Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis.

Copper levels are known to be elevated in inflamed and malignant tissues. But the mechanism underlying this selective enrichment has been elusive. In this study, we report a axis by which inflammatory cytokines, such as IL-17, drive cellular copper uptake via the induction of a metalloreductase, STEAP4. IL-17-induced elevated intracellular copper level leads to the activation of an E3-ligase, XIAP, which potentiates IL-17-induced NFκB activation and suppresses the caspase 3 activity. Importantly, this IL-17-induced STEAP4-dependent cellular copper uptake is critical for colon tumor formation in a murine model of colitis-associated tumorigenesis and STEAP4 expression correlates with IL-17 level and XIAP activation in human colon cancer. In summary, this study reveals a IL-17-STEAP4-XIAP axis through which the inflammatory response induces copper uptake, promoting colon tumorigenesis

Advection-Dominated Accretion and the Spectral States of Black Hole X-Ray Binaries: Application to Nova Muscae 1991

We present a self-consistent model of accretion flows which unifies four distinct spectral states observed in black hole X-ray binaries: quiescent, low, intermediate and high states. In the quiescent, low and intermediate states, the flow consists of an inner hot advection-dominated part extending from the black hole horizon to a transition radius and an outer thin disk. In the high state the thin disk is present at all radii. The model is essentially parameter-free and treats consistently the dynamics of the accretion flow, the thermal balance of the ions and electrons, and the radiation processes in the accreting gas. With increasing mass accretion rate, the model goes through a sequence of stages for which the computed spectra resemble very well observations of the four spectral states; in particular, the low-to-high state transition observed in black hole binaries is naturally explained as resulting from a decrease in the transition radius. We also make a tentative proposal for the very high state, but this aspect of the model is less secure. We test the model against observations of the soft X-ray transient Nova Muscae during its 1991 outburst. The model reproduces the observed lightcurves and spectra surprisingly well, and makes a number of predictions which can be tested with future observations.Comment: 68 pages, LaTeX, includes 1 table (forgotten in the previous version) and 14 figures; submitted to The Astrophysical Journa

The staggered domain wall fermion method

A different lattice fermion method is introduced. Staggered domain wall fermions are defined in 2n+1 dimensions and describe 2^n flavors of light lattice fermions with exact U(1) x U(1) chiral symmetry in 2n dimensions. As the size of the extra dimension becomes large, 2^n chiral flavors with the same chiral charge are expected to be localized on each boundary and the full SU(2^n) x SU(2^n) flavor chiral symmetry is expected to be recovered. SDWF give a different perspective into the inherent flavor mixing of lattice fermions and by design present an advantage for numerical simulations of lattice QCD thermodynamics. The chiral and topological index properties of the SDWF Dirac operator are investigated. And, there is a surprise ending...Comment: revtex4, 7 figures, minor revisions, 2 references adde

Epidemiological trends and clinical outcomes of cryptococcosis in a medically insured population in the United States: a claims-based analysis from 2017 to 2019

Background: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. Objective: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. Methods: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. Results: Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). Conclusion: In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients

Pion-nucleus elastic scattering on 12C, 40Ca, 90Zr, and 208Pb at 400 and 500 MeV

Pion-nucleus elastic scattering at energies above the Delta(1232) resonance is studied using both pi+ and pi- beams on 12C, 40Ca, 90Zr, and 208Pb. The present data provide an opportunity to study the interaction of pions with nuclei at energies where second-order corrections to impulse approximation calculations should be small. The results are compared with other data sets at similar energies, and with four different first-order impulse approximation calculations. Significant disagreement exists between the calculations and the data from this experiment

Photoconductivity of biased graphene

Graphene is a promising candidate for optoelectronic applications such as photodetectors, terahertz imagers, and plasmonic devices. The origin of photoresponse in graphene junctions has been studied extensively and is attributed to either thermoelectric or photovoltaic effects. In addition, hot carrier transport and carrier multiplication are thought to play an important role. Here we report the intrinsic photoresponse in biased but otherwise homogeneous graphene. In this classic photoconductivity experiment, the thermoelectric effects are insignificant. Instead, the photovoltaic and a photo-induced bolometric effect dominate the photoresponse due to hot photocarrier generation and subsequent lattice heating through electron-phonon cooling channels respectively. The measured photocurrent displays polarity reversal as it alternates between these two mechanisms in a backgate voltage sweep. Our analysis yields elevated electron and phonon temperatures, with the former an order higher than the latter, confirming that hot electrons drive the photovoltaic response of homogeneous graphene near the Dirac point

