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We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on ESO/VLT. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3-4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided MUSE observations of fields selected from the GAMA survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (> 7 x 10^10 M_Sun) central galaxies at 0.25 < z <0.35 in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics (GLAO, 0.6-0.8 arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, e.g. SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at 0.25 < z <0.35, as well as hundreds of emission-line sources at z < 6. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at z ~ 0.3. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.

Sediment and water samples collected from 32 locations in Ulsan Bay and adjacent inland areas were analyzed for polycyclic aromatic hydrocabons (PAHs), nonylphenol (NP), octylphenol (OP), bisphenol A (BPA), organochlorine (OC) pesticides (HCB, HCHs, CHLs, and DDTs), and polychlorinated biphenyls (PCBs) to characterize their spatial distribution and contamination status. PAHs were detected in nearly all sediment and water extracts from Ulsan Bay and its inland locations. The sedimentary PAH concentrations ranged from 17 to 3,100 ng/g on a dry weight basis (DW), which were predominated by two- and three-ring aromatic hydrocarbons in river and/or stream, and four- to six-ring compounds in Ulsan Bay sediment. Concentrations of PAHs in pore water samples were generally two or three orders magnitude less than those of corresponding sediment samples. Maximum concentrations of NP, OP, and BPA in sediments were 1,040, 120, and 54 ng/g DW, respectively. Concentrations of OP and BPA were, on average, 5- to 13-fold less than those of NP. PCB concentrations in sediment ranged from 1.4 to 77 ng/g DW, which were predominated by lower chlorinated congeners such as di- through pentachlorinated biphenyls. Among different OC pesticides analyzed, concentrations of DDTs were the greatest, ranging from 0.02 to 41.9 ng/g DW. NP concentrations were greater at inner locations proximal to municipal wastewater discharges into rivers and/or streams, whereas the concentrations of PCBs and PAHs were great near the sites of high industrial activities. Sediment-pore water partitioning coefficients correlated with those of reported Koc or Kow values for selected PAHs in Ulsan Bay, but these varied by an order of magnitude for stream and/or river sediments.

Blue mussels (Mytilus edulis) collected from 34 locations along the south and east coast of Korea were analyzed for polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides. Maximum concentrations of PCBs and total OC pesticides were 98.5 and 20.5 ng/g, wet weight, respectively. Extracts were fractionated by Florisil chromatography and each fraction was screened for dioxin-like activity in vitro, using recombinant rat hepatoma cells (H4IIE-luc). Fraction 2 (F-2), which contained hexachlorocyclohexanes, chlordanes, p,p'-DDD, and p,p'-DDT, generally elicited significant dioxin-like activity compared to control, whereas Fraction 1 (F-1), which contained PCBs, p,p'-DDE, and hexachlorobenzene, did not. The greatest magnitude of dioxin-like response observed was 44% of the maximum response elicited by a 2,000 pM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) standard. The relatively low magnitudes of dioxin-like response observed for F-1 samples were consistent with the relatively low PCB concentrations. At concentrations equal to the maximum observed in the mussel samples, neither individual OC pesticides nor a mixture of OC pesticides yielded a significant dioxin-like response in the H4IIE-luc assay. Thus, the concentrations of OC pesticides in F-2 did not appear to have accounted for the dioxin-like activity observed. This suggests the presence of unidentified and/or unknown, acid-stable, dioxin-like compounds in F-2. This study suggests that in vitro bioassays are useful in assessing the contamination of mussels collected from coastal marine locations.

