Astronomical component estimation (ACE v.1) by time-variant sinusoidal modeling

Accurately deciphering periodic variations in paleoclimate proxy signals is essential for cyclostratigraphy. Classical spectral analysis often relies on methods based on (fast) Fourier transformation. This technique has no unique solution separating variations in amplitude and frequency. This characteristic can make it difficult to correctly interpret a proxy's power spectrum or to accurately evaluate simultaneous changes in amplitude and frequency in evolutionary analyses. This drawback is circumvented by using a polynomial approach to estimate instantaneous amplitude and frequency in orbital components. This approach was proven useful to characterize audio signals (music and speech), which are non-stationary in nature. Paleoclimate proxy signals and audio signals share similar dynamics; the only difference is the frequency relationship between the different components. A harmonic-frequency relationship exists in audio signals, whereas this relation is non-harmonic in paleoclimate signals. However, this difference is irrelevant for the problem of separating simultaneous changes in amplitude and frequency. Using an approach with overlapping analysis frames, the model (Astronomical Component Estimation, version 1: ACE v.1) captures time variations of an orbital component by modulating a stationary sinusoid centered at its mean frequency, with a single polynomial. Hence, the parameters that determine the model are the mean frequency of the orbital component and the polynomial coefficients. The first parameter depends on geologic interpretations, whereas the latter are estimated by means of linear least-squares. As output, the model provides the orbital component waveform, either in the depth or time domain. Uncertainty analyses of the model estimates are performed using Monte Carlo simulations. Furthermore, it allows for a unique decomposition of the signal into its instantaneous amplitude and frequency. Frequency modulation patterns reconstruct changes in accumulation rate, whereas amplitude modulation identifies eccentricity-modulated precession. The functioning of the time-variant sinusoidal model is illustrated and validated using a synthetic insolation signal. The new modeling approach is tested on two case studies: (1) a Pliocene-Pleistocene benthic delta O-18 record from Ocean Drilling Program (ODP) Site 846 and (2) a Danian magnetic susceptibility record from the Contessa Highway section, Gubbio, Italy

Targeting Survivin with YM155 (Sepantronium Bromide): A novel therapeutic strategy for paediatric acute myeloid leukaemia

Despite aggressive chemotherapy, approximately one-third of children with acute myeloid leukaemia(AML) relapse. More effective treatments are urgently needed. Survivin is an inhibitor-of-apoptosis protein with key roles in regulating cell division, proliferation and apoptosis. Furthermore, high expression of Survivin has been associated with poor clinical outcome in AML. The Survivin suppressant YM155 (Sepantronium Bromide) has pre-clinical activity against a range of solid cancers and leukemias, although data in AML is limited. Therefore, we undertook a comprehensive pre-clinical evaluation of YM155 in paediatric AML. YM155 potently inhibited cell viability in a diverse panel of AML cell lines. All paediatric cell lines were particularly sensitive, with a median IC50 of 0.038 mu M. Cell cycle analyses demonstrated concentration-dependent increases in a sub-G1 population with YM155 treatment, suggestive of apoptosis that was subsequently confirmed by an increase in annexin-V positivity. YM155-mediated apoptosis was confirmed across a panel of 8 diagnostic bone marrow samples from children with AML. Consistent with the proposed mechanism of action, YM155 treatment was associated with down-regulation of Survivin mRNA and protein expression and induction of DNA damage

Programming of 3-Axis Hybrid Kinematics CNC Machine for Rapid Prototyping Using Subtractive and Additive Processes

The paper presents the programming and program verification on a 3-axis hybrid kinematics CNC machine for rapid prototyping using subtractive and additive processes. The original hybrid (parallel-serial) 3-axis O-X glide mechanism developed to build a rapid prototyping machine and multifunctional machine tools is presented. The paper analyzes the available programming software, which can be one of the standard CAD/CAM systems or a specialized CAM system, for subtractive processes, i.e. desktop milling. For the additive processes, the software for generating G code based on the STL file as well as the possibility of simulating the machine when working is considered. To verify the program, the simulation of material removal for subtractive processes as well as the simulation of material addition for additive processes were considered. The paper presents the prototype of a hybrid kinematics CNC machine and some of the results of testing with an open control system based on the LinuxCNC

