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Abstract The eruption of the Hunga-Tonga volcano in the South Pacific Ocean on January 15, 2022, at about 4:15 UTC, generated a violent explosion, which created atmospheric pressure disturbances in the form of Rayleigh-Lamb waves detected all over the globe. Here we discuss the observation of the Hunga-Tonga shock-wave performed at the Ny-Ålesund Research Station on the Spitsbergen island, by the detectors of the PolarquEEEst experiment and their ancillary sensors. Online pressure data as well as the results of dedicated offline analysis are presented and discussed in details. Results include wave arrival times, wave amplitude measurements and wave velocity calculation. We observed five passages of the shock wave with a significance larger than 3 $$\sigma$$ σ and an amplitude up to 1 hPa. The average propagation velocity resulted to be (308 ± 0.6) m/s. Possible effects of the atmospheric pressure variation associated with the shock-wave multiple passages on the cosmic-ray rate at ground level are also investigated. We did not find any significant evidence of this effect.

Muscle synergy analyses are used to enhance our understanding of motor control. Spatially fixed synergy weights coordinate multiple co-active muscles through activation commands, known as activation coefficients. To gain a more comprehensive understanding of motor learning, it is essential to understand how activation coefficients vary during a learning task and at different levels of movement proficiency. Participants walked on a line, a beam, and learned to walk on a tightrope—tasks that represent different levels of proficiency. Muscle synergies were extracted from electromyography signals across all conditions and the number of synergies was determined by the knee-point of the total variance accounted for (tVAF) curve. The results indicated that the tVAF of one synergy decreased with task proficiency, with the tightrope task resulting in the highest tVAF compared to the line and beam tasks. Furthermore, with increasing proficiency and after a learning process, trial-to-trial similarity increased and temporal overlap of synergy activation coefficients decreased. Consequently, we propose that precise adjustment and refinement of synergy activation coefficients play a pivotal role in motor learning. [ABSTRACT FROM AUTHOR]

A common theory of motor control posits that movement is controlled by muscle synergies. However, the behavior of these synergies during highly complex movements remains largely unexplored. Skateboarding is a hardly researched sport that requires rapid motor control to perform tricks. The objectives of this study were to investigate three key areas: (i) whether motor complexity differs between skateboard tricks, (ii) the inter-participant variability in synergies, and (iii) whether synergies are shared between different tricks. Electromyography data from eight muscles per leg were collected from seven experienced skateboarders performing three different tricks (Ollie, Kickflip, 360°-flip). Synergies were extracted using non-negative matrix factorization. The number of synergies (NoS) was determined using two criteria based on the total variance accounted for (tVAF > 90% and adding an additional synergy does not increase tVAF > 1%). In summary: (i) NoS and tVAF did not significantly differ between tricks, indicating similar motor complexity. (ii) High inter-participant variability exists across participants, potentially caused by the low number of constraints given to perform the tricks. (iii) Shared synergies were observed in every comparison of two tricks. Furthermore, each participant exhibited at least one synergy vector, which corresponds to the fundamental 'jumping' task, that was shared through all three tricks. [ABSTRACT FROM AUTHOR]

In the growing landscape of interest in natural surfactants, selecting the appropriate one for specific applications remains challenging. The extensive, yet often unsystematized, knowledge of microbial surfactants, predominantly represented by rhamnolipids (RLs), typically does not translate beyond the conditions presented in scientific publications. This limitation stems from the numerous variables and their interdependencies that characterize microbial surfactant production. We hypothesized that a computational recipe for biosynthesizing RLs with targeted applicational properties could be developed from existing literature and experimental data. We amassed literature data on RL biosynthesis and micellar solubilization and augmented it with our experimental results on the solubilization of triglycerides (TGs), a topic underrepresented in current literature. Utilizing this data, we constructed mathematical models that can predict RL characteristics and solubilization efficiency, represented as logPRL = f(carbon and nitrogen source, parameters of biosynthesis) and logMSR = f(solubilizate, rhamnolipid (e.g. logPRL), parameters of solubilization), respectively. The models, characterized by robust R2 values of respectively 0.581–0.997 and 0.804, enabled the ranking of descriptors based on their significance and impact—positive or negative—on the predicted values. These models have been translated into ready-to-use calculators, tools designed to streamline the selection process for identifying a biosurfactant optimally suited for intended applications. [ABSTRACT FROM AUTHOR]

