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Novels in verse are a staple for young readers who often have not yet absorbed many adults' negative associations with poetry as something obscure, difficult, and intimidating. In fact, verse [...]

This article describes an on-line condition monitoring system for a countrywide distribution network together with the reasons for adopting it, its architecture, the measurement approach, and the case studies obtained during the early stages of its adoption.

Humans are capable of generating extraordinarily diverse articulatory movement combinations to produce meaningful speech. This ability to orchestrate specific phonetic sequences, and their syllabification and inflection over subsecond timescales allows us to produce thousands of word sounds and is a core component of language1,2. The fundamental cellular units and constructs by which we plan and produce words during speech, however, remain largely unknown. Here, using acute ultrahigh-density Neuropixels recordings capable of sampling across the cortical column in humans, we discover neurons in the language-dominant prefrontal cortex that encoded detailed information about the phonetic arrangement and composition of planned words during the production of natural speech. These neurons represented the specific order and structure of articulatory events before utterance and reflected the segmentation of phonetic sequences into distinct syllables. They also accurately predicted the phonetic, syllabic and morphological components of upcoming words and showed a temporally ordered dynamic. Collectively, we show how these mixtures of cells are broadly organized along the cortical column and how their activity patterns transition from articulation planning to production. We also demonstrate how these cells reliably track the detailed composition of consonant and vowel sounds during perception and how they distinguish processes specifically related to speaking from those related to listening. Together, these findings reveal a remarkably structured organization and encoding cascade of phonetic representations by prefrontal neurons in humans and demonstrate a cellular process that can support the production of speech.

Abstract.Positive orientation (PO) is a basic predisposition that consists in a positive outlook toward oneself, one’s life, and one’s future, which is associated to many desirable outcomes connected to health and to the general quality of life. We performed a lexical study for identifying a set of markers of PO, developed an Implicit Association Test (the PO-IAT), and investigated its psychometric properties. The PO-IAT proved to be a reliable measure with a clear pattern of convergent validity, both with respect to self-report scales connected to PO and with respect to an indirect measure of self-esteem. A secondary aim of our studies was to validate a new brief adjective scale to assess PO, the POAS. Our results show that both the PO-IAT and the self-reported PO predict the frequency of depressive symptoms and of self-perceived intelligence.

From sequences of speech sounds1,2or letters3, humans can extract rich and nuanced meaning through language. This capacity is essential for human communication. Yet, despite a growing understanding of the brain areas that support linguistic and semantic processing4–12, the derivation of linguistic meaning in neural tissue at the cellular level and over the timescale of action potentials remains largely unknown. Here we recorded from single cells in the left language-dominant prefrontal cortex as participants listened to semantically diverse sentences and naturalistic stories. By tracking their activities during natural speech processing, we discover a fine-scale cortical representation of semantic information by individual neurons. These neurons responded selectively to specific word meanings and reliably distinguished words from nonwords. Moreover, rather than responding to the words as fixed memory representations, their activities were highly dynamic, reflecting the words’ meanings based on their specific sentence contexts and independent of their phonetic form. Collectively, we show how these cell ensembles accurately predicted the broad semantic categories of the words as they were heard in real time during speech and how they tracked the sentences in which they appeared. We also show how they encoded the hierarchical structure of these meaning representations and how these representations mapped onto the cell population. Together, these findings reveal a finely detailed cortical organization of semantic representations at the neuron scale in humans and begin to illuminate the cellular-level processing of meaning during language comprehension.