Extracts of sediment and water samples collected from Ulsan Bay, Korea, were screened for their ability to induce dioxin-like and estrogenic gene expression in vitro. Each sample was tested as raw extract (RE) and fractionated extract (FE). Based on the initial screening of RE, 23 of 31 sediment samples showed significant dioxin-like activity in H4IIE-luc bioassay, whereas most sediment samples did not elicit estrogenic response in MVLN bioassay. Most of the activities associated with FE samples revealed that mid-polar (F2) and most polar (F3) fractions were responsible for the significant reporter gene expression in H4IIE-luc bioassay. The results suggest that complex interactions may have depressed the activities of the known arylhydrocarbon receptor (AhR) agonists present in F1 samples. The F2 samples were the most active fraction. All F2 samples except one induced significant dioxin-like activity, and over half of the F2 samples induced significant estrogenic activity. Ten of the F2 samples produced magnitudes of response in H4IIE-luc bioassay similar to those induced by a 2,3,7,8-tetrachlorodibenzo-p-dioxin standard. Sediment associated with F2 samples was estimated to contain 24.9-826 pg TCDD-EQ/g DW. Based on a qualitative mass balance analysis, polycyclic aromatic hydrocarbons (PAHs) appeared to account for both the estrogenic and dioxin-like responses observed. Over half of the F3 samples were either cytotoxic or caused morphological changes in both H4IIE-luc and MVLN cells. Known concentrations of alkylphenols and bisphenol A were not great enough to account for both the estrogenic response and cytotoxicity observed for F3 samples. Despite the apparent toxic or stressful effects, most of F3 samples induced significant dioxin-like activity in vitro, adding to a growing body of evidence that suggests the presence of unidentified, relatively polar, AhR agonists in sediment from some areas.

Artemisinin resistance in Plasmodium falciparum lengthens parasite clearance half-life during artemisinin monotherapy or artemisinin-based combination therapy. Absence of in-vitro and ex-vivo correlates of artemisinin resistance hinders study of this phenotype. We aimed to assess whether an in-vitro ring-stage survival assay (RSA) can identify culture-adapted P falciparum isolates from patients with slow-clearing or fast-clearing infections, to investigate the stage-dependent susceptibility of parasites to dihydroartemisinin in the in-vitro RSA, and to assess whether an ex-vivo RSA can identify artemisinin-resistant P falciparum infections. We culture-adapted parasites from patients with long and short parasite clearance half-lives from a study done in Pursat, Cambodia, in 2010 (registered with ClinicalTrials.gov, number NCT00341003) and used novel in-vitro survival assays to explore the stage-dependent susceptibility of slow-clearing and fast-clearing parasites to dihydroartemisinin. In 2012, we implemented the RSA in prospective parasite clearance studies in Pursat, Preah Vihear, and Ratanakiri, Cambodia (NCT01736319), to measure the ex-vivo responses of parasites from patients with malaria. Continuous variables were compared with the Mann-Whitney U test. Correlations were analysed with the Spearman correlation test. In-vitro survival rates of culture-adapted parasites from 13 slow-clearing and 13 fast-clearing infections differed significantly when assays were done on 0–3 h ring-stage parasites (10·88% vs 0·23%; p=0·007). Ex-vivo survival rates significantly correlated with in-vivo parasite clearance half-lives (n=30, r=0·74, 95% CI 0·50–0·87; p<0·0001). The in-vitro RSA of 0–3 h ring-stage parasites provides a platform for the molecular characterisation of artemisinin resistance. The ex-vivo RSA can be easily implemented where surveillance for artemisinin resistance is needed. Institut Pasteur du Cambodge and the Intramural Research Program, NIAID, NIH.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-ALL often associated with genetic variants that alter cytokine receptor signaling, including mutations in the interleukin-7 receptor (IL7R). To investigate whether IL7R variants are leukemia-initiating, we built mouse models expressing activated Il7r (aIL7R). B-cell intrinsic aIL7R mice developed spontaneous B-ALL, demonstrating sufficiency of Il7r activating mutations in leukemogenesis. Concomitant introduction of a knock-out allele in the associated adapter protein Lnk (encoded by Sh2b3) or a dominant-negative variant of the transcription factor Ikaros (Ikzf1) increased disease penetrance. The resulting murine leukemias displayed monoclonality and recurrent somatic Kras mutations and efficiently engrafted into immunocompetent mice. Phosphoproteomic analyses of aIL7R leukemic cells revealed constitutive Stat5 signaling and B cell receptor (BCR)-like signaling despite the absence of surface pre-BCR. Finally, in vitro treatment of aIL7R leukemic B-cells with Jak, mTOR, or Syk inhibitors blocked growth, confirming that each pathway is active in this mouse model of IL7R-driven B-ALL.

