A perspective on epigenomic aging processes in the human brain and their plasticity in patients with mental disorders - a systematic review.

The debate surrounding nature versus nurture remains a central question in neuroscience, psychology, and in psychiatry, holding implications for both aging processes and the etiology of mental illness. Epigenetics can serve as a bridge between genetic predisposition and environmental influences, thus offering a potential avenue for addressing these questions. Epigenetic clocks, in particular, offer a theoretical framework for measuring biological age based on DNA methylation signatures, enabling the identification of disparities between biological and chronological age. This structured review seeks to consolidate current knowledge regarding the relationship between mental disorders and epigenetic age within the brain. Through a comprehensive literature search encompassing databases such as EBSCO, PubMed, and ClinicalTrials.gov, relevant studies were identified and analyzed. Studies that met inclusion criteria were scrutinized, focusing on those with large sample sizes, analyses of both brain tissue and blood samples, investigation of frontal cortex markers, and a specific emphasis on schizophrenia and depressive disorders. Our review revealed a paucity of significant findings, yet notable insights emerged from studies meeting specific criteria. Studies characterized by extensive sample sizes, analysis of brain tissue and blood samples, assessment of frontal cortex markers, and a focus on schizophrenia and depressive disorders yielded particularly noteworthy results. Despite the limited number of significant findings, these studies shed light on the complex interplay between epigenetic aging and mental illness. While the current body of literature on epigenetic aging in mental disorders presents limited significant findings, it underscores the importance of further research in this area. Future studies should prioritize large sample sizes, comprehensive analyses of brain tissue and blood samples, exploration of specific brain regions such as the frontal cortex, and a focus on key mental disorders. Such endeavors will contribute to a deeper understanding of the relationship between epigenetic aging and mental illness, potentially informing novel diagnostic and therapeutic approaches.

Deterministic storage and retrieval of telecom light from a quantum dot single-photon source interfaced with an atomic quantum memory.

A hybrid interface of solid-state single-photon sources and atomic quantum memories is a long sought-after goal in photonic quantum technologies. Here, we demonstrate deterministic storage and retrieval of light from a semiconductor quantum dot in an atomic ensemble quantum memory at telecommunications wavelengths. We store single photons from an indium arsenide quantum dot in a high-bandwidth rubidium vapor-based quantum memory, with a total internal memory efficiency of (12.9 ± 0.4)%. The signal-to-noise ratio of the retrieved light field is 18.2 ± 0.6, limited only by detector dark counts.

Remanufacturing Perovskite Solar Cells and Modules-A Holistic Case Study.

While perovskite photovoltaic (PV) devices are on the verge of commercialization, promising methods to recycle or remanufacture fully encapsulated perovskite solar cells (PSCs) and modules are still missing. Through a detailed life-cycle assessment shown in this work, we identify that the majority of the greenhouse gas emissions can be reduced by re-using the glass substrate and parts of the PV cells. Based on these analytical findings, we develop a novel thermally assisted mechanochemical approach to remove the encapsulants, the electrode, and the perovskite absorber, allowing reuse of most of the device constituents for remanufacturing PSCs, which recovered nearly 90% of their initial performance. Notably, this is the first experimental demonstration of remanufacturing PSCs with an encapsulant and an edge-seal, which are necessary for commercial perovskite solar modules. This approach distinguishes itself from the "traditional" recycling methods previously demonstrated in perovskite literature by allowing direct reuse of bulk materials with high environmental impact. Thus, such a remanufacturing strategy becomes even more favorable than recycling, and it allows us to save up to 33% of the module's global warming potential. Remarkably, this process most likely can be universally applied to other PSC architectures, particularly n-i-p-based architectures that rely on inorganic metal oxide layers deposited on glass substrates. Finally, we demonstrate that the CO2-footprint of these remanufactured devices can become less than 30 g/kWh, which is the value for state-of-the-art c-Si PV modules, and can even reach 15 g/kWh assuming a similar lifetime.

Multifunctional sulfonium-based treatment for perovskite solar cells with less than 1% efficiency loss over 4,500-h operational stability tests.

