21 research outputs found
Atomistic defect states as quantum emitters in monolayer MoS
Quantum light sources in solid-state systems are of major interest as a basic
ingredient for integrated quantum device technologies. The ability to tailor
quantum emission through deterministic defect engineering is of growing
importance for realizing scalable quantum architectures. However, a major
difficulty is that defects need to be positioned site-selectively within the
solid. Here, we overcome this challenge by controllably irradiating
single-layer MoS using a sub-nm focused helium ion beam to
deterministically create defects. Subsequent encapsulation of the ion bombarded
MoS flake with high-quality hBN reveals spectrally narrow emission lines
that produce photons at optical wavelengths in an energy window of one to two
hundred meV below the neutral 2D exciton of MoS. Based on ab-initio
calculations we interpret these emission lines as stemming from the
recombination of highly localized electron-hole complexes at defect states
generated by the helium ion bombardment. Our approach to deterministically
write optically active defect states in a single transition metal
dichalcogenide layer provides a platform for realizing exotic many-body
systems, including coupled single-photon sources and exotic Hubbard systems.Comment: Main: 9 pages, 3 figures + SI: 19 pages, 10 figure
The Guinea Pig as a model for sporadic Alzheimer's Disease (AD): the impact of cholesterol intake on expression of AD-related genes
Extent: 12p.We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes.Mathew J. Sharman, Seyyed H. Moussavi Nik, Mengqi M. Chen, Daniel Ong, Linda Wijaya, Simon M. Laws, Kevin Taddei, Morgan Newman, Michael Lardelli, Ralph N. Martins, Giuseppe Verdil
Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer's disease
Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most frequent cause of dementia. To date, there are only a few approved drugs for AD, which show little or no effect on disease progression. Impaired intracellular calcium homeostasis is believed to occur early in the cascade of events leading to AD. Here, we examined the possibility of normalizing the disrupted calcium homeostasis in the endoplasmic reticulum (ER) store as an innovative approach for AD drug discovery. High-throughput screening of a small-molecule compound library led to the identification of tetrahydrocarbazoles, a novel multifactorial class of compounds that can normalize the impaired ER calcium homeostasis. We found that the tetrahydrocarbazole lead structure, first, dampens the enhanced calcium release from ER in HEK293 cells expressing familial Alzheimer's disease (FAD)-linked presenilin 1 mutations. Second, the lead structure also improves mitochondrial function, measured by increased mitochondrial membrane potential. Third, the same lead structure also attenuates the production of amyloid-beta (A beta) peptides by decreasing the cleavage of amyloid precursor protein (APP) by beta-secretase, without notably affecting alpha- and gamma-secretase cleavage activities. Considering the beneficial effects of tetrahydrocarbazoles addressing three key pathological aspects of AD, these compounds hold promise for the development of potentially effective AD drug candidates
Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons
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Hydrogen evolution activity of individual mono-, bi-, and few-layer MoS2 towards photocatalysis
We investigate the hydrogen evolution activity in the dark and under illumination above the band gap of individual mono-, bi- and few-layer (bulk) MoS2 flakes. We demonstrate that the electrocatalytic activity of 2H-MoS2 immersed in 1 M H2SO4 increases with decreasing number of layers. For monolayers, we observe the highest exchange current density, which is one magnitude larger than in the bulk case. The onset potential scales with the number of layers, which is consistent with a previous report, suggesting that hopping transport across inter-layer barriers within the MoS2 flakes is responsible for this scaling. A specially designed micro-sized catalytic cell enables us to investigate individual MoS2 flakes with well-known geometry and edge-to-surface ratio. Taking these geometric parameters into account, we tentatively attribute the catalytic activity mainly to sulfur vacancies in the basal planes acting as active sites. The associated turn over frequencies (TOF) for mono- and bi-layer MoS2 yield values higher than 103 s−1 at an overpotential of −0.2 V vs. RHE. In view of light driven hydrogen evolution as a means of solar energy conversion, we investigate the photocatalytic activity of few-layer MoS2 under white light illumination
Surface chemistry of 1- and 3-Hexyne on Pt(111): desorption, decomposition and dehydrocyclization
Despite their industrial use in selective hydrogenation reactions, the surface chemistry of long-chained alkynes on transition metals is not well understood. To this end, the two C6-alkynes 1- and 3-hexyne were studied on Pt(111) using temperature-programmed desorption (TPD), electron emission spectroscopies (MIES/UPS), and infrared reflection–absorption spectroscopy (IRRAS). Besides the formation of graphitic carbon residues, both molecules mainly undergo desorption, self-hydrogenation, and dehydrocyclization to form benzene during temperature-programmed desorption, similar to the analogous alkenes. The dehydrocyclization to benzene is shown to be ubiquitous to unsaturated hydrocarbons on Pt(111) regardless of the degree of unsaturation and its position within the molecule. A reaction mechanism for dehydrocyclization is proposed based on dehydrogenation followed by ring-closure. This work extends the understanding of alkyne chemistry on Pt-based catalysts and may aid to identify additional reaction mechanisms leading to undesired coke formation
Surface Chemistry of 1- and 3‑Hexyne on Pt(111): Desorption, Decomposition, and Dehydrocyclization
Despite
their industrial use in selective hydrogenation reactions,
the surface chemistry of long-chained alkynes on transition metals
is not well understood. To this end, the two C<sub>6</sub>-alkynes
1- and 3-hexyne were studied on Pt(111) using temperature-programmed
desorption (TPD), electron emission spectroscopies (MIES/UPS), and
infrared reflection–absorption spectroscopy (IRRAS). Besides
the formation of graphitic carbon residues, both molecules mainly
undergo desorption, self-hydrogenation, and dehydrocyclization to
form benzene during temperature-programmed desorption, similar to
the analogous alkenes. The dehydrocyclization to benzene is shown
to be ubiquitous to unsaturated hydrocarbons on Pt(111) regardless
of the degree of unsaturation and its position within the molecule.
A reaction mechanism for dehydrocyclization is proposed based on dehydrogenation
followed by ring-closure. This work extends the understanding of alkyne
chemistry on Pt-based catalysts and may aid to identify additional
reaction mechanisms leading to undesired coke formation
Prevalence of Intrathecal Acyclovir Resistant Virus in Herpes Simplex Encephalitis Patients.
Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR-associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients
Viral thymidine kinase polymorphisms in clinical samples obtained from herpes simplex encephalitis patients.
<p>Viral thymidine kinase polymorphisms in clinical samples obtained from herpes simplex encephalitis patients.</p
Demographics and clinical characteristics of herpes simplex encephalitis patients.
<p>Demographics and clinical characteristics of herpes simplex encephalitis patients.</p