Localized holes and delocalized electrons in photoexcited inorganic perovskites: Watching each atomic actor by picosecond X-ray absorption spectroscopy

We report on an element-selective study of the fate of charge carriers in photoexcited inorganic CsPbBr3 and CsPb(ClBr)3 perovskite nanocrystals (NCs) in toluene solutions using time-resolved X-ray absorption spectroscopy with 80 ps time resolution. Probing the Br K-edge, the Pb L3-edge and the Cs L2-edge, we find that holes in the valence band are localized at Br atoms, forming small polarons, while electrons appear as delocalized in the conduction band. No signature of either electronic or structural changes are observed at the Cs L2-edge. The results at the Br and Pb edges suggest the existence of a weakly localized exciton, while the absence of signatures at the Cs edge indicates that the Cs+ cation plays no role in the charge transport, at least beyond 80 ps. These results can explain the rather modest charge carrier mobilities in these materials.Comment: 19 pages, 3 figure

The search for the lost attractor

N-body systems characterized by inverse square attractive forces may display a self similar collapse known as the gravo-thermal catastrophe. In star clusters, collapse is halted by binary stars, and a large fraction of Milky Way clusters may have already reached this phase. It has been speculated -- with guidance from simulations -- that macroscopic variables such as central density and velocity dispersion are governed post-collapse by an effective, low-dimensional system of ODEs. It is still hard to distinguish chaotic, low dimensional motion, from high dimensional stochastic noise. Here we apply three machine learning tools to state-of-the-art dynamical simulations to constrain the post collapse dynamics: topological data analysis (TDA) on a lag embedding of the relevant time series, Sparse Identification of Nonlinear Dynamics (SINDY), and Tests of Accuracy with Random Points (TARP).Comment: Accepted by ML4PS workshop at NeurIPS 202

KLRC1 knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors

IntroductionNatural Killer (NK) cells hold the potential to shift cell therapy from a complex autologous option to a universal off-the-shelf one. Although NK cells have demonstrated efficacy and safety in the treatment of leukemia, the limited efficacy of NK cell-based immunotherapies against solid tumors still represents a major hurdle. In the immunosuppressive tumor microenvironment (TME), inhibitory interactions between cancer and immune cells impair antitumoral immunity. KLRC1 gene encodes the NK cell inhibitory receptor NKG2A, which is a potent NK cell immune checkpoint. NKG2A specifically binds HLA-E, a non-classical HLA class I molecule frequently overexpressed in tumors, leading to the transmission of inhibitory signals that strongly impair NK cell function.MethodsTo restore NK cell cytotoxicity against HLA-E+ tumors, we have targeted the NKG2A/HLA-E immune checkpoint by using a CRISPR-mediated KLRC1 gene editing.ResultsKLRC1 knockout resulted in a reduction of 81% of NKG2A+ cell frequency in ex vivo expanded human NK cells post-cell sorting. In vitro, the overexpression of HLA-E by tumor cells significantly inhibited wild-type (WT) NK cell cytotoxicity with p-values ranging from 0.0071 to 0.0473 depending on tumor cell lines. In contrast, KLRC1KO NK cells exhibited significantly higher cytotoxicity when compared to WT NK cells against four different HLA-E+ solid tumor cell lines, with p-values ranging from<0.0001 to 0.0154. Interestingly, a proportion of 43.5% to 60.2% of NKG2A− NK cells within the edited NK cell population was sufficient to reverse at its maximum the HLA-E-mediated inhibition of NK cell cytotoxicity. The expression of the activating receptor NKG2C was increased in KLRC1KO NK cells and contributed to the improved NK cell cytotoxicity against HLA-E+ tumors. In vivo, the adoptive transfer of human KLRC1KO NK cells significantly delayed tumor progression and increased survival in a xenogeneic mouse model of HLA-E+ metastatic breast cancer, as compared to WT NK cells (p = 0.0015).ConclusionsOur results demonstrate that KLRC1 knockout is an effective strategy to improve NK cell antitumor activity against HLA-E+ tumors and could be applied in the development of NK cell therapy for solid tumors

Shapes of rotating normal fluid 3He versus superfluid 4He droplets in molecular beams

