Measurement of the 2νββ Decay Rate and Spectral Shape of ^{100}Mo from the CUPID-Mo Experiment.

Neutrinoless double beta decay (0νββ) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νββ) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νββ decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.

LiMoO Scintillating Bolometers for Rare-Event Search Experiments.

We report on the development of scintillating bolometers based on lithium molybdate crystals that contain molybdenum that has depleted into the double-β active isotope 100Mo (Li2100deplMoO4). We used two Li2100deplMoO4 cubic samples, each of which consisted of 45-millimeter sides and had a mass of 0.28 kg; these samples were produced following the purification and crystallization protocols developed for double-β search experiments with 100Mo-enriched Li2MoO4 crystals.

Cryopreserved Stem Cells Incur Damages Due To Terrestrial Cosmic Rays Impairing Their Integrity Upon Long-Term Storage.

Stem cells have the capacity to ensure the renewal of tissues and organs. They could be used in the future for a wide range of therapeutic purposes and are preserved at liquid nitrogen temperature to prevent any chemical or biological activity up to several decades before their use. We show that the cryogenized cells accumulate damages coming from natural radiations, potentially inducing DNA double-strand breaks (DSBs).

Arginase 1-Based Immune Modulatory Vaccines Induce Anticancer Immunity and Synergize with Anti-PD-1 Checkpoint Blockade.

Expression of the L-arginine catabolizing enzyme arginase 1 (ARG1) is a central immunosuppressive mechanism mediated by tumor-educated myeloid cells. Increased activity of ARG1 promotes the formation of an immunosuppressive microenvironment and leads to a more aggressive phenotype in many cancers. Intrinsic T-cell immunity against ARG1-derived epitopes in the peripheral blood of cancer patients and healthy subjects has previously been demonstrated.

New Limit for Neutrinoless Double-Beta Decay of ^{100}Mo from the CUPID-Mo Experiment.

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νββ experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νββ decay in ^{100}Mo.

Arrayed Molecular Barcoding of Leukemic Stem Cells.

Functional screens on cancer cells using compound or protein libraries are usually performed in vitro. However, to assess the effects on leukemia stem cells (LSCs) in a screening setting, methodologies that allow for a high-throughput in vivo readout of leukemia-initiating activity are needed. One experimental approach to solve this issue is to genetically label, also referred to as "barcoding," the leukemia cells in an arrayed format prior to exposing them to separate experimental conditions.

First Germanium-Based Constraints on Sub-MeV Dark Matter with the EDELWEISS Experiment.

We present the first Ge-based constraints on sub-MeV/c^{2} dark matter (DM) particles interacting with electrons using a 33.4 g Ge cryogenic detector with a 0.53 electron-hole pair (rms) resolution, operated underground at the Laboratoire Souterrain de Modane.

CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia cells in vivo without impairing their homing to the bone marrow.

Arrayed molecular barcoding identifies TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells.

Dysregulation of cytokines in the bone marrow (BM) microenvironment promotes acute myeloid leukemia (AML) cell growth. Due to the complexity and low throughput of stem-cell based assays, studying the role of cytokines in the BM niche in a screening setting is challenging. Here, we developed an cytokine screen using 11 arrayed molecular barcodes, allowing for a competitive readout of leukemia-initiating capacity.

Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NFκB-dependent differentiation of AML cells.

Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34CD38 cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 in -driven human AML resulted in induction of apoptosis by p38 MAPK-dependent activation of Caspase 3 and myeloid differentiation in a NFκB-dependent manner.

Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner.

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures.

Development of -containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search.

This paper reports on the development of a technology involving -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ), high optical quality, radiopure -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.

BMP2, a key to uncover luminal breast cancer origin linked to pollutant effects on epithelial stem cells niche.

