MIP4IBD: An Easy and Rapid Genotyping-by-Sequencing Assay for the Inflammatory Bowel Diseases Risk Loci.

Background: Inflammatory bowel diseases (IBD) are polygenic, with many genetic variants contributing to disease risk. Knowing the genotype of specific variants or calculating a combined genetic risk score benefits translational and functional research. To address this, we developed MIP4IBD, a flexible and cost-effective genotyping-by-sequencing assay using molecular inversion probes (MIPs).

Improvement of the Ferroelectric Response of La-Doped Hafnium Zirconium Oxide Employing Tungsten Oxide Interfacial Layer with Back-End-of-Line Compatibility.

In this work, the impact of a tungsten oxide (WO) seed and capping layer for ferroelectric La-doped (Hf, Zr)O (La:HZO) based capacitors, designed with back-end-of-line (BEOL) compatibility, is systematically investigated. The WO capping layer supplies oxygen to the La:HZO layer throughout the fabrication process and during device cycling. This facilitates the annihilation of oxygen vacancies (V) within the La:HZO layer, thereby stabilizing its ferroelectric orthorhombic phase and resulting in an increase of the remanent polarization (P) value in the capacitor.

Comprehensive Investigation of Constant Voltage Stress Time-Dependent Breakdown and Cycle-to-Breakdown Reliability in Y-Doped and Si-Doped HfO Metal-Ferroelectric-Metal Memory.

In this study, we comprehensively investigate the constant voltage stress (CVS) time-dependent breakdown and cycle-to-breakdown while considering metal-ferroelectric-metal (MFM) memory, which has distinct domain sizes induced by different doping species, i.e., Yttrium (Y) (Sample A) and Silicon (Si) (Sample B).

Diversity and Clonality of T Cell Receptor Repertoire and Antigen Specificities in Small Joints of Early Rheumatoid Arthritis.

Objective: CD4+ T cells are implicated in rheumatoid arthritis (RA) pathology from the strong association between RA and certain HLA class II gene variants. This study was undertaken to examine the synovial T cell receptor (TCR) repertoire, T cell phenotypes, and T cell specificities in small joints of RA patients at time of diagnosis before therapeutic intervention.

Methods: Sixteen patients, of whom 11 patients were anti-citrullinated protein antibody (ACPA)-positive and 5 patients were ACPA-, underwent ultrasound-guided synovial biopsy of a small joint (n = 13) or arthroscopic synovial biopsy of a large joint (n = 3), followed by direct sorting of single T cells for paired sequencing of the αβ TCR together with flow cytometry analysis.

Comparative analysis of antibody- and lipid-based multiplexing methods for single-cell RNA-seq.

Background: Multiplexing of samples in single-cell RNA-seq studies allows a significant reduction of the experimental costs, straightforward identification of doublets, increased cell throughput, and reduction of sample-specific batch effects. Recently published multiplexing techniques using oligo-conjugated antibodies or -lipids allow barcoding sample-specific cells, a process called "hashing."

Results: Here, we compare the hashing performance of TotalSeq-A and -C antibodies, custom synthesized lipids and MULTI-seq lipid hashes in four cell lines, both for single-cell RNA-seq and single-nucleus RNA-seq.

A FeFET with a novel MFMFIS gate stack: towards energy-efficient and ultrafast NVMs for neuromorphic computing.

The discovery of ferroelectricity in the fluorite structure based hafnium oxide (HfO) material sparked major efforts for reviving the ferroelectric field effect transistor (FeFET) memory concept. A Novel metal-ferroelectric-metal-ferroelectric-insulator-semiconductor (MFMFIS) FeFET memory is reported based on dual ferroelectric integration as an MFM and MFIS in a single gate stack using Si-doped Hafnium oxide (HSO) ferroelectric (FE) material. The MFMFIS top and bottom electrode contacts, dual HSO based ferroelectric layers, and tailored MFM to MFIS area ratio (AR-TB) provide a flexible stack structure tuning for improving the FeFET performance.

Ferroelectricity in Si-Doped Hafnia: Probing Challenges in Absence of Screening Charges.

The ability to develop ferroelectric materials using binary oxides is critical to enable novel low-power, high-density non-volatile memory and fast switching logic. The discovery of ferroelectricity in hafnia-based thin films, has focused the hopes of the community on this class of materials to overcome the existing problems of perovskite-based integrated ferroelectrics. However, both the control of ferroelectricity in doped-HfO and the direct characterization at the nanoscale of ferroelectric phenomena, are increasingly difficult to achieve.

Author Correction: Gene-associated markers provide tools for tackling illegal fishing and false eco-certification.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Positive non-linear capacitance: the origin of the steep subthreshold-slope in ferroelectric FETs.

We show that the non-linear positive capacitance (PC) of ferroelectrics (FE) can explain the steep subthreshold-slope (SS) observed in FE based MOSFETs and often attributed to the existence of a negative capacitance in FE capacitors. Physically attainable and unattainable regions of the S-shape curve used in the negative capacitance theory are investigated by self-consistently solving Landau-Khalatnikov and Maxwell equations and by experimental validation. Finally, the conditions for attaining a steep SS in FE based MOSFETs assuming only positive capacitances are discussed.

DNA barcoding fishes from the Congo and the Lower Guinean provinces: Assembling a reference library for poorly inventoried fauna.

The Congolese and Lower Guinean ichthyological provinces are understudied hotspots of the global fish diversity. Here, we barcoded 741 specimens from the Lower and Middle Congo River and from three major drainage basins of the Lower Guinean ichthyological province, Kouilou-Niari, Nyanga and Ogowe. We identified 194 morphospecies belonging to 82 genera and 25 families.

ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart.

Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR-/-; ob/ob, DKO) relative to the healthy, control heart (C57BL/6, WT) and the transcriptional changes induced by ACE-inhibition in those hearts. RNA-Seq, differential gene expression and transcription factor analysis identified 288 genes differentially expressed between DKO and WT hearts implicating 72 pathways.

Describing the Reportable Range Is Important for Reliable Treatment Decisions: A Multiple Laboratory Study for Molecular Tumor Profiling Using Next-Generation Sequencing.

Because interpretation of next-generation sequencing (NGS) data remains challenging, optimization of the NGS process is needed to obtain correct sequencing results. Therefore, extensive validation and continuous monitoring of the quality is essential. NGS performance was compared with traditional detection methods and technical quality of nine NGS technologies was assessed.

The flexoelectric effect in Al-doped hafnium oxide.

After the successful introduction as a replacement for the SiO2 gate dielectric in metal-oxide-semiconductor field-effect transistors, HfO2 is currently one of the most studied binary oxide systems with ubiquitous applications in nanoelectronics. For years, the interest of microelectronic downscaling has focused on tuning the dielectric constant of HfO2, particularly for monoclinic and tetragonal phases. Recently, Müller et al.

Neurogenomic Profiling Reveals Distinct Gene Expression Profiles Between Brain Parts That Are Consistent in Cichlids.

The detection of external and internal cues alters gene expression in the brain which in turn may affect neural networks that underly behavioral responses. Previous studies have shown that gene expression profiles differ between major brain regions within individuals and between species with different morphologies, cognitive abilities and/or behaviors. A detailed description of gene expression in all macroanatomical brain regions and in species with similar morphologies and behaviors is however lacking.

Performance and precision of double digestion RAD (ddRAD) genotyping in large multiplexed datasets of marine fish species.

The development of Genotyping-By-Sequencing (GBS) technologies enables cost-effective analysis of large numbers of Single Nucleotide Polymorphisms (SNPs), especially in "non-model" species. Nevertheless, as such technologies enter a mature phase, biases and errors inherent to GBS are becoming evident. Here, we evaluated the performance of double digest Restriction enzyme Associated DNA (ddRAD) sequencing in SNP genotyping studies including high number of samples.

Acute Drug Effects on the Human Placental Tissue: The Development of a Placental Murine Xenograft Model.

Objective: A pilot study was conducted to establish a human placental xenograft, which could serve as a model to evaluate the effect of toxic exposures during pregnancy.

Study Design: The protocol consisted of engraftment of third-trimester human placental tissue in immunocompromised mice, after induction of a pseudo-pregnancy state by ovariectomy and progesterone supplementation. To validate the model, the placental tissue before and after engraftment was examined by immunohistochemistry, fluorescence-activated cell sorting (FACS), single-nucleotide polymorphism (SNP) genotyping, and whole transcriptome sequencing (WTSS).

Spatial dynamics and mixing of bluefin tuna in the Atlantic Ocean and Mediterranean Sea revealed using next-generation sequencing.

The Atlantic bluefin tuna is a highly migratory species emblematic of the challenges associated with shared fisheries management. In an effort to resolve the species' stock dynamics, a genomewide search for spatially informative single nucleotide polymorphisms (SNPs) was undertaken, by way of sequencing reduced representation libraries. An allele frequency approach to SNP discovery was used, combining the data of 555 larvae and young-of-the-year (LYOY) into pools representing major geographical areas and mapping against a newly assembled genomic reference.

Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for Long-term Toxicity Applications: A Multicenter Study.

Primary human hepatocytes (PHHs) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHHs are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids.

Antibiotic Resistance Plasmids Cointegrated into a Megaplasmid Harboring the Carbapenemase Gene.

OXA-427 is a new class D carbapenemase encountered in different species of in a Belgian hospital. To study the dispersal of this gene, we performed a comparative analysis of two plasmids containing the gene, isolated from a strain and an complex strain. The two IncA/C2 plasmids containing share the same backbone; in the strain, however, this plasmid is cointegrated into an IncFIb plasmid, forming a 321-kb megaplasmid with multiple multiresistance regions.

In vitro Phase I- and Phase II-Drug Metabolism in The Liver of Juvenile and Adult Göttingen Minipigs.

Purpose: In view of pediatric drug development, juvenile animal studies are gaining importance. However, data on drug metabolizing capacities of juvenile animals are scarce, especially in non-rodent species. Therefore, we aimed to characterize the in vitro biotransformation of four human CYP450 substrates and one UGT substrate in the livers of developing Göttingen minipigs.

Distinct Effects of T-705 (Favipiravir) and Ribavirin on Influenza Virus Replication and Viral RNA Synthesis.

T-705 (favipiravir) is a new antiviral agent in advanced clinical development for influenza therapy. It is supposed to act as an alternative substrate for the viral polymerase, causing inhibition of viral RNA synthesis or virus mutagenesis. These mechanisms were also proposed for ribavirin, an established and broad antiviral drug that shares structural similarity with T-705.

A catalog of hemizygous variation in 127 22q11 deletion patients.

The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.

Polymerase specific error rates and profiles identified by single molecule sequencing.

DNA polymerases have an innate error rate which is polymerase and DNA context specific. Historically the mutational rate and profiles have been measured using a variety of methods, each with their own technical limitations. Here we used the unique properties of single molecule sequencing to evaluate the mutational rate and profiles of six DNA polymerases at the sequence level.