Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial Calcium Uptake Declines during Aging and is Directly Activated by Oleuropein to Boost Energy Metabolism and Skeletal Muscle Performance

Mitochondrial calcium (mtCa2+) uptake via the Mitochondrial Calcium Uniporter (MCU) couples the regulation of calcium homeostasis to energy production. mtCa2+ uptake is rate-limiting for mitochondrial activation during muscle contraction, but how MCU is affected during physiopathology and whether it can be stimulated therapeutically remains largely uncharacterized. By profiling human and preclinical aging of skeletal muscle, we discovered a conserved down-regulation of MCUR1 during aging that decreases mtCa2+ uptake and drives sarcopenia. Through a screen of 5000 bioactive nutrients, we identify the natural polyphenol Oleuropein as a specific MCU activator that stimulates mitochondrial respiration via binding to MICU1. Oleuropein activates mtCa2+ uptake and oxidative energy metabolism to enhance endurance and limit fatigue in vivo both in young and aged. These effects of Oleuropein are mediated by an MCU-dependent mechanism in skeletal muscle as they are lost upon muscle-specific MCU KO. Our work demonstrates that impaired mtCa2+ uptake causes mitochondrial dysfunction during aging and establishes Oleuropein as a novel nutrient that specifically targets MCU to stimulate mitochondrial bioenergetics and muscle performance.
Physical condition for absolute instability in inviscid hydroelastic coupling

In this paper the instability of infinitely long cylindrical structures submerged in a uniform inviscid flow is investigated. When the flow velocity is zero, two families of hydroelastic waves exist, with phase velocities that are equal in magnitude and have opposite signs. Positive values of the fluid velocity increase the magnitude of the phase velocity of the waves that propagate in the same direction as the flow, and decrease the magnitude of the phase velocity of the waves propagating opposite to the flow. It is shown by constructing an energy conservation law for the linearized equations of motion that both types of waves have initially positive energy, in the sense that they both require an energy source to be sustained. After a critical value of fluid velocity is exceeded the slow waves acquire negative energy, in the sense that they require an energy sink to be sustained. Coalescence between the ‘‘fast’’ (positive energy) and the ‘‘slow’’ (negative energy) waves creates waves with zero energy whi.
Active maintenance of CD8+ T cell naïvety through regulation of global genome architecture

The differentiation of naïve CD8+ cytotoxic T lymphocytes (CTLs) into effector and memory states results in large scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organisation reflect or underpin these transcriptional programs. We utilised Hi-C to map changes in the spatial organisation of long-range genome contacts within naïve, effector and memory virus-specific CD8+ T cells. We observed that the architecture of the naive CD8+ T cell genome was distinct from effector and memory genome configurations with extensive changes within discrete functional chromatin domains. However, deletion of the BACH2 or SATB1 transcription factors was sufficient to remodel the naïve chromatin architecture and engage transcriptional programs characteristic of differentiated cells. This suggests that the chromatin architecture within naïve CD8+ T cells is preconfigured to undergo autonomous remodelling upon activation, with key transcription factors restraining differentiation by actively enforcing the unique naïve chromatin state. One Sentence Summary CD8+ T cell naïvety is actively maintained by transcription factors that enforce a distinct, naïve chromatin architecture. Highlights CD8+ T cell differentiation states are underscored by distinct chromatin looping architectures. Chromatin loops juxtapose CTL state appropriate enhancers, transcription factors and genes. Effector and memory CTLs have similar genome architectures, explaining rapid memory recall. CTL differentiation is restrained by BACH2 and SATB1, which enforce a naïve loop architecture.
Biologically informed NeuralODEs for genome-wide regulatory dynamics

