Vibrational pocket modes: predictions by the embedded crystallite method and their experimental observation

Simulation studies based on the embedded crystallite method are used to predict, with no free parameters, complex dynamical behavior for a simple alkali halide defect system, Na+ in KI. Far infrared spectroscopic measurements, including uniaxial stress, confirm the predicted vibrational properties, indicating that this methodology can readily be used for complex and extended defects in ionic crystals

Aspects of Discrete Breathers and New Directions

We describe results concerning the existence proofs of Discrete Breathers (DBs) in the two classes of dynamical systems with optical linear phonons and with acoustic linear phonons. A standard approach is by continuation of DBs from an anticontinuous limit. A new approach, which is purely variational, is presented. We also review some numerical results on intraband DBs in random nonlinear systems. Some non-conventional physical applications of DBs are suggested. One of them is understanding slow relaxation properties of glassy materials. Another one concerns energy focusing and transport in biomolecules by targeted energy transfer of DBs. A similar theory could be used for describing targeted charge transfer of nonlinear electrons (polarons) and, more generally, for targeted transfer of several excitations (e.g. Davydov soliton).Comment: to appear in the Proceedings of NATO Advanced Research Workshop "Nonlinearity and Disorder: Theory and Applications", Tashkent,Uzbekistan,October 1-6, 200

The origin of defects induced in ultra-pure germanium by Electron Beam Deposition

The creation of point defects in the crystal lattices of various semiconductors by subthreshold events has been reported on by a number of groups. These observations have been made in great detail using sensitive electrical techniques but there is still much that needs to be clarified. Experiments using Ge and Si were performed that demonstrate that energetic particles, the products of collisions in the electron beam, were responsible for the majority of electron-beam deposition (EBD) induced defects in a two-step energy transfer process. Lowering the number of collisions of these energetic particles with the semiconductor during metal deposition was accomplished using a combination of static shields and superior vacuum resulting in devices with defect concentrations lower than $10^{11}\,$cm$^{-3}$, the measurement limit of our deep level transient spectroscopy (DLTS) system. High energy electrons and photons that samples are typically exposed to were not influenced by the shields as most of these particles originate at the metal target thus eliminating these particles as possible damage causing agents. It remains unclear how packets of energy that can sometimes be as small of 2eV travel up to a $\mu$m into the material while still retaining enough energy, that is, in the order of 1eV, to cause changes in the crystal. The manipulation of this defect causing phenomenon may hold the key to developing defect free material for future applications.Comment: 18 pages, 9 figure

Vectorial Control of Magnetization by Light

Coherent light-matter interactions have recently extended their applications to the ultrafast control of magnetization in solids. An important but unrealized technique is the manipulation of magnetization vector motion to make it follow an arbitrarily designed multi-dimensional trajectory. Furthermore, for its realization, the phase and amplitude of degenerate modes need to be steered independently. A promising method is to employ Raman-type nonlinear optical processes induced by femtosecond laser pulses, where magnetic oscillations are induced impulsively with a controlled initial phase and an azimuthal angle that follows well defined selection rules determined by the materials' symmetries. Here, we emphasize the fact that temporal variation of the polarization angle of the laser pulses enables us to distinguish between the two degenerate modes. A full manipulation of two-dimensional magnetic oscillations is demonstrated in antiferromagnetic NiO by employing a pair of polarization-twisted optical pulses. These results have lead to a new concept of vectorial control of magnetization by light

How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design

OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients (mean AF burden: 12±22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. RESULTS: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations. CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00806689

Rate theory of acceleration of the defect annealing driven by discrete breathers

Novel mechanisms of defect annealing in solids are discussed, which are based on the large amplitude anharmonic lattice vibrations, a.k.a. intrinsic localized modes or discrete breathers (DBs). A model for amplification of defect annealing rate in Ge by low energy plasma-generated DBs is proposed, in which, based on recent atomistic modelling, it is assumed that DBs can excite atoms around defects rather strongly, giving them energy $\gg k_BT$ for $\sim$100 oscillation periods. This is shown to result in the amplification of the annealing rates proportional to the DB flux, i.e. to the flux of ions (or energetic atoms) impinging at the Ge surface from inductively coupled plasma (ICP)Comment: 18 pages, 11 figures. arXiv admin note: text overlap with arXiv:1406.394

