Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA ...sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is not achieved, local phasing (across >150-kb regions) is routine, as molecules from the parental chromosomes are examined separately. In one experiment, we generated genome maps from a trio from the 1000 Genomes Project, compared the maps against that derived from the reference human genome, and identified structural variations that are >5 kb in size. We find that these individuals have many more structural variants than those published, including some with the potential of disrupting gene function or regulation.
The corresponding energy landscape and surface potential are deduced from the experimental ferroelectricity of HfZrO 2 (HZO) for low-power steep-slope transistor applications. The anti-ferroelectric ...(AFE) in annealed 600°C HZO extracted electrostatic potential gain from the measured polarization hysteresis loop and calculated subthreshold swing 33 mV/dec over six decades of I DS . A feasible concept of coupling the AFE HZO is experimentally established with the validity of negative capacitance and beneficial for steep-slope FET development in future generation.
Dielectric constant of non-fullerene acceptors plays a critical role in organic solar cells in terms of exciton dissociation and charge recombination. Current acceptors feature a dielectric constant ...of 3-4, correlating to relatively high recombination loss. We demonstrate that selenium substitution on acceptor central core can effectively modify molecule dielectric constant. The corresponding blend film presents faster hole-transfer of ~5 ps compared to the sulfur-based derivative (~10 ps). However, the blends with Se-acceptor also show faster charge recombination after 100 ps upon optical pumping, which is explained by the relatively disordered stacking of the Se-acceptor. Encouragingly, dispersing the Se-acceptor in an optimized organic solar cell system can interrupt the disordered aggregation while still retain high dielectric constant. With the improved dielectric constant and optimized fibril morphology, the ternary device exhibits an obvious reduction of non-radiative recombination to 0.221 eV and high efficiency of 19.0%. This work unveils heteroatom-substitution induced dielectric constant improvement, and the associated exciton dynamics and morphology manipulation, which finally contributes to better material/device design and improved device performance.
Summary
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by extensive epidermal detachment and mucositis. Both are associated with a high ...mortality rate and significant long‐term morbidity. Since the initial report introducing the term TEN in 1956, diagnosis of the condition has been fraught with difficulties that continue to exist today. The terms ‘erythema multiforme major’ (EMM) and SJS, and their relationship to TEN have also been confusing to clinicians. It is now recognized that EMM is a different entity from SJS and TEN in terms of demographics, causality and severity. SJS and TEN represent a continuum of disease, and differ only by the extent of epidermal detachment and therefore severity. The term ‘epidermal necrolysis’ (EN) is used in this article to describe the spectrum of disease that includes SJS and TEN. Important advances in understanding the pathomechanism and treatment of EN have been made over the years. These include the recognition of human leucocyte antigen (HLA) associations (e.g. HLA‐B*1502 with carbamazepine‐induced TEN) and understanding of the pathogenic roles of drug‐specific cytotoxic T cells and granulysin. It was previously believed that widespread keratinocyte death in EN is predominantly mediated by soluble Fas‐ligand and that intravenous immunoglobulin therapy is useful in blocking this mechanism with resultant survival benefits. Further studies have since proven these theories to be incorrect. This short review describes the key advances in the terminology, classification, causality and treatment of EN, and identifies future priorities and challenges in the understanding and management of this condition.
The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 (
) and
(
) transcription factors, when they either are expressed alone or are coexpressed, ...are ill-defined. We created a mouse model for the campomelic dysplasia
mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that
causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea. By contrast, conditional heterozygous
-null mice are normal. During the ES development of
heterozygotes,
and genes important for ionic homeostasis are down-regulated, and there is developmental persistence of progenitors, resulting in fewer mature cells.
heterozygous null mutants also display persistence of ES/duct progenitors. By contrast, SOX10 retains its expression in the early
mutant cochlea. Later, in the postnatal stria vascularis, dominant interference by SOX9
is implicated in impairing the normal cooperation of SOX9 and SOX10 in repressing the expression of the water channel Aquaporin 3, thereby contributing to endolymphatic hydrops. Our study shows that for a functioning endolymphatic system in the inner ear, SOX9 regulates
, and depending on the cell type and target gene, it works either independently of or cooperatively with SOX10. SOX9
can interfere with the activity of both SOXE factors, exerting effects that can be classified as haploinsufficient/hypomorphic or dominant negative depending on the cell/gene context. This model of disruption of transcription factor partnerships may be applicable to congenital deafness, which affects ∼0.3% of newborns, and other syndromic disorders.
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