Almost 30% of all acute myeloid leukemias (AML) are associated with an internal tandem duplication (ITD) in the juxtamembrane domain of FMS-like tyrosine kinase 3 receptor (FLT3). Patients with ...FLT3-ITD mutations tend to have a poor prognosis. MicroRNAs (miRNAs) have a pivotal role in myeloid differentiation and leukemia. MiRNA-155 (MiR-155) was found to be upregulated in FLT3-ITD-associated AMLs. In this study, we discovered that FLT3-ITD signaling induces the oncogenic miR-155. We show in vitro and in vivo that miR-155 expression is regulated by FLT3-ITD downstream targets nuclear factor-κB (p65) and signal transducer and activator of transcription 5 (STAT5). Further, we demonstrate that miR-155 targets the myeloid transcription factor PU.1. Knockdown of miR-155 or overexpression of PU.1 blocks proliferation and induces apoptosis of FLT3-ITD-associated leukemic cells. Our data demonstrate a novel network in which FLT3-ITD signaling induces oncogenic miR-155 by p65 and STAT5 in AML, thereby targeting transcription factor PU.1.
Locomotor skill transfer is an essential feature of motor adaptation and represents the generalization of learned skills. We previously showed that gait adaptation after crossing virtual obstacles ...did not transfer to the untrained limb and suggested it may be due to missing feedback of performance. This study investigated whether providing feedback and an explicit goal during training would lead to transfer of adaptive skills to the untrained limb. Thirteen young adults crossed 50 virtual obstacles with one (trained) leg. Subsequently, they performed 50 trials with their other (transfer) leg upon notice about the side change. Visual feedback about crossing performance (toe clearance) was provided using a color scale. In addition, joint angles of the ankle, knee, and hip were calculated for the crossing legs. Toe clearance decreased with repeated obstacle crossing from 7.8 ± 2.7 cm to 4.6 ± 1.7 cm for the trained leg and from 6.8 ± 3.0 cm to 4.4 ± 2.0 cm (p < 0.05) for the transfer leg with similar adaptation rates between limbs. Toe clearance was significantly higher for the first trials of the transfer leg compared to the last trials of the training leg (p < 0.05). Furthermore, statistical parametric mapping revealed similar joint kinematics for trained and transfer legs in the initial training trials but differed in knee and hip joints when comparing the last trials of the trained leg with the first trials of the transfer leg. We concluded that locomotor skills acquired during a virtual obstacle crossing task are limb-specific and that enhanced awareness does not seem to improve interlimb transfer.
Obstacle avoidance is one of the skills required in coping with challenging situations encountered during walking. This study examined adaptation in gait stability and its interlimb transfer in a ...virtual obstacle avoidance task. Twelve young adults walked on a treadmill while wearing a virtual reality headset with their body state represented in the virtual environment. At random times, but always at foot touchdown, 50 virtual obstacles of constant size appeared 0.8 m in front of the participant requiring a step over with the right leg. Early, mid and late adaptation phases were investigated by pooling data from trials 1–3, 24–26 and 48–50. One left-leg obstacle appearing after 50 right-leg trials was used to investigate interlimb transfer. Toe clearance and the anteroposterior margin of stability (MoS) at foot touchdown were calculated for the stepping leg. Toe clearance decreased over repeated practice between early and late phases from 0.13 ± 0.05 m to 0.09 ± 0.04 m (mean ± SD, p < 0.05). MoS increased from 0.05 ± 0.02 m to 0.08 ± 0.02 m (p < 0.05) between early and late phases, with no significant differences between mid and late phases. No differences were found in toe clearance and MoS between the practiced right leg for early phase and the single trial of the left leg. Obstacle avoidance during walking in a virtual environment stimulated adaptive gait improvements that were related in a nonlinear manner to practice dose, though such gait adaptations seemed to be limited in their transferability between limbs.