Chronic exposure of epithelial cells to high levels of bone morphogenetic protein 2 (BMP2) has recently been demonstrated to initiate stem cell transformation toward a luminal tumor-like phenotype through a BMP2-BMPR1B-dependent mechanism. Carcinogen-driven deregulation of the stem cell niche could therefore represent a driving force to promote transformation and dictate the ultimate breast tumor subtype.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis.

The effect of environmental chemicals on the tumor microenvironment.

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment.

Disequilibrium of BMP2 levels in the breast stem cell niche launches epithelial transformation by overamplifying BMPR1B cell response.

Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer.

Perfusion studies in senology.

Microcirculation imaging in breast cancer involves studying tissue enhancement after contrast injection, which is used to calculate perfusion and permeability. The magnitude of enhancement reflects blood and interstitial volumes. This technique has benefitted from advances in MRI, which allow large volumes to be acquired with a good compromise between temporal and spatial resolution.

Diffusion-weighted MRI in pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer.

Purpose: To evaluate the accuracy of the apparent diffusion coefficient (ADC) provided by diffusion-weighted imaging (DWI) in predicting the response to neoadjuvant chemotherapy (NACT) at baseline in patients according to their breast tumour phenotypes.

Materials & Methods: This retrospective study was approved by our institutional review board. One hundred eighteen consecutive women with locally advanced breast cancer who had undergone NACT followed by breast surgery were included.

[BMP and cancer: the Yin and Yang of stem cells].

In a normal context, bone morphogenetic proteins (BMPs), members of the TGFβ superfamily, are key players in adult stem cell biology. They are involved in the control of the overall functional and phenotypic properties of the stem cell population (self-renewal, proliferation, differentiation, apoptosis, quiescence, etc.).

A protocol to quantify mammary early common progenitors from long-term mammosphere culture.

Here we describe a protocol established in our laboratory to quantify early common progenitors/stem cells grown as spheres in non-adherent culture conditions. This protocol is based on the combination of two functional tests: the mammosphere assay to maintain and enrich early mammary progenitors/stem cells, and the epithelial colony-forming cells (E-CFC) assay to identify and quantify further differentiated epithelial progenitors. Primary spheres mainly contain progenitors and rare stem/early common progenitor cells while secondary and tertiary spheres contain progenitor cells derived from the early common progenitor/stem cell population maintained through passages and partially differentiated.

Cross-disciplinary problem-solving workshop: a pedagogical approach to anticipate ergonomist engineering design collaboration.

The aims of this paper are to present concept and results of an innovative educational model approach based on ergonomics involvement in industrial project. First we present Cross disciplinary Problem solving Workshop by answering three questions:1) What is a CPW: A partnership between Universities and one or several companies, purposes of it are first to increase health, well being, companies teams competencies, and competitiveness, second to train the "IPOD generation" to include risks prevention in design. 2) How does it work? CPW allows cooperation between experience and new insight through inductive methods.

Breast inflammation: indications for MRI and PET-CT.

Breast MRI should not be used for differential diagnosis between inflammatory breast cancer and acute mastitis (AM) prior to treatment. When mastitis symptoms persist after 10 to 15 days of well-managed medical treatment, MRI may be performed in addition to an ultrasound examination, a mammogram and to taking histological samples, in order to eliminate inflammatory breast cancer (IBC). For staging, MRI would seem to be useful in looking for a contralateral lesion, PET-CT for finding information about remote metastases and in certain centres, for information about the initial extension to local/regional lymph nodes, which would guide the fields of irradiation (since patients can become lymph node negative after neoadjuvant chemotherapy).

The CD10 enzyme is a key player to identify and regulate human mammary stem cells.

The major components of the mammary ductal tree are an inner layer of luminal cells, an outer layer of myoepithelial cells, and a basement membrane that separates the ducts from the underlying stroma. Cells in the outer layer express CD10, a zinc-dependent metalloprotease that regulates the growth of the ductal tree during mammary gland development. To define the steps in the human mammary lineage at which CD10 acts, we have developed an in vitro assay for human mammary lineage progression.