Influence of PbX2 (X = F, Cl, Br) content and thermal treatment on structure and optical properties of lead borate glasses doped with rare earth ions

Oxyhalide lead borate glasses doped with rare earth ions have been studied before and after thermal treatment. The rare earths as optically active ions were limited to the Er3+ ions. Near-infrared luminescence due to the main 4I13/2–4I15/2 laser transition of Er3+ was registered. The introduction of PbX2 to the borate glass results in a reduction of spectral linewidth and an increase of luminescence lifetime of 4I13/2 state of Er3+ ions. The unusual large spectral linewidth for 4I13/2–4I15/2 transition of Er3+ in the oxide glass host was obtained, whereas the luminescence decay from 4I13/2 state is longer for a sample with PbF2 than PbCl2 and PbBr2. Heat treatment introduces transformation from a glass to transparent glass-ceramic (TGC). The coordination sphere around Er3+ ions is changed, giving important contribution to the luminescence characteristics. The spectroscopic consequence of this transformation is the increase of luminescence lifetime and the narrowing of spectral lines of Er3+

Carbon nanoparticles fabricated by infrared laser ablation of graphite and polycrystalline diamond targets

This paper presents the results of carbon nanoparticles (CNPs) production by infrared laser ablation of a graphite or a polycrystalline diamond target, submerged in one of two solvents, water or isopropanol. The targets were irradiated using a SPI fibre laser with a wavelength of 1064nm being operated at different average powers. After laser-assisted synthesis of CNPs, the resulting colloids, i.e particles in a liquid medium, were examined using the analytical techniques of dynamic light scattering, UV-Vis, Raman spectroscopy and fluorescence spectroscopy. The results show that the properties of CNPs strongly depend on processing conditions of the liquid phase-pulsed laser ablation (LP-PLA) process. In particular, the size of nanoparticles produced are affected by the processing parameters of the laser ablation. The results show that the laser processing of a graphite target in deionised water and in isopropanol produces carbon nanoparticles with properties that are beneficial for various biochemical and biomedical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Subjective and objective assessment of physical activity in multiple sclerosis and their relation to health-related quality of life

Background Physical activity (PA) is frequently restricted in people with multiple sclerosis (PwMS) and aiming to enhance PA is considered beneficial in this population. We here aimed to explore two standard methods (subjective plus objective) to assess PA reduction in PwMS and to describe the relation of PA to health-related quality of life (hrQoL). Methods PA was objectively measured over a 7-day period in 26 PwMS (EDSS 1.5–6.0) and 30 matched healthy controls (HC) using SenseWear mini® armband (SWAmini) and reported as step count, mean total and activity related energy expenditure (EE) as well as time spent in PA of different intensities. Measures of EE were also derived from self-assessment with IPAQ (International Physical Activity Questionnaire) long version, which additionally yielded information on the context of PA and a classification into subjects’ PA levels. To explore the convergence between both types of assessment, IPAQ categories (low, moderate, high) were related to selected PA parameters from objective assessment using ANOVA. Group differences and associated effect sizes for all PA parameters as well as their relation to clinical and hrQoL measures were determined. Results Both, SWAmini and IPAQ assessment, captured differences in PA between PwMS and HC. IPAQ categories fit well with common cut-offs for step count (p = 0.002) and mean METs (p = 0.004) to determine PA levels with objective devices. Correlations between specifically matched pairs of IPAQ and SWAmini parameters ranged between r .288 and r .507. Concerning hrQoL, the lower limb mobility subscore was related to four PA measures, while a relation with patients’ report of general contentment was only seen for one. Conclusions Both methods of assessment seem applicable in PwMS and able to describe reductions in daily PA at group level. Whether they can be used to track individual effects of interventions to enhance PA levels needs further exploration. The relation of PA measures with hrQoL seen with lower limb mobility suggests lower limb function not only as a major target for intervention to increase PA but also as a possible surrogate for PA changes

A role for monoubiquitinated FANCD2 at telomeres in ALT cells

Both Fanconi anemia (FA) and telomere dysfunction are associated with chromosome instability and an increased risk of cancer. Because of these similarities, we have investigated whether there is a relationship between the FA protein, FANCD2 and telomeres. We find that FANCD2 nuclear foci colocalize with telomeres and PML bodies in immortalized telomerase-negative cells. These cells maintain telomeres by alternative lengthening of telomeres (ALT). In contrast, FANCD2 does not colocalize with telomeres or PML bodies in cells which express telomerase. Using a siRNA approach we find that FANCA and FANCL, which are components of the FA nuclear core complex, regulate FANCD2 monoubiquitination and the telomeric localization of FANCD2 in ALT cells. Transient depletion of FANCD2, or FANCA, results in a dramatic loss of detectable telomeres in ALT cells but not in telomerase-expressing cells. Furthermore, telomere loss following depletion of these proteins in ALT cells is associated with decreased homologous recombination between telomeres (T-SCE). Thus, the FA pathway has a novel function in ALT telomere maintenance related to DNA repair. ALT telomere maintenance is therefore one mechanism by which monoubiquitinated FANCD2 may promote genetic stability

