Nanocasting is a powerful method for creating materials that are more difficult to synthesize by conventional processes. We summarize recent developments in the synthesis of various structured porous ...solids, covering silica, carbon, and other nonsiliceous solids that are created by a nanocasting pathway. Structure replication on the nanometer length scale allows materials' properties to be manipulated in a controlled manner, such as tunable composition, controllable structure and morphology, and specific functionality. The nanocasting pathway with hard templates opens the door to the design of highly porous solids with multifunctional properties and interesting application perspectives.
The nanocasting pathway from hard templates, a versatile synthetic strategy, has successfully been applied for the creation of porous solids (see figure). The obtained structures can be precisely tailored by selecting a suitable template, precursor, and synthetic conditions, and the resulting materials lend themselves to further, spatially controlled modification.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Objective To evaluate the prevalence of and characterize resistant hypertension in a large representative population with successful hypertension management and reliable health information. ...Patient and Methods We performed a cross-sectional study using clinical encounter, laboratory, and administrative information from the Kaiser Permanente Southern California health system between January 1, 2006, and December 31, 2007. From individuals older than 17 years with hypertension, resistant hypertension was identified and prevalence was determined. Multivariable logistic regression was used to calculate odds ratios (ORs), with adjustments for demographic characteristics, clinical variables, and medication use. Results Of 470,386 hypertensive individuals, 60,327 (12.8%) were identified as having resistant disease, representing 15.3% of those taking medications. Overall, 37,061 patients (7.9%) had uncontrolled hypertension while taking 3 or more medicines. The ORs (95% CIs) for resistant hypertension were greater for black race (1.68 1.62-1.75), older age (1.11 1.10-1.11 for every 5-year increase), male sex (1.06 1.03-1.10), and obesity (1.46 1.42-1.51). Medication adherence rates were higher in those with resistant hypertension (93% vs 89.8%; P <.001). Chronic kidney disease (OR, 1.84; 95% CI, 1.78-1.90), diabetes mellitus (OR, 1.58; 95% CI, 1.53-1.63), and cardiovascular disease (OR, 1.34; 95% CI, 1.30-1.39) were also associated with higher risk of resistant hypertension. Conclusion In a more standardized hypertension treatment environment, we observed a rate of resistant hypertension comparable with that of previous studies using more fragmented data sources. Past observations have been limited due to nonrepresentative populations, reliability of the data, heterogeneity of the treatment environments, and less than ideal control rates. This cohort, which was established using an electronic medical record–based approach, has the potential to provide a better understanding of resistant hypertension and outcomes.
The thermodynamic aspects of various 2D materials are explored using Density Functional Theory (DFT). Various metal chalcogenides (MX2, M = metal, chalcogen X = S, Se, Te) are investigated with ...respect to their interaction and stability under different ambient conditions met in the integration process of a transistor device. Their interaction with high-κ dielectrics is also addressed, in order to assess their possible integration in Complementary Metal Oxide Semiconductor (CMOS) field effect transistors. 2D materials show promise for high performance nanoelectronic devices, but the presence of defects (vacancies, grain boundaries,…) can significantly impact their electronic properties. To assess the impact of defects, their enthalpies of formation and their signature levels in the density of states have been studied. We find, consistently with literature reports, that chalcogen vacancies are the most likely source of defects. It is shown that while pristine 2D materials are in general stable whenever set in contact with different ambient atmospheres, the presence of defective sites affects the electronic properties of the 2D materials to varying degrees. We observe that all the 2D materials studied in the present work show strong reactivity towards radical oxygen plasma treatments while reactivity towards other common gas phase chemical such as O2 and H2O and groups present at the high-κ surface varies significantly between species. While energy band-gaps, effective masses and contact resistivities are key criteria in selection of 2D materials for scaled CMOS and tunneling based devices, the phase and ambient stabilities might also play a very important role in the development of reliable nanoelectronic applications.
Shear-induced segregation, by particle size, is known in the flow of colloids and granular media, but is unexpected at the atomic level in the deformation of solid materials, especially at room ...temperature. In nanoscale wear tests of an Fe-based bulk metallic glass at room temperature, without significant surface heating, we find that intense shear localization under a scanned indenter tip can induce strong segregation of a dilute large-atom solute (Y) to planar regions that then crystallize as a Y-rich solid solution. There is stiffening of the material, and the underlying chemical and structural effects are characterized by transmission electron microscopy. The key influence of the soft Fe-Y interatomic interaction is investigated by ab-initio calculation. The driving force for the induced segregation, and its mechanisms, are considered by comparison with effects in other sheared media.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Two-dimensional (2D) materials such as graphene (Gr), molybdenum disulfide and hexagonal boron nitride (hBN) hold great promise for low-cost and ubiquitous electronics for flexible displays, solar ...cells or smart sensors. To implement this vision, scalable production, transfer and patterning technologies of 2D materials are needed. Recently, roll-to-roll (R2R) processing, a technique that is widely used in industry and known to be cost-effective and scalable, was applied to continuously grow and transfer graphene. However, more work is needed to understand the possibilities and limitations of this technology to make R2R processing of 2D materials feasible. In this work, we fabricated a custom R2R transferring system that allows the accurate control of the process parameters. We employ continuous electrochemical delamination, known as "bubble transfer", to eliminate chemical etchant waste and enable the continuous transfer of 2D materials from metal foils. This also makes our transfer method a renewable and environmentally friendly process. We investigate the surface topology as well as the electrical parameters of roll-to-roll transferred graphene on polyethylene terephthalate (PET) coated with ethylene-vinyl acetate (EVA). Furthermore, we demonstrate for the first time the stacking of two layers of graphene or graphene on hBN by repeated lamination and delamination onto EVA/PET. These results are an important contribution to creating low-cost, large scale and flexible electronics based on 2D materials.