In this paper, we propose a simple method for the modification of the unit cells in the lattice metamaterials that provides an improvement of their impact strength. The idea is based on the introduction of small mutual offsets of the interconnected struts inside the unit cells. In such way, the joints between the struts become asymmetric and the overall geometry of the unit cells can be defined as the quasi-cubic with the axis of chirality. Considering four types of cubic lattices with BCC, BCT, FCC and octahedron structures, we modified their geometry and investigated the influence of the offsets and the unit cell size on the overall performance in static and dynamic tests. From the experiments we found that the small offsets (less than the strut diameter) can allow to increase the impact strength of 3d-printed polymeric specimens in 1.5–3 times remaining almost the same density and static mechanical properties. Based on the numerical simulations, we show that the explanation of the observed phenomena can be related to the increase of plastic deformations and damage accumulation in the unit-cells with asymmetric joints leading to the transition from the quasi-brittle to the ductile type of fracture in tested specimens. [ABSTRACT FROM AUTHOR]

To prepare a reliable method for predicting the properties of devulcanized rubbers a nitrile rubber (NBR) compound was prepared and masticated before vulcanization for 0, 30 and 60 min under mechanical stress to prepare NBRs with different molecular weights. The masticated samples were vulcanized at different accelerator contents to prepare damples with different crosslink densities. The physical/mechanical/thermal properties (i.e. crosslink density, tensile strength, modulus, modulus at 100 and 300% elongation, elongation at break, hardness, curing behavior and molecular weight) of the samples were experimentally evaluated. In the next step, the prepared samples were assumed as devulcanized NBRs that underwent chains scission (masticated samples) or crosslinks breakage (vulcanized at different accelerator contents). On this basis, hypothetical devulcanization routes were considered between each sample that underwent chains scission or crosslinks breakage. Based on the results, numerical relationships between the number of chains scission or crosslinks breakage and decrease in the properties were obtained. Finally, the numerical reationships were used to calculate the properties of the samples that underwent both of chains scission and crosslinks breakage. It was found that the calculated contents of hardness, modulus at 100% and molecular weight (MZ) using the prepared method were very close to the evaluated ones. [ABSTRACT FROM AUTHOR]

Bone remodeling is an extraordinarily complex process involving a variety of factors, such as genetic, metabolic, and environmental components. Although genetic factors play a particularly important role, many have not been identified. In this study, we investigated the role of transmembrane 161a (Tmem161a) in bone structure and function using wild-type (WT) and Tmem161a-depleted (Tmem161aGT/GT) mice. Mice femurs were examined by histological, morphological, and bone strength analyses. Osteoblast differentiation and mineral deposition were examined in Tmem161a-overexpressed, -knockdown and -knockout MC3T3-e1 cells. In WT mice, Tmem161a was expressed in osteoblasts of femurs; however, it was depleted in Tmem161aGT/GT mice. Cortical bone mineral density, thickness, and bone strength were significantly increased in Tmem161aGT/GT mice femurs. In MC3T3-e1 cells, decreased expression of alkaline phosphatase (ALP) and Osterix were found in Tmem161a overexpression, and these findings were reversed in Tmem161a-knockdown or -knockout cells. Microarray and western blot analyses revealed upregulation of the P38 MAPK pathway in Tmem161a-knockout cells, which referred as stress-activated protein kinases. ALP and flow cytometry analyses revealed that Tmem161a-knockout cells were resistant to oxidative stress. In summary, Tmem161a is an important regulator of P38 MAPK signaling, and depletion of Tmem161a induces thicker and stronger bones in mice. [ABSTRACT FROM AUTHOR]

The negative impact of cigarette smoking on the skin includes accelerated aging, pigmentation disorders, and impaired wound healing, but its effect on the skin barrier is not completely understood. Here, we studied the changes in selected epidermal proteins and lipids between smokers (45–66 years, smoking > 10 years, > 10 cigarettes per day) and non-smokers. Volar forearm epidermal and stratum corneum samples, obtained by suction blister and tape stripping, respectively, showed increased thickness in smokers. In the epidermis of smokers, we observed a significant upregulation of filaggrin, loricrin, and a trend of increased involucrin but no differences were found in the case of transglutaminase 1 and kallikrein-related peptidase 7, on the gene and protein levels. No significant changes were observed in the major skin barrier lipids, except for increased cholesterol sulfate in smokers. Liquid chromatography coupled with mass spectrometry revealed shorter acyl chains in ceramides, and an increased proportion of sphingosine and 6-hydroxysphingosine ceramides (with C4 trans-double bond) over dihydrosphingosine and phytosphingosine ceramides in smokers, suggesting altered desaturase 1 activity. Smokers had more ordered lipid chains found by infrared spectroscopy. In conclusion, cigarette smoking perturbs the homeostasis of the barrier proteins and lipids even at a site not directly exposed to smoke. [ABSTRACT FROM AUTHOR]

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery., (© 2024. The Author(s).)

Digital restoration is a rapidly growing methodology within the field of heritage conservation, especially for early cinematic films which have intrinsically unstable dye colourants that suffer from irreversible colour fading. Although numerous techniques to restore film digitally have emerged recently, complex degradation remains a challenging problem. This paper proposes a novel vector quantization (VQ) algorithm for restoring movie frames based on the acquisition of spectroscopic data with a custom-made push-broom VNIR hyperspectral camera (380–780 nm). The VQ algorithm utilizes what we call a multi-codebook that correlates degraded areas with corresponding non-degraded ones selected from reference frames. The spectral-codebook was compared with a professional commercially available film restoration software (DaVinci Resolve 17) tested both on RGB and on hyperspectral providing better results in terms of colour reconstruction. [ABSTRACT FROM AUTHOR]

The eruption of the Hunga-Tonga volcano in the South Pacific Ocean on January 15, 2022, at about 4:15 UTC, generated a violent explosion, which created atmospheric pressure disturbances in the form of Rayleigh-Lamb waves detected all over the globe. Here we discuss the observation of the Hunga-Tonga shock-wave performed at the Ny-Ålesund Research Station on the Spitsbergen island, by the detectors of the PolarquEEEst experiment and their ancillary sensors. Online pressure data as well as the results of dedicated offline analysis are presented and discussed in details. Results include wave arrival times, wave amplitude measurements and wave velocity calculation. We observed five passages of the shock wave with a significance larger than 3 σ and an amplitude up to 1 hPa. The average propagation velocity resulted to be (308 ± 0.6) m/s. Possible effects of the atmospheric pressure variation associated with the shock-wave multiple passages on the cosmic-ray rate at ground level are also investigated. We did not find any significant evidence of this effect. [ABSTRACT FROM AUTHOR]

Workload Control (WLC) is a production planning and control system conceived to reduce queuing times of job-shop systems, and to offer a solution to the lead time syndrome; a critical issue that often bewilders make-to-order manufacturers. Nowadays, advantages of WLC are unanimously acknowledged, but real successful stories are still limited. This paper starts from the lack of a consistent way to assess performance of WLC, an important burden for its acceptance in the industry. As researchers often put more focus on the performance measures that better confirm their hypotheses, many measures, related to different WLC features, have emerged over years. However, this excess of measures may even mislead practitioners, in the evaluation of alternative production planning and control systems. To close this gap, we propose quantifying the main benefit of WLC in economic terms, as this is the easiest, and probably only way, to compare different and even conflicting performance measures. Costs and incomes are identified and used to develop an overall economic measure that can be used to evaluate, or even to fine tune, the operating features of WLC. The quality of our approach is finally demonstrated via simulation, considering the 6-machines job-shop scenario typically adopted as benchmark in technical literature. [ABSTRACT FROM AUTHOR]