Models that are formulated as ordinary differential equations (ODEs) can accurately explain temporal gene expression patterns and promise to yield new insights into important cellular processes, disease progression, and intervention design. Learning such ODEs is challenging, since we want to predict the evolution of gene expression in a way that accurately encodes the causal gene-regulatory network (GRN) governing the dynamics and the nonlinear functional relationships between genes. Most widely used ODE estimation methods either impose too many parametric restrictions or are not guided by meaningful biological insights, both of which impedes scalability and/or explainability. To overcome these limitations, we developed PHOENIX, a modeling framework based on neural ordinary differential equations (NeuralODEs) and Hill-Langmuir kinetics, that can flexibly incorporate prior domain knowledge and biological constraints to promote sparse, biologically interpretable representations of ODEs. We test accuracy of PHOENIX in a series of in silico experiments benchmarking it against several currently used tools for ODE estimation. We also demonstrate PHOENIX’s flexibility by studying oscillating expression data from synchronized yeast cells and assess its scalability by modelling genome-scale breast cancer expression for samples ordered in pseudotime. Finally, we show how the combination of user-defined prior knowledge and functional forms from systems biology allows PHOENIX to encode key properties of the underlying GRN, and subsequently predict expression patterns in a biologically explainable way.
Mutual regulation of transcriptomes between pneumocytes and fibroblasts mediates alveolar regeneration

Alveolar type 2 (AT2) and club cells are part of the stem cell niche of the lung and their differentiation is required for pulmonary homeostasis and tissue regeneration. A disturbed crosstalk between fibroblasts and epithelial cells contributes to the loss of lung structure in chronic lung diseases. Therefore, it is important to understand how fibroblasts and lung epithelial cells interact during regeneration. Here we analyzed the interaction of fibroblasts and the alveolar epithelium modelled in air-liquid interface cultures. Single-cell transcriptomics showed that co-cultivation with fibroblasts leads to increased expression of type 2 markers in pneumocytes, activation of regulons associated with maintenance of alveolar type 2 cells, and trans-differentiation of club cells towards pneumocytes. This was accompanied by an intensified transepithelial barrier. Vice versa, activation of NFκB pathways and the CEBPB regulon as well as the expression of IL-6 and other differentiation factors (e.g. FGFs) were increased in fibroblasts co-cultured with epithelial cells. Recombinant IL-6 enhanced epithelial barrier formation. Therefore, in our co-culture model, regulatory loops were identified by which lung epithelial cells mediate regeneration and differentiation of the alveolar epithelium in a cooperative manner with the mesenchymal compartment.
A statistical framework for the analysis of multivariate infectious disease surveillance counts

A framework for the statistical analysis of counts from infectious disease surveillance databases is proposed. In its simplest form, the model can be seen as a Poisson branching process model with immigration. Extensions to include seasonal effects, time trends and overdispersion are outlined. The model is shown to provide an adequate fit and reliable one-step-ahead prediction intervals for a typical infectious disease time series. In addition, a multivariate formulation is proposed, which is well suited to capture space-time dependence caused by the spatial spread of a disease over time. An analysis of two multivariate time series is described. All analyses have been done using general optimization routines, where ML estimates and corresponding standard errors are readily available.
Medikamentöse Schmerztherapie

Die menschliche Schmerzwahrnehmung lässt sich gezielt mit Arzneimitteln beeinflussen. Das WHO-Stufenschema bietet eine Richtlinie, wann welches Medikament in welcher Kombination eingesetzt wird. Entscheidend für den Erfolg der Pharmakotherapie sind eine fundierte Schmerzdiagnostik und die richtige Kommunikation. So sollten sich Physiotherapeuten gegenüber ihren Patienten nur mit Bedacht und Fachwissen über Medikamente äußern, um deren Wirksamkeit nicht negativ zu beeinflussen.
The Number of Permutation Polynomials of a Given Degree Over a Finite Field

We relate the number of permutation polynomials in F"q[x] of degree [email protected]? q-2 to the solutions (x"1,x"2,.,x"q) of a system of linear equations over F"q, with the added restriction that x"i 0 and x"i x"j whenever i j. Using this we find an expression for the number of permutation polynomials of degree p-2 in F"p[x] in terms of the permanent of a Vandermonde matrix whose entries are the primitive pth roots of unity. This leads to nontrivial bounds for the number of such permutation polynomials. We provide numerical examples to illustrate our method and indicate how our results can be generalised to polynomials of other degrees.
Two types of vowel devoicing in Japanese: Evidence from articulatory data