Ground Truth for Evaluation of Ischemic Stroke Hybrid Segmentation in a Rat Model of Temporary Middle Cerebral Artery Occlusion

In vivo rodent models of focal cerebral ischemia have been developed to investigate stroke therapy. Typically these models require rapid quantification of cerebral infarct volumes using vital stains with tetrazolium salts to delineate the extent of neuronal death. To avoid animal sacrifice, we sought a study with MR acquired volumetric rata data where surrogate of ground truth is obtained by repeated manual delineation by experts, and an automated hybrid segmentation is evaluated for accuracy. We propose a rating system for the expert delineations that captures intra- and inter-expert discrepancy. Our preliminary results show that surrogate ground truth derived from MR data is at least as good as the one derived from histologic stained slices. Hence animal sacrifice is not necessary to evaluate ischemic stroke automated segmentation in a rat model of temporary middle cerebral artery occlusion

Evaluation of Ischemic Stroke Hybrid Segmentation in a Rat Model of Temporary Middle Cerebral Artery Occlusion using Ground Truth from Histologic and MR data

A segmentation method that quantifies cerebral infarct using rat data with ischemic stroke is evaluated using ground truth from histologic and MR data. To demonstrate alternative approach to rapid quantification of cerebral infarct volumes using histologic stained slices that requires scarifying animal life, a study with MR acquire volumetric rat data is proposed where ground truth is obtained by manual delineations by experts and automated segmentation is assessed for accuracy. A framework for evaluation of segmentation is used that provides more detailed accuracy measurements than mere cerebral infarct volume. Our preliminary experiment shows that ground truth derived from MRI data is at least as good as the one obtained from the histologic slices for evaluating segmentation algorithms for accuracy. Therefore we can develop and evaluate automated segmentation methods for rapid quantification of stroke without the necessitating animal sacrifice

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640

HP1-Mediated Formation of Alternative Lengthening of Telomeres-Associated PML Bodies Requires HIRA but Not ASF1a

Approximately 10% of cancers use recombination-mediated Alternative Lengthening of Telomeres (ALT) instead of telomerase to prevent telomere shortening. A characteristic of cells that utilize ALT is the presence of ALT-associated PML nuclear bodies (APBs) containing (TTAGGG)n DNA, telomere binding proteins, DNA recombination proteins, and heterochromatin protein 1 (HP1). The function of APBs is unknown and it is possible that they are functionally heterogeneous. Most ALT cells lack functional p53, and restoration of the p53/p21 pathway in these cells results in growth arrest/senescence and a substantial increase in the number of large APBs that is dependent on two HP1 isoforms, HP1α and HP1γ. Here we investigated the mechanism of HP1-mediated APB formation, and found that histone chaperones, HIRA and ASF1a, are present in APBs following activation of the p53/p21 pathway in ALT cells. HIRA and ASF1a were also found to colocalize inside PML bodies in normal fibroblasts approaching senescence, providing evidence for the existence of a senescence-associated ASF1a/HIRA complex inside PML bodies, consistent with a role for these proteins in induction of senescence in both normal and ALT cells. Moreover, knockdown of HIRA but not ASF1a significantly reduced p53-mediated induction of large APBs, with a concomitant reduction of large HP1 foci. We conclude that HIRA, in addition to its physical and functional association with ASF1a, plays a unique, ASF1a-independent role, which is required for the localization of HP1 to PML bodies and thus for APB formation

The G-Quadruplex Ligand Telomestatin Impairs Binding of Topoisomerase IIIα to G-Quadruplex-Forming Oligonucleotides and Uncaps Telomeres in ALT Cells

In Alternative Lengthening of Telomeres (ALT) cell lines, specific nuclear bodies called APBs (ALT-associated PML bodies) concentrate telomeric DNA, shelterin components and recombination factors associated with telomere recombination. Topoisomerase IIIα (Topo III) is an essential telomeric-associated factor in ALT cells. We show here that the binding of Topo III to telomeric G-overhang is modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming oligonucleotides was strongly inhibited by telomestatin, a potent and specific G-quadruplex ligand. In ALT cells, telomestatin treatment resulted in the depletion of the Topo III/BLM/TRF2 complex and the disruption of APBs and led to the segregation of PML, shelterin components and Topo III. Interestingly, a DNA damage response was observed at telomeres in telomestatin-treated cells. These data indicate the importance of G-quadruplex stabilization during telomere maintenance in ALT cells. The function of TRF2/Topo III/BLM in the resolution of replication intermediates at telomeres is discussed