Iron is important in regulating the ocean carbon cycle1. Although several dissolved and particulate species participate in oceanic iron cycling, current understanding emphasizes the importance of complexation by organic ligands in stabilizing oceanic dissolved iron concentrations2–6. However, it is difficult to reconcile this view of ligands as a primary control on dissolved iron cycling with the observed size partitioning of dissolved iron species, inefficient dissolved iron regeneration at depth or the potential importance of authigenic iron phases in particulate iron observational datasets7–12. Here we present a new dissolved iron, ligand and particulate iron seasonal dataset from the Bermuda Atlantic Time-series Study (BATS) region. We find that upper-ocean dissolved iron dynamics were decoupled from those of ligands, which necessitates a process by which dissolved iron escapes ligand stabilization to generate a reservoir of authigenic iron particles that settle to depth. When this ‘colloidal shunt’ mechanism was implemented in a global-scale biogeochemical model, it reproduced both seasonal iron-cycle dynamics observations and independent global datasets when previous models failed13–15. Overall, we argue that the turnover of authigenic particulate iron phases must be considered alongside biological activity and ligands in controlling ocean-dissolved iron distributions and the coupling between dissolved and particulate iron pools.

Bupropion is an atypical antidepressant agent approved for treating major depressive disorders and prescribed for smoking cessation, attention deficit hyperactive disorder (ADHD), and sexual dysfunction. In a few cases, bupropion was associated with myoclonus. We present a case of a 58-year-old male, a heavy smoker seeking smoking cessation, was prescribed bupropion 150 mg twice daily. The subject doubled the dosage without medical advice. After 3 days of the increased dosage, he started to experience abnormal movements in his upper limbs associated with diffuse facial twitching. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Bupropion was discontinued, and clonazepam was initiated. The subject fully recovered within 24 hours. To the authors’ knowledge, only 8 cases of bupropion-induced myoclonus were reported in the literature. Bupropion discontinuation was the most common management. All individuals except 2 cases fully recovered after bupropion withdrawal. The mechanism of bupropion is probably associated with the serotoninergic pathway.

Neuropixels are silicon-based electrophysiology-recording probes with high channel count and recording-site density. These probes offer a turnkey platform for measuring neural activity with single-cell resolution and at a scale that is beyond the capabilities of current clinically approved devices. Our team demonstrated the first-in-human use of these probes during resection surgery for epilepsy or tumors and deep brain stimulation electrode placement in patients with Parkinson’s disease. Here, we provide a better understanding of the capabilities and challenges of using Neuropixels as a research tool to study human neurophysiology, with the hope that this information may inform future efforts toward regulatory approval of Neuropixels probes as research devices. In perioperative procedures, the major concerns are the initial sterility of the device, maintaining a sterile field during surgery, having multiple referencing and grounding schemes available to de-noise recordings (if necessary), protecting the silicon probe from accidental contact before insertion and obtaining high-quality action potential and local field potential recordings. The research team ensures that the device is fully operational while coordinating with the surgical team to remove sources of electrical noise that could otherwise substantially affect the signals recorded by the sensitive hardware. Prior preparation using the equipment and training in human clinical research and working in operating rooms maximize effective communication within and between the teams, ensuring high recording quality and minimizing the time added to the surgery. The perioperative procedure requires ~4 h, and the entire protocol requires multiple weeks.

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Robust optimisation is a well-established concept to deal with uncertainty. In particular, recovery-robust models are suitable for real-world contexts, where a certain amount of recovery--although limited--is often available. In this [...]

At Ciena, we use a hybrid approach to human resources development (HRD) and learning. This model is closely tied to our business strategies, addresses the individual characteristics of varying work [...]

The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings.

Overcoming the systemic administration of chemotherapy to reduce drug toxicity and the application of personalised medicine are two of the major challenges in the treatment of cancer. To this aim, efforts are focused on finding novel nanomaterials for the targeted administration of drugs and bioactive molecules in the tumor sites. DNA-based hydrogels are promising candidates for these applications. However, while such materials are fairly known from a structural and physical standpoint, their effects on cell cultures are far less investigated. Here, we studied the biological response of three different cell lines (clear cell renal cell carcinoma 786-O, lung adenocarcinoma H1975 and glioblastoma U87MG) to the treatment with DNA-GEL – a DNA-based hydrogel composed of interacting DNA nanostars. Additionally, we investigated the structural modification of DNA-GELs under cell culture conditions. The results we collected show a cell type specificity of the response, with interesting implications for future applications.

The train timetabling problem aims at determining a periodic timetable for a set of trains that does not violate track capacities and satisfies some operational constraints. In particular, we concentrate [...]

An algorithmic solution is presented addressing the set covering problem in scheduling management. The algorithm is based on a dynamic variable pricing scheme, subgradient optimization, and the utilization of column fixing to improve outcomes.

Foot drop is a condition characterized by impairment of the ability to dorsiflex the foot at the ankle joint. We aim to review the literature and report a case of isolated unilateral foot drop of central causes. A 59-year-old male previously healthy presenting with a right foot drop was admitted. Severe weakness of ankle dorsiflexion with intact plantar flexion was observed. Deep tendon reflexes were normal, no clonus was appreciated, and a plantar response resulted in flexion of all toes. Neuroimaging showed a lesion in the high left frontal lobe, centered along the medial aspect of the precentral gyrus. Levetiracetam and dexamethasone were started, and after four days, the patient reported a slight improvement in his ability to dorsiflex his ankle. Abdominal imaging showed a large right renal mass with invasion of the renal pelvis fat, suggestive of renal cell carcinoma, and cytology diagnosed clear cell renal cell carcinoma. There are 25 articles containing 33 individuals with unilateral foot drop secondary to non-traumatic central causes in the literature. The mean and median age were 50.26 (SD = 20.57) and 55.5 years old (12 - 79 years). Most of the patients were males, which accounted for 55.88% (19/34). The side of the foot drop was right at 58.82% (20/34).

Purpose To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA).Methods Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA?+?OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy.Results Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p?=?0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p?=?0.775 and p?=?0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups.Conclusions Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.

Objective: We investigated the metabolic profile, reactive species production, and inflammatory parameters in patients with epilepsy. Furthermore, we investigated whether there is any relationship between these parameters and seizure type. Methods: Patients with epilepsy (n=43) and healthy subjects (control group; n=41) were recruited to participate in the study. Initially, the participants were submitted to a clinical questionnaire and patients with epilepsy were classified according to seizure type. Metabolic markers and inflammatory and oxidative factors were also measured in specific blood samples. We compared these results with data from the control subjects. Results: Statistical analyses showed that patients with epilepsy presented with higher levels of glycolipid, oxidative stress, and inflammatory parameters compared to the control subjects. Interestingly, patients with generalized seizures presented with higher MnSOD activity and metabolic parameters (total cholesterol, low‐density lipoprotein, glucose and triglyceride levels) compared to the partial seizure and control groups. Furthermore, patients with generalized epilepsy demonstrated a significant correlation between TNF‐α and caspase 8 (p<0.05), caspase 3 (p<0.05), and Picogreen (p<0.001). Significance: This study supports evidence that the levels of inflammatory, glycolipid, and oxidative factors are higher in epilepsy patients, especially those with generalized epilepsy.

•Left and right are political constructs whose meanings and function need to be historically and contextually situated.•Despite similarities in functions/contents, left/right and liberal/conservative distinctions correspond to unique ideological divides.•The cleavage between left/right is mostly about equality, whereas the liberals/conservatives’ divide is mostly about liberty.•A unidimensional conceptualization of left/right ideology allows us to satisfy multiple functions for parties and citizens.•Left and right’s cogency rests upon the extent to which they find resonance in citizens’ personalities.

Supplemental digital content is available in the text.

