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Efficient pluripotent stem cell guidance protocols for the production of human posterior cranial placodes such as the otic placode that gives rise to the inner ear do not exist. Here we use a systematic approach including defined monolayer culture, signaling modulation, and single-cell gene expression analysis to delineate a developmental trajectory for human otic lineage specification in vitro. We found that modulation of bone morphogenetic protein (BMP) and WNT signaling combined with FGF and retinoic acid treatments over the course of 18 days generates cell populations that develop chronological expression of marker genes of non-neural ectoderm, preplacodal ectoderm, and early otic lineage. Gene expression along this differentiation path is distinct from other lineages such as endoderm, mesendoderm, and neural ectoderm. Single-cell analysis exposed the heterogeneity of differentiating cells and allowed discrimination of non-neural ectoderm and otic lineage cells from off-target populations. Pseudotemporal ordering of human embryonic stem cell and induced pluripotent stem cell-derived single-cell gene expression profiles revealed an initially synchronous guidance toward non-neural ectoderm, followed by comparatively asynchronous occurrences of preplacodal and otic marker genes. Positive correlation of marker gene expression between both cell lines and resemblance to mouse embryonic day 10.5 otocyst cells implied reasonable robustness of the guidance protocol. Single-cell trajectory analysis further revealed that otic progenitor cell types are induced in monolayer cultures, but further development appears impeded, likely because of lack of a lineage-stabilizing microenvironment. Our results provide a framework for future exploration of stabilizing microenvironments for efficient differentiation of stem cell-generated human otic cell types.

In the U.S., individual states enact Renewable Portfolio Standards (RPSs) for renewable electricity production with little coordination. Each state imposes restrictions on the amounts and locations of qualifying renewable generation. Using a co-optimization (transmission and generation) planning model, we quantify the long run economic benefits of allowing flexibility in the trading of Renewable Energy Credits (RECs) among the U.S. states belonging to the Western Electricity Coordinating Council (WECC). We characterize flexibility in terms of the amount and geographic eligibility of out-of-state RECs that can be used to meet a state's RPS goal. Although more trade would be expected to have economic benefits, neither the size of these benefits nor the effects of such trading on infrastructure investments, CO₂ emissions and energy prices have been previously quantified. We find that up to 90% of the economic benefits are captured if approximately 25% of unbundled RECs are allowed to be acquired from out of state. Furthermore, increasing REC trading flexibility does not necessarily result in either higher transmission investment costs or a substantial impact on CO₂ emissions. Finally, increasing REC trading flexibility decreases energy prices in some states and increases them elsewhere, while the WECC-wide average energy price decreases.

Quantifying symptoms of tar spot of corn has been conducted through visual-based estimations of the proportion of leaf area covered by the pathogenic structures generated by Phyllachora maydis (stromata). However, this traditional approach is costly in terms of time and labor, as well as prone to human subjectivity. An objective and accurate method, which is also time and labor-efficient, is of an urgent need for tar spot surveillance and high-throughput disease phenotyping. Here, we present the use of contour-based detection of fungal stromata to quantify disease intensity using Red-Green-Blue (RGB) images of tar spot-infected corn leaves. Image blocks ( n = 1,130) generated by uniform partitioning the RGB images of leaves, were analyzed for their number of stromata by two independent, experienced human raters using ImageJ (visual estimates) and the experimental stromata contour detection algorithm (SCDA; digital measurements). Stromata count for each image block was then categorized into five classes and tested for the agreement of human raters and SCDA using Cohen's weighted kappa coefficient (κ). Adequate agreements of stromata counts were observed for each of the human raters to SCDA (κ = 0.83) and between the two human raters (κ = 0.95). Moreover, the SCDA was able to recognize “true stromata,” but to a lesser extent than human raters (average median recall = 90.5%, precision = 89.7%, and Dice = 88.3%). Furthermore, we tracked tar spot development throughout six time points using SCDA and we obtained high agreement between area under the disease progress curve (AUDPC) shared by visual disease severity and SCDA. Our results indicate the potential utility of SCDA in quantifying stromata using RGB images, complementing the traditional human, visual-based disease severity estimations, and serve as a foundation in building an accurate, high-throughput pipeline for the scoring of tar spot symptoms.

This work investigates the performance of a polyvinyl alcohol/acrylamide-based photopolymer (PVA/AA) under pulsed and continuous-wave (CW) laser exposure for holographic recording. Using a versatile setup that allows direct comparison between both regimes, diffraction efficiency (DE), angular responses, and material parameters were analyzed. Comparable maximum DE was achieved with both CW and pulsed laser exposure; however, the pulsed regime produces stronger attenuation along the grating depth, which emphasizes the need to lower the dye concentration. Furthermore, the temporal evolution of DE reveals a smaller influence of oxygen inhibition under CW exposure. Finally, second-order angular reconstructions confirm that pulsed gratings exhibit a better sinusoidal modulation, especially at low frequency rates. These results enhance the understanding of how pulsed exposure affects holographic recording and open pathways for optimizing photopolymer systems in advanced technologies.

