Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, ...depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the ID edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
The nuclear envelope represents a key barrier to successful nonviral transfection and gene therapy both in vitro and in vivo. Although the main purpose of the nuclear envelope is to partition the ...cell to maintain cytoplasmic components in the cytoplasm and nuclear components, most notably genomic DNA, in the nucleus, this function poses a problem for transfections in which exogenous DNA is delivered into the cytoplasm. After delivery to the cytoplasm, nucleic acids rapidly become complexed with cellular proteins that mediate interactions with the cellular machinery for trafficking. Thus, it is these proteins that, in essence, control the nuclear import of DNA, and we must also understand their activities in cells. In this review, we will discuss the principles of nuclear import of proteins and DNA-protein complexes, as well as the various approaches that investigators have used to improve nuclear targeting of plasmids. These approaches include complexation of plasmids with peptides, native and engineered proteins, ligands and polymers, as well as the inclusion of transcription factor-binding sites for general and cell-specific delivery.
nonviral gene transfermid R:plasmidmid R:nuclear pore complexmid R:importinmid R:nuclear localization signalmid R:karyopherin.
The terahertz (THz) frequency quantum cascade laser (QCL) is a compact source of THz radiation offering high power, high spectral purity and moderate tunability. As such, these sources are ...particularly suited to the application of THz frequency imaging across a range of disciplines, and have motivated significant research interest in this area over the past decade. In this paper we review the technological approaches to THz QCL-based imaging and the key advancements within this field. We discuss in detail a number of imaging approaches targeted to application areas including multiple-frequency transmission and diffuse reflection imaging for the spectral mapping of targets; as well as coherent approaches based on the self-mixing phenomenon in THz QCLs for long-range imaging, three-dimensional imaging, materials analysis, and high-resolution inverse synthetic aperture radar imaging.
Au‐ff on a trip: Chiral ligands (L*) and chiral anions (S)‐TriPAg are employed in the gold(I)‐catalyzed enantioselective intramolecular additions of hydrazines and hydroxylamines to allenes. These ...complementary methods allow access to chiral vinyl isoxazolidines, oxazines, and differentially protected pyrazolidines. PNB=para‐nitrobenzoyl.
Abstract Background It has been suggested that health care professional (HCP) attitudes and beliefs may negatively influence the beliefs of patients with low back pain (LBP), but this has not been ...systematically reviewed. This review aimed to investigate the association between HCP attitudes and beliefs and the attitudes and beliefs, clinical management, and outcomes of this patient population. Methods Electronic databases were systematically searched for all types of studies. Studies were selected by predefined inclusion criteria. Methodological quality was appraised and strength of evidence was determined. Results Seventeen studies from eight countries which investigated the attitudes and beliefs of general practitioners, physiotherapists, chiropractors, rheumatologists, orthopaedic surgeons and other paramedical therapists were included. There is strong evidence that HCP beliefs about back pain are associated with the beliefs of their patients. There is moderate evidence that HCPs with a biomedical orientation or elevated fear avoidance beliefs are more likely to advise patients to limit work and physical activities, and are less likely to adhere to treatment guidelines. There is moderate evidence that HCP attitudes and beliefs are associated with patient education and bed rest recommendations. There is moderate evidence that HCP fear avoidance beliefs are associated with reported sick leave prescription and that a biomedical orientation is not associated with the number of sickness certificates issued for LBP. Conclusion HCPs need to be aware of the association between their attitudes and beliefs and the attitudes and beliefs and clinical management of their patients with LBP.
This Letter reports the first measurement of the 235U $\bar{ν}$e energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MWth highly ...enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) $\bar{ν}$e-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to 235U. Despite broad agreement, comparison of the Huber 235U model to the measured spectrum produces a χ2/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured 235U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the $\bar{ν}$e energy region of 5–7 MeV.
We have reported that a rapid tail vein injection of a large volume of plasmid DNA solution into a mouse results in high level of transgene expression in the liver. Gene transfer efficiency of this ...hydrodynamics-based procedure is determined by the combined effect of a large volume and high injection speed. Here, we show that the hydrodynamic injection induces a transient irregularity of heart function, a sharp increase in venous pressure, an enlargement of liver fenestrae, and enhancement of membrane permeability of the hepatocytes. At the cellular level, our results suggest that hepatic delivery by the hydrodynamic injection is accomplished by the generation of membrane pores in the hepatocytes.
This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor ...Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.
The fallopian tube epithelium (FTE) is one of the progenitor populations for high-grade serous ovarian cancer (HGSC). Loss of PAX2 is the earliest known molecular aberration in the FTE occurring in ...serous carcinogenesis followed by a mutation in p53. Pathological studies report consistent loss of PAX2 in benign lesions as well as serous tumors. In the current study, the combined loss of PAX2 and expression of the R273H p53 mutant protein in murine oviductal epithelial (MOE) cells enhanced proliferation and growth in soft agar in vitro but was insufficient to drive tumorigenesis in vivo. A serially passaged model was generated to investigate the role of aging, but was also insufficient to drive tumorigenesis. These models recapitulate early benign lesions and suggest that a latency period exists between loss of PAX2, p53 mutation and tumor formation. Stathmin and fut8 were identified as downstream targets regulated by loss of PAX2 and mutation of p53 in MOE cells. Re-expression of PAX2 in PAX2-null human HGSC cells reduced cell survival via apoptosis. Phosphatase and tensin homolog (PTEN)
negatively regulated PAX2 expression and stable re-expression of PAX2 in MOE:PTEN
cells significantly reduced proliferation and peritoneal tumor formation in athymic nude mice. PAX2 was determined to be a direct transcriptional target that was activated by wild-type p53, whereas mutant p53 inhibited PAX2 transcription in MOE cells. A small molecule screen using the proximal PAX2 promoter driving luciferase identified four small molecules that were able to enhance PAX2 mRNA expression in MOE cells. PAX2 re-expression in HGSC cells and PTEN-deficient oviductal tumors may have the potential to induce apoptosis. In summary, mutant p53 and PTEN loss negatively regulated PAX2 and PAX2 re-expression in HGSC cells induced cell death.
The design of minimum CRISPR RNA (crRNA) sets for detection of diverse RNA targets using sequence degeneracy has not been systematically addressed. We tested candidate degenerate Cas13a crRNA sets ...designed for detection of diverse RNA targets (Lassa virus). A decision tree machine learning (ML) algorithm (RuleFit) was applied to define the top attributes that determine the specificity of degenerate crRNAs to elicit collateral nuclease activity. Although the total number of mismatches (0-4) is important, the specificity depends as well on the spacing of mismatches, and their proximity to the 5' end of the spacer. We developed a predictive algorithm for design of candidate degenerate crRNA sets, allowing improved discrimination between "included" and "excluded" groups of related target sequences. A single degenerate crRNA set adhering to these rules detected representatives of all Lassa lineages. Our general ML approach may be applied to the design of degenerate crRNA sets for any CRISPR/Cas system.
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