Particulate phases transport trace metals (TM) and thereby exert a major control on TM distribution in the ocean. Particulate TMs can be classified by their origin as lithogenic (crustal material), biogenic (cellular), or authigenic (formed in situ), but distinguishing these fractions analytically in field samples is a challenge often addressed using operational definitions and assumptions. These different phases require accurate characterization because they have distinct roles in the biogeochemical iron cycle. Particles collected from the upper 2,000 m of the northwest subtropical Atlantic Ocean over four seasonal cruises throughout 2019 were digested with a chemical leach to operationally distinguish labile particulate material from refractory lithogenics. Direct measurements of cellular iron (Fe) were used to calculate the biogenic contribution to the labile Fe fraction, and any remaining labile material was defined as authigenic. Total particulate Fe (PFe) inventories varied <15% between seasons despite strong seasonality in dust inputs. Across seasons, the total PFe inventory (±1SD) was composed of 73 ± 13% lithogenic, 18 ± 7% authigenic, and 10 ± 8% biogenic Fe above the deep chlorophyll maximum (DCM), and 69 ± 8% lithogenic, 30 ± 8% authigenic, and 1.1 ± 0.5% biogenic Fe below the DCM. Data from three other ocean regions further reveal the importance of the authigenic fraction across broad productivity and Fe gradients, comprising ca. 20%–27% of total PFe. The availability of dissolved iron controls phytoplankton growth in much of the ocean. Most oceanic iron is contained in particles that are a mixture of live and dead cells (biogenics), crustal material (lithogenics), and minerals that have precipitated in seawater (authigenics). Each of these materials has different chemical properties that determine how iron cycles through the ocean and regulate how much iron is available for uptake by phytoplankton. Specifically, authigenic and biogenic forms are more accessible to phytoplankton but are often measured as one fraction despite formation by different processes. We measured different forms of iron in particles across seasons and environmental gradients and found that 20%–30% of iron is authigenic. Iron in phytoplankton accounts for <80% of chemically labile Fe and does not exceed 0.1 nMBiogenic Fe is a small and relatively invariant component of particulate Fe (PFe) pools, even across seasonal and regional gradientsAuthigenic Fe is a significant fraction of particulate Fe across seasons and productivity gradients Iron in phytoplankton accounts for <80% of chemically labile Fe and does not exceed 0.1 nM Biogenic Fe is a small and relatively invariant component of particulate Fe (PFe) pools, even across seasonal and regional gradients Authigenic Fe is a significant fraction of particulate Fe across seasons and productivity gradients

Purpose: Pregorexia is a phenomenon posited to occur in the peripartum, characterized by an attempt to counter pregnancy’s physiological changes in body shape through reduced calorie intake or increased physical activity. Methods: In this pre-registered systematic review and meta-analysis, body image dissatisfaction and eating psychopathology in the peripartum according to gestational age were formally assessed. PubMed was searched up to May 2023. Selection criteria were represented by studies on body image concerns or eating psychopathology in the peripartum (up to 1 year after delivery). The population needed to include women from the general population or among patients with a history of (or current) eating disorder. For the meta-analysis, 17 studies were included: 10 for body image dissatisfaction (2625 individuals overall), 7 for eating behaviors (2551 individuals overall). The interplay between body image and the following themes was examined in depth: the adoption of breastfeeding, peripartum depression, sociocultural influences on body image, sexual disturbances, experiencing or reporting an altered food intake. Results: Progressive dissatisfaction with body image during pregnancy by gestational age was observed, stably elevated for at least 12 months postpartum. Eating psychopathology was observed as elevated only at 12 months in the postpartum, but not during pregnancy. Discussion: The current work offers normative values of body image satisfaction and eating psychopathology in the peripartum by gestational age. The relevance of current results was discussed, in order to inform both current clinical practice and future public policies. Level of Evidence: Level I—Evidence obtained from: systematic reviews and meta-analyses.

In multi-orbital materials, superconductivity can exhibit several coupled condensates. In this context, quantum confinement in two-dimensional superconducting oxide interfaces offers new degrees of freedom to engineer the band structure and selectively control the occupancy of 3dorbitals by electrostatic doping. Here, we use resonant microwave transport to extract the superfluid stiffness of the (110)-oriented LaAlO3/SrTiO3interface in the entire phase diagram. We provide evidence of a transition from single-condensate to two-condensate superconductivity driven by continuous and reversible electrostatic doping, which we relate to the Lifshitz transition between 3dbands based on numerical simulations of the quantum well. We find that the superconducting gap is suppressed while the second band is populated, challenging Bardeen–Cooper–Schrieffer theory. We ascribe this behaviour to the existence of superconducting order parameters with opposite signs in the two condensates due to repulsive coupling. Our findings offer an innovative perspective on the possibility to tune and control multiple-orbital physics in superconducting interfaces. Electrostatic doping drives a transition from single condensate to two condensate superconductivity at the (110)-oriented LaAlO3/SrTiO3interface.