Single-pixel cameras allow to obtain images in a wide range of challenging scenarios, including broad regions of the electromagnetic spectrum and through scattering media. However, there still exist several drawbacks that single-pixel architectures must address, such as acquisition speed and imaging in the presence of ambient light. In this work we introduce balanced detection in combination with simultaneous complementary illumination in a single-pixel camera. This approach enables to acquire information even when the power of the parasite signal is higher than the signal itself. Furthermore, this novel detection scheme increases both the frame rate and the signal-to-noise ratio of the system. By means of a fast digital micromirror device together with a low numerical aperture collecting system, we are able to produce a live-feed video with a resolution of 64 × 64 pixels at 5 Hz. With advanced undersampling techniques, such as compressive sensing, we can acquire information at rates of 25 Hz. By using this strategy, we foresee real-time biological imaging with large area detectors in conditions where array sensors are unable to operate properly, such as infrared imaging and dealing with objects embedded in turbid media.

c-MYC oncogene is deregulated in most human tumours. Histone marks associated with transcriptionally active genes define high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are unknown. Here we report that c-MYC interacts with BPTF, a core subunit of the NURF chromatin-remodelling complex. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to decreased c-MYC recruitment to DNA and changes in chromatin accessibility. In Bptf -null MEFs, BPTF is necessary for c-MYC-driven proliferation, G1–S progression and replication stress, but not for c-MYC-driven apoptosis. Bioinformatics analyses unveil that BPTF levels correlate positively with c-MYC-driven transcriptional signatures. In vivo , Bptf inactivation in pre-neoplastic pancreatic acinar cells significantly delays tumour development and extends survival. Our findings uncover BPTF as a crucial c-MYC co-factor required for its biological activity and suggest that the BPTF-c-MYC axis is a potential therapeutic target in cancer. c-MYC genomic distribution is dictated by the epigenetic context but the mechanisms are unknown. Here, the authors show that c-MYC requires the chromatin reader BPTF to activate its transcriptional program and promote tumour development in vivo , suggesting that BPTF is a potential target for cancer therapy.

Here it is investigated the effect of the antiferromagnet Cr 2 O 3 on the magnetic properties of ferromagnetic Fe 72 Ga 28 thin films. Sputtered Fe 72 Ga 28 layers have their magnetization in the sample plane with a magnetic fluctuation that gives rise to magnetic ripple. In order to turn its magnetization into the out of plane (OOP) direction, it has been magnetically coupled with Cr 2 O 3 that has magnetic moments along the c -axis, that is the perpendicular direction when properly aligned. Cr 2 O 3 has been obtained from Cr oxidation, whereas Fe 72 Ga 28 has been deposited on top of it by sputtering in the ballistic regime. Although a uniaxial in-plane magnetic anisotropy is expected for Fe 72 Ga 28 thickness above 100 nm, the interfacial coupling with Cr 2 O 3 prevents this anisotropy. The formation of stripe domains in Fe 72 Ga 28 above a critical thickness reveals the enhancement of the out of plane component of the Fe 72 Ga 28 magnetization with respect to uncoupled layers. Due to the interface coupling, the Fe 72 Ga 28 magnetization turns into the out-of-plane direction as its thickness is gradually reduced, and a perpendicular magnetic anisotropy of 3·10 6 erg·cm −3 is inferred from experimental results. Eventually, the coupling between Cr 2 O 3 and Fe 72 Ga 28 promotes an exchange-bias effect that has been well fitted by means of the random field model.

Aliphatics prevail in asteroids, comets, meteorites and other bodies in our solar system. They are also found in the interstellar and circumstellar media both in gas-phase and in dust grains. Among aliphatics, linear alkanes ( n -C n H 2n+2 ) are known to survive in carbonaceous chondrites in hundreds to thousands of parts per billion, encompassing sequences from CH 4 to n -C 31 H 64 . Despite being systematically detected, the mechanism responsible for their formation in meteorites has yet to be identified. Based on advanced laboratory astrochemistry simulations, we propose a gas-phase synthesis mechanism for n-alkanes starting from carbon and hydrogen under conditions of temperature and pressure that mimic those found in carbon-rich circumstellar envelopes. We characterize the analogs generated in a customized sputter gas aggregation source using a combination of atomically precise scanning tunneling microscopy, non-contact atomic force microscopy and ex-situ gas chromatography-mass spectrometry. Within the formed carbon nanostructures, we identify the presence of n -alkanes with sizes ranging from n -C 8 H 18 to n -C 32 H 66 . Ab-initio calculations of formation free energies, kinetic barriers, and kinetic chemical network modelling lead us to propose a gas-phase growth mechanism for the formation of large n -alkanes based on methyl-methylene addition (MMA). In this process, methylene serves as both a reagent and a catalyst for carbon chain growth. Our study provides evidence of an aliphatic gas-phase synthesis mechanism around evolved stars and provides a potential explanation for its presence in interstellar dust and meteorites. Extraterrestrial organic matter found in meteorites may hold a unique record of its synthesis, and chemical and thermal alterations in the parent body, however, the origin of such aliphatics remains enigmatic. Here, the authors propose sequential gas-phase methyl-methylene addition growth of n -C 8 H 18 to n -C 32 H 66 alkanes based on a series of sputter gas aggregation source experiments and DFT calculations.

