Density Functional Theory screening of gas-treatment strategies for stabilization of high energy-density lithium metal anodes

To explore the potential of molecular gas treatment of freshly cut lithium foils in non-electrolyte based passivation of high energy-density Li anodes, density functional theory (DFT) has been used to study the decomposition of molecular gases on metallic lithium surfaces. By combining DFT geometry optimization and Molecular Dynamics, the effects of atmospheric (N2, O2, CO2) and hazardous (F2, SO2) gas decomposition on Li(bcc) (100), (110), and (111) surfaces on relative surface energies, work functions, and emerging electronic and elastic properties are investigated. The simulations suggest that exposure to different molecular gases can be used to induce and control reconstructions of the metal Li surface and substantial changes (up to over 1 eV) in the work function of the passivated system. Contrary to the other considered gases, which form metallic adlayers, SO2 treatment emerges as the most effective in creating an insulating passivation layer for dosages <= 1 mono-layer. The substantial Li->adsorbate charge transfer and adlayer relaxation produce marked elastic stiffening of the interface, with the smallest change shown by nitrogen-treated adlayers

The rs72613567:TA polymorphism in HSD17B13 is associated with survival benefit after development of hepatocellular carcinoma

BACKGROUND: The influence of genetic factors on survival following a diagnosis of hepatocellular carcinoma (HCC) remains unclear. AIM: To assess whether genetic polymorphisms influencing the susceptibility to develop HCC are also associated with HCC prognosis. METHODS: We included United Kingdom Biobank (UKB) participants diagnosed with HCC after study enrolment. The primary outcome was all-cause mortality. Patients were followed from the date of HCC diagnosis to death or the registry completion date. Five HCC susceptibility loci were investigated: rs738409 (PNPLA3), rs58542926 (TM6SF2); rs72613567 (HSD17B13); rs2242652 (TERT) and rs708113 (WNT3A). The associations between these genetic variants and HCC mortality risk were assessed using Cox regression, adjusted for age, sex, ethnicity, aetiology, severity of the underlying liver disease and receipt of curative HCC treatment. RESULTS: The final sample included 439 patients; 74% had either non-alcoholic fatty liver disease or alcohol-related liver disease. There were 321 deaths during a mean follow-up of 1.9 years per participant. Kaplan-Meier survival estimates at 1, 3 and 5 years were 53.2%, 31.2% and 22.6% respectively. In multivariate analysis, rs72613567:TA (HSD17B13) was the only genetic susceptibility variant significantly associated with all-cause mortality risk (aHR: 0.74; 95% CI: 0.61-0.90; p = 0.003). Other associated factors were Baveno stage 3-4 (aHR: 1.65; 95% CI: 1.05-2.59; p = 0.03) and HCC treatment with curative intent (aHR: 0.25; 95% CI: 0.17-0.37; p < 0.001). CONCLUSIONS: The rs72613567:TA polymorphism in HSD17B13 is not only associated with a reduction in the risk of developing HCC but with a survival benefit in HCC once established. Therapeutic inhibition of HSD17B13 may augment survival in individuals with HCC

The evolution of platform business models: Exploring competitive battles in the world of platforms

In recent decades, multi-sided platform business models have become an important avenue for value creation and capture, but the phenomenon itself remains under-theorized. We address this gap and present new, empirically-driven insights into how platform business models evolve in a context of fierce competition. Through a longitudinal, qualitative study of twelve multi-sided platforms that operate under challenging industry conditions, we discover that success in platform battles can plausibly be explained by a combination of complexity in the business model design, and the simultaneous use of innovation and imitation to create highly intricate systems of activities. We further discuss how our findings open several new avenues for future platform research