The stabilization of grain boundaries and surfaces of the perovskite layer is critical to extend the durability of perovskite solar cells. Here we introduced a sulfonium-based molecule, dimethylphenethylsulfonium iodide (DMPESI), for the post-deposition treatment of formamidinium lead iodide perovskite films. The treated films show improved stability upon light soaking and remains in the black α phase after two years ageing under ambient condition without encapsulation. The DMPESI-treated perovskite solar cells show less than 1% performance loss after more than 4,500 h at maximum power point tracking, yielding a theoretical T80 of over nine years under continuous 1-sun illumination. The solar cells also display less than 5% power conversion efficiency drops under various ageing conditions, including 100 thermal cycles between 25 °C and 85 °C and an 1,050-h damp heat test.

Rapid and sensitive detection of genome contamination at scale with FCS-GX.

Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI's Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 min. Testing FCS-GX on artificially fragmented genomes demonstrates high sensitivity and specificity for diverse contaminant species. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination, comprising 0.16% of total bases, with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/ or https://doi.org/10.5281/zenodo.10651084 .

Machine learning enhanced evaluation of semiconductor quantum dots.

A key challenge in quantum photonics today is the efficient and on-demand generation of high-quality single photons and entangled photon pairs. In this regard, one of the most promising types of emitters are semiconductor quantum dots, fluorescent nanostructures also described as artificial atoms. The main technological challenge in upscaling to an industrial level is the typically random spatial and spectral distribution in their growth. Furthermore, depending on the intended application, different requirements are imposed on a quantum dot, which are reflected in its spectral properties. Given that an in-depth suitability analysis is lengthy and costly, it is common practice to pre-select promising candidate quantum dots using their emission spectrum. Currently, this is done by hand. Therefore, to automate and expedite this process, in this paper, we propose a data-driven machine-learning-based method of evaluating the applicability of a semiconductor quantum dot as single photon source. For this, first, a minimally redundant, but maximally relevant feature representation for quantum dot emission spectra is derived by combining conventional spectral analysis with an autoencoding convolutional neural network. The obtained feature vector is subsequently used as input to a neural network regression model, which is specifically designed to not only return a rating score, gauging the technical suitability of a quantum dot, but also a measure of confidence for its evaluation. For training and testing, a large dataset of self-assembled InAs/GaAs semiconductor quantum dot emission spectra is used, partially labelled by a team of experts in the field. Overall, highly convincing results are achieved, as quantum dots are reliably evaluated correctly. Note, that the presented methodology can account for different spectral requirements and is applicable regardless of the underlying photonic structure, fabrication method and material composition. We therefore consider it the first step towards a fully integrated evaluation framework for quantum dots, proving the use of machine learning beneficial in the advancement of future quantum technologies.

NCBI GEO: archive for gene expression and epigenomics data sets: 23-year update.

The Gene Expression Omnibus (GEO) is an international public repository that archives gene expression and epigenomics data sets generated by next-generation sequencing and microarray technologies. Data are typically submitted to GEO by researchers in compliance with widespread journal and funder mandates to make generated data publicly accessible. The resource handles raw data files, processed data files and descriptive metadata for over 200 000 studies and 6.5 million samples, all of which are indexed, searchable and downloadable. Additionally, GEO offers web-based tools that facilitate analysis and visualization of differential gene expression. This article presents the current status and recent advancements in GEO, including the generation of consistently computed gene expression count matrices for thousands of RNA-seq studies, and new interactive graphical plots in GEO2R that help users identify differentially expressed genes and assess data set quality. The GEO repository is built and maintained by the National Center for Biotechnology Information (NCBI), a division of the National Library of Medicine (NLM), and is publicly accessible at https://www.ncbi.nlm.nih.gov/geo/.

A Unipolar Quantum Dot Diode Structure for Advanced Quantum Light Sources.

