Around 40-50% of patients with chronic myeloid leukemia (CML) who achieve a stable complete molecular response (CMR; undetectable breakpoint cluster region-Abelson leukemia gene human homolog 1 ...(BCR-ABL1) mRNA) on imatinib can stop therapy and remain in CMR, at least for several years. This raises the possibility that imatinib therapy may not need to be continued indefinitely in some CML patients. Two possible explanations for this observation are (1) CML has been eradicated or (2) residual leukemic cells fail to proliferate despite the absence of ongoing kinase inhibition. We used a highly sensitive patient-specific nested quantitative PCR to look for evidence of genomic BCR-ABL1 DNA in patients who sustained CMR after stopping imatinib therapy. Seven of eight patients who sustained CMR off therapy had BCR-ABL1 DNA detected at least once after stopping imatinib, but none has relapsed (follow-up 12-41 months). BCR-ABL1 DNA levels increased in all of the 10 patients who lost CMR soon after imatinib cessation, whereas serial testing of patients in sustained CMR showed a stable level of BCR-ABL1 DNA. This more sensitive assay for BCR-ABL1 provides evidence that even patients who maintain a CMR after stopping imatinib may harbor residual leukemia. A search for intrinsic or extrinsic (for example, immunological) causes for this drug-free leukemic suppression is now indicated.
Lanthanides have been investigated extensively for potential applications in quantum information processing and high-density data storage at the molecular and atomic scale. Experimental achievements ...include reading and manipulating single nuclear spins, exploiting atomic clock transitions for robust qubits and, most recently, magnetic data storage in single atoms. Single-molecule magnets exhibit magnetic hysteresis of molecular origin-a magnetic memory effect and a prerequisite of data storage-and so far lanthanide examples have exhibited this phenomenon at the highest temperatures. However, in the nearly 25 years since the discovery of single-molecule magnets, hysteresis temperatures have increased from 4 kelvin to only about 14 kelvin using a consistent magnetic field sweep rate of about 20 oersted per second, although higher temperatures have been achieved by using very fast sweep rates (for example, 30 kelvin with 200 oersted per second). Here we report a hexa-tert-butyldysprosocenium complex-Dy(Cp
)
B(C
F
)
, with Cp
= {C
H
Bu
-1,2,4} and
Bu = C(CH
)
-which exhibits magnetic hysteresis at temperatures of up to 60 kelvin at a sweep rate of 22 oersted per second. We observe a clear change in the relaxation dynamics at this temperature, which persists in magnetically diluted samples, suggesting that the origin of the hysteresis is the localized metal-ligand vibrational modes that are unique to dysprosocenium. Ab initio calculations of spin dynamics demonstrate that magnetic relaxation at high temperatures is due to local molecular vibrations. These results indicate that, with judicious molecular design, magnetic data storage in single molecules at temperatures above liquid nitrogen should be possible.
We report the first near-linear bis(amide) 4f-block compound and show that this novel structure, if implemented with dysprosium(III), would have unprecedented single molecule magnet (SMM) properties ...with an energy barrier, Ueff, for reorientation of magnetization of 1800 cm(-1).
Using spectral line observations of HNCO, N2H+, and HNC, we investigate the kinematics of dense gas in the central ∼250 pc of the Galaxy. We present scouse (Semi-automated multi-COmponent Universal ...Spectral-line fitting Engine), a line-fitting algorithm designed to analyse large volumes of spectral line data efficiently and systematically. Unlike techniques which do not account for complex line profiles, scouse accurately describes the {l, b, v
LSR} distribution of Central Molecular Zone (CMZ) gas, which is asymmetric about Sgr A* in both position and velocity. Velocity dispersions range from 2.6 km s−1 < σ < 53.1 km s−1. A median dispersion of 9.8 km s−1, translates to a Mach number,
$\mathcal {M}_{\rm 3D}\ge 28$
. The gas is distributed throughout several ‘streams’, with projected lengths ∼100–250 pc. We link the streams to individual clouds and sub-regions, including Sgr C, the 20 and 50 km s−1 clouds, the dust ridge, and Sgr B2. Shell-like emission features can be explained by the projection of independent molecular clouds in Sgr C and the newly identified conical profile of Sgr B2 in {l, b, v
LSR} space. These features have previously invoked supernova-driven shells and cloud–cloud collisions as explanations. We instead caution against structure identification in velocity-integrated emission maps. Three geometries describing the 3D structure of the CMZ are investigated: (i) two spiral arms; (ii) a closed elliptical orbit; (iii) an open stream. While two spiral arms and an open stream qualitatively reproduce the gas distribution, the most recent parametrization of the closed elliptical orbit does not. Finally, we discuss how proper motion measurements of masers can distinguish between these geometries, and suggest that this effort should be focused on the 20 km s−1 and 50 km s−1 clouds and Sgr C.
