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Recent advances enabled the discovery of heterometallic molecules for many metals: main group, d-block, lanthanides, and some actinides (U, Th). These complexes have at least two different metals joined by bridging ligands or by direct metal-metal bonding interactions. They are attractive because they can enable chemical cooperativity between metals from different parts of the periodic table. Some heterometallics provide access to unique reactivity and others exhibit physical properties that cannot be accessed by homometallic species. We envisioned that transuranic heterometallics might similarly enable new transuranic chemistry, though synthetic routes to such compounds have yet to be developed. Reported here is the first synthesis of a molecular transuranic complex that contains plutonium (Pu) and cobalt (Co). Our analyses of PuCl3{CoCp[OP(OEt)2]3} showed Pu(iv) and Co(iii) were present and suggested that the Pu(iv) oxidation state was stabilized by the electron donating phosphite ligands. This synthetic method - and the demonstration that Pu(iv) can be stabilized in a heterobimetallic molecular setting - provides a foundation for further exploration of transuranic multimetallic chemistry.
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Research on the transfer of skill from the circumstances in which it was learned to partially or completely novel tasks or situations is a foundational topic in the study of learning, memory, education, and expertise. A long history of transfer research has led to the conclusion that skill learning is generally domain specific. One important transfer problem occurs when a domain of expertise undergoes a fundamental shift, as when experts must adapt to changes in technology, rules, or professional practice. Here we examine skill maintenance in StarCraft 2, a video game of skills which undergoes frequent changes due to updates and includes a variety of gameplay options. Of particular interest are two competing predictions about how transfer will interact with expertise in this domain. The first approach emphasizes perceived similarity of the domains and predicts that skilled individuals will exhibit more favourable transfer than novices as these people will know enough to avoid processes, methods, and strategies which no longer apply after a domain change. The second emphasizes maximal adaptation to task constraints and predicts that experts will suffer the most during a domain change because of the loss of exploitable affordances. Neither approach did a good job explaining behaviour after the major game update called 'StarCraft 2: Heart of the Swarm,' perhaps because transfer was generally strong across all players. However, when examining transfer in the context of larger changes to gameplay, transfer seemed slightly better in more experienced players. The theoretical implications of this apparent interaction effect, and of the apparent resilience of more experienced StarCraft 2 players to transfer costs, are discussed.
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Aprendizaje , Juegos de Video , HumanosRESUMEN
The nature of charge degrees-of-freedom distinguishes scenarios for interpreting the character of a second order magnetic transition at zero temperature, that is, a magnetic quantum critical point (QCP). Heavy-fermion systems are prototypes of this paradigm, and in those, the relevant question is where, relative to a magnetic QCP, does the Kondo effect delocalize their f-electron degrees-of-freedom. Herein, we use pressure-dependent Hall measurements to identify a finite-temperature scale Eloc that signals a crossover from f-localized to f-delocalized character. As a function of pressure, Eloc(P) extrapolates smoothly to zero temperature at the antiferromagnetic QCP of CeRhIn5 where its Fermi surface reconstructs, hallmarks of Kondo-breakdown criticality that generates critical magnetic and charge fluctuations. In 4.4% Sn-doped CeRhIn5, however, Eloc(P) extrapolates into its magnetically ordered phase and is decoupled from the pressure-induced magnetic QCP, which implies a spin-density-wave (SDW) type of criticality that produces only critical fluctuations of the SDW order parameter. Our results demonstrate the importance of experimentally determining Eloc to characterize quantum criticality and the associated consequences for understanding the pairing mechanism of superconductivity that reaches a maximum Tc in both materials at their respective magnetic QCP.