Japanese high vowels [i, u] become devoiced when they occur between voiceless segments: e.g., [kita] ‘‘north. ’’ Vowel devoicing (VD) occurs systematically, except when a high vowel appears between two voiceless fricatives, where VD is less consistent and nonobligatory. The present study examined the laryngeal gestures during the production of Japanese vowels in various phonological contexts using fiberscopic and electromyographic techniques. Stimuli consisted of [CiCe] words, where the consonants were stops (S) or fricatives (F). The results revealed that the glottal gestures for typical devoiced vowels (those in [SiSe], [FiSe], or [SiFe]) and devoiced vowels in [FiFe] were distinct, although the two types were indistinguishable in the spectrograms. Consistent with observations in a previous study [H. Hirose, Phonetica 23, 156–170 (1971)], [CiC] sequences with typical devoiced vowels were produced with a wide open glottis accompanied with high activities of the abductor muscle. In contrast, in [FiF] seque.
Low Molecular Weight Heparin (KABI2165) as Thromboprophylaxis in Elective Visceral Surgery

Summary In two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The first study comparing 1 x 7′500 anti-factor Xa IU LMW heparin daily with 2 x 5′000 IU UF heparin was interrupted because of excessive bleeding complications (LMW heparin: 11/23 pts, UF heparin: 2/20 pts, p <0.01). In the second study (146 pts) the dose of LMW heparin was reduced to 1 x 2′500 anti-factor Xa IU. Bleeding complications (LMW heparin: 14.9%, UF heparin: 15.3%) and thromboembolic events (LMW heparin: 2.86%, UF heparin: 2.94%) were equal among the two groups. 2′500 anti-factor Xa IU/day of this LMW heparin fragment, corresponding to 15 mg/day, is the lowest dose of a LMW heparin used in a randomized clinical trial and was found to be a safe and efficient regimen in perioperative thrombosis prophylaxis. An advantage of LMW heparin over UF heparin is its once daily administration.
Transverse Injection from Circular and Elliptic Nozzles into a Supersonic Crossflow

An investigation of sonictransverse injection from circular and elliptic nozzles into a supersoniccrosse ow using planar Rayleigh/Mie scattering is reported. Instantaneous images allow examination of the structural details, whereas ensemble-averaged images provide transverse penetration and lateral spread data for each jet. Standard deviation images produce information regarding the large-scale mixing/entrainment and reveal the mixing zones. Results show a highly three-dimensional near-e eld interaction dominated by shear-layer eddies and a counterrotating vortex pair. Ensemble-averaged results show that the elliptic jet spreads more rapidly in the lateral direction than the circular jet, cone rming that an axis-switching phenomenon is present. Near-e eld transverse penetration data collapse well with low-speed scaling conventions; however, the jet produced by the elliptic nozzle suffersa20%reductioninpenetrationcomparedto thecircularjet.Compressibilityleveldoesnotplaya signie cant roleintheaveragepenetrationorspreadofthesejets,althoughitstronglyaffectsthemixing/entrainmentandlargescale structure. Analysis of mixing potential from the standard deviation images indicates that the low and high convective Mach number Mc injection cases are signie cantly different; low Mc injection yields better large-scale mixing potential than high Mc injection regardless of the injector geometry.
J. Turunen and F. Wyrowski (eds.), Diffractive Optics for Industrial and Commercial Applications , Akademie Verlag, Berlin, Germany, 1997. 426 pp.