Triggered, indistinguishable single photons are crucial in various quantum photonic implementations. Here, we realize a novel n+-i-n++ diode structure embedding semiconductor quantum dots: the gated device enables spectral tuning of the transitions and deterministic control of the charged states. Blinking-free single-photon emission and high two-photon indistinguishability are observed. The line width's temporal evolution is investigated across over 6 orders of magnitude time scales, combining photon-correlation Fourier spectroscopy, high-resolution photoluminescence spectroscopy, and two-photon interference (visibility of VTPI,2ns = (85.8 ± 2.2)% and VTPI,9ns = (78.3 ± 3.0)%). Most of the dots show no spectral broadening beyond ∼9 ns time scales, and the photons' line width ((420 ± 30) MHz) deviates from the Fourier-transform limit by a factor of 1.68. The combined techniques verify that most dephasing mechanisms occur at time scales ≤2 ns, despite their modest impact. The presence of n-doping implies higher carrier mobility, enhancing the device's appeal for high-speed tunable, high-performance quantum light sources.

A New Family of Layered Metal-Organic Semiconductors: Cu/V-Organophosphonates.

Herein, we report the design and synthesis of a layered redox-active, antiferromagnetic metal organic semiconductor crystals with the chemical formula [Cu(H2 O)2 V(µ-O)(PPA)2 ] (where PPA is phenylphosphonate). The crystal structure of [Cu(H2 O)2 V(µ-O)(PPA)2 ] shows that the metal phosphonate layers are separated by phenyl groups of the phenyl phosphonate linker. Tauc plotting of diffuse reflectance spectra indicates that [Cu(H2 O)2 V(µ-O)(PPA)2 ] has an indirect band gap of 2.19 eV. Photoluminescence (PL) spectra indicate a complex landscape of energy states with PL peaks at 1.8 and 2.2 eV. [Cu(H2 O)2 V(µ-O)(PPA)2 ] has estimated hybrid ionic and electronic conductivity values between 0.13 and 0.6 S m-1 . Temperature-dependent magnetization measurements show that [Cu(H2 O)2 V(µ-O)(PPA)2 ] exhibits short range antiferromagnetic order between Cu(II) and V(IV) ions. [Cu(H2 O)2 V(µ-O)(PPA)2 ] is also photoluminescent with photoluminescence quantum yield of 0.02%. [Cu(H2 O)2 V(µ-O)(PPA)2 ] shows high electrochemical, and thermal stability.

Rapid and sensitive detection of genome contamination at scale with FCS-GX.

Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI's Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 minutes. Testing FCS-GX on artificially fragmented genomes demonstrates sensitivity >95% for diverse contaminant species and specificity >99.93%. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination (0.16% of total bases), with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/.

Nanoarchitectonics in fully printed perovskite solar cells with carbon-based electrodes.

A sacrificial film of polystyrene nanoparticles was utilized to introduce nano-cavities into mesoporous metal oxide layers. This enabled the growth of larger perovskite crystals inside the oxide scaffold with significantly suppressed non-radiative recombination and improved device performance. This work exemplifies potential applications of such nanoarchitectonic approaches in perovskite opto-electronic devices.

Tuning Structural and Optical Properties of Porphyrin-based Hydrogen-Bonded Organic Frameworks by Metal Insertion.

Herein, a simple way of tuning the optical and structural properties of porphyrin-based hydrogen-bonded organic frameworks (HOFs) is reported. By inserting transition metal ions into the porphyrin cores of GTUB-5 (p-H8 -TPPA (5,10,15,20-Tetrakis[p-phenylphosphonic acid] HOF), the authors show that it is possible to generate HOFs with different band gaps, photoluminescence (PL) life times, and textural properties. The band gaps of the resulting HOFs (viz., Cu-, Ni-, Pd-, and Zn-GTUB-5) are measured by diffuse reflectance and PL spectroscopy, as well as calculated via DFT, and the PL lifetimes are measured. Across the series, the band gaps vary over a narrow range from 1.37 to 1.62 eV, while the PL lifetimes vary over a wide range from 2.3 to 83 ns. These differences ultimately arise from metal-induced structural changes, viz., changes in the metal-to-nitrogen distances, number of hydrogen bonds, and pore volumes. DFT reveals that the band gaps of Cu-, Zn-, and Pd- GTUB-5 are governed by highest occupied/lowest unoccupied crystal orbitals (HOCO/LUCO) composed of π- orbitals on the porphyrin linkers, while that of Ni-GTUB-5 is governed by a HOCO and LUCO composed of Ni dorbitals. Overall, our findings show that metal-insertion can be used to optimize HOFs for optoelectronics and small-molecule capture applications.