Previous single-pulse extreme ultraviolet and X-ray coherent diffraction studies revealed that superfluid 4He droplets obtained in free jet expansion acquire sizable angular momentum, resulting in significant centrifugal distortion. Similar experiments with normal fluid 3He droplets may help elucidating the origin of the of the large degree of rotational excitation and highlight similarities and differences of dynamics in normal and superfluid droplets. Here, we present the first comparison of the shapes of isolated 3He and 4He droplets following expansion of the corresponding fluids in vacuum at temperatures as low as ~ 2 K. Large 3He and 4He droplets with average radii of ~160 nm and ~350 nm, respectively, were produced. We find that the majority of the 3He droplets in the beam correspond to rotating oblate spheroids with reduced average angular momentum ($\Lambda$) and reduced angular velocities ($\Omega$) similar to that of 4He droplets. Given the different physical nature of 3He and 4He, this similarity in $\Lambda$ and $\Omega$ may be surprising and suggest that similar mechanisms induce rotation regardless of the isotope. We hypothesized that the observed distribution of droplet sizes and angular momenta stem from processes in the dense region close to the nozzle. In this region, the significant velocity spread and collisions between the droplets induce excessive rotation followed by droplet fission. The process may repeat itself several times before the droplets enter the collision-fee high vacuum region further downstream.Comment: 29 pages, 6 figure

The true cost of food: a preliminary assessment

Ensuring sustainable food systems requires vastly reducing their environmental and health costs while making healthy and sustainable food affordable to all. One of the central problems of current food systems is that many of the costs of harmful foods are externalized, i.e., are not reflected in market prices. At the same time, the benefits of healthful foods are not appreciated. Due to externalities, sustainable and healthy food is often less affordable to consumers and less profitable for businesses than unsustainable and unhealthy food. Externalities and other market failures lead to unintended consequences for present and future generations, destroying nature and perpetuating social injustices such as underpay for workers, food insecurity, illness, premature death and other harms. We urgently need to address the fundamental causes of these problems. This chapter sets out the results of an analysis to determine the current cost of externalities in food systems and the potential impact of a shift in diets to more healthy and sustainable production and consumption patterns. The current externalities were estimated to be almost double (19.8 trillion USD) the current total global food consumption (9 trillion USD). These externalities accrue from 7 trillion USD (range 4–11) in environmental costs, 11 trillion USD (range 3–39) in costs to human life and 1 trillion USD (range 0.2–1.7) in economic costs. This means that food is roughly a third cheaper than it would be if these externalities were included. More studies are needed to quantify the costs and benefits of food systems that would support a global shift to more sustainable and healthy diets. However, the evidence presented in this chapter points to the urgent need for a system reset to account for these ‘hidden costs’ in food systems and calls for bold actions to redefine the incentives for producing and consuming healthier and more sustainable diets. The first step to correct for these ‘hidden costs’ is to redefine the value of food through true-cost accounting (TCA) so as to address externalities and other market failures. TCA reveals the true value of food by making the benefits of affordable and healthy food visible and revealing the costs of damage to the environment and human health 3

Estudo comparativo entre métodos de coloração para a pesquisa do bacilo álcool-ácido resistente em secreções pulmonares

Apresentação do resultado comparativo entre dois métodos de coloração Osol e Ziehl-Neelsen para a pesquisa do bacilo álcool-ácido resistente, em 337 amostras secreção pulmonar. Foi realizada uma avaliação cultural de 287 amostras, mostrando que o método de Osol apresenta-se melhor nas baciloscopias discordantes e que há tendência em apresentar maior riqueza de germe.The comparative results obtained with the study of two staining methods, the Ziehl-Neelsen and the Osol ones, are presented. The study was performed with the alcohol acid resistant bacilli of 337 pulmonary secretion specimens. Evaluation cultures of 287 of these specimens were made. The Osol method proved to be better than the Ziehl-Neelsen one when dealing with discordant baciloscopic evidence. There tended to be a larger ammount of bacilli, too, when the former was used

NOTCH3 Expression Is Linked to Breast Cancer Seeding and Distant Metastasis

Background: Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods: We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database. Results: In this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens. Conclusions: These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts