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Although the accepted Ni-W phase diagram does not reveal the existence of h.c.p.-based phases, h.c.p.-like stacking sequences were observed in magnetron-co-sputtered Ni-W thin films at W contents of 20 to 25 at. %, by using transmission electron microscopy and X-ray diffraction. The occurrence of this h.c.p.-like solid-solution phase could be rationalized by first-principles calculations, showing that the vicinity of the system's ground-state line is populated with metastable h.c.p.-based superstructures in the intermediate concentration range from 20 to 50 at. % W. The h.c.p.-like stacking in Ni-W films was observed to be thermally persistent, up to temperatures as high as at least 850 K, as evidenced by extensive X-ray diffraction analyses on specimens before and after annealing treatments. The tendency of Ni-W for excessive planar faulting is discussed in the light of these new findings. [ABSTRACT FROM AUTHOR]

The substitutional ordering phenomena of face-centered cubic Ni-rich Ni-W alloys are investigated by means of cluster-expansion Hamiltonians based on density functional theory calculations. We observe a strong tendency for ordering in Ni-W characterized by the formation of tungsten chains along the 〈 100 〉 direction. While previous studies only report a D1a-type compound at a stoichiometry of Ni4W with this 〈 100 〉-ordering tendency, we predict that within the solubility range of tungsten in nickel, structures with tungsten 〈 100 〉-chains are the predominant form of short-range order even at elevated temperatures. In particular, we find a Pt8Ti-structured compound (which also shows this 〈 100 〉-ordering) to be stable in Ni-W at low temperatures and low tungsten contents. Even at high temperatures, Ni-W solid solutions are found to exhibit strong remnant order. The implications of these findings are discussed from a metallurgical perspective with an emphasis on the stiffening effect of tungsten alloying on Ni-rich matrices. Using these insights on the short-range order, we then determine a parametrization of the composition-dependent stiffening cij - (xW) and ∂ cij - / ∂ xW. [ABSTRACT FROM AUTHOR]

Gallium-rich supported catalytically active liquid metal solutions (SCALMS) were recently introduced as a new way towards heterogeneous single atom catalysis. SCALMS were demonstrated to exhibit a certain resistance against coking during the dehydrogenation of alkanes using Ga-rich alloys of noble metals. Here, the conceptual catalytic application of SCALMS in dry reforming of methane (DRM) is tested with non-noble metal (Co, Cu, Fe, Ni) atoms in the gallium-rich liquid alloy. This study introduces SCALMS to high-temperature applications and an oxidative reaction environment. Most catalysts were shown to undergo severe oxidation during DRM, while Ga-Ni SCALMS retained a certain level of activity. This observation is explained by a kinetically controlled redox process, namely oxidation to gallium oxide species and re-reduction via H 2 activation over Ni. Consequentially, this redox process can be shifted to the metallic side when using increasing concentrations of Ni in Ga, which strongly suppresses coke formation. Density-functional theory (DFT) based ab initio molecular dynamics (AIMD) simulations were performed to confirm the increased availability of Ni at the liquid alloy-gas interface. However, leaching of gallium via the formation of volatile oxidic species during the hypothesised redox cycles was identified indicating a critical instability of Ga-Ni SCALMS for prolonged test durations., (© 2023. Springer Nature Limited.)

Isolated active sites have great potential to be highly efficient and stable in heterogeneous catalysis, while enabling low costs due to the low transition metal content. Herein, we present results on the synthesis, first catalytic trials, and characterization of the Ga 9 Rh 2 phase and the hitherto not-studied Ga 3 Rh phase. We used XRD and TEM for structural characterization, and with XPS, EDX we accessed the chemical composition and electronic structure of the intermetallic compounds. In combination with catalytic tests of these phases in the challenging propane dehydrogenation and by DFT calculations, we obtain a comprehensive picture of these novel catalyst materials. Their specific crystallographic structure leads to isolated Rhodium sites, which is proposed to be the decisive factor for the catalytic properties of the systems., (© 2023. The Author(s).)

Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. Yet, their downstream oncogenic signaling mechanisms are poorly understood. We used global phosphoproteomics and kinase activity profiling to map conserved signaling outputs driven by a range of genetic changes that activate PKA in human cancer. Two signaling networks were identified downstream of PKA: RAS/MAPK components and an Aurora Kinase A (AURKA)/glycogen synthase kinase (GSK3) sub-network with activity toward MYC oncoproteins. Findings were validated in two PKA-dependent cancer models: a novel, patient-derived fibrolamellar carcinoma (FLC) line that expresses a DNAJ-PKAc fusion and a PKA-addicted melanoma model with a mutant type I PKA regulatory subunit. We identify PKA signals that can influence both de novo translation and stability of the proto-oncogene c-MYC. However, the primary mechanism of PKA effects on MYC in our cell models was translation and could be blocked with the eIF4A inhibitor zotatifin. This compound dramatically reduced c-MYC expression and inhibited FLC cell line growth in vitro. Thus, targeting PKA effects on translation is a potential treatment strategy for FLC and other PKA-driven cancers., Competing Interests: GC, SM, YH, BP, RW, PV, KP, MB, HK, HL, DL, RY, PS, DS, NK, RT, KR, JS, NB, JG No competing interests declared, (© 2023, Chan et al.)

The [n]cycloparaphenylenes ([n]CPPs)-n para-linked phenylenes that form a closed-loop-have attracted substantial attention due to their unique cyclic structure and highly effective para-conjugation leading to a myriad of fascinating electronic and optoelectronic properties. However, their strained topology prevents the π-extension of CPPs to convert them either into armchair nanobelts or planarized CPP macrocycles. Here we successfully tackle this long-standing challenge and present the bottom-up synthesis and characterization of atomically precise in-plane π-extended [12]CPP on Au(111) by low-temperature scanning probe microscopy and spectroscopy combined with density functional theory. The planar π-extended CPP is a nanographene with an all-armchair edge topology. The exclusive para-conjugation at the periphery yields delocalized electronic states and the planarization maximizes the overlap of p orbitals, which both reduce the bandgap compared to conventional CPPs. Calculations predict ring currents and global aromaticity in the doubly charged system. The intriguing planar ring topology and unique electronic properties make planar π-extended CPPs promising quantum materials., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose of Review: To summarize recent innovations in cardiac rehabilitation and provide a view towards the future of cardiac rehabilitation as it adjusts to the pressures of a global pandemic., Recent Findings: Although cardiac rehabilitation has been shown to result in a mortality benefit, research continues to enumerate the benefits of cardiac rehabilitation to patient function and quality of life in a growing range of cardiovascular diseases. In addition, new methodologies and new models of cardiac rehabilitation have emerged with the goal of increasing patient referral and participation., Summary: Cardiac rehabilitation continues to evolve and adapt to serve a growing and diversifying number of patients with cardiovascular disease with the goal of both decreasing mortality and improving patient function., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We have examined model systems for the recently reported Pd-Ga Supported Catalytically Active Liquid Metal Solutions (SCALMS) catalysts using near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) under oxidizing conditions. Gallium is known to be highly prone to oxidation and in practical applications, handling of the catalyst material in air or the presence of traces of oxygen in the reactor are unavoidable. Therefore, we expect our results to be of high relevance for the application of Ga-based SCALMS catalysts. Pd-Ga alloy samples of 1.3 and 1.8 at% Pd content were exposed to molecular oxygen at different pressures between 3 × 10-7 and 1 mbar and a temperature of 550 K. We observe the formation of wetting Ga2O3 films upon exposure to molecular oxygen. The absolute thicknesses of the oxide films depend on oxygen pressure, with values ranging from ∼12 Å at 10-7 to 10-5 mbar to ∼50 Å at 1 mbar. The formed metal-oxide interface leads to a redistribution of Pd, which accumulates at the boundary between the wetting oxide film and the metal substrate as a response to the oxide film growth. A maximum Pd 3d intensity is observed at an oxide thickness of 5 Å. For thicker films, the Pd 3d signal and the Ga 3d signal ascribed to the metallic substrate decrease in parallel, which is attributed to the oxide layer growing on top of the liquid metal alloy. From this observation, we conclude that no significant amount of Pd is bound in the newly formed oxide film. Density-functional theory (DFT) calculations support the experimental observations.

We present an embedded atom model (EAM) potential for modeling Ga-Pd interactions within intermetallic solids and liquid alloys. The molecular mechanics potential was parameterized on the basis of the structure and mechanical properties of GaPd 2 , whereas a series of other Ga x Pd 1-x phases and liquid alloy systems allowed rigorous benchmarking. For the intermetallic solids, structures and elastic moduli were found in very reasonable agreement with experimental structures and results from DFT calculations. The liquid models were characterized from molecular dynamics simulations that also showed nice agreement with experimental and ab initio reference data. Moreover, the perspectives of the EAM model are illustrated by the elucidation of an alloy nanodroplet model whose characterization includes the kinetics of Pd dopant diffusion from the Ga droplet surface to the bulk liquid and vice versa.

Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed a CDH1 mutation and MET amplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.

Supported catalytically active liquid metal solutions have been receiving increasing attention recently. We investigated the oxidation behavior of macroscopic Rh-Ga alloy droplets and Rh-Ga model catalyst nanoparticles supported on SiO 2 /Si(100) with low Rh content (<2.5 at. %) by x-ray photoelectron spectroscopy in ultra-high vacuum and under near-ambient pressure conditions using different photon energies and also using transmission electron microscopy. The experiments are accompanied by computational studies on the Ga oxide/Rh-Ga interface and Rh-Ga intermetallic compounds. For both Rh-Ga alloy droplets and Rh-Ga model catalyst nanoparticles, exposure to molecular oxygen leads to the formation of an oxide shell in which Rh is enriched. Transmission electron microscopy on the Rh-Ga nanoparticles confirms the formation of an ∼4 nm thick gallium oxide film containing Rh. Based on ab initio molecular dynamics and computational studies on the Ga 2 O 3 /Ga interface, it is concluded that Rh incorporation into the Ga 2 O 3 film occurs by substituting octahedrally coordinated Ga.

According to Secretary Azar of Health and Human Services, implementing international reference pricing (IPI) in Medicare Part B will have minimal impacts. He has stated, "These savings, while substantial for American patients and taxpayers, cannot possibly pull out more than 1 percent of R&D." As companies traditionally spend 20% of free cash flow on R&D, we have measured the IPI impact according to industry standard metrics. The potential negative impacts of the international reference pricing plan, as it is currently structured, are numerous. Companies are likely to avoid developing Medicare Bart B physician-administered drugs in the future if it comes to fruition. Further, if distributing in any of the included countries in the benchmarking exercise that traditionally have prices far below that of the United States has the impact of creating lower US prices where the industry currently derives more than 80% of their global profit, companies will simply not seek market access in those benchmarked countries and patients in those countries will not receive the medicines they need. The idea that companies will be able to unilaterally raise prices in Europe defies logic and practice. Many countries in the EU have been threatening IP rights under the TRIPS clauses of the WTO for several years because of their belief that pharmaceutical pricing is unacceptably high right now, without the IPI. Harnessing real-world evidence would allow for increased competition by faster time to market. One wonders why an approach encompassing the improved time to market was not considered, as the reference pricing proposal as it stands now, ultimately, will reduce R&D budgets, impair the overall investment climate, and deprive patients the new medicines.

Our contribution demonstrates that rhodium, an element that has barely been reported as an active metal for selective dehydrogenation of alkanes becomes a very active, selective, and robust dehydrogenation catalyst when exposed to propane in the form of single atoms at the interface of a solid-supported, highly dynamic liquid Ga-Rh mixture. We demonstrate that the transition to a fully liquid supported alloy droplet at Ga/Rh ratios above 80, results in a drastic increase in catalyst activity with high propylene selectivity. The combining results from catalytic studies, X-ray photoelectron spectroscopy, IR-spectroscopy under reaction conditions, microscopy, and density-functional theory calculations, we obtained a comprehensive microscopy picture of the working principle of the Ga-Rh supported catalytically active liquid metal solution., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Background: Colorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors., Methods: We conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer., Results: All patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified., Discussion: CRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

Supported catalytically active liquid metal solutions (SCALMS) represent a class of catalytic materials that have only recently been developed, but have already proven to be highly active, e.g., for dehydrogenation reactions. Previous studies attributed the catalytic activity to isolated noble metal atoms at the surface of a liquid and inert Ga matrix. In this study, we apply diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) with CO as a probe molecule to Ga/Al 2 O 3 , Pt/Al 2 O 3 , and Ga 37 Pt/Al 2 O 3 catalysts, to investigate in detail the nature of the active Pt species. Comparison of CO adsorption on Pt/Al 2 O 3 and Ga 37 Pt/Al 2 O 3 shows that isolated Pt atoms are, indeed, present at the surface of the liquid SCALMS. Combining DRIFTS with online gas chromatography (GC), we investigated the Ga/Al 2 O 3 , Pt/Al 2 O 3 , and Ga 37 Pt/Al 2 O 3 systems under operando conditions during propane dehydrogenation in CO/propane and in Ar/propane. We find that the Pt/Al 2 O 3 sample is rapidly poisoned by CO adsorption and coke, whereas propane dehydrogenation over Ga 37 Pt/Al 2 O 3 SCALMS leads to higher conversion with no indication of poisoning effects. We show under operando conditions that isolated Pt atoms are present at the surface of SCALMS during the dehydrogenation reaction. IR spectra and density-functional theory (DFT) suggest that both the Ga matrix and the presence of coadsorbates alter the electronic properties of the surface Pt species., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