It has been known for many years that an electron and its antiparticle, the positron, may together form a metastable hydrogen-like atom, known as positronium or Ps (ref. 1). In 1946, Wheeler ...speculated that two Ps atoms may combine to form the di-positronium molecule (Ps2), with a binding energy of 0.4 eV. More recently, this molecule has been studied theoretically; however, because Ps has a short lifetime and it is difficult to obtain low-energy positrons in large numbers, Ps2 has not previously been observed unambiguously. Here we show that when intense positron bursts are implanted into a thin film of porous silica, Ps2 is created on the internal pore surfaces. We found that molecule formation occurs much more efficiently than the competing process of spin exchange quenching, which appears to be suppressed in the confined pore geometry. This result experimentally confirms the existence of the Ps2 molecule and paves the way for further multi-positronium work. Using similar techniques, but with a more intense positron source, we expect to increase the Ps density to the point where many thousands of atoms interact and can undergo a phase transition to form a Bose-Einstein condensate. As a purely leptonic, macroscopic quantum matter-antimatter system this would be of interest in its own right, but it would also represent a milestone on the path to produce an annihilation gamma-ray laser.
Molecular recognition between complementary strands of DNA allows construction
on a nanometre length scale. For example, DNA tags may be used to organize
the assembly of colloidal particles, and DNA ...templates can
direct the growth of semiconductor nanocrystals and metal wires. As a structural material in its own right, DNA can be used to make
ordered static arrays of tiles, linked rings
and polyhedra. The construction of active devices is also possible-for
example, a nanomechanical switch, whose conformation is changed
by inducing a transition in the chirality of the DNA double helix. Melting
of chemically modified DNA has been induced by optical absorption,
and conformational changes caused by the binding of oligonucleotides or other
small groups have been shown to change the enzymatic activity of ribozymes. Here we report the construction of a DNA machine in
which the DNA is used not only as a structural material, but also as 'fuel'.
The machine, made from three strands of DNA, has the form of a pair of tweezers.
It may be closed and opened by addition of auxiliary strands of 'fuel'
DNA; each cycle produces a duplex DNA waste product.
The origin of 60 K magnetic hysteresis in the dysprosocenium complex Dy(Cpttt)2B(C6F5)4 (Cpttt = C5H2 tBu3-1,2,4, 1-Dy) remains mysterious, thus we envisaged that analysis of a series of ...Ln(Cpttt)2+ (Ln = lanthanide) cations could shed light on these properties. Herein we report the synthesis and physical characterization of a family of isolated Ln(Cpttt)2+ cations (1-Ln; Ln = Gd, Ho, Er, Tm, Yb, Lu), synthesized by halide abstraction of Ln(Cpttt)2(Cl) (2-Ln; Ln = Gd, Ho, Er, Tm, Yb, Lu). Complexes within the two families 1-Ln and 2-Ln are isostructural and display pseudo-linear and pseudo-trigonal crystal fields, respectively. This results in archetypal electronic structures, determined with CASSCF-SO calculations and confirmed with SQUID magnetometry and EPR spectroscopy, showing easy-axis or easy-plane magnetic anisotropy depending on the choice of Ln ion. Study of their magnetic relaxation dynamics reveals that 1-Ho also exhibits an anomalously low Raman exponent similar to 1-Dy, both being distinct from the larger and more regular Raman exponents for 2-Dy, 2-Er, and 2-Yb. This suggests that low Raman exponents arise from the unique spin-phonon coupling of isolated Ln(Cpttt)2+ cations. Crucially, this highlights a direct connection between ligand coordination modes and spin-phonon coupling, and therefore we propose that the exclusive presence of multihapto ligands in 1-Dy is the origin of its remarkable magnetic properties. Controlling the spin-phonon coupling through ligand design thus appears vital for realizing the next generation of high-temperature single-molecule magnets.
The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory ...authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data‐driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three‐grade‐based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.
In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. ...The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.
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