Strain effects on halide perovskite solar cells.

Halide perovskite solar cells (PSCs) have achieved power conversion efficiencies (PCEs) approaching 26%, however, the stability issue hinders their commercialization. Due to the soft ionic nature of perovskite materials, the strain effect on perovskite films has been recently recognized as one of the key factors that affects their opto-electronic properties and the device stability. Herein, we summarized the origins of strain, characterization techniques, and implications of strain on both perovskite film and solar cells as well as various strategies to control the strain. Finally, we proposed effective strategies for future strain engineering. We believe this comprehensive review could further facilitate researchers with a deeper understanding of strain effect and enhance the research activity in engineering the strain to further improve performance and especially the device stability toward commercialization.

Hypermethylation of RAD9A intron 2 in childhood cancer patients, leukemia and tumor cell lines suggest a role for oncogenic transformation.

Most childhood cancers occur sporadically and cannot be explained by an inherited mutation or an unhealthy lifestyle. However, risk factors might trigger the oncogenic transformation of cells. Among other regulatory signals, hypermethylation of RAD9A intron 2 is responsible for the increased expression of RAD9A protein, which may play a role in oncogenic transformation. Here, we analyzed the RAD9A intron 2 methylation in primary fibroblasts of 20 patients with primary cancer in childhood and second primary cancer (2N) later in life, 20 matched patients with only one primary cancer in childhood (1N) and 20 matched cancer-free controls (0N), using bisulfite pyrosequencing and deep bisulfite sequencing (DBS). Four 1N patients and one 2N patient displayed elevated mean methylation levels (≥ 10 %) of RAD9A. DBS revealed ≥ 2 % hypermethylated alleles of RAD9A, indicative for constitutive mosaic epimutations. Bone marrow samples of NHL and AML tumor patients (n=74), EBV (Epstein Barr Virus) lymphoblasts (n=6), tumor cell lines (n=5) and FaDu subclones (n=13) were analyzed to substantiate our findings. We find a broad spectrum of tumor entities with an aberrant methylation of RAD9A. We detected a significant difference in mean methylation of RAD9A for NHL versus AML patients (p ≤0.025). Molecular karyotyping of AML samples during therapy with hypermethylated RAD9A showed an evolving duplication of 1.8 kb on Chr16p13.3 including the PKD1 gene. Radiation, colony formation assays, cell proliferation, PCR and molecular karyotyping SNP-array experiments using generated FaDu subclones suggest that hypermethylation of RAD9A intron 2 is associated with genomic imbalances in regions with tumor-relevant genes and survival of the cells. In conclusion, this is the very first study of RAD9A intron 2 methylation in childhood cancer and Leukemia. RAD9A epimutations may have an impact on leukemia and tumorigenesis and can potentially serve as a biomarker.

Interfacial Passivation Engineering of Perovskite Solar Cells with Fill Factor over 82% and Outstanding Operational Stability on n-i-p Architecture.

Tremendous efforts have been dedicated toward minimizing the open-circuit voltage deficits on perovskite solar cells (PSCs), and the fill factors are still relatively low. This hinders their further application in large scalable modules. Herein, we employ a newly designed ammonium salt, cyclohexylethylammonium iodide (CEAI), for interfacial engineering between the perovskite and hole-transporting layer (HTL), which enhanced the fill factor to 82.6% and consequent PCE of 23.57% on the target device. This can be associated with a reduction of the trap-assisted recombination rate at the 3D perovskite surface, via formation of a 2D perovskite interlayer. Remarkably, the property of the 2D perovskite interlayer along with the cyclohexylethyl group introduced by CEAI treatment also determines a pronounced enhancement in the surface hydrophobicity, leading to an outstanding stability of over 96% remaining efficiency of the passivated devices under maximum power point tracking with one sun illumination under N2 atmosphere at room temperature after 1500 h.

Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study.