The field of diffractive optics is at the same time old and young. Diffraction gratings have been known for two centuries and used extensively in spectroscopy, for example. Also the theoretical understanding of the basic properties of grating diffraction has been well developed since that time. Until the 1960s, the technological foundation of grating manufacture used to be precision mechanics. It was then, when with the advent of the laser, things gradually started to change. On the one hand, laser interferometry became an additional tool to fabricate grating structures with very small periods. On the other hand, many new applications for optics started to develop based on the use of different types of laser sources. Some examples that may be mentioned are—besides modern spectroscopic techniques—areas like material processing, optical communications and information processing, optical data storage, etc. Consequently, the term “diffractive optics” has obtained a different flavor during the past 20–30 years. New types of diffractive elements were being developed with new technologies. This started in the mid-1960s with the invention of computer-generated holography which allowed to create “arbitrary” wavefronts (this means, within practical limits) by diffracting a light wave at an irregular binary structure. The computation and fabrication of computer-generated holograms was made possible by then newly available digital computers and plotting equipment. Since the early 1970s, people started to make diffractive elements using microfabrication techniques (lithography, etching, etc.) adapted from the processing of electronic circuits. These ideas were initially demonstrated in industrial research laboratories like Philips and Thomson-CSF.
Nodal structure of chaotic eigenfunctions

We investigate the distribution of nodes at and beyond the classical turning point of idealized chaotic quantum eigenfunctions. A formula for the density of nodes is derived in the semiclassical limit, and the rate at which this density falls off as one moves into the forbidden region is also studied. The discussion is supported by numerical results. Corrections to the Bessel function correlation in the classically allowed region are necessary for finite ℏ and are given here.
ACCURATE ANALYTICAL SELF-CONSISTENT FIELD FUNCTIONS FOR ATOMS. II. LOWEST CONFIGURATIONS OF THE NEUTRAL FIRST ROW ATOMS

Self-consistent-field wave functions are obtained for the ground states of the first-row atoms and for the excited states belonging to the same configurations. The wave functions are the solution of the variational problem of finding the best orbitals for a given state, without any additional approximations except those inherent in the expansion method. (auth)
Interpretation of microlensing events in Q2237 + 0305

We point out the uncertainties in the potential models of the foreground galaxy in the gravitational lens Q2237 + 0305. The surface densities and external shears are uncertain by a factor of appproximately less than 2. Very long light curves are calculated for different models using the method developed by Witt (1993) and Lewis et al. (1993). We find that the probability of images being in a quiescent state depends strongly on the potential models and the direction of the source motion relative to the alignment of the (gravitational lens) shear term of the macroimages. For example, the probabilities of finding variations smaller than 0.1 mag and for a period of longer than 0.5 Einstein radii (approximately equals 3-5 yr) in image C and D are approximately 30%. This offers an explanation of why image C and D showed relatively small variations. The quiescent images are more likely to be demagnified, consistent with the observations. Further, the higher the magnification of the macroimages, the weaker are the microlensing events. In addition, we conclude that a simple Gaussian profile has some difficulties in explaining the asymmetric shape and the small amplitude of the observed high-magnification events if they are typical. Source models in which the emission is produced by a brightt compact core and a more extended halo can occur better explain the observed double peak events. More data are needed to clearly distinguish different galaxy potential models.
Communicating the Probabilities of Extreme Surface Temperature Outcomes

The magnitude of the future global warming is uncertain, but the possible dramatic changes associated with high temperatures have seen rising attention in the literature. Projections of temperature change in the literature are often presented in probabilistic terms and typically highlight the most likely ranges of future temperature under assumed emission scenarios. However, focusing on these high probability outcomes of global warming omits important information related to the threats of low-probability but high-impact outcomes under more extreme change. As such, we argue that the literature should place more emphasis on communicating the probabilities of extreme temperature change, in a way that is accessible to policymakers and the general public. The damage associated with climate change is likely to be non-linear with temperature, and thus extreme temperature changes may pose a larger risk than the most likely outcomes. We use a simple climate model to explore the probabilities of high surface temperature under business as usual emissions scenarios, given current knowledge of the climate system. In a business as usual scenario (A1FI) we find the probability of “likely” warming (central 66%) to be approximately 4.4°C-6.9°C in 2100 (above 1900 levels). However, we find extreme (>7°C) warming to embody a notable portion of damage risk compared to this likely range.
A Parametric Study of Fine-Scale Turbulence Mixing Noise

