In a study involving patients with non–small-cell lung cancer with a
MET
exon 14 skipping mutation, the use of tepotinib (a selective MET inhibitor) was associated with a partial response in ...approximately half the patients. The main adverse event was peripheral edema.
Oceanic mesoscale eddies contribute important horizontal heat and salt transports on a global scale. Here we show that eddy transports are mainly due to individual eddy movements. Theoretical and ...observational analyses indicate that cyclonic and anticyclonic eddies move westwards, and they also move polewards and equatorwards, respectively, owing to the β of Earth's rotation. Temperature and salinity (T/S) anomalies inside individual eddies tend to move with eddies because of advective trapping of interior water parcels, so eddy movement causes heat and salt transports. Satellite altimeter sea surface height anomaly data are used to track individual eddies, and vertical profiles from co-located Argo floats are used to calculate T/S anomalies. The estimated meridional heat transport by eddy movement is similar in magnitude and spatial structure to previously published eddy covariance estimates from models, and the eddy heat and salt transports both are a sizeable fraction of their respective total transports.
Methanol, being electron rich and derivable from methane or CO2, is a potentially renewable one-carbon (C1) feedstock for microorganisms. Although the ribulose monophosphate (RuMP) cycle used by ...methylotrophs to assimilate methanol differs from the typical sugar metabolism by only three enzymes, turning a non-methylotrophic organism to a synthetic methylotroph that grows to a high cell density has been challenging. Here we reprogrammed E. coli using metabolic robustness criteria followed by laboratory evolution to establish a strain that can efficiently utilize methanol as the sole carbon source. This synthetic methylotroph alleviated a so far uncharacterized hurdle, DNA-protein crosslinking (DPC), by insertion sequence (IS)-mediated copy number variations (CNVs) and balanced the metabolic flux by mutations. Being capable of growing at a rate comparable with natural methylotrophs in a wide range of methanol concentrations, this synthetic methylotrophic strain illustrates genome editing and evolution for microbial tropism changes and expands the scope of biological C1 conversion.
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•E. coli was engineered to grow on methanol alone by rational design and evolution•A doubling time of 8.5 h and maximum OD of 2 were achieved•Formaldehyde-induced DNA-protein crosslinking was identified and solved•Copy number variation of a region spanning 70kb facilitates carbon source shifts
Chen et al. demonstrate genetic reprogramming of E. coli to efficiently grow with methanol as the sole carbon source.
Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests ...that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Buckling is exploited to design a new class of three‐dimensional metamaterials with negative Poisson's ratio. A library of auxetic building blocks is identified and procedures are defined to guide ...their selection and assembly. The auxetic properties of these materials are demonstrated both through experiments and finite element simulations and exhibit excellent qualitative and quantitative agreement.
Cellular solids (e.g., foams and honeycombs) are widely found in natural and engineering systems because of their high mechanical efficiency and tailorable properties. While these materials are often ...based on polycrystalline or amorphous constituents, here we report an unusual dual-scale, single-crystalline microlattice found in the biomineralized skeleton of the knobby starfish,
. This structure has a diamond-triply periodic minimal surface geometry (lattice constant, approximately 30 micrometers), the 111 direction of which is aligned with the
-axis of the constituent calcite at the atomic scale. This dual-scale crystallographically coaligned microlattice, which exhibits lattice-level structural gradients and dislocations, combined with the atomic-level conchoidal fracture behavior of biogenic calcite, substantially enhances the damage tolerance of this hierarchical biological microlattice, thus providing important insights for designing synthetic architected cellular solids.
Feature matching, which refers to establishing the correspondence of regions between two images (usually voxel features), is a crucial prerequisite of feature-based registration. For deformable image ...registration tasks, traditional feature-based registration methods typically use an iterative matching strategy for interest region matching, where feature selection and matching are explicit, but specific feature selection schemes are often useful in solving application-specific problems and require several minutes for each registration. In the past few years, the feasibility of learning-based methods, such as VoxelMorph and TransMorph, has been proven, and their performance has been shown to be competitive compared to traditional methods. However, these methods are usually single-stream, where the two images to be registered are concatenated into a 2-channel whole, and then the deformation field is output directly. The transformation of image features into interimage matching relationships is implicit. In this paper, we propose a novel end-to-end dual-stream unsupervised framework, named TransMatch, where each image is fed into a separate stream branch, and each branch performs feature extraction independently. Then, we implement explicit multilevel feature matching between image pairs via the query-key matching idea of the self-attention mechanism in the Transformer model. Comprehensive experiments are conducted on three 3D brain MR datasets, LPBA40, IXI, and OASIS, and the results show that the proposed method achieves state-of-the-art performance in several evaluation metrics compared to the commonly utilized registration methods, including SyN, NiftyReg, VoxelMorph, CycleMorph, ViT-V-Net, and Trans- Morph, demonstrating the effectiveness of our model in deformable medical image registration.
