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The contiguity and phase of sequence information are intrinsic to obtain complete understanding of the genome and its relationship to phenotype. We report the fabrication and application of a novel nanochannel design that folds megabase lengths of genomic DNA into a systematic back-and-forth meandering path. Such meandering nanochannels enabled us to visualize the complete 5.7 Mbp (1mm) stained DN
Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. Here, we report that inhibition of the epigenetic regulator Lysine-specific histone demethylase 1A (LSD1) induces a rapid expansion of human cord blood derived CD34+ cells and promotes in vitro propagation of long-term repopulating HSCs by preventing differentiation. The phenot
Background: Procalcitonin (PCT) is a biomarker used to differentiate between viral and bacterial infections, though the underlying mechanisms are not yet fully understood. This study aimed to identify genetic variants associated with plasma PCT concentrations and explore the associations of genetically predicted PCT with a wide range of disease related traits in a PheWAS. Methods: We conducted GWA
Studies of the surface chemistry of the first few cycles of atomic layer deposition (ALD) using in situ and time-resolved operando techniques are attractive for realizing, understanding, and obtaining true mechanistic information during the deposition. However, the latter techniques are yet to be applied to ALD of metal nitrides. Here, we present a surface-chemistry investigation through a time-re
X-rays are commonly used in imaging experiments due to their penetration power, which enables non-destructive resolution of internal structures in samples that are opaque to visible light. Time-resolved X-ray tomography is the state-of-the-art method for obtaining volumetric 4D (3D + time) information by rotating the sample and acquiring projections from different angular viewpoints over time. Thi
In recent years, the automotive industry has increasingly prioritized comfort to meet rising consumer expectations for luxurious car experiences. Comfort, a subjective concept associated with well-being and relaxation, encompasses multidimensional aspects rooted in physical, psychological, and functional aspects. While existing comfort models focus mainly on seated positions and sensations like fa
Time- and Angle-Resolved Photoelectron Spectroscopy (tr-ARPES) is employed to monitor photoexcited electrons in the 2D hybrid perovskite (BA) (Formula presented.) (MA) (Formula presented.) (Formula presented.) (Formula presented.). Photoelectron intensity maps are in good agreement with ab-initio calculations of the band structure. The effective mass is (Formula presented.) and (Formula presented.
Multi-beam ptychography (MBP) offers a scalable solution to improve the throughput of state-of-the-art ptychography by increasing the number of coherent beams that illuminate the sample simultaneously. However, increasing the number of beams in ptychography makes ptychographical reconstructions more challenging and less robust. It has been demonstrated that MBP reconstructions can be made more rob
Heterochromatin is characterized by an inaccessibility to the transcriptional machinery and is associated with the histone mark H3K9me3. However, studying the functional consequences of heterochromatin loss in human cells has been challenging. Here, we used CRISPRi-mediated silencing of the histone methyltransferase SETDB1 to remove H3K9me3 heterochromatin in human neural progenitor cells. Despite
Background: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) enables sensitive detection and staging of prostate cancer, yet its relationship with long-term survival remains unclear. This study aimed to assess whether total lesion volume (TLV) measured on [18F]PSMA-1007 PET/CT predicts overall survival (OS) in prostate cancer patients. Methods: A co
The proline-rich domain (PRD) of the tumor suppressor p53 plays a central role in modulating conformational dynamics and molecular interactions, yet its intrinsic structural behavior remains incompletely understood. Here, we combine extensive all-atom molecular dynamics simulations with biophysical validation to characterize the conformational ensemble of the p53 PRD. The domain behaves as an intr
Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid l
The leading cause of morbidity and mortality worldwide is atherosclerotic cardiovascular disease, most commonly caused by rupture of a high-risk plaque and subsequent thrombosis resulting in stroke, myocardial infarction or sudden death depending on the affected arterial territory. Accurate, non-invasive methods to identify such lesions known as vulnerable or high-risk plaques are currently sub-op
The antibody microarrays have become widespread, but their use for quantitative analyses in clinical samples has not yet been established. We investigated an immunoassay based on nanoporous silicon antibody microarrays for quantification of total prostate-specific-antigen (PSA) in 80 clinical plasma samples, and provide quantitative data from a duplex microarray assay that simultaneously quantifie
Previous studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans.
Prostate specific antigen (PSA) is a well-established tumor marker, which is frequently employed as model biomarker to develop and evaluate emerging quantitative proteomics techniques, partially due to wide access to commercialized immunoassays serving as "gold standard". We designed a multiple reaction monitoring (MRM) assay to detect PSA proteoforms in clinical samples (n=72), utilizing specific
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. There have been several reports of miRNA deregulation in prostate cancer and the biological evidence for an involvement of miRNAs in prostate tumorigenesis is increasing. In this study, we show that miR-34c is downregulated in prostate cancer (p = 0.0005) by performing qRT-PCR on 49 TURPs from prosta
To evaluate the progression of carotid intima-media thickness (IMT) in the common carotid artery (CCA) and the bifurcation over a mean follow-up of 16 years in relation to cardiovascular risk factors.