The present paper is a study of aerodynamic noise spectra from model functions that describe the source. The study is motivated by the need to improve the spectral shape of the MGBK jet noise prediction methodology at high frequency. The predicted spectral shape usually appears less broadband than measurements and faster decaying at high frequency. Theoretical representation of the source is based on Lilley’s equation. Numerical simulations of high-speed subsonic jets as well as some recent turbulence measurements reveal a number of interesting statistical properties of turbulence correlation functions that may have a bearing on radiated noise. These studies indicate that an exponential spatial function may be a more appropriate representation of a two-point correlation compared to its Gaussian counterpart. The effect of source non-compactness on spectral shape is discussed. It is shown that source non-compactness could well be the differentiating factor between the Gaussian and exponential model functions. In particular, the fall-off of the noise spectra at high frequency is studied and it is shown that a non-compact source with an exponential model function results in a broader spectrum and better agreement with data. A recent source model proposed by Tam et al. that represents the source as a covariance of the convective derivative of fine-scale turbulence kinetic energy is also examined.
Wide Band Gap Semiconductor Devices for Power Electronic Converters

Wide Band Gap (WBG) semiconductors provide superior material qualities that could allow for the functioning of prospective power devices at higher temperatures, voltages, and switching rates than is now possible with Si technology. However, Si is reaching its limits, and as a result, Si-based semiconductors have restricted voltage blocking, limited heat transmission, limited efficiency, and limited maximum junction temperature. Wide-band gap materials like Silicon Carbide (SiC) and Gallium Nitride (GaN) have recently been used to construct power semiconductor devices. The development of new power converters and the significant improvement in the performance of current ones will be made possible using these new power semiconductor devices, resulting in an improvement in the efficiency of the electric energy transformations and more intelligent use of the electric energy. Due to their exceptional qualities, commercial availability of starting material, and maturity of their technological processes, SiC and GaN are now the more promising semiconductor materials for these new power devices. The introduction of these novel components in the converter has several ramifications that must be understood to fully profit from these devices. This study serves as a review that enumerates the traits and advancement of contemporary GaN and SiC power devices and assesses the condition of the research, and projects the future of semiconductor device applications. The issues and difficulties with GaN and SiC devices are also covered.
Scalable Modular Measurement System For Continuous Blood Monitoring With Piezoelectric Mems Resonators

This paper reports on a novel scalable modular measurement system for continuous monitoring of the conductance spectrum of a piezoelectric MEMS resonator in blood either in standing or continuous flow conditions. Resonance frequency and quality factor of the resonator are extracted by automatic data fitting of the conductance spectrum. Both quantities can be monitored over extended periods of multiple hours and the sensor can be reused after cleaning. After careful sensor calibration, the dynamic viscosity can be extracted from the quality factor. This system allows for simultaneous dynamic viscosity measurements of multiple blood samples due to several modules arranged in parallel.
High-Throughput Mass Measurement Of Single Bacterial Cells By Silicon Nitride Membrane Resonators

We present a technological approach to precisely measure the dry mass of many individual cells of a bacteria colony. In this technique, bacteria are transported from aqueous solution into gas phase and subsequently guided to the surface of a silicon nitride membrane resonator. Abrupt downshifts in the membrane eigenfrequencies are measured upon every bacterium adhesion and are related to the dry mass of the cell by theoretical methods. We measure the dry mass of Escherichia coli K-12 and Staphylococcus epidermidis with an unprecedented throughput of 20 cells/min and with a mass resolution of ⁓1%. Finally, we apply the Koch & Schaechter model to assess the intrinsic sources of growth stochasticity.
Mechanism of leakage current through the nanoscale SiO2 layer

We clarify the mechanism of leakage current through the nanoscale ultrathin silicon dioxide (SiO2) layer in a metal‐insulator‐semiconductor structure based on the multiple scattering theory when technologically important phosphorus doped polycrystalline silicon is adopted as the gate electrode. We also derive an analytic expression for the direct tunneling current, and show that its measurement presents an excellent opportunity to determine the effective mass of an electron in the SiO2.