Four types of dust samples and nine categories of locally produced staple foods were collected from a mega e-waste recycling industrial park and its surrounding regions, and simultaneously analyzed ...for short-chain and medium-chain chlorinated paraffins (CPs) to estimate dust and dietary exposure and their combined effects on occupational workers and local residents. All samples related to e-waste activities contained considerably high concentrations of CPs. The highest dust concentration was found in e-waste workshops. CPs were highly accumulated in local plant and animal origin foods, most markedly in fish, vegetables, and rice. The main contribution to CP intake under a median exposure scenario was from the diet, and vegetables, fish, and rice were the three largest dietary intake sources. Only the combined dust and food exposure from the present study has approached or even exceeded the highest tolerable daily intake (TDI) set up by the International Program on Chemical Safety (IPCS). However, due to lack of official threshold values for CP exposure on adverse human health, there are limitations on accurate risk assessment. Considering the presence of other exposure pathways, CPs’ endocrine disrupter properties, as well as the multicomponent chemical “cocktails” effects, potential high risks from CP exposure may be posed to e-waste workers and local residents.
The hippocampal-entorhinal system is important for spatial and relational memory tasks. We formally link these domains, provide a mechanistic understanding of the hippocampal role in generalization, ...and offer unifying principles underlying many entorhinal and hippocampal cell types. We propose medial entorhinal cells form a basis describing structural knowledge, and hippocampal cells link this basis with sensory representations. Adopting these principles, we introduce the Tolman-Eichenbaum machine (TEM). After learning, TEM entorhinal cells display diverse properties resembling apparently bespoke spatial responses, such as grid, band, border, and object-vector cells. TEM hippocampal cells include place and landmark cells that remap between environments. Crucially, TEM also aligns with empirically recorded representations in complex non-spatial tasks. TEM also generates predictions that hippocampal remapping is not random as previously believed; rather, structural knowledge is preserved across environments. We confirm this structural transfer over remapping in simultaneously recorded place and grid cells.
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•Common principles for space and relational memory in the hippocampal formation•Explains hippocampal generalization in both spatial and non-spatial problems•Accounts for many reported hippocampal and entorhinal cell types from such tasks•Predicts how hippocampus remaps in both spatial and non-spatial tasks
The Tolman-Eichenbaum Machine, named in honor of Edward Chace Tolman and Howard Eichenbaum for their contributions to cognitive theory, provides a unifying framework for the hippocampal role in spatial and nonspatial generalization and unifying principles underlying many entorhinal and hippocampal cell types.
Summary Background Neuroendocrine tumours (NETs) can secrete bioactive amines into the bloodstream, causing carcinoid syndrome, with symptoms including flushing and diarrhoea. However, carcinoid ...syndrome frequency in the NET population has never been rigorously assessed, nor has its relationship to presenting clinicopathological characteristics. This analysis assessed the proportion of patients with NETs and carcinoid syndrome in the USA and associated clinical factors. Methods We identified patients (≥65 years of age) from the Surveillance, Epidemiology, and End Results-Medicare database, excluding those with pancreatic tumours or small-cell or large-cell lung cancer, as well as those without complete data. We assessed the incidence of patients with at least two insurance claims of flushing, diarrhoea, or carcinoid syndrome during the 3 months before and after NET diagnosis. We compared demographic and clinical characteristics between patients with and without carcinoid syndrome using χ2 tests. We used the Cochran-Armitage trend test to identify trends in carcinoid syndrome incidence and Cox regression to assess the relationship between carcinoid syndrome and survival. Findings Between April 1, 2000, and Dec 31, 2011, 9512 eligible patients were diagnosed with NETs, of whom 1786 (19%) had carcinoid syndrome. The number of patients with NETs and carcinoid syndrome increased from 50 (11%) of 465 patients in 2000 to 160 (19%) of 854 in 2011 (p<0·0001). The proportion of patients with carcinoid syndrome compared with those without did not differ significantly with respect to age at diagnosis (p=0·65), geographical region (p=0·054), or urban versus rural status (p=0·53). Patients with carcinoid syndrome were more frequently female than male (p=0·0003). Race was associated with a significant difference in the reported incidence of carcinoid syndrome (p<0·0001), as was tumour grade, stage, and primary tumour site (all p<0·0001). Patients with carcinoid syndrome had a shorter overall survival (median 5 years 95% CI 4·5–5·4) than did those without carcinoid syndrome (5·6 years 5·4–5·9; hazard ratio 1·102 1·016–1·194; p=0·019). Use of octreotide (p<0·0001) and chemotherapy (p=0·003) were more common in patients with carcinoid syndrome than in those without it, whereas surgery was used more frequently in patients without carcinoid syndrome (p=0·009); use of radiotherapy was not significantly associated with the presence of carcinoid syndrome at diagnosis (p=0·07). Interpretation This population-based analysis reveals that carcinoid syndrome is significantly associated with tumour grade, stage, and primary tumour site, and leads to shorter survival compared with those patients without carcinoid syndrome. An improved understanding of the heterogeneity of presenting symptoms among patients with NETs might permit more tailored assessment and management than at present and enable future research into the effect of carcinoid syndrome control on patient survival. Funding Ipsen.
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