In aluminum die casting damage mechanisms, such as abrasive and adhesive wear, corrosion due to metallic melt as well as heat-shock cracks by thermo-cyclical load, have significant influence on tool ...life and product quality. Multilayer coatings like CrN/AlN/Al2O3 based on transition metal nitrides such as CrN and AlN and oxide toplayers such as Al2O3 deposited via physical vapor deposition (PVD), offer high potential to be used as protective coatings due to their high hardness and chemical inertness. The present work deals with the investigation of a CrN/AlN/Al2O3 coating deposited by using pulsed cathodic arc evaporation and two industrially used hard coatings on AISI H11 (1.2343) hot work steel. In a first step the coatings were investigated after application related tribological rotating immersion tests. In a second step a damage analysis of coated die casting cores after application in an industrial aluminum die casting machine was carried out. In order to investigate the temperature stability of the Al2O3 toplayer of CrN/AlN/Al2O3, the coating was annealed at T=600°C for t=2h and analyzed by means of high-resolution transmission electron microscopy (HRTEM) and selected area diffraction (SAD). For the purpose of analyzing the corrosion resistance of the coatings against aluminum die casting melt A333.1 (EN AC-46000), rotating immersion tests at T=680°C were conducted. The tested samples were analyzed by means of SEM and electron probe micro analysis (EPMA). Further, the coated die casting cores were applied in an industrial aluminum die casting machine. After 5884 shots the coated cores were analyzed by means of SEM and energy-dispersive X-ray spectroscopy (EDS). Analyses of the thermal stability by means of TEM showed that the Al2O3 toplayer of the CrN/AlN/Al2O3 coating was deposited in an amorphous state and transformed into partially crystalline γ-Al2O3. Nevertheless, the results of the core analyses after 5884 die casting shots indicate a good performance of CrN/AlN/Al2O3, also in comparison to industrially used coatings.
•CrN/AlN/Al2O3 and industrial coatings were applied in rotating immersion tests.•Die casting cores were coated with CrN/AlN/Al2O3 and industrial coatings.•5884 engine blocks were produced using coated die casting cores.•Damage analysis was carried out by means of SEM and EDS.•CrN/AlN/Al2O3 exhibits a good performance in aluminum die casting.
•La1.85Sr0.15CuO4/La0.7Sr0.3MnO3 nanowire network hybrid system is fabricated.•For each nanowire in the system, only one phase can be found.•The competition of the superconductivity and the ...ferromagnetism is present.
We prepared La1.85Sr0.15CuO4/La0.7Sr0.3MnO3 nanowire network hybrid systems by means of electrospinning. From observation by scanning electron microscopy, the average diameter of the nanowires is around 220 nm and the average length can reach over 50 μm. The randomly aligned La1.85Sr0.15CuO4 and La0.7Sr0.3MnO3 nanowires exhibit numerous interconnects among each other and form a complicated, non woven hybrid network system. The nanowires are polycrystalline with a grain size at around 30 nm as confirmed by transmission electron microscopy. According to four-probe electrical transportation and magnetization measurements, superconductivity of the sample is suppressed and a positive magnetoresistance effect is observed. Measurements of M(T) and M(H) were carried out as well, revealing the soft magnetic character of the hybrid nanowire network samples.
•Pornographic pictures affect working memory performance in an n-back task.•Patients with compulsive sexual behaviour show slowed reaction times when presented with pornographic distractors.•Decrease ...of performance is related to pornography consumption in the last week.•Activity in lingual gyrus is associated with poorer performance.
Pornography has been repeatedly at the centre of public attention and has been controversially discussed for a long time. However, little is known about the connection between pornographic stimuli and individual (neuronal) processing of attention and memory. Here, the impact and neural underpinnings of pornographic pictures on working memory processes in a sample of subjects with compulsive sexual behaviour was investigated. Therefore, whilst using functional magnetic resonance imaging (fMRI), a letter n-back task with neutral or pornographic pictures in the background was employed in 38 patients and 31 healthy controls. On the behavioural level, patients were slowed down by pornographic material depending on their pornography consumption in the last week, which was reflected by a higher activation in the lingual gyrus. In addition, the lingual gyrus showed a higher functional connectivity to the insula during processing of pornographic stimuli in the patient group. In contrast, healthy subjects showed faster responses when confronted with pornographic pictures only with high cognitive load. Also, patients showed a better memory for pornographic pictures in a surprise recognition task compared to controls, speaking for a higher relevance of pornographic material in the patient group. These findings are in line with the incentive salience theory of addiction, especially the higher functional connectivity to the salience network with the insula as a key hub and the higher lingual activity during processing of pornographic pictures depending on recent pornography consumption.