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Objectives: This study examines the conduct of systematic reviews during the early stages of the COVID-19 pandemic, including compliance to protocol registration and duplication of reviews on similar topics. The methodological and reporting quality were also explored. Methods: A cross-sectional, bibliometric study was undertaken of all systematic review manuscripts on a COVID-19 intervention published between January 1st and June 30th, 2020. Protocol registration on a publicly accessible database was recorded. Duplication was determined by systematically recording the number of reviews published on each topic of analysis. Methodological quality and reporting quality were assessed using the AMSTAR-2 and PRISMA 2009 instruments, respectively. Results: Thirty-one eligible systematic reviews were identified during the inclusion period. The protocol of only four (12.9%) studies was registered on a publicly accessible database. Duplication was frequent, with 15 (48.4%) of the 31 included studies focusing on either hydroxychloroquine (and/or chloroquine) or corticosteroids. Only one study (3.2%) was of "high" methodological quality, four (12.9%) were "low" quality, and the remainder (n = 26, 83.9%) were of "critically low" quality. The median completeness of reporting was 20 out of 27 items (74.1%) with a range of 5-26 (interquartile range: 14-23). Conclusion: Systematic reviews during the early stages of the COVID-19 pandemic were uncommonly registered, frequently duplicated, and mostly of low methodological quality. In contrast, the reporting quality of manuscripts was generally good but varied substantially across published reports. There is a need for heightened stewardship of systematic review research, particularly during times of medical crisis where the generation of primary evidence may be rapid and unstable.
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We report point-contact spectroscopy measurements on heavy fermion cousins CeCoIn5, Ce2PdIn8and Ce3PdIn11to systematically study the hybridization betweenfand conduction electrons. Below a temperatureT*, the spectrum of each compound exhibits an evolving Fano-like conductance shape, superimposed on a sloping background, that suggests the development of hybridization between localfand itinerant conduction electrons in the coherent heavy fermion state belowT*. We present a quantitative analysis of the conductance curves with a two-channel model to compare the tunneling process between normal metallic silver particles in our soft point-contact and heavy-fermion single crystals CeCoIn5, Ce2PdIn8and Ce3PdIn11.
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Active sensing theory is founded upon the dynamic relationship between information sampling and an observer's evolving goals. Oculomotor activity is a well studied method of sampling; a mouse or a keyboard can also be used to access information past the current screen. We examine information access patterns of StarCraft 2 players at multiple skill levels. The first measures are analogous to existing eye-movement studies: fixation frequency, fixation targets, and fixation duration all change as a function of skill, and are commensurate with known properties of eye movements in learning. Actions that require visual attention at moderate skill levels are eventually performed with little visual attention at all. This (a) confirms the generalizability of laboratory studies of attention and learning using eye movements to digital interface use, and (b) suggests that a wide variety of information access behaviors may be considered as a unified set of phenomena.
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Movimientos Oculares , Aprendizaje , Juegos de Video , Atención , Fijación Ocular , Humanos , Movimientos Sacádicos , Percepción VisualRESUMEN
Objects passed from one player to another have not been assessed for their ability to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the surface of sport balls, notably a football, tennis ball, golf ball, and cricket ball could not harbour inactivated virus when it was swabbed onto the surface, even for 30 âs. However, when high concentrations of 5000 âdC/mL and 10,000 âdC/mL are directly pipetted onto the balls, it could be detected after for short time periods. Sports objects can only harbour inactivated SARS-CoV-2 under specific, directly transferred conditions, but wiping with a dry tissue or moist 'baby wipe' or dropping and rolling the balls removes all detectable viral traces. This has helpful implications to sporting events.
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Angioimmunoblastic T-cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T-cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T-cell receptor ß (TRB) rearrangement in 119 AITL, 11 peripheral T-cell lymphomas with T follicular helper phenotype (PTCL-TFH), and 25 PTCL-NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL-TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL-TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2-4) in 18 cases (24%). In selected cases, we confirmed bi-clonal T-cell populations and further demonstrated that these independent T-cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T-cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL-TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL-TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Proteínas de Unión al ADN/genética , Linfadenopatía Inmunoblástica/inmunología , Linfoma de Células T/inmunología , Proteínas Proto-Oncogénicas/genética , Anciano , Alelos , Dioxigenasas , Frecuencia de los Genes , Humanos , Linfadenopatía Inmunoblástica/genética , Linfadenopatía Inmunoblástica/patología , Linfoma de Células T/genética , Linfoma de Células T/patología , Persona de Mediana Edad , Mutación , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/patologíaRESUMEN
Using a Burkitt lymphoma-like gene expression signature, we recently defined a high-risk molecular high-grade (MHG) group mainly within germinal centre B-cell like diffuse large B-cell lymphomas (GCB-DLBCL), which was enriched for MYC/BCL2 double-hit (MYC/BCL2-DH). The genetic basis underlying MHG-DLBCL and their aggressive clinical behaviour remain unknown. We investigated 697 cases of DLBCL, particularly those with MYC/BCL2-DH (n = 62) by targeted sequencing and gene expression profiling. We showed that DLBCL with MYC/BCL2-DH, and those with BCL2 translocation, harbour the characteristic mutation signatures that are associated with follicular lymphoma and its high-grade transformation. We identified frequent MYC hotspot mutations that affect the phosphorylation site (T58) and its adjacent amino acids, which are important for MYC protein degradation. These MYC mutations were seen in a subset of cases with MYC translocation, but predominantly in those of MHG. The mutations were more frequent in double-hit lymphomas with IG as the MYC translocation partner, and were associated with higher MYC protein expression and poor patient survival. DLBCL with MYC/BCL2-DH and those with BCL2 translocation alone are most likely derived from follicular lymphoma or its precursor lesion, and acquisition of MYC pathogenic mutations may augment MYC function, resulting in aggressive clinical behaviour.
