•We took 8 sediment cores and 27 ponar grabs from Lake Michigan in 2010.•Samples were extracted for total fluorine, extractable fluorine and 25 PFCs.•PFOS and PFOA are the predominant PFCs in ...sediment cores.•PFBS and PFBA are appearing in upper sections at concentrations similar to PFOS and PFOA.•TF and EOF concentrations are orders of magnitude higher than PFCs.
Total fluorine (TF), extractable organic fluorine (EOF) and poly- and per-fluorinated compounds (PFCs) were measured in eight dated cores of sediment taken along with 27 surface sediments from Lake Michigan in 2010. Based on rates of sedimentation, total concentrations of PFCs (∑PFCs) reached a maximum in the later 1990s and early 2000s. This result is consistent with rapid changes in production and subsequent sedimentation. Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are still the predominant PFCs in the cores, but in surface sediments, concentrations of perfluorobutane sulfonate (PFBS) and perfluorobutanoic acid (PFBA) are now occurring at concentrations comparable to those of PFOS and PFOA. This observation is consistent with shifts in patterns of production and use in the US and Canada. Concentrations of TF in sediments were greater than those of EOF. This result is consistent with a larger proportion of un-extractable fluorinated material in both surface sediments and in cores.
Abstract
Geometric electron optics may be implemented in solids when electron transport is ballistic on the length scale of a device. Currently, this is realized mainly in 2D materials characterized ...by circular Fermi surfaces. Here we demonstrate that the nearly perfectly hexagonal Fermi surface of PdCoO
2
gives rise to highly directional ballistic transport. We probe this directional ballistic regime in a single crystal of PdCoO
2
by use of focused ion beam (FIB) micro-machining, defining crystalline ballistic circuits with features as small as 250 nm. The peculiar hexagonal Fermi surface naturally leads to enhanced electron self-focusing effects in a magnetic field compared to circular Fermi surfaces. This super-geometric focusing can be quantitatively predicted for arbitrary device geometry, based on the hexagonal cyclotron orbits appearing in this material. These results suggest a novel class of ballistic electronic devices exploiting the unique transport characteristics of strongly faceted Fermi surfaces.
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.
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.
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.
There has been widespread interest in using interfaces of transition-metal oxides as a platform to control not only their electronic structure, as in semiconductor heterostructures, but also to tune ...between different collective phases. A major goal is to realize states of the quantum many-body system that are not found in the bulk phase diagrams of the constituent materials. Here, we perform a combined experimental and theoretical study of the delafossite oxide metals PdCoO
2
and PdCrO
2
, finding how electronic reconstructions at their polar surfaces drive instabilities to itinerant surface ferromagnetism. Neither compound supports ferromagnetism in bulk, with PdCrO
2
a bulk antiferromagnet, demonstrating how a delicate competition of magnetic correlations can be engineered by intrinsic self-doping at a polar surface or interface.
The ability to modulate the collective properties of correlated electron systems at their interfaces and surfaces underpins the burgeoning field of “designer” quantum materials. Here, we show how an electronic reconstruction driven by surface polarity mediates a Stoner-like magnetic instability to itinerant ferromagnetism at the Pd-terminated surface of the nonmagnetic delafossite oxide metal PdCoO
2
. Combining angle-resolved photoemission spectroscopy and density-functional theory calculations, we show how this leads to a rich multiband surface electronic structure. We find similar surface state dispersions in PdCrO
2
, suggesting surface ferromagnetism persists in this sister compound despite its bulk antiferromagnetic order.
DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we ...show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell lymphoma and reveal functional cooperation between mutant DDX3X and MYC. DDX3X promotes the translation of mRNA encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y chromosome homolog, the expression of which is normally restricted to the testis. These findings show that DDX3X loss of function can buffer MYC-driven proteotoxic stress and highlight the capacity of male B cell lymphomas to then compensate for this loss by ectopic DDX3Y expression.
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•Loss-of-function mutations of DDX3X are frequent in MYC-driven B cell lymphomas•DDX3X promotes translation of mRNAs encoding the core protein synthesis machinery•Loss of DDX3X buffers MYC-driven global protein synthesis and proteotoxic stress•DDX3X loss is later rescued by ectopic expression of Y-chromosome-encoded DDX3Y
Gong et al. show that during the early stages of lymphoma development, loss-of-function mutations in the RNA helicase DDX3X allow human B cells to tolerate the forced expression of MYC. In contrast, established tumors restore DDX3 helicase activity by ectopic expression of the Y-chromosome-encoded homolog DDX3Y.
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.
Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum ...gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.
We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.
We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.
No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).
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