13 research outputs found
Hydraulic Transport Across Hydrophilic and Hydrophobic Nanopores: Flow Experiments with Water and n-Hexane
We experimentally explore pressure-driven flow of water and n-hexane across
nanoporous silica (Vycor glass monoliths with 7 or 10 nm pore diameters,
respectively) as a function of temperature and surface functionalization
(native and silanized glass surfaces). Hydraulic flow rates are measured by
applying hydrostatic pressures via inert gases (argon and helium, pressurized
up to 70 bar) on the upstream side in a capacitor-based membrane permeability
setup. For the native, hydrophilic silica walls, the measured hydraulic
permeabilities can be quantitatively accounted for by bulk fluidity provided we
assume a sticking boundary layer, i.e. a negative velocity slip length of
molecular dimensions. The thickness of this boundary layer is discussed with
regard to previous capillarity-driven flow experiments (spontaneous imbibition)
and with regard to velocity slippage at the pore walls resulting from dissolved
gas. Water flow across the silanized, hydrophobic nanopores is blocked up to a
hydrostatic pressure of at least 70 bar. The absence of a sticking boundary
layer quantitatively accounts for an enhanced n-hexane permeability in the
hydrophobic compared to the hydrophilic nanopores.Comment: 15 pages, 7 figures, in press, Physical Review E 201
Clinician's guide to genes associated with Rett-like phenotypes - Investigation of a Danish cohort and review of the literature
The differential diagnostics in Rett syndrome has evolved with the development of next generation sequencing-based techniques and many patients have been diagnosed with other syndromes or variants in newly described genes where the associated phenotype(s) is yet to be fully explored. The term Rett-like refers to phenotypes with distinct overlapping features of Rett syndrome where the clinical criteria are not completely fulfilled. In this study we have combined a review of Rett-like disorders with data from a Danish cohort of 35 patients with Rett-like phenotypes emphasizing the diagnostic overlap with Pitt-Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants. We also found a patient with a pathogenic variant in KCNB1, which has not been previously linked to a Rett-like phenotype. This study underlines the clinical and genetic heterogeneity of a Rett syndrome spectrum, and provides an overview of the Rett syndrome-related genes described to date, and hence serves as a guide for diagnosing patients with Rett-like phenotypes
Predicting drug susceptibility of non–small cell lung cancers based on genetic lesions
Somatic genetic alterations in cancers have been linked with response to targeted therapeutics by creation of specific dependency on activated oncogenic signaling pathways. However, no tools currently exist to systematically connect such genetic lesions to therapeutic vulnerability. We have therefore developed a genomics approach to identify lesions associated with therapeutically relevant oncogene dependency. Using integrated genomic profiling, we have demonstrated that the genomes of a large panel of human non–small cell lung cancer (NSCLC) cell lines are highly representative of those of primary NSCLC tumors. Using cell-based compound screening coupled with diverse computational approaches to integrate orthogonal genomic and biochemical data sets, we identified molecular and genomic predictors of therapeutic response to clinically relevant compounds. Using this approach, we showed that v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations confer enhanced Hsp90 dependency and validated this finding in mice with KRAS-driven lung adenocarcinoma, as these mice exhibited dramatic tumor regression when treated with an Hsp90 inhibitor. In addition, we found that cells with copy number enhancement of v-abl Abelson murine leukemia viral oncogene homolog 2 (ABL2) and ephrin receptor kinase and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (SRC) kinase family genes were exquisitely sensitive to treatment with the SRC/ABL inhibitor dasatinib, both in vitro and when it xenografted into mice. Thus, genomically annotated cell-line collections may help translate cancer genomics information into clinical practice by defining critical pathway dependencies amenable to therapeutic inhibition
Additional file 1 of Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning
Supplementary Material 1: Figure 1. Flow chart demonstrating the number of AATD and Non-AATD patients at each research database and the respective recording perio