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Biomarcadores de Tumor/genética , Evolución Clonal , Linfoma de Células B Grandes Difuso/genética , Mutación , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Femenino , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Reordenamiento Génico , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Tasa de Supervivencia , Translocación GenéticaRESUMEN
PURPOSE: Biologic heterogeneity is a feature of diffuse large B-cell lymphoma (DLBCL), and the existence of a subgroup with poor prognosis and phenotypic proximity to Burkitt lymphoma is well known. Conventional cytogenetics identifies some patients with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphomas) who are increasingly treated with more intensive chemotherapy, but a more biologically coherent and clinically useful definition of this group is required. PATIENTS AND METHODS: We defined a molecular high-grade (MHG) group by applying a gene expression-based classifier to 928 patients with DLBCL from a clinical trial that investigated the addition of bortezomib to standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The prognostic significance of MHG was compared with existing biomarkers. We performed targeted sequencing of 70 genes in 400 patients and explored molecular pathology using gene expression signature databases. Findings were validated in an independent data set. RESULTS: The MHG group comprised 83 patients (9%), with 75 in the cell-of-origin germinal center B-cell-like group. MYC rearranged and double-hit groups were strongly over-represented in MHG but comprised only one half of the total. Gene expression analysis revealed a proliferative phenotype with a relationship to centroblasts. Progression-free survival rate at 36 months after R-CHOP in the MHG group was 37% (95% CI, 24% to 55%) compared with 72% (95% CI, 68% to 77%) for others, and an analysis of treatment effects suggested a possible positive effect of bortezomib. Double-hit lymphomas lacking the MHG signature showed no evidence of worse outcome than other germinal center B-cell-like cases. CONCLUSION: MHG defines a biologically coherent high-grade B-cell lymphoma group with distinct molecular features and clinical outcomes that effectively doubles the size of the poor-prognosis, double-hit group. Patients with MHG may benefit from intensified chemotherapy or novel targeted therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Bortezomib/administración & dosificación , Ciclofosfamida/administración & dosificación , Bases de Datos Genéticas , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Prednisona/administración & dosificación , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Rituximab/administración & dosificación , Transcriptoma , Vincristina/administración & dosificaciónRESUMEN
We study how physicians respond to financial incentives imposed by episode-based payment (EBP), which encourages lower spending and improved quality for an entire episode of care. Specifically, we study the impact of the Arkansas Health Care Payment Improvement Initiative, a multi-payer program that requires providers to enter into EBP arrangements for perinatal care, covering the majority of births in the state. Unlike fee-for-service reimbursement, EBP holds physicians responsible for all care within a discrete episode, rewarding physicians for efficient use of their own services and for efficient management of other health care inputs. In a difference-in-differences analysis of commercial claims, we find that perinatal spending in Arkansas decreased by 3.8% overall under EBP, compared to surrounding states. The decrease was driven by reduced spending on non-physician health care inputs, specifically the prices paid for inpatient facility care. We additionally find a limited improvement in quality of care under EBP.