The Epidermal Growth Factor Receptor (EGFR) is frequently mutated and overexpressed in metastatic cancer. Although EGFR is a transmembrane tyrosine kinase localized to the basolateral membrane in normal epithelium, it is frequently found intracellularly localized in transformed cells. We have previously demonstrated the epithelial adaptor protein mucin 1 (MUC1) alters trafficking of EGFR, inhibiting its degradation and promoting its translocation to the nucleus, where it can directly modulate gene transcription. Here, we demonstrate that MUC1 promotes the retention of EGF-bound EGFR in Early Endosome Antigen1 (EEA1)-positive vesicles while preventing its trafficking to the lysosome. These events result in the accumulation of endosomal vesicles harboring active receptor throughout the cell and a reorganization of the actin cytoskeleton. EGF-dependent cell migration and filopodia formation is reliant upon this altered trafficking, and can be prevented by blocking retrograde trafficking. Together, these results indicate that intracellular EGFR may play an essential role in cancer metastasis and a potential mechanism for the failure of therapeutic antibodies in EGFR-driven metastatic breast cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

We have previously demonstrated that Llgl1 loss results in a gain of mesenchymal phenotypes and a loss of apicobasal and planar polarity. We now demonstrate that these changes represent a fundamental shift in cellular phenotype. Llgl1 regulates the expression of multiple cell identity markers, including CD44, CD49f, and CD24, and the nuclear translocation of TAZ and Slug. Cells lacking Llgl1 form mammospheres, where survival and transplantability is dependent upon the Epidermal Growth Factor Receptor (EGFR). Additionally, Llgl1 loss allows cells to grow in soft-agar and maintain prolonged survival as orthotopic transplants in NOD-SCIDmice. Lineage tracing and wound healing experiments demonstrate that mammosphere survival is due to enhanced EGF-dependent migration. The loss of Llgl1 drives EGFR mislocalization and an EGFR mislocalization point mutation (P667A) drives these same phenotypes, including activation of AKT and TAZ nuclear translocation. Together, these data indicate that the loss of Llgl1 results in EGFR mislocalization, promoting pre-neoplastic changes., Competing Interests: We have no conflict of interest to report with this research.

The ongoing characterization of novel species creates the need for a molecular marker which can be used for species- and, simultaneously, for mega-systematics. Recently, the use of the internal transcribed spacer 2 (ITS2) sequence was suggested, as it shows a high divergence in sequence with an assumed conservation in structure. This hypothesis was mainly based on small-scale analyses, comparing a limited number of sequences. Here, we report a large-scale analysis of more than 54,000 currently known ITS2 sequences with the goal to evaluate the hypothesis of a conserved structural core and to assess its use for automated large-scale phylogenetics. Structure prediction revealed that the previously described core structure can be found for more than 5000 sequences in a wide variety of taxa within the eukaryotes, indicating that the core secondary structure is indeed conserved. This conserved structure allowed an automated alignment of extremely divergent sequences as exemplified for the ITS2 sequences of a ctenophorean eumetazoon and a volvocalean green alga. All classified sequences, together with their structures can be accessed at http://www.biozentrum.uni-wuerzburg.de/bioinformatik/projects/ITS2.html. Furthermore, we found that, although sample sequences are known for most major taxa, there exists a profound divergence in coverage, which might become a hindrance for general usage. In summary, our analysis strengthens the potential of ITS2 as a general phylogenetic marker and provides a data source for further ITS2-based analyses.

Government agencies have used uncorrected visual acuity (UVA) standards for many years for police officer applicants. With the passage of the Americans With Disabilities Act of 1990, public employers have concern about the validity of these standards. This report shows how data can be used to set a reasonable standard. The report includes a description of a survey of incumbents, acuity testing of a sample of incumbents, collection of essential task information, and experimentation based on the essential tasks. A series of focus group meetings resulted in agreement that 2 essential tasks officers must be able to perform when visually incapacitated are identifying a weapon in a typical room and finding spectacles that have been dislodged. The experimentation showed that a noticeable performance decrement begins to appear at 20/125 level of acuity. As a result of the research, the City of Columbus, Ohio, changed the UVA standard from 20/40 to 20/125.