Open Systems Viewed Through Their Conservative Extensions

A typical linear open system is often defined as a component of a larger conservative one. For instance, a dielectric medium, defined by its frequency dependent electric permittivity and magnetic permeability is a part of a conservative system which includes the matter with all its atomic complexity. A finite slab of a lattice array of coupled oscillators modelling a solid is another example. Assuming that such an open system is all one wants to observe, we ask how big a part of the original conservative system (possibly very complex) is relevant to the observations, or, in other words, how big a part of it is coupled to the open system? We study here the structure of the system coupling and its coupled and decoupled components, showing, in particular, that it is only the system's unique minimal extension that is relevant to its dynamics, and this extension often is tiny part of the original conservative system. We also give a scenario explaining why certain degrees of freedom of a solid do not contribute to its specific heat.Comment: 51 page

Polaron Physics in Optical Lattices

We investigate the effects of a nearly uniform Bose-Einstein condensate (BEC) on the properties of immersed trapped impurity atoms. Using a weak-coupling expansion in the BEC-impurity interaction strength, we derive a model describing polarons, i.e., impurities dressed by a coherent state of Bogoliubov phonons, and apply it to ultracold bosonic atoms in an optical lattice. We show that, with increasing BEC temperature, the transport properties of the impurities change from coherent to diffusive. Furthermore, stable polaron clusters are formed via a phonon-mediated off-site attraction.Comment: 4 pages, 4 figure

Attosecond spectroscopy reveals alignment dependent core-hole dynamics in the ICl molecule.

The removal of electrons located in the core shells of molecules creates transient states that live between a few femtoseconds to attoseconds. Owing to these short lifetimes, time-resolved studies of these states are challenging and complex molecular dynamics driven solely by electronic correlation are difficult to observe. Here, we obtain few-femtosecond core-excited state lifetimes of iodine monochloride by using attosecond transient absorption on iodine 4d-16p transitions around 55 eV. Core-level ligand field splitting allows direct access of excited states aligned along and perpendicular to the ICl molecular axis. Lifetimes of 3.5 ± 0.4 fs and 4.3 ± 0.4 fs are obtained for core-hole states parallel to the bond and 6.5 ± 0.6 fs and 6.9 ± 0.6 fs for perpendicular states, while nuclear motion is essentially frozen on this timescale. Theory shows that the dramatic decrease of lifetime for core-vacancies parallel to the covalent bond is a manifestation of non-local interactions with the neighboring Cl atom of ICl

Regulatory interactions of αβ and γλ T cells in glomerulonephritis

Regulatory interactions of αβ and γλ T cells in glomerulonephritis.BackgroundSeveral lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis.MethodsThe roles of αβ and γλ T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)β and TCRλ knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice.ResultsMice deficient in either αβ or γλ T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In γλ T-cell–deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while αβ T-cell–deficient mice had no autologous IgG production. Autologous antibody production was not required for the development of glomerulonephritis since mice that lack IgG and B cells (μ-chain-/-) developed similar proteinuria to that observed in wild-type mice.ConclusionsThese studies suggest a proinflammatory role for both αβ and γλ T cells in glomerular injury, independent of the humoral response. This is the first demonstration, to our knowledge, that both T-cell subsets contribute to the progression of a disease, and it suggests that complex regulatory interactions between αβ and γλ T cells play a role in glomerular injury

The Metropolis algorithm: A useful tool for epidemiologists

The Metropolis algorithm is a Markov chain Monte Carlo (MCMC) algorithm used to simulate from parameter distributions of interest, such as generalized linear model parameters. The "Metropolis step" is a keystone concept that underlies classical and modern MCMC methods and facilitates simple analysis of complex statistical models. Beyond Bayesian analysis, MCMC is useful for generating uncertainty intervals, even under the common scenario in causal inference in which the target parameter is not directly estimated by a single, fitted statistical model. We demonstrate, with a worked example, pseudo-code, and R code, the basic mechanics of the Metropolis algorithm. We use the Metropolis algorithm to estimate the odds ratio and risk difference contrasting the risk of childhood leukemia among those exposed to high versus low level magnetic fields. This approach can be used for inference from Bayesian and frequentist paradigms and, in small samples, offers advantages over large-sample methods like the bootstrap.Comment: 26 pages, 3 figure

Theoretical Analysis of the Influence of the Thermal Diffusivity of Ceramic Tile on the Thermal Energy Distribution

The influence of the thermal diffusivity of the ceramic tile on the thermal energy distribution was analysed using one dimensional heat equation, which was solved by using method of separation of variables. In the analysis, heat was assumed to be propagated along a rectangular moulded ceramic tile with length (l) and the width being considered negligible with different temperatures ranging from 3000c to 13000c, within a specified time frame. Some parameters such as thermal conductivity, specific heat and mass per unit length of the material were specified. The variation of thermal conductivity and diffusivity with temperature were analysed while that of thermal energy flux u(x,t) variation with position and time for different lengths werealso take into consideration. The distribution of temperature as a function of time for different values of thermal diffusivity was also considered

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Unconventional Hund Metal in a Weak Itinerant Ferromagnet

The physics of weak itinerant ferromagnets is challenging due to their small magnetic moments and the ambiguous role of local interactions governing their electronic properties, many of which violate Fermi liquid theory. While magnetic fluctuations play an important role in the materials' unusual electronic states, the nature of these fluctuations and the paradigms through which they arise remain debated. Here we use inelastic neutron scattering to study magnetic fluctuations in the canonical weak itinerant ferromagnet MnSi. Data reveal that short-wavelength magnons continue to propagate until a mode crossing predicted for strongly interacting quasiparticles is reached, and the local susceptibility peaks at a coherence energy predicted for a correlated Hund metal by first-principles many-body theory. Scattering between electrons and orbital and spin fluctuations in MnSi can be understood at the local level to generate non-Fermi liquid character. These results provide crucial insight into the role of interorbital Hund's exchange within the broader class of enigmatic multiband itinerant, weak ferromagnets.Comment: 17 pages, 4 figure

Domain Growth in a 1-D Driven Diffusive System

The low-temperature coarsening dynamics of a one-dimensional Ising model, with conserved magnetisation and subject to a small external driving force, is studied analytically in the limit where the volume fraction \mu of the minority phase is small, and numerically for general \mu. The mean domain size L(t) grows as t^{1/2} in all cases, and the domain-size distribution for domains of one sign is very well described by the form P_l(l) \propto (l/L^3)\exp[-\lambda(\mu)(l^2/L^2)], which is exact for small \mu (and possibly for all \mu). The persistence exponent for the minority phase has the value 3/2 for \mu \to 0.Comment: 8 pages, REVTeX, 7 Postscript figures, uses multicol.sty and epsf.sty. Submitted to Phys. Rev.