Oral antifungal prophylaxis with extended-spectra azoles is widely used in pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), while controlled studies for oral ...antifungal prophylaxis after bone marrow transplantation in children are not available. This survey analyzed patients who had received either itraconazole, voriconazole, or posaconazole. We focused on the safety, feasibility, and initial data of efficacy in a cohort of pediatric patients and adolescents after high-dose chemotherapy and HSCT. Fifty consecutive pediatric patients received itraconazole, 50 received voriconazole, and 50 pediatric patients received posaconazole after HSCT as oral antifungal prophylaxis. The observation period lasted from the start of oral prophylactic treatment with itraconazole, voriconazole, or posaconazole until two weeks after terminating the oral antifungal prophylaxis. No incidences of proven or probable invasive mycosis were observed during itraconazole, voriconazole, or posaconazole treatment. A total of five possible invasive fungal infections occurred, two in the itraconazole group (4 %) and three in the voriconazole group (6 %). The percentage of patients with adverse events potentially related to clinical drugs were 14 % in the voriconazole group, 12 % in the itraconazole group, and 8 % in the posaconazole group. Itraconazole, voriconazole, and posaconazole showed comparable efficacy as antifungal prophylaxis in pediatric patients after allogeneic HSCT.
Aiming at intramolecular frustrated Lewis pairs (FLPs) based on soft Lewis acidic bismuth centers, a phosphine function was combined with a dichloridobismuthane unit on a phenylene backbone utilizing ...a scrambling approach. The reaction between two equivalents of BiCl3 and (o‐(Ph2P)C6H4)3Bi yielded (o‐(Ph2P)C6H4)BiCl2(THF), the structure of which indicated Bi…P interactions and thus a pronounced Lewis acidity at the bismuth center that was confirmed by the Gutmann‐Beckett method. However, the system turned out to be insufficient to be utilized for FLP reactivity. Hence, the chloride ligands were exchanged by iodide and C2F5 substituents, respectively. Despite a lower electronegativity the iodide compound exhibits a shorter Bi…P contact, while the C2F5 substituents led to a further decrease of the Lewis acidity, despite their high group electronegativity. DFT calculations rationalized this by a quenching of the Lewis acidity inherent to the σ*(Bi―C) orbital by negative hyperconjugation from occupied p‐orbitals at the F atoms. Furthermore, it turned out that the strength of the covalent Bi‐X σ‐bond is a more important factor than the charge at Bi in determining the energetic accessibility and thus Lewis acidity of the antibonding σ*(Bi―C) orbital.
Electrospun, superconducting nanowires are characterized concerning the grain orientation, their texture and the respective grain boundary misorientations by means of electron backscatter diffraction ...(EBSD) analysis. The individual nanowires in such electrospun, nonwoven nanowire networks of Bi2Sr2CaCu2Ox (Bi-2212) are polycrystalline, have average diameters up to 250 nm and their grains are in the 20-50 nm range. This requires a high spatial resolution for the analysis in the scanning electron microscope. However, the small diameter of the nanowires enables the application of the newly developed transmission EBSD (t-EBSD) technique without the preparation of TEM slices. Here, we present TEM images of individual nanowires and several EBSD mappings on Bi-2212 nanowires and compare their microstructure to those of filaments of the first generation tapes.
Low latency serial communication for MEG II trigger system Francesconi, M.; Baldini, A.M.; Cei, F. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2019, Letnik:
936
Journal Article
Recenzirano
In the framework of the upgrade of the MEG experiment a new trigger system with demanding performances in terms of latency was designed. To achieve the goal of 512 ns latency the serial connections ...between trigger boards have been optimized so that they only rely on serial to parallel shift registers for the data flow, minimizing the amount of logic to be crossed by data. A dedicated Finite State Machine (FSM) was designed to select the sampling point of the serial stream with respect to an external precision clock used by both transmitter and receiver. As a proof of concept a 16000 channel weighted waveform sum including pedestal suppression, was computed, resulting in 700 ns of latency.
PDF