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Planes de Aranceles por Servicios/economía , Gastos en Salud , Aceptación de la Atención de Salud , Atención Perinatal/economía , Arkansas , Episodio de Atención , Planes de Aranceles por Servicios/estadística & datos numéricos , Femenino , Gastos en Salud/estadística & datos numéricos , Humanos , Modelos Económicos , Aceptación de la Atención de Salud/estadística & datos numéricos , Atención Perinatal/organización & administración , Atención Perinatal/estadística & datos numéricos , Planes de Incentivos para los Médicos/economía , Planes de Incentivos para los Médicos/estadística & datos numéricos , EmbarazoRESUMEN
DNA samples from formalin-fixed paraffin-embedded tissues are highly degraded with variable quality, and this imposes a big challenge for targeted sequencing due to false positives, largely caused by PCR errors and cytosine deamination. To eliminate false positives, a common practice is to validate the detected variants by Sanger sequencing or perform targeted sequencing in duplicate. Technically, PCR errors could be removed by molecular barcoding of template DNA prior to amplification as in the HaloPlexHS design. Nonetheless, it is uncertain to what extent variants detected using this approach should be further validated. Here, we addressed this question by correlating variant reproducibility with DNA quality using HaloPlexHS target enrichment and Illumina HiSeq4000, together with an in-house validated variant calling algorithm. The overall sequencing coverage, as shown by analyses of 70 genes in 266 cases of large B-cell lymphoma, was excellent (98%) in DNA samples amenable for PCR of ≥400 bp, but suboptimal (92%) and poor (80%) in those amenable for PCR of 300 bp and 200 bp respectively. By mutation analysis in duplicate in 93 cases, we demonstrated that 20 alternative allele depth (AAD) was an optimal cut-off value for separating reproducible from non-reproducible variants in DNA samples amenable for PCR of ≥300 bp, with 97% sensitivity and 100% specificity. By cross validation with a previously established targeted sequencing protocol by Fluidigm-PCR and Illumina MiSeq, the HaloPlexHS protocol was shown to be highly sensitive and specific in mutation screening. To conclude, we proposed a stratified approach for mutation screening by HaloplexHS and Illumina HiSeq4000 according to DNA quality. DNA samples with good quality (≥400 bp) are amenable for mutation analysis with a single replicate, with only variants at 15-20 AAD requiring for further validation, while those with suboptimal quality (300 bp) are better analysed in duplicate with reproducible variants at >15 AAD regarded as true genetic changes.
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Análisis Mutacional de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Adhesión en Parafina/métodos , Fijación del Tejido/métodos , ADN/química , ADN/genética , ADN/metabolismo , Formaldehído , Humanos , Reacción en Cadena de la Polimerasa/métodos , Reproducibilidad de los ResultadosRESUMEN
Mucosa-associated lymphoid tissue (MALT) lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterized. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors (GPR34 and CCR6) not previously reported in human malignancies, 3 genes (PIK3CD, TET2, TNFRSF14) not previously implicated in MALT lymphoma, and a further 2 genes (TBL1XR1, NOTCH1) recently described in MALT lymphoma. The majority of mutations in GPR34 and CCR6 were nonsense and frameshift changes clustered in the C-terminal cytoplasmic tail, and would result in truncated proteins that lack the phosphorylation motif important for ß-arrestin-mediated receptor desensitization and internalization. Screening of these newly identified mutations, together with previously defined genetic changes, revealed distinct mutation profiles in MALT lymphoma of various sites, with those of salivary gland characterized by frequent TBL1XR1 and GPR34 mutations, thyroid by frequent TET2, TNFRSF14 and PIK3CD mutations, and ocular adnexa by frequent TNFAIP3 mutation. Interestingly, in MALT lymphoma of the salivary gland, there was a significant positive association between TBL1XR1 mutation and GPR34 mutation/translocation (P=0.0002). In those of ocular adnexa, TBL1XR1 mutation was mutually exclusive from TNFAIP3 mutation (P=0.049), but significantly associated with IGHV3-23 usage (P=0.03) and PIK3CD mutation (P=0.009). These findings unravel novel insights into the molecular mechanisms of MALT lymphoma and provide further evidence for potential oncogenic co-operation between receptor signaling and genetic changes.
