A composite solution to the EDGES anomaly

Subcomponent millicharged dark matter that cools baryons via Coulomb interactions has been invoked to explain the EDGES anomaly. However, this model is in severe tension with constraints from cosmology and stellar emissions. In this work, we consider the consequences of these millicharged particles existing in composite blobs. The relevant degrees of freedom at high temperature are minuscule elementary charges, which fuse at low temperatures to make up blobs of larger charge. These blobs serve as the degrees of freedom relevant in cooling the baryons sufficiently to account for the EDGES anomaly. In such a model, cosmology and stellar constraints (which involve high-temperature processes) apply only to the feebly-interacting elementary charges and not to the blobs. This salvages a large range of parameter space for millicharged blobs that can explain the EDGES anomaly. It also opens up new parameter space for direct detection, albeit at low momentum transfers.Comment: 8 pages, 3 figure

Improvements to the Copernicus Trajectory Design and Optimization System for Complex Space Trajectories

The purpose of this assessment was to develop updates and new features for the NASA Copernicus Spacecraft Trajectory Design and Optimization analysis tool (version 5.0) for application to NASA programs and projects. These updates will significantly improve the ability to design and optimize complex trajectories over multiple trajectory phases; will allow the use of unique vehicle-specific guidance, control, and trajectory strategies and constraints; and the creation of an almost unlimited number of unique user-defined capabilities. The primary stakeholders for this assessment are the trajectory design and optimization analysts and engineers, and the chief engineers and project managers for existing programs, projects, and/or tasks that involve impulsive, finite burn, and/or continuous thrust trajectories (e.g., Sun, planet, comet, asteroid, halo orbit, Lagrange point, and distant retrograde orbit). The breadth of application spans the preliminary engineering and mission design concepts and optimization, to the development of candidate reference missions and integrated mission design for vehicle system design and operation, to the design and development of flight trajectories and associated propulsive maneuvers for real-time operations

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch

Atopic dermatitis (AD) is the most common skin disease in children. It is characterized by relapsing inflammation, skin-barrier defects, and intractable itch. However, the pathophysiology of itch in AD remains enigmatic. Here, we examine the contribution of Tmem79, an orphan transmembrane protein linked to AD in both mice and humans. We show that Tmem79 is expressed by both keratinocytes and sensory neurons, but that loss of keratinocytic Tmem79 is sufficient to elicit robust scratching. Tmem79 -/- mice demonstrate an accumulation of dermal mast cells, which are diminished following chronic treatment with cyclooxygenase inhibitors and an EP3 receptor antagonist. In Tmem79 -/- mice, mast cell degranulation produces histaminergic itch in a histamine receptor 1/histamine receptor 4 (H4R/H1R)-dependent manner that may involve activation of TRPV1- afferents. TMEM79 has limited sequence homology to a family of microsomal glutathione transferases and confers protection from cellular accumulation of damaging reactive species, and may thus play a role in regulating oxidative stress. In any case, mechanistic insights from this model suggest that therapeutics targeting PGE2 and/or H1R/H4R histaminergic signaling pathways may represent useful avenues to treat Tmem79-associated AD itch. Our findings suggest that individuals with mutations in Tmem79 develop AD due to the loss of protection from oxidative stress

Regulation of metastatic potential by drug repurposing and mitochondrial targeting in colorectal cancer cells

Abstract Background Increased mitochondrial activities contributing to cancer cell proliferation, invasion, and metastasis have been reported in different cancers; however, studies on the therapeutic targeting of mitochondria in regulating cell proliferation and invasiveness are limited. Because mitochondria are believed to have evolved through bacterial invasion in mammalian cells, antibiotics could provide an alternative approach to target mitochondria, especially in cancers with increased mitochondrial activities. In this study, we investigated the therapeutic potential of bacteriostatic antibiotics in regulating the growth potential of colorectal cancer (CRC) cells, which differ in their metastatic potential and mitochondrial functions. Methods A combination of viability, cell migration, and spheroid formation assays was used to measure the effect on metastatic potential. The effect on mitochondrial mechanisms was investigated by measuring mitochondrial DNA copy number by qPCR, biogenesis (by qPCR and immunoblotting), and functions by measuring reactive oxygen species, membrane potential, and ATP using standard methods. In addition, the effect on assembly and activities of respiratory chain (RC) complexes was determined using blue native gel electrophoresis and in-gel assays, respectively). Changes in metastatic and cell death signaling were measured by immunoblotting with specific marker proteins and compared between CRC cells. Results Both tigecycline and tetracycline effectively reduced the viability, migration, and spheroid-forming capacity of highly metastatic CRC cells. This increased sensitivity was attributed to reduced mtDNA content, mitochondrial biogenesis, ATP content, membrane potential, and increased oxidative stress. Specifically, complex I assembly and activity were significantly inhibited by these antibiotics in high-metastatic cells. Significant down-regulation in the expression of mitochondrial-mediated survival pathways, such as phospho-AKT, cMYC, phospho-SRC, and phospho-FAK, and upregulation in cell death (apoptosis and autophagy) were observed, which contributed to the enhanced sensitivity of highly metastatic CRC cells toward these antibiotics. In addition, the combined treatment of the CRC chemotherapeutic agent oxaliplatin with tigecycline/tetracycline at physiological concentrations effectively sensitized these cells at early time points. Conclusion Altogether, our study reports that bacterial antibiotics, such as tigecycline and tetracycline, target mitochondrial functions specifically mitochondrial complex I architecture and activity and would be useful in combination with cancer chemotherapeutics for high metastatic conditions

Primary Apocrine Adenocarcinoma of the Axilla

Primary apocrine adenocarcinoma (AA) is a rare malignant cutaneous neoplasm that typically arises in areas of high apocrine gland density such as the axillae and the anogenital region. Due to the nonspecific clinical manifestation of AA, the differential diagnosis may be broad. The rarity of this neoplasm has led to a relative lack of well-established histologic and immunohistochemical diagnostic criteria, further complicating the diagnosis of AA. We report the case of a 49-year-old man with primary AA of the left axilla and provide a review of the clinical and histologic findings, epidemiology, and treatment modalities of this rare cutaneous neoplasm

T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype

IL-23, an IL-12-related cytokine, induces an IL-17-secreting T-helper phenotype that is involved in autoimmune diseases and host defense against certain pathogens. Although the transcription factors required for development of IL-23-stimulated cells are unknown, we show that T-bet is a critical negative regulator of the IL-23-primed T-cell phenotype, which we term Th1β. Th1 or Th1β Tbx21-/- cultures secrete higher than WT levels of IL-17 in response to T-cell receptor (TCR) or IL-23 + IL-18 stimulation. Ectopic T-bet expression in Th1β cells promotes IFN-γ secretion but decreases IL-17 production. Although antigen-receptor stimulation of Th1β cells stimulates IL-17 production, it also induces the IFN-γ-independent expression of T-bet and progression to a Th1 cytokine secretion pattern. T-bet is required for the progression to the Th1 phenotype, because Tbx21-/- Th1β cultures maintain the IL-17-secreting phenotype after 2 weeks of culture. Addition of IFN-γ to Tbx21-/- Th1β cultures cannot recover the progression to the Th1 phenotype, suggesting T-bet, rather than IFN-γ, mediates Th1β to Th1 progression. The transient nature of the Th1β phenotype suggests that these cells are a component of type I immunity and that T-bet expression is a critical determinant of Th1 versus Th1β cell fate