Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic analysis of the sphingomyelin synthase family in C. elegans

Sphingomyelin (SM) is a major component of mammalian cell membranes and particularly abundant in the myelin sheath that surrounds nerve fibers. Its production is catalyzed by SM synthases SMS1 and SMS2, which interconvert phosphatidylcholine and ceramide to diacylglycerol and SM in the Golgi and at the plasma membrane, respectively. As the lipids participating in this reaction fulfill both structural and signaling functions, SMS enzymes have considerable potential to influence diverse important cellular processes. The nematode Caenorhabditis elegans is an attractive model for studying both animal development and human disease. The organism contains five SMS homologues but none of these have been characterized in any detail. Here, we carried out the first systematic analysis of SMS family members in C. elegans. Using heterologous expression systems, genetic ablation, metabolic labeling and lipidome analyses, we show that C. elegans harbors at least three distinct SM synthases and one ceramide phosphoethanolamine (CPE) synthase. Moreover, C. elegans SMS family members have partially overlapping but also unique subcellular distributions and together occupy all principal compartments of the secretory pathway. Our findings shed light on crucial aspects of sphingolipid metabolism in a valuable animal model and opens avenues for exploring the role of SM and its metabolic intermediates in organismal development.
Changes in spatial self-consciousness elicit grid cell-like representation in entorhinal cortex

Grid cells in entorhinal cortex (EC) encode an individual’s location in space and rely on environmental cues and multisensory bodily cues. Body-derived signals are also primary signals for the sense of self as the continuous application of visuo-tactile bodily stimuli elicits illusory drifts in perceived self-location. It is unknown whether illusory changes in self-location are sufficient to elicit grid cell like representation (GCLR) in EC and how this compares to GCLR during conventional virtual navigation. Our results show that illusory changes in perceived self-location (independent of changes in environmental navigation cues and explicit imagined navigation) evoke entorhinal GCLR, correlating in strength with the magnitude of perceived self-location, and characterized by similar grid orientation as during conventional virtual navigation. These data demonstrate that the same grid-like representation is recruited when navigating based on environmental, mainly visual cues, or when experiencing illusory forward drifts in self-location, driven by perceptual multisensory bodily cues.
The maintenance of centriole appendages and motile cilia basal body anchoring relies on TBCCD1

Centrosomes are organelles consisting of two structurally and functionally distinct centrioles, with the mother centriole having complex distal (DA) and subdistal appendages (SDA). Despite their importance, how appendages are assembled and maintained remains unclear. This study investigated human TBCCD1, a centrosomal protein essential for centrosome positioning, to uncover its localization and role at centrioles. We found that TBCCD1 localizes at both proximal and distal regions of the two centrioles, forming a complex structure spanning from SDA to DA and extending inside and outside the centriole lumen. TBCCD1 depletion caused centrosome mispositioning, which was partially rescued by taxol, and the loss of microtubules (MTs) anchored to centrosomes. TBCCD1 depletion also reduced levels of SDA proteins involved in MT anchoring such as Centriolin/CEP110, Ninein, and CEP170. Additionally, TBCCD1 was essential for the correct positioning of motile cilia basal bodies and associated structures in Paramecium. This study reveals that TBCCD1 is an evolutionarily conserved protein essential for centriole and basal body localization and appendage assembly and maintenance. A BioID screening also linked TBCCD1 to ciliopathy-associated protein networks.
Solutions to ellipsoidal boundary value problems for gravity field modelling