Local control of improper ferroelectric domains in YMnO3_3

Improper ferroelectrics are described by two order parameters: a primary one, driving a transition to long-range distortive, magnetic or otherwise non-electric order, and the electric polarization, which is induced by the primary order parameter as a secondary, complementary effect. Using low-temperature scanning probe microscopy, we show that improper ferroelectric domains in YMnO$_3$ can be locally switched by electric field poling. However, subsequent temperature changes restore the as-grown domain structure as determined by the primary lattice distortion. The backswitching is explained by uncompensated bound charges occuring at the newly written domain walls due to the lack of mobile screening charges at low temperature. Thus, the polarization of improper ferroelectrics is in many ways subject to the same electrostatics as in their proper counterparts, yet complemented by additional functionalities arising from the primary order parameter. Tailoring the complex interplay between primary order parameter, polarization, and electrostatics is therefore likely to result in novel functionalities specific to improper ferroelectrics

Paired EMI-HIMU hotspots in the South Atlantic-Starting plume heads trigger compositionally distinct secondary plumes?

Age-progressive volcanism is generally accepted as the surface expression of deep-rooted mantle plumes, which are enigmatically linked with the African and Pacific large low-shear velocity provinces (LLSVPs). We present geochemical and geochronological data collected from the oldest portions of the age-progressive enriched mantle one (EMI)-type Tristan-Gough track. They are part of a 30- to 40-million year younger age-progressive hotspot track with St. Helena HIMU (high time-integrated U-238/Pb-204) composition, which is also observed at the EMI-type Shona hotspot track in the southernmost Atlantic. Whereas the primary EMI-type hotspots overlie the margin of the African LLSVP, the HIMU-type hotspots are located above a central portion of the African LLSVP, reflecting a large-scale geochemical zonation. We propose that extraction of large volumes of EMI-type mantle from the margin of the LLSVP by primary plume heads triggered upwelling of HIMU material from a more internal domain of the LLSVP, forming secondary plumes

The evolution of platform business models: exploring competitive battles in the world of platforms

In recent decades, multi-sided platform business models have become an important avenue for value creation and capture, but the phenomenon itself remains under-theorized. We address this gap and present new, empirically-driven insights into how platform business models evolve in a context of fierce competition. Through a longitudinal, qualitative study of twelve multi-sided platforms that operate under challenging industry conditions, we discover that success in platform battles can plausibly be explained by a combination of complexity in the business model design, and the simultaneous use of innovation and imitation to create highly intricate systems of activities. We further discuss how our findings open several new avenues for future platform research

In vivo targeting of adoptively transferred T-cells with antibody- and cytokine-conjugated liposomes

In adoptive cell therapy (ACT), autologous tumor-specific T-cells isolated from cancer patients are activated and expanded ex vivo, then infused back into the individual to eliminate metastatic tumors. A major limitation of this promising approach is the rapid loss of ACT T-cell effector function in vivo due to the highly immunosuppressive environment in tumors. Protection of T-cells from immunosuppressive signals can be achieved by systemic administration of supporting adjuvant drugs such as interleukins, chemotherapy, and other immunomodulators, but these adjuvant treatments are often accompanied by serious toxicities and may still fail to optimally stimulate lymphocytes in all tumor and lymphoid compartments. Here we propose a novel strategy to repeatedly stimulate or track ACT T-cells, using cytokines or ACT-cell-specific antibodies as ligands to target PEGylated liposomes to transferred T-cells in vivo. Using F(ab′)[subscript 2] fragments against a unique cell surface antigen on ACT cells (Thy1.1) or an engineered interleukin-2 (IL-2) molecule on an Fc framework as targeting ligands, we demonstrate that > 95% of ACT cells can be conjugated with liposomes following a single injection in vivo. Further, we show that IL-2-conjugated liposomes both target ACT cells and are capable of inducing repeated waves of ACT T-cell proliferation in tumor-bearing mice. These results demonstrate the feasibility of repeated functional targeting of T-cells in vivo, which will enable delivery of imaging contrast agents, immunomodulators, or chemotherapy agents in adoptive cell therapy regimens.National Institutes of Health (U.S.) (CA140476)National Institutes of Health (U.S.) (CA172164)United States. Dept. of Defense (Contract W81XWH-10-1-0290)National Cancer Institute (U.S.) (Koch Institute Support (core) Grant P30-CA14051