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Linfoma de Células B de la Zona Marginal/genética , Mutación , Receptores CCR6/genética , Receptores Lisofosfolípidos/genética , Perfil Genético , Humanos , Linfoma de Células B de la Zona Marginal/patología , Neoplasias de las Glándulas Salivales/genética , Neoplasias de la Tiroides/genética , Secuenciación del ExomaRESUMEN
Low-dimensional electronic systems with confined electronic wave functions have attracted interest due to their propensity toward novel quantum phases and their use in wide range of nanotechnologies. The newly discovered chalcogenide Nb2PdS5 possesses a quasi-one-dimensional electronic structure and becomes superconducting. Here, we report spectroscopic evidence for two-band superconductivity, where soft point-contact spectroscopic measurements in the superconducting (SC) state reveal Andreev reflection in the differential conductance G. Multiple peaks in G are observed at 1.8 K and explained by the two-band Blonder-Tinkham-Klapwijk model with two gaps Δ1 = 0.61 meV and Δ2 = 1.20 meV. The progressive evolution of G with temperature and magnetic field corroborates the multiple nature of the SC gaps.
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We report on an optical technique for measuring thermal expansion and magnetostriction at cryogenic temperatures and under applied hydrostatic pressures of 2.0 GPa. Optical fiber Bragg gratings inside a clamp-type pressure chamber are used to measure the strain in a millimeter-sized sample of CeRhIn5. We describe the simultaneous measurement of two Bragg gratings in a single optical fiber using an optical sensing instrument capable of resolving changes in length [dL/L = (L- L0)/L0] on the order of 10-7. Our results demonstrate the possibility of performing high-resolution thermal expansion measurements under hydrostatic pressure, a capability previously hindered by the small working volumes typical of pressure cells.
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Resonant x-ray scattering (RXS) has recently become an increasingly important tool for the study of ordering phenomena in correlated electron systems. Yet, the interpretation of RXS experiments remains theoretically challenging because of the complexity of the RXS cross section. Central to this debate is the recent proposal that impurity-induced Friedel oscillations, akin to quasi-particle interference signals observed with a scanning tunneling microscope (STM), can lead to scattering peaks in RXS experiments. The possibility that quasi-particle properties can be probed in RXS measurements opens up a new avenue to study the bulk band structure of materials with the orbital and element selectivity provided by RXS. We test these ideas by combining RXS and STM measurements of the heavy fermion compound CeMIn5 (M = Co, Rh). Temperature- and doping-dependent RXS measurements at the Ce-M4 edge show a broad scattering enhancement that correlates with the appearance of heavy f-electron bands in these compounds. The scattering enhancement is consistent with the measured quasi-particle interference signal in the STM measurements, indicating that the quasi-particle interference can be probed through the momentum distribution of RXS signals. Overall, our experiments demonstrate new opportunities for studies of correlated electronic systems using the RXS technique.
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The synthesis, electronic structure, and characterization via single-crystal X-ray diffraction, nuclear magnetic resonance (NMR) spectroscopy, and magnetic susceptibility of (Me4N)2PuCl6 are reported. NMR measurements were performed to both search for the direct (239)Pu resonance and to obtain local magnetic and electronic information at the Cl site through (35)Cl and (37)Cl spectra. No signature of (239)Pu NMR was observed. The temperature dependence of the Cl spectra was simulated by diagonalizing the Zeeman and quadrupolar Hamiltonians for (35)Cl, (37)Cl, and (14)N isotopes. Electronic structure calculations predict a magnetic Γ5 triplet ground state of Pu(IV) in the crystalline electric field of the undistorted PuCl6 octahedron. A tetragonal distortion would result in a very small splitting (â¼20 cm(-1)) of the triplet ground state into a nonmagnetic singlet and a doublet state. The Cl shifts have an inflection point at T ≈ 15 K, differing from the bulk susceptibility, indicating a nonmagnetic crystal field ground state. The Cl spin-lattice relaxation time is constant to T = 15 K, below which it rapidly increases, also supporting the nonmagnetic crystal field ground state.
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Black TiO2 nanoparticles with a crystalline core and amorphous-shell structure exhibit superior optoelectronic properties in comparison with pristine TiO2. The fundamental mechanisms underlying these enhancements, however, remain unclear, largely due to the inherent complexities and limitations of powder materials. Here, we fabricate TiO2 homojunction films consisting of an oxygen-deficient amorphous layer on top of a highly crystalline layer, to simulate the structural/functional configuration of black TiO2 nanoparticles. Metallic conduction is achieved at the crystalline-amorphous homointerface via electronic interface reconstruction, which we show to be the main reason for the enhanced electron transport of black TiO2. This work not only achieves an unprecedented understanding of black TiO2 but also provides a new perspective for investigating carrier generation and transport behavior at oxide interfaces, which are of tremendous fundamental and technological interest.