Density functional theory (DFT) has transformed our ability to investigate and understand electronic ground states. In its original formulation, however, DFT is not suited to addressing (e.g.) degenerate ground states, mixed states with different particle numbers, or excited states. All these issues can be handled, in principle exactly, via ensemble DFT (EDFT). This Perspective provides a detailed introduction to and analysis of EDFT, in an in-principle exact framework that is constructed to avoid uncontrolled errors and inconsistencies that may be associated with ad hoc extensions of conventional DFT. In particular, it focuses on the "ensemblization" of both exact and approximate density functionals, a term that we coined to describe a rigorous approach that lends itself to the construction of novel approximations consistent with the general ensemble framework, yet applicable to practical problems where traditional DFT tends to fail or does not apply at all. In particular, symmetry considerations and ensemble properties are shown to enable each other in shaping a practical DFT-based methodology that extends beyond the ground state and, in doing so, highlights the need to look outside the standard ground state Kohn-Sham treatment.
Intermediate mass ratio inspirals (IMRIs) of binary black holes with mass ratios 10(-4) less than or similar to q less than or similar to 0.1 are astrophysically interesting sources of gravitational waves. Mergers of intermediate-mass black holes (IMBHs) with stellar-mass black holes would be IMRIs, so their detection can help us probe the formation mechanisms of IMBHs. They can also help us perform precise tests of general relativity due to the presence of strong higher-order mode emission. We perform a search for aligned-spin IMRIs within the data of the two LIGO detectors in the third observing run (O3) of the LIGO-Virgo-KAGRA (LVK) Collaboration, including higher modes in the template banks for the first time. We use the IAS-HM pipeline for our search and construct template banks in the range 1/100 < q < 1/18 using the SEOBNRv5HM waveform model. Our banks retain a similar level of effectualness for IMRPhenomXHM and BHPTNRSur2dq1e3 waveforms, making our search results relatively robust against waveform systematics. We show that the sensitivity volume of the search increases by up to similar to 500% upon inclusion of higher modes. We do not find any significant candidates with inverse false alarm rate (IFAR) > 1 year in the O3 data. This gives us upper limits on the IMRI merger rate in the local Universe, ranging from similar to 30 to 10(3) Gpc(-3) yr(-1) depending on the masses of the black holes in the binary. These constraints are consistent with rate predictions in the literature. Our projections indicate that we would be able to detect IMRIs or constrain some of their proposed formation channels in the fourth (O4) and fifth (O5) observing runs.
Besor 37 is an open-air site in the northwestern Negev Desert (Israel). Excavations at the site in 2020 uncovered a rich, in situ Middle Paleolithic assemblage composed of flint and limestone artifacts, animal bones and charcoal. The good preservation of the site is due to its rapid burial by overbank deposition of fluvially reworked loess. Dating using both Optically Stimulated Luminescence and 14C suggests an average age of 46.6 ± 2.4 ka. Using a macro and micro-archaeological approach, we determined the technological organization and the nature of occupation with reference to spatial patterning of the assemblages. To integrate the site into a regional perspective we used comparative data from four other Late Middle Paleolithic sites, also located in the southern Levantine desert region; Far’ah II, Rosh Ein Mor, Nahal Dimona 24 and Tor Faraj. We evaluate measures of curation, artifact density and assemblage composition to define site type and mobility system. We propose that Besor 37 represents an ephemeral residential occupation, frequented repeatedly by high mobility hunter-gatherers, possibly part of a larger seasonal, perhaps circular mobility pattern.
Approximately 50% of prostate cancer (PCa) patients harbor fusions involving the TMPRSS2 and ERG genes. Despite this, tailored therapies targeting the fused gene, tERG, remain undeveloped. Our study analyzed biopsy samples from two clinical trials assessing the efficacy of androgen receptor (AR) signaling inhibitors (ARSIs). The results revealed that tERG promotes resistance to ARSIs and is associated with elevated levels of the glucocorticoid receptor (GR). Subsequent assays showed that GR directly interacts with tERG, alleviates allosteric autoinhibition, and prevents chemotherapy-induced tERG degradation. In PCa models, either inhibiting GR or lowering cortisol levels suppressed tumor growth in tERG-positive models, but not in tERG-negative models. In addition, patient-derived fusion-positive xenografts displayed enhanced sensitivity to combined GR and AR inhibitors. Collectively, these findings highlight TMPRSS2-ERG as a new biomarker and propose that simultaneous inhibition of GR and AR may specifically benefit tERG-positive patients. However, GR stimulatory corticosteroid therapies may not be advisable for this patient subgroup.
Most of our intuition about the behavior of physical systems is shaped by observations at or near thermal equilibrium. However, even a thermal quench can lead to states far from thermal equilibrium, where counterintuitive, anomalous effects can occur. A prime example of anomalous thermal relaxation is the Mpemba effect, in which a system prepared at a hot temperature cools down to the temperature of the cold environment faster than an identical system prepared at a warm temperature. Although reported for water more than 2000 years ago by Aristotle, the recent observations of analogous relaxation speedups in a variety of systems have motivated the search for general explanations. We review anomalous relaxation effects, which all share a nonmonotonic dependence of relaxation time versus initial “distance" from the final state or from the phase transition. The final state can be an equilibrium or a nonequilibrium steady state. We first review the water experiments and classify the anomalous relaxation phenomena related to the Mpemba effect. We then provide a modern definition of the Mpemba effect, focusing on the theoretical frameworks of stochastic thermodynamics, kinetic theory, Markovian dynamics, and phase transitions. We discuss the recent experimental and numerical developments that followed these theoretical advances. These developments paved the way for the prediction and observation of novel phenomena, such as the inverse Mpemba effect. The review is self-contained and introduces anomalous relaxation phenomena in single- and many-body systems, both classical and quantum. We also discuss the broader relevance of the Mpemba effect, including its relation with phase transitions and its experimental implications. We end with perspectives that connect anomalous speedups to ideas for designing optimal heating/cooling protocols, heat engines, and efficient samplers.