Epidermal growth factor receptor (EGFR), a member of the HER family, is closely related to the development of multiple cancers. Herein, we report the discovery of small molecule EGFR degraders based ...on the proteolysis targeting chimera (PROTAC) strategy. In the present study, 13 EGFR degraders containing pyrido3,4-d pyrimidine moiety were designed and synthesized. Promising PROTACs 2 and 10 induced degradation of EGFR in HCC827 cells with the DC50 values of 45.2 and 34.8 nM, respectively. Cellular protein-controlling machinery ubiquitin proteasome system (UPS) was involved in the degradation process. Furthermore, the degraders 2 and 10 could significantly induce the apoptosis of HCC827 cells and arrest the cells in G1 phase. These findings demonstrated that compounds 2 and 10 could serve as effective EGFRdel19-targeting degraders in HCC827 cells. v.
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•We designed and synthesized novel PROTACs by tethering fourth generation EGFR-TKI 1 with CRBN or VHL ligands.•Compounds 2 (DC50 = 45.2 nM, Dmax = 87%) and 10 (DC50 = 34.8 nM, Dmax = 98%) potently degraded EGFRDel19 in HCC827 cells.•Compounds 2 and 10 significantly induced the apoptosis of HCC827 cells and arrest the cells in G1 phase.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•It is a mystery whether or not pure argon can exist as an amorphous solid.•An amorphous argon model containing triple-shell icosahedral clusters is shown to exist for more than one day below ...7 K.•The conjecture that every substance can exist as an amorphous solid is supported.•Our findings open new perspectives not only for making amorphous solids of substances such as pure noble gases and fcc metals which have not yet been put into the amorphous form but also for enhancing the stability of existing amorphous solids.
Many substances can exist as amorphous solids, but it is an open question whether or not all substances can be put into the amorphous form. It has been proposed that the demonstration of pure amorphous argon is the most convincing evidence for the universality of the amorphous state. However, theoretical studies have shown that a non-crystalline structure made by quenching liquid argon is not a solid, for it crystallizes immediately. Here, we demonstrate that amorphous argon model containing triple-shell icosahedral clusters can exist for more than one day below 7 K, supporting the universality of the amorphous state. Our findings open new perspectives not only for making amorphous solids of substances such as pure noble gases and fcc metals which have not yet been put into the amorphous form but also for enhancing the stability of existing amorphous solids.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Rad9-Rad1-Hus1 checkpoint clamp activates the DNA damage response and promotes DNA repair. DNA loading on the central channel of the Rad9-Rad1-Hus1 complex is required to execute its biological ...functions. Because Rad9A has the highest DNA affinity among the three subunits, we determined the domains and functional residues of human Rad9A that are critical for DNA interaction. The N-terminal globular domain (residues 1-133) had 3.7-fold better DNA binding affinity than the C-terminal globular domain (residues 134-266) of Rad9A.sup.1-266 . Rad9A.sup.1-266 binds DNA 16-, 60-, and 30-fold better than Rad9A.sup.1-133, Rad9A.sup.134-266, and Rad9A.sup.94-266, respectively, indicating that different regions cooperatively contribute to DNA binding. We show that basic residues including K11, K15, R22, K78, K220, and R223 are important for DNA binding. The reductions on DNA binding of Ala substituted mutants of these basic residues show synergistic effect and are dependent on their residential Rad9A deletion constructs. Interestingly, deletion of a loop (residues 160-163) of Rad9A.sup.94-266 weakens DNA binding activity by 4.1-fold as compared to wild-type (WT) Rad9A.sup.94-266 . Cellular sensitivity to genotoxin of rad9A knockout cells is restored by expressing WT-Rad9A.sup.full . However, rad9A knockout cells expressing Rad9A mutants defective in DNA binding are more sensitive to H.sub.2 O.sub.2 as compared to cells expressing WT-Rad9A.sup.full . Only the rad9A knockout cells expressing loop-deleted Rad9A mutant are more sensitive to hydroxyurea than cells expressing WT-Rad9A. In addition, Rad9A-DNA interaction is required for DNA damage signaling activation. Our results indicate that DNA association by Rad9A is critical for maintaining cell viability and checkpoint activation under stress.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related ...mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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