In the underdoped regime, the cuprate high-temperature superconductors exhibit a host of unusual collective phenomena, including unconventional spin and charge density modulations, Fermi surface reconstructions, and a pseudogap in various physical observables. Conversely, overdoped cuprates are generally regarded as conventional Fermi liquids possessing no collective electronic order. In partial contradiction to this widely held picture, we report resonant X-ray scattering measurements revealing incommensurate charge order reflections for overdoped (Bi,Pb)2.12Sr1.88CuO6+δ(Bi2201), with correlation lengths of 40–60 lattice units, that persist up to temperatures of at least 250 K. The value of the charge order wavevector decreases with doping, in line with the extrapolation of the trend previously observed in underdoped Bi2201. In overdoped materials, however, charge order coexists with a single, unreconstructed Fermi surface without nesting or pseudogap features. The discovery of re-entrant charge order in Bi2201 thus calls for investigations in other cuprate families and for a reconsideration of theories that posit an essential relationship between these phenomena. Observation of charge order in the overdoped (Bi,Pb)2Sr2CuO6+δsuperconductor using resonant X-ray scattering and angular-resolved photoemission spectroscopy, over a wide temperature range.

Adipocyte development and differentiation have an important role in the aetiology of obesity and its co-morbidities1,2. Although multiple studies have investigated the adipogenic stem and precursor cells that give rise to mature adipocytes3–14, our understanding of their in vivo origin and properties is incomplete2,15,16. This is partially due to the highly heterogeneous and unstructured nature of adipose tissue depots17, which has proven difficult to molecularly dissect using classical approaches such as fluorescence-activated cell sorting and Cre–lox lines based on candidate marker genes16,18. Here, using the resolving power of single-cell transcriptomics19in a mouse model, we reveal distinct subpopulations of adipose stem and precursor cells in the stromal vascular fraction of subcutaneous adipose tissue. We identify one of these subpopulations as CD142+adipogenesis-regulatory cells, which can suppress adipocyte formation in vivo and in vitro in a paracrine manner. We show that adipogenesis-regulatory cells are refractory to adipogenesis and that they are functionally conserved in humans. Our findings point to a potentially critical role for adipogenesis-regulatory cells in modulating adipose tissue plasticity, which is linked to metabolic control, differential insulin sensitivity and type 2 diabetes. Single-cell transcriptomics reveals that, in mice and humans, a population of cells in the stromal vascular fraction of adipose tissue regulates adipogenesis by suppressing adipocyte formation in a paracrine manner.

Introduction The epidemiology of lung cancer is changing worldwide, with smoking being the key driver of lung cancer incidence and mortality. Our aim is to analyze the incidence, survival and mortality trends in Italy in the framework of the 2017 survey on smoking behavior in Italy.Methods AIRTUM 2017 reports on cancer survival and incidence; 2017 survey on smoking behavior in Italy.Results Men achieved progress in lung cancer control characterized by a decrease in incidence and mortality and an increase in survival. The decreasing use of tobacco in men (from 60% in the 1960s to 24% in 2017) was most likely responsible for the decreasing incidence and mortality. Women showed no progress: although survival improved slightly, the incidence and mortality were both on the rise. This was most likely due to the increasing smoking rates in women in the 1970s and 80s. Of major concern is the accelerated rise in the number of smoking women from 4.6 million in 2016 to 5.7 million in 2017 compared to the decrease observed in men (from 6.9 to 6 million).Conclusions The incidence and mortality trends in males clearly demonstrate that primary prevention is the most effective way to reduce lung cancer mortality. By contrast, a 24% increase in the prevalence of smoking among women in just 1 year is extremely worrying for the future, and calls for immediate action by targeted strategies to reduce tobacco consumption in women and avert the dreadful prospect of a lung cancer epidemic in Italy.

