During different stages of tumor development the immune system can either identify and destroy tumors, or promote their growth. Therapies targeting the immune system have emerged as a promising ...treatment modality for breast cancer, and immunotherapeutic strategies are being examined in preclinical and clinical models. However, our understanding of the complex interplay between cells of the immune system and breast cancer cells is incomplete. In this article, we review recent findings showing how the immune system plays dual host-protective and tumor-promoting roles in breast cancer initiation and progression. We then discuss estrogen receptor α (ERα)-dependent and ERα-independent mechanisms that shield breast cancers from immunosurveillance and enable breast cancer cells to evade immune cell induced apoptosis and produce an immunosuppressive tumor microenvironment. Finally, we discuss protumorigenic inflammation that is induced during tumor progression and therapy, and how inflammation promotes more aggressive phenotypes in ERα positive breast cancers.
Transition metal (oxy)hydroxides are promising electrocatalysts for the oxygen evolution reaction
. The properties of these materials evolve dynamically and heterogeneously
with applied voltage ...through ion insertion redox reactions, converting materials that are inactive under open circuit conditions into active electrocatalysts during operation
. The catalytic state is thus inherently far from equilibrium, which complicates its direct observation. Here, using a suite of correlative operando scanning probe and X-ray microscopy techniques, we establish a link between the oxygen evolution activity and the local operational chemical, physical and electronic nanoscale structure of single-crystalline β-Co(OH)
platelet particles. At pre-catalytic voltages, the particles swell to form an α-CoO
H
0.5H
O-like structure-produced through hydroxide intercalation-in which the oxidation state of cobalt is +2.5. Upon increasing the voltage to drive oxygen evolution, interlayer water and protons de-intercalate to form contracted β-CoOOH particles that contain Co
species. Although these transformations manifest heterogeneously through the bulk of the particles, the electrochemical current is primarily restricted to their edge facets. The observed Tafel behaviour is correlated with the local concentration of Co
at these reactive edge sites, demonstrating the link between bulk ion-insertion and surface catalytic activity.
In 1998, a Wyoming cyclist noticed what he initially thought was a scarecrow was actually a person. When he took the time to investigate, he found Matthew Shepherd bound to a fence, beaten and left ...for dead, attacked for being gay. This heinous act of hatred represented a shift in how the United States treats hate crimes, leveeing severe ramifications for the motivations themselves. Although progress has been made, many in medicine who identify in as LGBTQI+ choose to conceal their truths out of fear. With available evidence suggesting a worsening shortage of surgeons in the country, populations of interested people cannot be excluded. Data on representation is severely lacking but is key to attract candidates; inclusivity, modern vocabularies, and the demonstration of engagement are important. Surgical organizations must understand the importance of being a welcoming, mentoring, and allying environment for interested LGBTQI+ candidates, serving as beacons for their interest, or we will simply remain complicit in seeing only scarecrows.
Layered oxides widely used as lithium-ion battery electrodes are designed to be cycled under conditions that avoid phase transitions. Although the desired single-phase composition ranges are well ...established near equilibrium, operando diffraction studies on many-particle porous electrodes have suggested phase separation during delithiation. Notably, the separation is not always observed, and never during lithiation. These anomalies have been attributed to irreversible processes during the first delithiation or reversible concentration-dependent diffusion. However, these explanations are not consistent with all experimental observations such as rate and path dependencies and particle-by-particle lithium concentration changes. Here, we show that the apparent phase separation is a dynamical artefact occurring in a many-particle system driven by autocatalytic electrochemical reactions, that is, an interfacial exchange current that increases with the extent of delithiation. We experimentally validate this population-dynamics model using the single-phase material Li
(Ni
Mn
Co
)O
(0.5 < x < 1) and demonstrate generality with other transition-metal compositions. Operando diffraction and nanoscale oxidation-state mapping unambiguously prove that this fictitious phase separation is a repeatable non-equilibrium effect. We quantitatively confirm the theory with multiple-datastream-driven model extraction. More generally, our study experimentally demonstrates the control of ensemble stability by electro-autocatalysis, highlighting the importance of population dynamics in battery electrodes (even non-phase-separating ones).