IntroductionPregnancy is a high-risk period for major affective disorders and can lead to a destabilizing period for our patients. Standard pharmacological strategies must be carefully evaluated due to potential teratogenic or side effects. We present a case of bipolar disorder type I with challenging-to-control maniac episodes during pregnancy, which has required Electroconvulsive Therapy for its management.ObjectivesPresenting maintenance electroconvulsive therapy (ECT) as a safe and effective therapeutic strategy during pregnancy, with the presentation of a case in which it has been administered every 3 weeks from the second trimester until the baby’s birth at 37 weeksMethodsThis concerns a 28-year-old immigrant woman, married, with a 10-year-old child. She was diagnosed with bipolar disorder type I at the age of 16 when she experienced her first manic episode in her country of origin. Subsequently, during her first pregnancy, she required hospitalization for electroconvulsive therapy (ECT) treatment, with a positive response after a single session. She remained stable for several years without maintenance pharmacological treatment or follow-up until the ninth week of her second pregnancy when she experienced a manic episode requiring hospitalization.ResultsShe was initially treated with Olanzapine and Lorazepam with a positive response, but three weeks later, she was readmitted with a similar episode. These decompensations occurred almost monthly, leading to the consideration of introducing mood stabilizers after the first trimester. However, due to the patient’s severe hyperemesis gravidarum, this stabilizing treatment was ruled out due to the difficulty in controlling its blood levels and the associated risk of intoxication. During the fifth admission at the 20th week of gestation, the decision was made to initiate ECT treatment, which yielded an excellent response and subsequent maintenance.ConclusionsThe indications for electroconvulsive therapy (ECT) during pregnancy are the same as in the rest of adult patients. In individuals with a psychiatric history, it is possible for a relapse of mental illness to occur during pregnancy, although the risk is considerably higher during the postpartum period. ECT is considered an effective and safe treatment option in all three trimesters of pregnancy and the postpartum period. During the informed consent process, patients should be informed about the potential impact of ECT as well as alternative treatment options.Disclosure of InterestNone Declared

IntroductionThe lack of insight can be present among patients with a diagnosis of schizophrenia, which often results in lack of adherence to pharmacological treatments1 and, subsequently, in treatment discontinuation and relapses2. This vicious pattern leads to further clinical deterioration, impaired functioning, and reduced quality of life 3. There is a plethora of evidence supporting the fact that long-acting injectable and depot antipsychotics can increase adherence to treatment, reduce the risk of discontinuation and hospital admissions4. It is also known that low fluctuations between peaks and lows in plasma drug levels could be related to a better tolerability profiles5. A new paliperidone palmitate prolonged release formulation, which is administered twice annually, has been approved as maintenance treatment for patients with schizophrenia who are already stable on the monthly or quarterly prolonged release paliperidone palmitate6.ObjectivesWe aimed to evaluate the transition of monthly and quarterly paliperidone palmitate to the new six-monthly formulation and patients’ satisfaction with it in a real-world clinical setting.MethodsWe collected a basic epidemiologic questionnaire, responses to a query about local pain after administration, and the Drugs Attitude Inventory (DAI).ResultsA total of 21 patients from an outpatient clinic for severe mental disorders with a long evolution of their disease in Salamanca, Spain, were included. All of them had a DSM5-TR diagnosis of Schizophrenia. Sixteen were male and 5 female. The mean age was 42.6 years. 14 were receiving quartlery paliperidone palmitate (10 with high doses (525 mg) and 4 with moderate doses (350 mg)) and 7 were on monthly injections (6 with high doses (150 mg) and 1 with a moderate dose (100 mg)). Those receiving moderate doses of quarterly or monthly paliperidone palmitate were administered 700 mg of six-monthly paliperidone palmitate; 1000 mg were injected to those with higher doses. The mean score on the DAI scale was 8. Only one patient reported an increase in local pain after the injection, and another reported dissatisfaction with the administration in the gluteus instead of the deltoid muscle. The first administration of the new formulation in our site was on June 26th; to date none of these patients have required hospital admission due to relapse.ConclusionsSix-monthly prolonged release paliperidone palmitate seems to be an effective maintenance treatment for schizophrenia. In addition, this new formulation is well received and tolerated by patients previously on monthly or quarterly formulations of the same drug.Disclosure of InterestNone Declared