Background: IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results: A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

Double-Mesoscopic Hole-Transport-Material-Free Perovskite Solar Cells: Overcoming Charge-Transport Limitation by Sputtered Ultrathin Al2O3 Isolating Layer.

The electrically insulating space layer takes a fundamental role in monolithic carbon-graphite based perovskite solar cells (PSCs) and it has been established to prevent the charge recombination of electrons at the mp-TiO2/carbon-graphite (CG) interface. Thick 1 µm printed layers are commonly used for this purpose in the established triple-mesoscopic structures to avoid ohmic shunts and to achieve a high open circuit voltage. In this work, we have developed a reproducible large-area procedure to replace this thick space layer with an ultra-thin dense 40 nm sputtered Al2O3 which acts as a highly electrically insulating layer preventing ohmic shunts. Herewith, transport limitations related so far to the hole diffusion path length inside the thick mesoporous space layer have been omitted by concept. This will pave the way toward the development of next generation double-mesoscopic carbon-graphite-based PSCs with highest efficiencies. Scanning electron microscope, energy dispersive X-ray analysis, and atomic force microscopy measurements show the presence of a fully oxidized sputtered Al2O3 layer forming a pseudo-porous covering of the underlying mesoporous layer. The thickness has been finely tuned to achieve both electrical isolation and optimal infiltration of the perovskite solution allowing full percolation and crystallization. Photo voltage decay, light-dependent, and time-dependent photoluminescence measurements showed that the optimal 40 nm thick Al2O3 not only prevents ohmic shunts but also efficiently reduces the charge recombination at the mp-TiO2/CG interface and, at the same time, allows efficient hole diffusion through the perovskite crystals embedded in its pseudo-pores. Thus, a stable V OC of 1 V using CH3NH3PbI3 perovskite has been achieved under full sun AM 1.5 G with a stabilized device performance of 12.1%.

Distinguishing crystallization stages and their influence on quantum efficiency during perovskite solar cell formation in real-time.

Relating crystallization of the absorber layer in a perovskite solar cell (PSC) to the device performance is a key challenge for the process development and in-depth understanding of these types of high efficient solar cells. A novel approach that enables real-time photo-physical and electrical characterization using a graphite-based PSC is introduced in this work. In our graphite-based PSC, the device architecture of porous monolithic contact layers creates the possibility to perform photovoltaic measurements while the perovskite crystallizes within this scaffold. The kinetics of crystallization in a solution based 2-step formation process has been analyzed by real-time measurement of the external photon to electron quantum efficiency as well as the photoluminescence emission spectra of the solar cell. With this method it was in particular possible to identify a previously overlooked crystallization stage during the formation of the perovskite absorber layer. This stage has significant influence on the development of the photocurrent, which is attributed to the formation of electrical pathways between the electron and hole contact, enabling efficient charge carrier extraction. We observe that in contrast to previously suggested models, the perovskite layer formation is indeed not complete with the end of crystal growth.

Therapeutic drug monitoring for colistin therapy in severe multi-resistant Acinetobacter intracerebral abscess: A single case study with high-dose colistin and review of literature.

OBJECTIVES: Intracranial infections due to multidrug- resistant (MDR) gram-negative pathogens are associated with increased morbidity and mortality. As therapeutic options are limited and systemic drug penetration into the infection focus is difficult, intraventricular therapy has been described. METHODS: We report on a patient with intracranial abscess caused by MDR Acinetobacter baumannii. RESULTS: He was treated with high doses of intravenous and intraventricular colistin resulting in microbiological clearance and clinical cure. Therapy was controlled by therapeutic drug monitoring (TDM) of serum and liquor colistin levels. About 100 cases with intraventricular or intrathecal colistin are reported in literature but data on TDM are sparse. CONCLUSIONS: This is one of the first cases providing data on TDM for locally administered high dose colistin therapy for the treatment of intracranial abscess formations. Based on these findings, increasing the intraventricular application interval paralleled with intravenous colistin could possibly be sufficient to achieve appropriate therapeutic drug levels. Further studies are needed to support alternative dosing strategies in similar cases.

Database resources of the National Center for Biotechnology Information.

In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Website. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Genome and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Probe, Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.