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg(®)) in children with relapsed/refractory myeloid leukemia

BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2(nd )relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases. METHODS: GO was administered alone, at a unit dose of 3–9 mg/m(2), once (3 patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean follow-up was 128 days (8–585 d). RESULTS: There were three complete responses (25%) leading to further curative treatment (SCT). Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12), hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There was only one major adverse event (grade IV allergy). No case of sinusoidal obstruction syndrome occurred. CONCLUSION: These results warrant a prospective trial of GO in a larger population of children with AML

Adverse anthropometric risk profile in biochemically controlled acromegalic patients: comparison with an age- and gender-matched primary care population

GH and IGF-1 play an important role in the regulation of metabolism and body composition. In patients with uncontrolled acromegaly, cardiovascular morbidity and mortality are increased but are supposed to be normalised after biochemical control is achieved. We aimed at comparing body composition and the cardiovascular risk profile in patients with controlled acromegaly and controls. A cross-sectional study. We evaluated anthropometric parameters (height, weight, body mass index (BMI), waist and hip circumference, waist to height ratio) and, additionally, cardiovascular risk biomarkers (fasting plasma glucose, HbA1c, triglycerides, total cholesterol, HDL, LDL, and lipoprotein (a), in 81 acromegalic patients (58% cured) compared to 320 age- and gender-matched controls (ratio 1:4), sampled from the primary care patient cohort DETECT. The whole group of 81 acromegalic patients presented with significantly higher anthropometric parameters, such as weight, BMI, waist and hip circumference, but with more favourable cardiovascular risk biomarkers, such as fasting plasma glucose, total cholesterol, triglycerides and HDL levels, in comparison to their respective controls. Biochemically controlled acromegalic patients again showed significantly higher measurements of obesity, mainly visceral adiposity, than age- and gender-matched control patients (BMI 29.5 ± 5.9 vs. 27.3 ± 5.8 kg/m2; P = 0.020; waist circumference 100.9 ± 16.8 vs. 94.8 ± 15.5 cm; P = 0.031; hip circumference 110.7 ± 9.9 vs. 105.0 ± 11.7 cm; P = 0.001). No differences in the classical cardiovascular biomarkers were detected except for fasting plasma glucose and triglycerides. This effect could not be attributed to a higher prevalence of type 2 diabetes mellitus in the acromegalic patient group, since stratified analyses between the subgroup of patients with acromegaly and controls, both with type 2 diabetes mellitus, revealed that there were no significant differences in the anthropometric measurements. Biochemically cured acromegalic patients pertain an adverse anthropometric risk profile, mainly because of elevated adiposity measurements, such as BMI, waist and hip circumference, compared to an age- and gender-matched primary care population

Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

Structure of the C-terminal domain of the Prokaryotic Sodium Channel Orthologue NsvBa

Crystallographic and electrophysiological studies have recently provided insight into the structure, function and drug binding of prokaryotic sodium channels. These channels exhibit significant sequence identities, especially in their transmembrane regions, with human voltage-gated sodium channels. However, rather than being single polypeptides with four homologous domains, they are tetramers of single domain polypeptides, with a C-terminal domain (CTD) composed of an inter-subunit four helix coiled-coil. The structures of the CTDs differ between orthologues. In NavBh and NavMs, the C-termini form a disordered region adjacent to the final transmembrane helix, followed by a coiled-coil region, as demonstrated by synchrotron radiation circular dichroism (SRCD) and double electron-electron resonance electron paramagnetic resonance spectroscopic measurements. In contrast, in the crystal structure of the NavAe orthologue, the entire C-terminus is comprised of a helical region followed by a coiled-coil. In this study we have examined the CTD of the NsvBa from Bacillus alcalophilus, which unlike other orthologues is predicted by different methods to have different types of structures: either a disordered adjacent to the transmembrane region, followed by a helical coiled-coil, or a fully helical CTD. To discriminate between the two possible structures we have used SRCD spectroscopy to experimentally determine the secondary structure of the C-terminus of this orthologue and used the results as the basis for modelling the transition between open and closed conformations of the channel