Digital twin control of multi-axis wood CNC machining center based on LinuxCNC

Abstrack: This paper presents an application of an open architecture control system implemented on a multi-axis wood computer numerical control milling machining center, as a digital twin control. The development of the digital twin control system was motivated by research and educational requirements, especially in the field of configuring a new control system by “virtual commissioning”, enabling the validation of the developed controls, program verification, and analysis of the machining process and monitoring. The considered wood computer numerical control (CNC) machining system is supported by an equivalent virtual machine in a computer-aided design and computer-aided manufacturing (CAD/CAM) environment, as well as in the control system, as a digital twin. The configured virtual machines are used for the verification of the machining program and programming system via machining simulation, which is extremely important in multi-axis machining. Several test wood workpieces were machined to validate the effectiveness of the developed control system based on LinuxCNC

Concomitant multiple anomalies of renal vessels and collecting system

Although anomalies of renal vessels and collecting system are relatively frequent, their concomitant occurrence is a rare event. During dissection of a 75-year-old male formalin-embalmed cadaver, we found multiple variations in the renal vessels and renal collecting system. Both kidneys were normal in size and anteriorly malrotated, with duplex collecting system and duplex ureter. One ureter drained the upper part of the kidney and the second ureter drained the lower part of the kidney. Superior and inferior collecting systems were separated by renal parenchyma. The right kidney had two renal arteries, the first renal artery (main renal artery) originating from the abdominal aorta, passing behind the inferior vena cava (IVC) and entering the kidney through the superior and inferior renal hilum. The second artery was the inferior polar artery. In addition, the right kidney had two renal veins as well. Three renal tributaries emerged from the upper and lower portion of the right renal hilum, and they joined to form the main renal vein which drained into the IVC. The lower renal vein was the inferior polar vein. The left kidney had four renal arteries (two hilar arteries and two polar arteries). The main left renal vein emerged from both superior and inferior left renal hilum, passed in front of the abdominal aorta and drained into the IVC. The left kidney also had the inferior polar vein which was divided behind the aorta (retro aortic vein) into two venous trunks. These venous trunks drained separately into posteromedialaspect of the IVC. Finally, the right testicular vein was formed by two tributaries and drained into the IVC, whereas the two left testicular veins drained separately into the left main renal vein

Exploring the Conformational Landscape of Bioactive Small Molecules

By using a combination of classical Hamiltonian replica exchange with high-level quantum mechanical calculations on more than one hundred drug-like molecules, we explored here the energy cost associated with binding of drug-like molecules to target macromolecules. We found that, in general, the drug-like molecules present bound to proteins in the Protein Data Bank (PDB) can access easily the bioactive conformation and in fact for 73% of the studied molecules the bioactiveconformation is within 3kBT from the most-stable conformation in solution as determined by DFT/SCRF calculations. Cases with large differences between the most-stable and the bioactive conformations appear in ligands recognized by ionic contacts, or very large structures establishing many favorable interactions with the protein. There are also a few cases where we observed a non-negligible uncertainty related to the experimental structure deposited in PDB. Remarkably, the rough automatic force field used here provides reasonable estimates of the conformational ensemble of drugs in solution. The outlined protocol can be used to better estimate the cost of adopting the bioactive conformation

Sex dimorphism of postural parameters of the human acetabulum

The aim of this investigation was to examine normal acetabular morphometry, its sex dimorphism and the acetabular dysplasia rate in Serbian adults. For each hip, the centre-edge angle of Wiberg, the acetabular angle of Sharp, acetabular depth and acetabular roof obliquity were measured. The center-edge angle of Wiberg correlated negatively with the acetabular angle of Sharp and acetabular roof obliquity, but positively correlated with acetabular depth. Our results suggest that the prevalence of acetabular dysplasia in the Serbian population is lower than in Western countries. We confirmed the existence of significant gender differences in acetabular morphology among the subjects of our study. These sex-related differences in acetabular morphology were the cause for more dysplastic female acetabula compared with male acetabula