The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy. Upon ETAR activation, β-arr1 acts as a transcription co-activator that binds β-catenin, thereby promoting nuclear complex with β-catenin/TFC4 and p300 and histone acetylation, inducing chromatin reorganization on target genes, such as ET-1. The enhanced transcription of ET-1 increases the self-sustained ET-1/β-catenin network. All these findings provide a strong rationale for targeting ET-1R to hamper downstream β-catenin/ET-1 autocrine circuit. Interestingly, treatment with macitentan, a dual ETAR and ETBR antagonist, able to interfere with tumor and microenvironment, disrupts the ET-1R/β-arr1-β-catenin interaction impairing pathways involved in cell survival, EMT, invasion, and enhancing sensitivity to oxaliplatin (OX) and 5-fluorouracil (5-FU). In CRC-SC xenografts, the combination of macitentan and OX or 5-FU enhances the therapeutic effects of cytotoxic drugs. Together, these results provide mechanistic insight into how ET-1R coopts β-catenin signaling and offer a novel therapeutic strategy to manage CRC based on the combination of macitentan and chemotherapy that might benefit patients whose tumors show high ETAR and β-catenin expression.

AbstractPrior to the current public health emergency following the emergence of chikungunya and Zika Virus Disease in the Americas during 2014 and 2015, multi-country research investigated between 2011 and 2013 the efficacy of novel Aedes aegyptiintervention packages through cluster randomised controlled trials in four Latin-American cities: Fortaleza (Brazil); Girardot (Colombia), Acapulco (Mexico) and Salto (Uruguay). Results from the trials led to a scaling up effort of the interventions at city levels. Scaling up refers to deliberate efforts to increase the impact of successfully tested health interventions to benefit more people and foster policy and program development in a sustainable way. The different scenarios represent examples for  a ‘vertical approach’ and a ‘horizontal approach’. This paper presents the analysis of a preliminary process evaluation of the scaling up efforts in the mentioned cites, with a focus on challenges and enabling factors encountered by the research teams, analysing the main social, political, administrative, financial and acceptance factors.

Constraining the role of dust deposition in regulating the concentration of the essential micronutrient iron in surface ocean waters requires knowledge of the flux of seawater‐soluble iron in aerosols and the replacement time of dissolved iron (DFe) in the euphotic zone. Here we estimate these quantities using seasonally resolved DFe data from the Bermuda Atlantic Time‐series Study region and weekly‐scale measurements of iron in aerosols and rain from Bermuda during 2019. In response to seasonal changes in vertical mixing, primary production and dust deposition, surface DFe concentrations vary from ∼0.2 nM in early spring to >1 nM in late summer, with DFe inventories ranging from ∼30 to ∼80 μmol/m2, respectively, over the upper 200 m. Assuming the upper ocean approximates steady state for DFe on an annual basis, our aerosol and rainwater data require a mean euphotic‐zone residence time of ∼0.8–1.9 years for DFe with respect to aeolian input. Primary production by phytoplankton in ocean surface waters is the foundation of the marine ecosystem, and plays a key role in maintaining the ocean‐atmosphere balance of carbon dioxide, which regulates global climate. Iron is an essential micronutrient that is required by phytoplankton, and the availability of dissolved iron (DFe) is thought to limit phytoplankton growth over large areas of the ocean. In this context, it is important to constrain the sources and persistence of DFe in surface ocean waters, which control the amount of DFe that is available to support phytoplankton growth. This study focuses on the Bermuda region of the North Atlantic Ocean, where deposition of airborne soil dust is the major source of DFe to surface waters. By combining measurements of the atmospheric loading and solubility of iron in soil dust over Bermuda with measurements of DFe in adjacent ocean waters over a full year, we are able to estimate the rate of supply of DFe from dust deposition in this region, as well as the average time that this DFe persists in the surface ocean. The latter, termed the DFe replacement time, is around 1 year, which agrees well with recent estimates from comparable ocean regions. An imbalance between input and removal produces an ∼3‐fold seasonal increase in the euphotic‐zone inventory of dissolved iron (DFe) near BermudaAnalyses of iron in seasonal‐scale aerosol, rain and water‐column samples allow direct estimates of the replacement time of DFeWe derive a mean residence time of ∼0.8–1.9 years for DFe in the euphotic zone (<200 m) of the Sargasso Sea near Bermuda An imbalance between input and removal produces an ∼3‐fold seasonal increase in the euphotic‐zone inventory of dissolved iron (DFe) near Bermuda Analyses of iron in seasonal‐scale aerosol, rain and water‐column samples allow direct estimates of the replacement time of DFe We derive a mean residence time of ∼0.8–1.9 years for DFe in the euphotic zone (<200 m) of the Sargasso Sea near Bermuda