► FXR is the bile acid nuclear receptor regulating lipid and glucose metabolism, and inflammatory responses. ► FXR-mediated activities have promoted a new understanding of bile acids as hormones with ...potential for multiple therapeutic applications. ► OCA is a potent and selective clinical-stage FXR agonist. ► Preclinical and clinical data support further clinical testing of OCA in NAFLD/NASH patients.
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition evolving in a proportion of patients into nonalcoholic steatohepatitis (NASH), an aggressive form of NAFLD associated with increased cardiovascular mortality and significant risk of progressive liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma. At present, no specific therapies for NASH exist. In this review, we examine the evidence supporting activation of the farnesoid X receptor (FXR), a nuclear hormone receptor regulated by bile acids (BAs), for the treatment of NASH. We also discuss the potential of the semi-synthetic BA derivative obeticholic acid (OCA), a first-in-class FXR agonist, as a safe and effective drug to address this significant unmet medical need.
The kinetics and uniformity of ion insertion reactions at the solid-liquid interface govern the rate capability and lifetime, respectively, of electrochemical devices such as Li-ion batteries. Using ...an operando x-ray microscopy platform that maps the dynamics of the Li composition and insertion rate in LixFePO₄, we found that nanoscale spatial variations in rate and in composition control the lithiation pathway at the subparticle length scale. Specifically, spatial variations in the insertion rate constant lead to the formation of nonuniform domains, and the composition dependence of the rate constant amplifies nonuniformities during delithiation but suppresses them during lithiation, and moreover stabilizes the solid solution during lithiation. This coupling of lithium composition and surface reaction rates controls the kinetics and uniformity during electrochemical ion insertion.
Fluorine doping of a compositionally graded cathode, with an average concentration of LiNi
0.80
Co
0.05
Mn
0.15
O
2
, yields a high discharge capacity of 216 mA h g
−1
with unprecedented cycling ...stability by retaining 78% of its initial capacity after 8000 cycles. The cathode is cycled at 100% depth of discharge (DOD), unlike the currently deployed layered cathode whose DOD is limited to 60-80% to compensate for capacity fading and guarantee the required battery life. Additionally, the capacity and cycling stability of the cathode easily surpass those of the existing state-of-the-art batteries, while achieving the energy density goal of 800 W h kg
−1
cathode
for electric vehicles (EV) with ultra-long cycle life. The structural and chemical stabilities of the cathode were provided by the compositional partitioning and unique microstructure of the compositionally graded cathode combined with the ordered site-intermixing of Li and transition metal (TM) ions discovered
via
transmission electron microscopy. F doping induced the formation of a 2
a
hex
× 2
a
hex
×
c
hex
superlattice from ordered Li occupation in TM slabs and
vice versa
, which has been proven to be essential for suppressing microcrack formation in deeply charged states, while maintaining the structural stability of the cathode during extended cycling. Furthermore, the proposed cathode allows for the recycling of used EV batteries in energy storage systems, thereby alleviating the negative environmental impact by reducing the CO
2
emissions and cost associated with disposing of dead batteries.
The observed ultra-long battery life of 8000 cycles demonstrated by the Ni-rich compositionally graded NCM cathode stems mainly from the cation ordered structure.
The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most ...contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca
of the interlayer. Dreierketten chain cross-links act as 'columns' to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a 'bottom-up' approach.
America’s first system for punishing criminals with solitary confinement began at the Walnut Street Jail, an institution that stood right behind Independence Hall in Philadelphia. Historical and ...archival evidence from that facility demonstrates that the unchecked use of solitary confinement in today’s correctional facilities contravenes norms that prevailed in the Constitution’s founding era. In the 1790s, a robust array of checks and balances cabined the discretion of corrections officials to isolate prisoners. Judges, legislatures, and high public officials regulated human isolation at the jail, leaving prison administrators relatively little power over solitary confinement. Most importantly, long periods of seclusion could be imposed only by courts acting pursuant to criminal sentencing statutes. Jail officials had the power to impose solitary confinement for disciplinary violations, but only for a matter of days or weeks. Today, however, deference to prison officials has swallowed these constraints. In the present regime, some prisoners remain isolated for years and decades based on decisions by prison officials that courts hesitate to second-guess. The historical record casts doubt upon any originalist argument that the founding generation would have embraced the contemporary regime of judicial deference in matters of human isolation.
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Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, PRFLJ, SAZU, UILJ, UKNU, UL, UM, UPUK
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