Tunable quantum emitters on large-scale foundry silicon photonics.

Controlling large-scale many-body quantum systems at the level of single photons and single atomic systems is a central goal in quantum information science and technology. Intensive research and development has propelled foundry-based silicon-on-insulator photonic integrated circuits to a leading platform for large-scale optical control with individual mode programmability. However, integrating atomic quantum systems with single-emitter tunability remains an open challenge.

Quantifying the impacts of future shoreline modification on biodiversity in a case study of coastal Georgia, United States.

People often modify the shoreline to mitigate erosion and protect property from storm impacts. The 2 main approaches to modification are gray infrastructure (e.g.

Quantifying the effects of sea level rise driven marsh migration on wave attenuation.

Sea level rise (SLR) is the most significant climate change-related threat to coastal wetlands, driving major transformations in coastal regions through marsh migration. Landscape transformations due to marsh migration are manifested in terms of horizontal and vertical changes in land cover and elevation, respectively. These processes will have an impact on saltmarsh wave attenuation that is yet to be explored.

Numerical modeling of wave attenuation: implications of representing vegetation found in coastal saltmarshes in the Chesapeake Bay.

Coastal communities are vulnerable to wave and storm surges during extreme events, highlighting the need to increase community resilience. The effectiveness of natural wetlands in attenuating waves is vital to designing strategies for protecting public safety. This study aimed to understand how vegetation attenuates waves and determine the best method for modeling vegetation's impact on wave dynamics.

Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia.

Unlabelled: Mutations in Fms-like tyrosine kinase 3 (FLT3) are common drivers in acute myeloid leukemia (AML) yet FLT3 inhibitors only provide modest clinical benefit. Prior work has shown that inhibitors of lysine-specific demethylase 1 (LSD1) enhance kinase inhibitor activity in AML. Here we show that combined LSD1 and FLT3 inhibition induces synergistic cell death in FLT3-mutant AML.

Asxl1 deletion disrupts MYC and RNA polymerase II function in granulocyte progenitors.

Mutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. However, the role of ASXL1 in myeloid lineage maturation is incompletely described. To define the role of ASXL1 in myelopoiesis, we employed single cell RNA sequencing and a murine model of hematopoietic-specific Asxl1 deletion.

GoPeaks: histone modification peak calling for CUT&Tag.

Genome-wide mapping of histone modifications is critical to understanding transcriptional regulation. CUT&Tag is a new method for profiling histone modifications, offering improved sensitivity and decreased cost compared with ChIP-seq. Here, we present GoPeaks, a peak calling method specifically designed for histone modification CUT&Tag data.

PU.1 and MYC transcriptional network defines synergistic drug responses to KIT and LSD1 inhibition in acute myeloid leukemia.

Responses to kinase-inhibitor therapy in AML are frequently short-lived due to the rapid development of resistance, limiting the clinical efficacy. Combination therapy may improve initial therapeutic responses by targeting pathways used by leukemia cells to escape monotherapy. Here we report that combined inhibition of KIT and lysine-specific demethylase 1 (LSD1) produces synergistic cell death in KIT-mutant AML cell lines and primary patient samples.

BET Bromodomain Inhibition Blocks an AR-Repressed, E2F1-Activated Treatment-Emergent Neuroendocrine Prostate Cancer Lineage Plasticity Program.

Purpose: Lineage plasticity in prostate cancer-most commonly exemplified by loss of androgen receptor (AR) signaling and a switch from a luminal to alternate differentiation program-is now recognized as a treatment resistance mechanism. Lineage plasticity is a spectrum, but neuroendocrine prostate cancer (NEPC) is the most virulent example. Currently, there are limited treatments for NEPC.

Combined inhibition of JAK/STAT pathway and lysine-specific demethylase 1 as a therapeutic strategy in CSF3R/CEBPA mutant acute myeloid leukemia.

Acute myeloid leukemia (AML) is a deadly hematologic malignancy with poor prognosis, particularly in the elderly. Even among individuals with favorable-risk disease, approximately half will relapse with conventional therapy. In this clinical circumstance, the determinants of relapse are unclear, and there are no therapeutic interventions that can prevent recurrent disease.

Alternative splicing of LSD1+8a in neuroendocrine prostate cancer is mediated by SRRM4.

Neuroendocrine prostate cancer (NEPC) is the most virulent form of prostate cancer. Importantly, our recent work examining metastatic biopsy samples demonstrates NEPC is increasing in frequency. In contrast to prostate adenocarcinomas that express a luminal gene expression program, NEPC tumors express a neuronal gene expression program.

Molecular Testing Identifies Determinants of Exceptional Response and Guides Precision Therapy in a Patient with Lethal, Treatment-emergent Neuroendocrine Prostate Cancer.

Nearly all prostate cancers start out as adenocarcinomas driven by the androgen receptor (AR). Neuroendocrine prostate cancer (NEPC) is a rare, AR-independent subtype with a poor prognosis and limited treatment options. Importantly, because of the widespread use of novel AR-targeting agents, the incidence of treatment-emergent (t)-NEPC is increasing in frequency.

BET bromodomain inhibition blocks the function of a critical AR-independent master regulator network in lethal prostate cancer.

BET bromodomain inhibitors block prostate cancer cell growth at least in part through c-Myc and androgen receptor (AR) suppression. However, little is known about other transcriptional regulators whose suppression contributes to BET bromodomain inhibitor anti-tumor activity. Moreover, the anti-tumor activity of BET bromodomain inhibition in AR-independent castration-resistant prostate cancers (CRPC), whose frequency is increasing, is also unknown.