The main challenge in disk laser design is the realization of efficient heat removal from the pumped area by optimizing the heat spreader design and the water impingement cooling. This generally requires the calculation of the temperature distribution in the disk by numerically solving the heat conduction equation using finite element algorithms. We have developed a simple method to calculate disk temperature profiles that is based on analytically solving the heat conduction equation in Hankel transform space. This method can be applied to disks that are mounted on multi-layered, water-cooled heat spreaders, which may include glue or solder layers and dielectric coating layers. The temperature and heat fluxes at the interfaces of the layers are connected via a heat transfer matrix, which allows for straightforward incorporation of additional heat sink layers or an undoped cap into the model. This generalized model allows for the parametric optimization of the heat distribution in pumped solid-state laser and semiconductor laser disks.

Temperature profiles in pumped solid-state laser disks are generally calculated numerically by using finite-element programs to solve the heat conduction equation in the disk and the heat spreader. Analytical expressions exist for the longitudinal temperature profile in the case of an infinitely thick heat spreader or in the limit of zero thickness of the disk. We are presenting a simplified, semi-analytical method to calculate the three-dimensional temperature profiles for any disk or heat spreader dimensions by solving the heat conduction equation using Hankel transforms. This method allows for straightforward optimization of the cooling properties of heat-sink-mounted solid-state and semiconductor disk lasers.

The endothelin-1 (ET-1)/ET A receptor (ETAR) signalling pathway is a well-established driver of epithelial ovarian cancer (EOC) progression. One key process promoted by ET-1 is tumor cell invasion, which requires the scaffolding functions of β-arrestin-1 (β-arr1) downstream of the receptor; however, the potential role of ET-1 in inducing invadopodia, which are crucial for cellular invasion and tumor metastasis, is completely unknown. We describe here that ET-1/ETAR, through β-arr1, activates RhoA and RhoC GTPase and downstream ROCK (Rho-associated coiled coil-forming kinase) kinase activity, promoting actin-based dynamic remodelling and enhanced cell invasion. This is accomplished by the direct interaction of β-arr1 with PDZ-RhoGEF (postsynaptic density protein 95/disc-large/zonula occludens-RhoGEF). Interestingly, ETAR-mediated invasive properties are related to the regulation of invadopodia, as evaluated by colocalization of actin with cortactin, as well as with TKS5 and MT1-MMP (membrane type 1-matrix metalloproteinase) with areas of matrix degradation, and activation of cofilin pathway, which is crucial for regulating invadopodia activity. Depletion of PDZ-RhoGEF, or β-arr1, or RhoC, as well as the treatment with the dual ET-1 receptor antagonist macitentan, significantly impairs invadopodia function, MMP activity and invasion, demonstrating that β-arr1/PDZ-RhoGEF interaction mediates ETAR-driven ROCK-LIMK-cofilin pathway through the control of RhoC activity. In vivo, macitentan is able to inhibit metastatic dissemination and cofilin phosphorylation. Collectively, our data unveil a noncanonical activation of the RhoC/ROCK pathway through the β-arr1/PDZ-RhoGEF complex as a regulator of ETAR-induced motility and metastasis, establishing ET-1 axis as a novel regulator of invadopodia protrusions through the RhoC/ROCK/LIMK/cofilin pathway during the initial steps of EOC invasion.