Magnetic Weyl semimetal phase in a Kagomé crystal Liu, D F; Liang, A J; Liu, E K ...
Science (American Association for the Advancement of Science),
09/2019, Letnik:
365, Številka:
6459
Journal Article
Recenzirano
Odprti dostop
Weyl semimetals are crystalline solids that host emergent relativistic Weyl fermions and have characteristic surface Fermi-arcs in their electronic structure. Weyl semimetals with broken time ...reversal symmetry are difficult to identify unambiguously. In this work, using angle-resolved photoemission spectroscopy, we visualized the electronic structure of the ferromagnetic crystal Co
Sn
S
and discovered its characteristic surface Fermi-arcs and linear bulk band dispersions across the Weyl points. These results establish Co
Sn
S
as a magnetic Weyl semimetal that may serve as a platform for realizing phenomena such as chiral magnetic effects, unusually large anomalous Hall effect and quantum anomalous Hall effect.
Synthesis of proteins by automated flow chemistry Hartrampf, N; Saebi, A; Poskus, M ...
Science (American Association for the Advancement of Science),
2020-May-29, 2020-05-29, 20200529, Letnik:
368, Številka:
6494
Journal Article
Recenzirano
Odprti dostop
Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the ...direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.
Gastroesophageal adenocarcinomas (GEAs) are heterogeneous cancers where immune checkpoint inhibitors have robust efficacy in heavily inflamed microsatellite instability (MSI) or Epstein-Barr virus ...(EBV)-positive subtypes. Immune checkpoint inhibitor responses are markedly lower in diffuse/genome stable (GS) and chromosomal instable (CIN) GEAs. In contrast to EBV and MSI subtypes, the tumor microenvironment of CIN and GS GEAs have not been fully characterized to date, which limits our ability to improve immunotherapeutic strategies.
Here we aimed to identify tumor-immune cell association across GEA subclasses using data from The Cancer Genome Atlas (N = 453 GEAs) and archival GEA resection specimen (N = 71). The Cancer Genome Atlas RNAseq data were used for computational inferences of immune cell subsets, which were correlated to tumor characteristics within and between subtypes. Archival tissues were used for more spatial immune characterization spanning immunohistochemistry and mRNA expression analyses.
Our results confirmed substantial heterogeneity in the tumor microenvironment between distinct subtypes. While MSI-high and EBV+ GEAs harbored most intense T cell infiltrates, the GS group showed enrichment of CD4+ T cells, macrophages and B cells and, in ∼50% of cases, evidence for tertiary lymphoid structures. In contrast, CIN cancers possessed CD8+ T cells predominantly at the invasive margin while tumor-associated macrophages showed tumor infiltrating capacity. Relatively T cell-rich ‘hot’ CIN GEAs were often from Western patients, while immunological ‘cold’ CIN GEAs showed enrichment of MYC and cell cycle pathways, including amplification of CCNE1.
These results reveal the diversity of immune phenotypes of GEA. Half of GS gastric cancers have tertiary lymphoid structures and are therefore promising candidates for immunotherapy. The majority of CIN GEAs, however, exhibit T cell exclusion and infiltrating macrophages. Associations of immune-poor CIN GEAs with MYC activity and CCNE1 amplification may enable new studies to determine precise mechanisms of immune evasion, ultimately inspiring new therapeutic modalities.
•There is large heterogeneity in the immune contexture of gastroesophageal adenocarcinoma (GEA) subtypes.•Chromosomal instable GEAs are often T cell excluded, which is associated with enhanced MYC and cell cycle pathways.•Genome stable cancers, contrarily, often have tertiary lymphoid structures.•This study argues for more personalized immunotargeting strategies in gastroesophageal cancer treatment.
Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an ...antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial-mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT-associated gene expression changes, including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes prometastatic behavior and angiogenesis. The inhibition of AXL and MET activity may overcome resistance induced by prolonged sunitinib therapy in metastatic RCC.
We use machine-learning methods on local structure to identify flow defects-or particles susceptible to rearrangement-in jammed and glassy systems. We apply this method successfully to two very ...different systems: a two-dimensional experimental realization of a granular pillar under compression and a Lennard-Jones glass in both two and three dimensions above and below its glass transition temperature. We also identify characteristics of flow defects that differentiate them from the rest of the sample. Our results show it is possible to discern subtle structural features responsible for heterogeneous dynamics observed across a broad range of disordered materials.
When deformed beyond their elastic limits, crystalline solids flow plastically via particle rearrangements localized around structural defects. Disordered solids also flow, but without obvious ...structural defects. We link structure to plasticity in disordered solids via a microscopic structural quantity, “softness,” designed by machine learning to be maximally predictive of rearrangements. Experimental results and computations enabled us to measure the spatial correlations and strain response of softness, as well as two measures of plasticity: the size of rearrangements and the yield strain. All four quantities maintained remarkable commonality in their values for disordered packings of objects ranging from atoms to grains, spanning seven orders of magnitude in diameter and 13 orders of magnitude in elastic modulus. These commonalities link the spatial correlations and strain response of softness to rearrangement size and yield strain, respectively.
Abstract
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for ...quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS
2
with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS
2
as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.
One of the most central scientific questions for plasma applications in healthcare and environmental remediation is the chemical identity and the dose profile of plasma-induced reactive oxygen and ...nitrogen species (ROS/RNS) that can act on an object inside a liquid. A logical focus is on aqueous physicochemical processes near a sample with a direct link to their upstream gaseous processes in the plasma region and a separation gap from the liquid bulk. Here, a system-level modeling framework is developed for indirect interactions of surface air plasma and a deionized water bulk and its predictions are found to be in good agreement with the measurement of gas-phase ozone and aqueous long-living ROS/RNS concentrations. The plasma region is described with a global model, whereas the air gap and the liquid region are simulated with a 1D fluid model. All three regions are treated as one integrated entity and computed simultaneously. With experimental validation, the system-level modeling shows that the dominant aqueous ROS/RNS are long-living species (e.g. H2O2aq, O3aq, nitrite/nitrate, H+aq). While most short-living gaseous species could hardly survive their passage to the liquid, aqueous short-living ROS/RNS are generated in situ through reactions among long-living plasma species and with water molecules. This plasma-mediated remote production of aqueous ROS/RNS is important for the abundance of aqueous HO2aq, HO3aq, OHaq and aq as well as NO2aq and NO3aq. Aqueous plasma chemistry offers a novel and significant pathway to activate a given biological outcome, as exemplified here for bacterial deactivation in plasma-activated water. Additional factors that may synergistically broaden the usefulness of aqueous plasma chemistry include an electric field by aqueous ions and liquid acidification. The system-modeling framework will be useful in assisting designs and analyses of future investigations of plasma-liquid and plasma-cell interactions.
The coupling of the ionosphere to processes from below remains an elusive and difficult problem, as rapidly changing external drivers from above mask variations related to lower atmospheric sources. ...Here we use superposition of unique circumstances, current deep solar minimum and a record‐breaking stratospheric warming event, to gain new insights into causes of ionospheric perturbations. We show large (50–150%) persistent variations in the low‐latitude ionosphere (200–1000 km) that occur several days after a sudden warming event in the high‐latitude winter stratosphere (∼30 km). We rule out solar irradiance and geomagnetic activity as explanations of the observed variation. Using a general circulation model, we interpret these observations in terms of large changes in atmospheric tides from their nonlinear interaction with planetary waves that are strengthened during sudden warmings. We anticipate that further understanding of the coupling processes with planetary waves, accentuated during the stratospheric sudden warming events, has the potential of enabling the forecast of low‐latitude ionospheric weather up to several days in advance.
PDF