Hole-Pairs in a Spin Liquid: Influence of Electrostatic Hole-Hole Repulsion

The stability of hole bound states in the t-J model including short-range Coulomb interactions is analyzed using computational techniques on ladders with up to $2 \times 30$ sites. For a nearest-neighbors (NN) hole-hole repulsion, the two-holes bound state is surprisingly robust and breaks only when the repulsion is several times the exchange $J$. At $\sim 10$ hole doping the pairs break only for a NN-repulsion as large as $V \sim 4J$. Pair-pair correlations remain robust in the regime of hole binding. The results support electronic hole-pairing mechanisms on ladders based on holes moving in spin-liquid backgrounds. Implications in two dimensions are also presented. The need for better estimations of the range and strength of the Coulomb interaction in copper-oxides is remarked.Comment: Revised version with new figures. 4 pages, 5 figure

AN ANALYSIS of the 20-year use of a deep Broward County lime-rock pit as a natural advanced wastewater treatment and groundwater recycling facility, with a recommendation that: with the large number of similar lime-rock pits in Southeast Florida, the opportunity for expanding the benefits of such inland wastewater retention should be given serious consideration instead of wastefully discharging the water into the ocean.

The benefits of the inland retention of freshwaters in South Florida are indisputable. During periods of prolonged drought, the maintenance of a higher groundwater table, which benefits terrestrial vegetation and retards saltwater intrusion, is clearly preferable to the alternative of discharging up to 400,000 gallons of freshwater per day into the ocean. Therefore, the only objections to the retention of treated sewage effluent in an inland lime-rock pit, with the physical, chemical and biologic characteristics of our pits, would have to do with possible detrimental effects to public health or the environment. The major public health concern involves the possible discharge of human pathogens. This can be prevented by high-level chlorination of well-treated effluent such as that of the Ferncrest Utilities. With the cooperation and help of the Nova University Oceanographic Center, the Florida Agricultural Research and Education Station, the Broward County Environmental Quality Control Board and the landowners, the Tindall Hammock Irrigation and Soil Conservation District and the Ferncrest Utilities respectfully submit that retention of the excellent tertiary-treated Ferncrest Utilities effluent in such a lime-rock pit accomplishes the following: • Provides an inexpensive, safe, practical, alternative, non-structural, natural, and environmentally sound drainage and wastewater pollutant treatment and inactivation facility that uses no energy except sunlight. • Conserves, stores and recycles stormwater and wastewater instead of wasteful discharge into canals or the ocean. • Helps to maintain a higher groundwater elevation, thereby reducing the volume of irrigation water needed for area lawns and shrubbery, and the energy and expense thereof. • Retards the rate of saltwater intrusion into the aquifer. • Enhances the U.S. EPA\u27s goal of fishable, swimmable public waters by complexing and precipitating runoff and wastewater pollutants, thereby keeping them out of the North New River Canal, the New River and the ocean. With the large number of similar lime-rock pits in Southeast Florida, the opportunity for expanding the benefits of such inland wastewater retention should be given serious consideration

Removal of ecotoxicity of 17α-ethinylestradiol using TAML/peroxide water treatment

17α -ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent. Ozone and activated carbon provide effective wastewater treatments, but their energy intensities and capital/operating costs are formidable barriers to adoption. Here we describe the technical and environmental performance of a fast- developing contender for mitigation of EE2 contamination of wastewater based upon smallmolecule, full-functional peroxidase enzyme replicas called “TAML activators”. From neutral to basic pH, TAML activators with H2O2 efficiently degrade EE2 in pure lab water, municipal effluents and EE2-spiked synthetic urine. TAML/H2O2 treatment curtails estrogenicity in vitro and substantially diminishes fish feminization in vivo. Our results provide a starting point for a future process in which tens of thousands of tonnes of wastewater could be treated per kilogram of catalyst. We suggest TAML/H2O2 is a worthy candidate for exploration as an environmentally compatible, versatile, method for removing EE2 and other pharmaceuticals from municipal wastewaters.Heinz Endowments, the Swiss National Science Foundation, the Steinbrenner Institute for a Steinbrenner Doctoral Fellowship. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)