CeRh2As2is an unconventional superconductor with multiple superconducting phases andTc=0.26K. WhenH∥c, it shows a field-induced transition atμ0H*=4Tfrom a low-field superconducting state SC1 to a high-field state SC2 with a large critical field ofμ0Hc2=14T. In contrast, forH⊥c, only the SC1 withμ0Hc2=2Tis observed. A simple model based on the crystal symmetry was able to reproduce the phase diagrams and their anisotropy, identifying SC1 and SC2 with even and odd parity superconducting states, respectively. However, additional orders were observed in the normal state which might have an influence on the change of the superconducting state atH*. Here, we present a comprehensive study of the angle dependence of the upper critical fields using magnetic ac susceptibility, specific heat, and torque on single crystals ofCeRh2As2. The experiments show that the state SC2 is strongly suppressed when rotating the magnetic field away from thecaxis and it disappears for an angle of 35°. This behavior agrees perfectly with our extended model of a pseudospin triplet state withd→vector in the plane and hence allows us to conclude that SC2 is indeed the suggested odd-parity state.

The regions near the Antarctic Peninsula in the Southern Ocean are highly productive, with notable phytoplanktonic blooms in the ice-free season. The primary productivity is sustained by the supply of nutrients from convective mixing with nutrient-rich subsurface waters, which promotes rapid phytoplankton growth as the sea ice melts in spring and summer. Surface waters are marked by the contrast between the warmer Drake Passage and the colder Weddell Sea, and seasonal duration of sea ice cover varies accordingly. Sea ice exerts multiple controls over primary production, by shading the light entering the ocean and stratifying the upper ocean with freshening by ice melt. However, the interaction between sea ice and productivity remains poorly characterized because satellites are unable to quantify biomass in partially ice-covered ocean, and direct measurements are too scarce to characterize the seasonally varying productivity. Here we evaluate productivity by assessing removal of nitrate from surface waters by biological nutrient utilization and study the associated change in δ15N of nitrate. We use a combination of bottle samples and in situ nitrate measurements from published databases, completed by two transects with isotopic measurements. The timing of sea ice melt date conditions the initiation of nitrate drawdown, but the annual minimum of nitrate only weakly correlates with sea ice concentration. As previously reported, we observe that δ15N of nitrate increases with nitrate depletion. Interestingly, the lowest nitrate depletion and δ15N values are found in the central region of N–S transects, where intermediate temperature and sea ice conditions prevail. Deeper mixing in waters that passed through the northern Bransfield Strait may explain higher nitrate concentration due to both a greater nitrate concentration at the beginning of the growth season and reduced productivity under light limitation in deeply mixed waters, confirmed by nitrogen isotope modeling. This highlights the importance of oceanographic controls on productivity patterns in sea ice regions in the Southern Ocean.

CeRh2As2has recently been reported to be a rare case of a multiphase unconventional superconductor close to a quantum critical point (QCP). Here, we present a comprehensive study of its normal-state properties and of the phase (I) belowT0≈0.4Kwhich preempts superconductivity atTc=0.26K. The second-order phase transition atT0presents signatures in specific heat and thermal expansion but none in magnetization and ac susceptibility, indicating a nonmagnetic origin of phase I. In addition, an upturn of the in-plane resistivity atT0points to a gap opening at the Fermi level in the basal plane. Thermal expansion indicates a strong-positive-pressure dependence ofT0,dT0/dp=1.5K/GPa, in contrast to the strong-negative-pressure coefficient observed for magnetic order in Ce-based Kondo lattices close to a QCP. Similarly, an in-plane magnetic field shiftsT0to higher temperatures and transforms phase I into another nonmagnetic phase (II) through a first-order phase transition at about 9 T. Using renormalized band-structure calculations, we find that the Kondo effect (TK≈30K) leads to substantial mixing of the excited crystalline-electric-field states into the ground state. This allows quadrupolar degrees of freedom in the resulting heavy bands at the Fermi level which are prone to nesting. The huge sensitivity of the quadrupole moment on hybridization together with nesting causes an unprecedented case of phase transition into a quadrupole-density-wave state at a temperatureT0≪TK, which explains the nature of phases I and II.

Background. Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method. We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results. FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0–F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions. FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.