89. The cell segmentation achieved a Dice score of 0.57 and 0.56 for nuclear-stained and pHH3-stained images, respectively, whereas the corresponding inter-observer Dice scores were 0.39 and 0.45, respectively. The proposed pipeline using the U-net CNN architecture can accelerate LSM image analysis and together with the annotated datasets can serve as a reference for comparison of more advanced LSM image segmentation methods in future.

This study explored longitudinal changes in contemporary mixed martial arts (MMA) combat within the Ultimate Fighting Championship (UFC). A secondary aim was to investigate how bout duration influences the contribution of performance indicators on outcome. Data were acquired via the official analytics provider to the UFC (FightMetric). Male fights with a winner from between 2000 and 2015 (n = 2,831) were examined, with 13 common performance indicators attained during each round for each participant along with duration (min) and year of fight. Non-metric dimensional scaling (nMDS) was used to examine bout characteristics by year. The Repeated Incremental Pruning to Produce Error Reduction (RIPPER) algorithm was run to determine a set of rules to explain bout outcome. The nMDS displayed that winning bout performance indicator attributes were dissimilar across the years. Eight rules were generated from the RIPPER, with fight duration featuring in three of eight rules. Distinct shifts occurred (albeit without linear trend) in performance indicator characteristics during the observed period. This was characterized by a more diverse combat style in the years following 2008. However, offensive grappling has remained a key factor regardless of year, and is influenced by bout duration.