The determination of the figure of the Earth and its gravity field has long relied on methodologies that approximate the Earth by a sphere, but this level of accuracy is no longer adequate for many applications, due to the advent of new and advanced measurement techniques. New, practical and highly accurate methodologies for gravity field modelling that describe the Earth as an oblate ellipsoid of revolution are therefore required. The foundation for these methodologies is formed by solutions to ellipsoidal geodetic boundary-value problems. In this thesis, new solutions to the ellipsoidal Dirichlet, Neumann and second-order boundary-value problems, as well as the fixedand free-geodetic boundary-value problems, are derived. These solutions do not rely on any spherical approximation, but are nevertheless completely based on a simple spherical harmonic expansion of the function that is to be determined. They rely on new relations among spherical harmonic base functions. In the new solutions, solid spherical harmonic coefficients of the desired function are expressed as a weighted summation over surface spherical harmonic coefficients of the data on the ellipsoidal boundary, or alternatively as a weighted summation over coefficients that are computed under the approximation that the boundary is a sphere. Specific applications of the new solutions are the computation of geopotential coefficients from terrestrial gravimetric data and local or regional gravimetric geoid determination. Numerical closed-loop simulations have shown that the accuracy of geopotential coefficients obtained with the new methods is significantly higher than the accuracy of existing methods that use the spherical harmonic framework. The ellipsoidal corrections to a Stokesian geoid determination computed from the new solutions show strong agreement with existing solutions. In addition, the importance of the choice of the reference sphere radius in Stokes’s formula and its effect on the magnitude and spectral sensitivity of the ellipsoidal corrections are pointed out.
Computational Engineering of a Therapeutic Antibody to Inhibit Multiple Mutants of HER2 Without Compromising Inhibition of the Canonical HER2

Genomic germline and somatic variations may impact drug binding and even lead to resistance. However, designing a different drug for each mutant may not be feasible. In this study, we identified the most common cancer somatic mutations from the Catalogue of Somatic Mutations in Cancer (COSMIC) that occur in structurally characterized binding sites of approved therapeutic antibodies. We found two HER2 mutations, S310Y and S310F, that substantially compromise binding of Pertuzumab, a widely used therapeutics, and lead to drug resistance. To address these mutations, we designed a multi-specific version of Pertuzumab, that retains original function while also bindings these HER2 variants. This new antibody is stable and inhibits HER3 phosphorylation in a cell-based assay for all three variants, suggesting it can inhibit HER2-HER3 dimerization in patients with any of the variants. This study demonstrates how a small number of carefully selected mutations can add new specificities to an existing antibody without compromising its original function, creating a single drug that targets multiple common variants, making a drug that is not personalized yet its activity may be.
APOE4/4 is linked to damaging lipid droplets in Alzheimer’s microglia

Several genetic risk factors for Alzheimer’s Disease (AD) implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and AD pathology remains poorly understood. Through single-nucleus RNA-sequencing of AD brain tissue, we have identified a microglial state defined by the expression of the lipid droplet (LD) associated enzyme ACSL1 with ACSL1-positive microglia most abundant in AD patients with the APOE4/4 genotype. In human iPSC-derived microglia (iMG) fibrillar Aβ (fAβ) induces ACSL1 expression, triglyceride synthesis, and LD accumulation in an APOE-dependent manner. Additionally, conditioned media from LD-containing microglia leads to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for AD with microglial LD accumulation and neurotoxic microglial-derived factors, potentially providing novel therapeutic strategies for AD.
Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo

ABSTRACT Trueperella pyogenes can cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined. T. pyogenes-induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS), and respiratory epithelium of mice remains unknown. In this study, we used T. pyogenes 20121 to infect PBECs in air-liquid interface conditions and porcine PCLS. T. pyogenes could adhere to, colonize, and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in the lungs of infected mice. Furthermore, western blot showed that the NOD-like receptor (NLR)/C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B pathway were involved in inflammation in PCLS and lungs of mice, which also confirms that porcine PCLS provide a platform to analyze the pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase, p-extracellular signal-regulated kinase, and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase and Akt pathways were also involved in inflammation in T. pyogenes-infected mice. In addition, we used T. pyogenes 20121 to infect tumor necrosis factor-alpha (tnf-α-/-) mice, and the results indicated that apoptosis and injury in respiratory epithelium of infected tnf-α-/- mice were alleviated. Thus, the pro-inflammatory cytokine TNF-α played a role in apoptosis and the respiratory epithelium injury in mouse lungs. Collectively, our study provides insight into the inflammatory injury induced by T. pyogenes and suggests that blocking NLR may be a potential therapeutic strategy against T. pyogenes infection.
Analysis of noise reduction characteristics of the diffuser surface roughness on interferometric images

Since the coherent noise in the interferometric system, the method of rotated diffuser would reduce the coherence of the light beam to suppress the noise of the interference image. By analyzing the coherent noise reduction characteristics of rotated diffuser with different surface roughness, the relationship between surface roughness and the noise contrast under different rotation speeds was simulated, and the effective roughness range with noise reduction effect would be selected. It would build a noise reduction system based on Fizeau interference, and collected and calculated the noise contrast of the interference image. The effective range of σh/λ was 0.2~0.5 when the rotation speed was 10r/s, while the effective range of σh/λ was 0.4~0.6 when the rotation speed is 100r/s. The experimental results showed that the surface roughness and wavelength ratio σh/λ of rotated diffuser increased when the noise contrast tended to 1, but the effective range of surface roughness decreases with the increase of the rotational speed of the diffuser.
Funktionelle und effektive Konnektivität

Das Konzept der funktionellen Spezialisierung nimmt an, dass lokale Hirnbereiche f ü r bestimmte Aspekte der Informationsverarbeitung spezialisiert sind, schlie ß t aber die M ö glichkeit ein, dass sich diese Spezialisierung in anatomisch segregierten Arealen in verschiedenen Hirnbereichen wiederfi nden l ä sst ( Marshall and Fink 2003 ). Die Mehrzahl der bisher durchgef ü hrten funktionellen Bildgebungsexperimente basiert auf diesem Konzept: die Areale, die bei einer bestimmten Aufgabe aktiviert sind, werden als Elemente eines verteilten Systems interpretiert. Allerdings beschreibt diese Sicht nicht, wie die verEinleitung & Zu den am h ä ufi gsten eingesetzten Methoden der kognitiven und klinischen Neurowissenschaften z ä hlen elektrophysiologische Methoden, zum Beispiel Elektroenzephalografi e (EEG) und Magnetenzephalografi e (MEG), sowie funktionelle Bildgebungstechniken, zum Beispiel Positronenemissionstomografi e (PET) und funktionelle Magnetresonanztomografi e (fMRI). Mit ihrer Hilfe wird die Funktion des Gehirns entlang zweier Dimensionen untersucht: funktioneller Spezialisierung und funktioneller Integration. Autoren K. E. Stephan 1 , 2 , L. Kasper 1 , 3 , K. H. Brodersen 1 , 4 , C. Mathys 1 , 3
On the Approximability for the Fault-Tolerant Facility Placement Problem with and without Rejection

SYNOPTIC ABSTRACT In the fault-tolerant facility placement problem with rejection, we are given a set of sites S and a set of customers C, and connection costs between customers and sites. We assume that the connection costs satisfy the metric principle. Each customer can be either assigned to some opened facilities in some sites to satisfy their demands or rejected by paying a reject cost. Each site may open an unbounded number of facilities. The goal is to minimize the sum of the cost of opening facilities at the sites, connecting the demands of the accepted customers to different open facilities, and the reject costs of the rejected customers. We show how to transform a linear programming-based (LP-based) ρ-approximation algorithm for the fault-tolerant facility placement problem without rejection into an LP-based (1+ρ)−approximation algorithm for the fault-tolerant facility placement problem with rejection. Finally, we obtain an approximation algorithm with the performance ratio of 2.515 for the fault-tolerant facility placement problem with rejection.
The creation of the motion pattern attended with emergence using evolutional computation

In this paper, we describe swing-up and stability control of Acrobot, an inverted pendulum with two links. Controlling Acrobot is very difficult, since it suffers from non-holonomic constraints. Genetic algorithm (GA) is used as a controller of swing-up and stability control of Acrobot. Therefore, we propose a new method that the gene length is changeable. In addition, we discuss a new cost function for emergence. The proposed scheme compares with the zero dynamics method developed by M. Spong. The simulation results are exemplified to show the validity of the proposed scheme.
Zur Drainage des Mittelohres

medialen Wand der Paukenhöhle gebildeten Winkel. Mit elnem feinen Federhalter wurden em oder mehrere Tuschepunkte in verschiedenen Arealen der Mittelohr-schleimhaut aufgebracht und der Abtransport zur Tube beobachtet. Die Transportzeiten und die Transportwege wurden fotografisch und videotechnisch dokumentiert und in Schemata des linken bzw. rechten Mittelohres des Meerschweinchens ubertragen.
Longitudinal rectification of chiral self-propelled particles induced by the transversal asymmetry

We numerically investigate the rectification transport of chiral self-propelled particles in a two-dimensional (2D) upper-lower asymmetric channel. The chiral particles perform a sliding movement along the walls due to the confinement of the channel. The longitudinal rectification can occur in the upper-lower asymmetric channel. In presence of a transverse force, the longitudinal rectification may be reduced or enhanced by the competition or the cooperation between the force and the channel asymmetry. A possible application for separating particles of different chiralities is also presented.
Evozierte otoakustische Emissionen zum Hörscreening bei Säuglingen*

Unser heutiges Wissen die Bedeutung kindlicher Hörstörungen sowie deren Folgen ist in den vergangenen Jahren deutlich angestiegen. Mit dem zunehmenden Interesse, Horstörungen zum fruhestmöglichen Zeitpunkt zu erfassen, sind auch zahlreiche Methoden zu ihrer Fruherkennung beschrieben worden (Weatherby und Bennet, 1980; Radü und Kauffmann, 1983; Kauffmann, 1986; Leonardy-Dollar und Sesterhenn, 1987; v. Wedel und Mitarb., 1988). Der aktuelle Stand in der Diagnostik kindlicher Hörstörungen und damit auch der Prävention moglicher Folgeerkrankungen ist jedoch eher enttäuschend. So wird die Erstdiagnose zur Zeit erst in einem Alter von ungefãhr 2,5 Jahren gestelit (Wedel v. und Mitarb., 1988), wobei statistische Untersuchungen zeigen, da1 der Verdacht auf eine kindliche Hörstörung in 60 % von den Eltern und in nur 8 % vom HNO-Arzt geauert wird (Hartmann, 1981; v. Wedel und Mitarb., 1988). Aus pädagogischer Sicht führt die fruhzeitig einsetzende Betreuung hörbehinderter Kinder auch bei nur geringem Restgehor zu erstaunlich guten sprachlichen und kognitiven Leistungen. Diese positiven Resultate der Sonderpadagogik finden em morphologisches Korrelat in tierexperimentellen Untersuchungen von Sytka und Aitkin (1981) sowie Ruben und Rapin (1980). Sie konnten unter anderem zeigen, da die Ausbildung funktionstuchtiger Synapsen in den Hörbahnkernen sowie der Hörrinde an die Aufnahme von Schalireizen im peripheren auditorischen System gebunden ist. Die Bedeutung der Frühdiagnostik kindlicher Hörstörungen wird auch durch die Untersuchungen von Downs (1984) unterstützt, wonach die statistische Häufigkeit auf 1: 1000 geschatzt wird, bei Risikokindern 1: 50.
Axial wave propagation and vibration of nonlocal nanorods with radial deformation and inertia

Longitudinal dynamic problems of nanorods or nanobars are analyzed based on the nonlocal elasticity theory and Bishop's assumptions. Radial deformation and inertia are considered. A governing equation for axial motion of circular nanorods is derived via Hamilton's principle. The phase speed of longitudinal waves is determined in explicit form and the dispersion curve is displayed. Exact frequency equations for clamped‐free, clamped‐clamped, and free‐free nanorods are obtained and mode shapes are derived. A unified approximation for low frequencies is given and compared with exact results. The Love theory of nonlocal rods is a special case of the present with shear stiffness vanishing. Classical Bishop and Love rod theories can be recovered only letting the size effect disappear. The simple nonlocal rod model is reduced if setting Poisson's ratio to zero. Illustrative examples of nanofibers and nanotubes are given to show the influence of the nonlocal scale parameter on the phase speed and the natural frequencies.
88.30 The invariance of the moment of inertia of magic squares

Magic squares are characterised by having the sum of the elements of all rows, columns, and main diagonals having the same sum. A new physical invariance for magic squares is reported for the moment of inertia of these squares which depends only on the order of the square. The numbers in the magic square are replaced by corresponding multiples of a unit mass placed on a square unit lattice. 1 Introduction Classical magic squares of the whole numbers, 1:::N, have the same line sum (magic constant) for each row, column, and main diagonals [1]: CN = N 2 (N + 1) (1) This line sum invariance depends only on the order, N , of the magic square. Here we report a second invariance which was found by considering the analogue of the physical moment of inertia of a square array of masses which are taken to be proportional to the numbers in the magic square. In the mathematical context this would be called the second moment. The smallest and earliest is the ancient Chinese 3 3 Lo-shu magic square of the sequence 1::9, with a magic constant of 15, as shown below: 4 9 2 3 5 7 8 1 6 (2) De ne the moment of inertia, IN , of a magic square of order N about an axis perpendicular to its centre by summing mr for each cell, where m is the
Effects of defect pixel correction algorithms for x-ray detectors on image quality in planar projection and volumetric CT data sets

In this study we compared various defect pixel correction methods for reducing artifact appearance within projection images used for computed tomography (CT) reconstructions. Defect pixel correction algorithms were examined with respect to their artifact behaviour within planar projection images as well as in volumetric CT reconstructions. We investigated four algorithms: nearest neighbour, linear and adaptive linear interpolation, and a frequency-selective spectral-domain approach. To characterise the quality of each algorithm in planar image data, we inserted line defects of varying widths and orientations into images. The structure preservation of each algorithm was analysed by corrupting and correcting the image of a slit phantom pattern and by evaluating its line spread function (LSF). The noise preservation was assessed by interpolating corrupted flat images and estimating the noise power spectrum (NPS) of the interpolated region. For the volumetric investigations, we examined the structure and noise preservation within a structured aluminium foam, a mid-contrast cone-beam phantom and a homogeneous Polyurethane (PUR) cylinder. The frequency-selective algorithm showed the best structure and noise preservation for planar data of the correction methods tested. For volumetric data it still showed the best noise preservation, whereas the structure preservation was outperformed by the linear interpolation. The frequency-selective spectral-domain approach in the correction of line defects is recommended for planar image data, but its abilities within high-contrast volumes are restricted. In that case, the application of a simple linear interpolation might be the better choice to correct line defects within projection images used for CT.
Laser diagnostics on atmospheric pressure discharge plasmas, including cryoplasmas, in environments around room and cryogenic temperature

Cryoplasmas, the plasma gas temperature (Tg) of which can be controlled continuously below room temperature, show various unique and advantageous properties depending on Tg. Recently, the Tg dependence of plasma chemistry related to metastable helium (Hem) has been revealed in helium cryoplasmas. However, Tg was only estimated by thermal calculation from the temperature outside the plasmas. In this study, for better evaluation of Tg, near-infrared laser heterodyne interferometry (NIR-LHI) measurements were conducted in atmospheric pressure helium pulsed discharge plasmas at around room and cryogenic ambient temperatures (Ta). The maximum difference between Tg and Ta was evaluated as 47 K at Ta = 300 K with 282 mW power consumption. To further investigate the Tg dependence of plasma chemical reactions related to Hem, laser absorption spectroscopy (LAS) was performed on the same discharge plasmas to measure the Hem density and lifetime. The Hem lifetime was longer at lower Tg, i.e. the lifetime at Tg = 145 K (9.6 µs) was seven times longer than that at Tg = 386 K (1.4 µs). By comparing the results with the numerically simulated rates of Hem quenching reactions taking Tg into account, the mechanism of the Hem quenching reaction was revealed to vary with Tg even though the main quenching reaction was a three-body collision at all Tg. In this manner, the combination of NIR-LHI with LAS led directly to the Tg dependence of Hem quenching reactions.