Maintenance of MYC expression promotes de novo resistance to BET bromodomain inhibition in castration-resistant prostate cancer.

The BET bromodomain protein BRD4 is a chromatin reader that regulates transcription, including in cancer. In prostate cancer, specifically, the anti-tumor activity of BET bromodomain inhibition has been principally linked to suppression of androgen receptor (AR) function. MYC is a well-described BRD4 target gene in multiple cancer types, and prior work demonstrates that MYC plays an important role in promoting prostate cancer cell survival.

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer.

Integrative molecular network analysis identifies emergent enzalutamide resistance mechanisms in prostate cancer.

Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC.

IL-1 Receptor-Knockout Mice Develop Epidermal Cysts and Show an Altered Innate Immune Response after Exposure to UVB Radiation.

In this study, we observed that mice lacking the IL-1 receptor (IL-1R) (IL1r) or deficient in IL1-β developed multiple epidermal cysts after chronic UVB exposure. Cysts that developed in IL1r mice were characterized by the presence of the hair follicle marker Sox 9, keratins 10 and 14, and normal melanocyte distribution and retinoid X receptor-α expression. The increased incidence of cysts in IL1r mice was associated with less skin inflammation as characterized by decreased recruitment of macrophages, and their skin also maintained epidermal barrier function compared with wild-type mice.

Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor.

Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) - the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR.

Enhanced removal of nickel(II) ions from aqueous solutions by SDS-functionalized graphene oxide.

In this paper, a one-pot and easy-to-handle method at room temperature without additional chemicals for the modification of graphene oxide (GO) with surfactant is found. Removal of nickel (II) ions from aqueous solutions by GO and surfactant (sodium dodecyl sulphate) modified graphene oxide (SDS-GO) was studied spectrophotometrically at room temperature as a function of time, initial concentration and pH. Adsorption capacity of the adsorbent was increased dramatically (from 20.

Coibamide A, a natural lariat depsipeptide, inhibits VEGFA/VEGFR2 expression and suppresses tumor growth in glioblastoma xenografts.

Coibamide A is a cytotoxic lariat depsipeptide isolated from a rare cyanobacterium found within the marine reserve of Coiba National Park, Panama. Earlier testing of coibamide A in the National Cancer Institute in vitro 60 human tumor cell line panel (NCI-60) revealed potent anti-proliferative activity and a unique selectivity profile, potentially reflecting a new target or mechanism of action. In the present study we evaluated the antitumor activity of coibamide A in several functional cell-based assays and in vivo.

Loss of keratinocytic RXRα combined with activated CDK4 or oncogenic NRAS generates UVB-induced melanomas via loss of p53 and PTEN in the tumor microenvironment.

Unlabelled: Understanding the molecular mechanisms behind formation of melanoma, the deadliest form of skin cancer, is crucial for improved diagnosis and treatment. One key is to better understand the cross-talk between epidermal keratinocytes and pigment-producing melanocytes. Here, using a bigenic mouse model system combining mutant oncogenic NRAS(Q61K) (constitutively active RAS) or mutant activated CDK4(R24C/R24C) (prevents binding of CDK4 by kinase inhibitor p16(INK4A)) with an epidermis-specific knockout of the nuclear retinoid X receptor alpha (RXRα(ep-/-)) results in increased melanoma formation after chronic ultraviolet-B (UVB) irradiation compared with control mice with functional RXRα.

Retinoid-X-receptors (α/β) in melanocytes modulate innate immune responses and differentially regulate cell survival following UV irradiation.

Understanding the molecular mechanisms of ultraviolet (UV) induced melanoma formation is becoming crucial with more reported cases each year. Expression of type II nuclear receptor Retinoid-X-Receptor α (RXRα) is lost during melanoma progression in humans. Here, we observed that in mice with melanocyte-specific ablation of RXRα and RXRβ, melanocytes attract fewer IFN-γ secreting immune cells than in wild-type mice following acute UVR exposure, via altered expression of several chemoattractive and chemorepulsive chemokines/cytokines.

Grp1-associated scaffold protein regulates skin homeostasis after ultraviolet irradiation.

Grp1-associated scaffold protein (Grasp), the product of a retinoic acid-induced gene in P19 embryonal carcinoma cells, is expressed primarily in brain, heart, and lung of the mouse. We report herein that Grasp transcripts are also found in mouse skin in which the Grasp gene is robustly induced following acute ultraviolet-B (UVB) exposure. Grasp(-/-) mice were found to exhibit delayed epidermal proliferation and a blunted apoptotic response after acute UVB exposure.

Determination of key structure-activity relationships in siRNA delivery with a mixed micelle system.

Short interfering ribonucleic acids (siRNAs) offer a highly specific and selective form of therapy for diseases with a genetic component; however the poor pharmacokinetic properties of the molecule have impeded its development into a therapeutic for use in vivo. Several different approaches have been taken to develop a successful siRNA delivery system but these systems lack the flexibility for easy optimisation. Here, we propose a polymeric nanoparticle (PNP) system consisting of two amphiphilic diblock copolymers which allow for the rapid determination of structure-activity relationships involving gene knockdown and toxicity.

Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis.

Keratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here, we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV-induced melanocyte homeostasis. Selective ablation of endothelin-1 (EDN1) in murine epidermis (EDN1(ep-/-) ) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin.