Memristive devices are an emerging technology that enables both rich interdisciplinary science and novel device functionalities, such as nonvolatile memories and nanoionics-based synaptic ...electronics. Recent work has shown that the reproducibility and variability of the devices depend sensitively on the defect structures created during electroforming as well as their continued evolution under dynamic electric fields. However, a fundamental principle guiding the material design of defect structures is still lacking due to the difficulty in understanding dynamic defect behavior under different resistance states. Here, we unravel the existence of threshold behavior by studying model, single-crystal devices: resistive switching requires that the pristine oxygen vacancy concentration reside near a critical value. Theoretical calculations show that the threshold oxygen vacancy concentration lies at the boundary for both electronic and atomic phase transitions. Through operando, multimodal X-ray imaging, we show that field tuning of the local oxygen vacancy concentration below or above the threshold value is responsible for switching between different electrical states. These results provide a general strategy for designing functional defect structures around threshold concentrations to create dynamic, field-controlled phases for memristive devices.
Due to their tunable bandgaps and strong spin-valley locking, transition metal dichalcogenides constitute a unique platform for hosting single-photon emitters. Here, we present a versatile approach ...for creating bright single-photon emitters in WSe2 monolayers by the deposition of gold nanostars. Our molecular dynamics simulations reveal that the formation of the quantum emitters is likely caused by the highly localized strain fields created by the sharp tips of the gold nanostars. The surface plasmon modes supported by the gold nanostars can change the local electromagnetic fields in the vicinity of the quantum emitters, leading to their enhanced emission intensities. Moreover, by correlating the emission energies and intensities of the quantum emitters, we are able to associate them with two types of strain fields and derive the existence of a low-lying dark state in their electronic structures. Our findings are highly relevant for the development and understanding of single-photon emitters in transition metal dichalcogenide materials.
Hydrogen donor doping of correlated electron systems such as vanadium dioxide (VO2) profoundly modifies the ground state properties. The electrical behavior of H x VO2 is strongly dependent on the ...hydrogen concentration; hence, atomic scale control of the doping process is necessary. It is however a nontrivial problem to quantitatively probe the hydrogen distribution in a solid matrix. As hydrogen transfers its sole electron to the material, the ionization mechanism is suppressed. In this study, a methodology mapping the doping distribution at subnanometer length scale is demonstrated across a H x VO2 thin film focusing on the oxygen–hydrogen bonds using electron energy loss spectroscopy (EELS) coupled with first-principles EELS calculations. The hydrogen distribution was revealed to be nonuniform along the growth direction and between different VO2 grains, calling for intricate hydrogenation mechanisms. Our study points to a powerful approach to quantitatively map dopant distribution in quantum materials relevant to energy and information sciences.
Dysphagia is a common symptom of esophageal cancer (EC). Esophagectomy should relieve the presenting dysphagia as the mechanical obstruction caused by the tumor is removed. However, the new onset ...oropharyngeal dysphagia develops after esophagectomy and the deficit may persist increasing the risk of aspiration pneumonia and mortality as well as adversely affecting quality of life (QOL). This study investigates the persistent swallowing deficits in long-term postesophagectomy patients and explores the factors associated with dysphagia severity, penetration, and aspiration. A better understanding of the swallowing function can aid future management of the condition. A total of 29 patients who were more than six months postesophagectomy for EC, had no history of disease that would likely affect swallowing function or vocal cord palsy underwent detailed videofluoroscopic swallow studies and completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and OES18 QOL questionnaires. Swallowing deficits were analyzed and rated using the videofluoroscopic dysphagia scale (VDS) and the penetration-aspiration scale (PAS). These variables were correlated with the clinical and QOL parameters to determine which factors would affect swallowing function. Our cohort consisted of 27 males and 2 females. The mean duration after esophagectomy when the swallowing study was performed was 3.2 years (range: 0.5-18.4 years). Swallowing deficits were mainly found in the pharyngeal phase of swallowing. The mean total VDS score was 36.1 (SD = 15.2, range: 11.0-69.5) out of a possible 100. The mean PAS score was 4.1 (SD = 2.5, range: 1-8) and 1.5 (SD = 0.9, range: 1-4) for thin and semisolids, respectively. Dysphagia was significantly more severe in males, those of more advanced age at esophagectomy and at swallowing assessment. Increasing pathological N stage significantly correlated with worse PAS score for thin fluid. Self-reports of more pain and less troubles with coughing were also associated with less penetration and aspiration. This study demonstrated that a mild to moderate pharyngeal dysphagia is present late after esophagectomy even in patients without VC palsy or anastomotic stricture. The long-term aspiration rate is comparable to the figures in the literature for those early after esophagectomy. It is suggested that damage to the intercostal nerves and the pulmonary vagus may affect oropharyngeal swallowing function in this population.
Functional interfaces between electronics and biological matter are essential to diverse fields including health sciences and bio-engineering. Here, we report the discovery of spontaneous (no ...external energy input) hydrogen transfer from biological glucose reactions into SmNiO
, an archetypal perovskite quantum material. The enzymatic oxidation of glucose is monitored down to ~5 × 10
M concentration via hydrogen transfer to the nickelate lattice. The hydrogen atoms donate electrons to the Ni d orbital and induce electron localization through strong electron correlations. By enzyme specific modification, spontaneous transfer of hydrogen from the neurotransmitter dopamine can be monitored in physiological media. We then directly interface an acute mouse brain slice onto the nickelate devices and demonstrate measurement of neurotransmitter release upon electrical stimulation of the striatum region. These results open up avenues for use of emergent physics present in quantum materials in trace detection and conveyance of bio-matter, bio-chemical sciences, and brain-machine interfaces.
To compare technical success, diagnostic accuracy, and histological yield of fine-needle aspiration cytology (FNAC), side-cutting (Temno) needle biopsy, and end-cutting (Franseen) needle biopsy for ...ultrasound-guided sampling of groin and axillary lymph nodes.
A total of 270 abnormal groin and axillary nodes were sampled using one of the three techniques. Nodes with a maximum length of <2.5 cm underwent FNAC or Franseen biopsy, while nodes >2.5 cm underwent Temno biopsy. Mean size of nodes sampled by FNAC (21.2 mm) and Franseen (19.7 mm) were similar while nodes sampled by Temno were larger (34.4 mm, p<0.0001).
Technical success rates of FNAC (82/93, 88%), Franseen (105/111, 95%), and Temno (59/66, 89%) biopsies were similar (p>0.05 for all). Lymphoid tissue yield by FNAC (mean total area 1.51 mm2) was less than that by Franseen (7.14 mm2, p=0.002) or Temno biopsy (19.44 mm2, p<0.0001). Diagnostic accuracy for malignancy was lower for FNAC (22/30, 73%) than Franseen (25/26, 96%, p=0.02) or Temno biopsy (32/32, 100%, p=0.002). For malignant nodes, determining the likely organ of origin was also lower for FNAC (7/30, 23%) than Franseen (19/26, 73%, p=0.0002) or Temno biopsy (29/32, 91%, p<0.0001), with a similar pattern observed in the identification of lymphoma.
For similarly sized nodes, Franseen biopsy provided more lymphoid material, a higher diagnostic accuracy for malignancy including lymphoma, and better identification of the likely organ of origin than FNAC. Routine use of Franseen biopsy is advocated rather than FNAC for percutaneous sampling of lymph nodes not suitable for side-cutting needle biopsy.
•Ultrasound-guided Franseen® biopsy had greater tissue yield and accuracy than FNAC.•Franseen® better identified organ of origin of malignancy and lymphoma than FNAC.•Franseen® biopsy and FNAC can be performed on similarly sized smaller lymph nodes.•Temno® biopsy should be performed for larger lymph nodes.•One should use end-cutting biopsy, rather than FNAC, for smaller lymph nodes.
The current pandemic demands a search for therapeutic agents against the novel coronavirus SARS-CoV-2. Here, we present an efficient computational strategy that combines machine learning (ML)-based ...models and high-fidelity ensemble docking studies to enable rapid screening of possible therapeutic ligands. Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host–virus interactions. Top scoring one hundred eighty-seven ligands (with 75 approved by the Food and Drug Administration) are further validated by all atom docking studies. Important molecular descriptors (2χ n , topological surface area, and ring count) and promising chemical fragments (oxolane, hydroxy, and imidazole) are identified to guide future experiments. Overall, this work expands our knowledge of small-molecule treatment against COVID-19 and provides a general screening pathway (combining quick ML models with expensive high-fidelity simulations) for targeting several chemical/biochemical problems.
The main goal of molecular simulation is to accurately predict experimental observables of molecular systems. Another long-standing goal is to devise models for arbitrary neutral organic molecules ...with little or no reliance on experimental data. While separately these goals have been met to various degrees, for an arbitrary system of molecules they have not been achieved simultaneously. For biophysical ensembles that exist at room temperature and pressure, and where the entropic contributions are on par with interaction strengths, it is the free energies that are both most important and most difficult to predict. We compute the free energies of solvation for a diverse set of neutral organic compounds using a polarizable force field fitted entirely to ab initio calculations. The mean absolute errors (MAE) of hydration, cyclohexane solvation, and corresponding partition coefficients are 0.2 kcal/mol, 0.3 kcal/mol and 0.22 log units, i.e. within chemical accuracy. The model (ARROW FF) is multipolar, polarizable, and its accompanying simulation stack includes nuclear quantum effects (NQE). The simulation tools' computational efficiency is on a par with current state-of-the-art packages. The construction of a wide-coverage molecular modelling toolset from first principles, together with its excellent predictive ability in the liquid phase is a major advance in biomolecular simulation.
MSTO1
encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype–phenotype spectrum remains to be explored, pathogenic variants in
MSTO1
have recently been ...reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of
MSTO1
-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA depletion syndromes, a clinically and genetically diverse class of mitochondrial diseases characterized by a reduction of cellular mtDNA content. However, the consequences of pathogenic variants in
MSTO1
on mtDNA maintenance remain poorly understood. We present extensive phenotypic and genetic data from 12 independent families, including 15 new patients harbouring a broad array of bi-allelic
MSTO1
pathogenic variants, and we provide functional characterization from seven
MSTO1
-related disease patient fibroblasts. Bi-allelic loss-of-function variants in
MSTO1
manifest clinically with a remarkably consistent phenotype of childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy. MSTO1 protein was not detectable in the cultured fibroblasts of all seven patients evaluated, suggesting that pathogenic variants result in a loss of protein expression and/or affect protein stability. Consistent with impaired mitochondrial fusion, mitochondrial networks in fibroblasts were found to be fragmented. Furthermore, all fibroblasts were found to have depletion of mtDNA ranging from 30 to 70% along with alterations to mtDNA nucleoids. Our data corroborate the role of MSTO1 as a mitochondrial fusion protein and highlight a previously unrecognized link to mtDNA regulation. As impaired mitochondrial fusion is a recognized cause of mtDNA depletion syndromes, this novel link to mtDNA depletion in patient fibroblasts suggests that MSTO1-deficiency should also be considered a mtDNA depletion syndrome. Thus, we provide mechanistic insight into the disease pathogenesis associated with
MSTO1
mutations and further define the clinical spectrum and the natural history of
MSTO1
-related disease.
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