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle 'metabolon' which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was present together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways. [ABSTRACT FROM AUTHOR]

The specific role of the various pathogens causing cardiac implantable electronic devices-(CIEDs)-related infections requires further understanding. The data of 1241 patients undergoing transvenous lead extraction because of lead-related infective endocarditis (LRIE-773 patients) and pocket infection (PI-468 patients) in two high-volume centers were analyzed. Clinical course and long-term prognosis according to the pathogen were assessed. Blood and generator pocket cultures were most often positive for methicillin-sensitive Staphylococcus aureus (MSSA: 22.19% and 18.13% respectively), methicillin-sensitive Staphylococcus epidermidis (MSSE: 17.39% and 15.63%) and other staphylococci (11.59% and 6.46%). The worst long-term prognosis both in LRIE and PI subgroup was in patients with infection caused by Gram-positive microorganisms, other than staphylococci. The most common pathogens causing CIED infection are MSSA and MSSE, however, the role of other Gram-positive bacteria and Gram-negative organisms is also important. Comparable, high mortality in patients with LRIE and PI requires further studies. [ABSTRACT FROM AUTHOR]

Over the years, an amount of models relying on effective parameters were implemented in the challenging issue of the topside ionosphere description. These models are based on different analytical functions, but all of them depend on a parameter called effective scale height, that is deduced from topside electron density measurements. As their names state, they are effective in reproducing the topside electron density profile only when applied to the analytical function used to derive them. Then, in principle, they do not have any physical meaning. It is the goal of this paper to mathematically link the effective scale height modeled through the Epstein layer to the vertical scale height theoretically deduced from the plasma ambipolar diffusion theory. Firstly, effective and theoretical scale heights are linked through a mathematical relation by showing that they tend to each other in the topside ionosphere. Secondly, their connection is preliminarily demonstrated by calculating effective scale height values from the entire COSMIC/FORMOSAT-3 radio occultation dataset. Thirdly, a possible connection between the vertical gradient of the topside scale height (as obtained by COSMIC/FORMOSAT-3 satellites) and the electron temperature (as obtained by ESA Swarm B satellite) is studied by highlighting corresponding similarities in the diurnal, seasonal, solar activity, and latitudinal variability. [ABSTRACT FROM AUTHOR]

The high plasticity of metallic glasses is highly desirable for a wide range of novel engineering applications. However, the physical origin of the ductile/brittle behaviour of metallic glasses with various compositions and thermal histories has not been fully clarified. Here we have found that metallic glasses with compositions at or near intermetallic compounds, in contrast to the ones at or near eutectics, are extremely ductile and also insensitive to annealing-induced embrittlement. We have also proposed a close correlation between the element distribution features and the plasticity of metallic glasses by tracing the evolutions of the element distribution rearrangement and the corresponding potential energy change within the sliding shear band. These novel results provide useful and universal guidelines to search for new ductile metallic glasses at or near the intermetallic compound compositions in a number of glass-forming alloy systems. [ABSTRACT FROM AUTHOR]

Magnesium-based bulk metallic glasses (BMG) have potential in applications ranging from biomedical to sports equipment and the Mg-Cu-Y system offers some of the most promising alloys. Phase relations and ternary solubility of the binary and ternary compounds of this system have been experimentally investigated. The Isothermal section of Mg-Cu-Y system at 673 K for the entire composition range has been constructed. Phase relations in the Cu-rich (>66 at.% Cu) region of the Mg-Cu-Y system has been determined for the first time. The homogeneity range of three ternary compounds has been determined. Solidifications behavior of several key alloys have been discussed based on the differential scanning calorimetry (DSC) experiments and thermodynamic calculations. Extensive analysis of the DSC curves has been carried out to relate them to the corresponding phase transformation reactions and temperatures. Some of the most promising metallic glass forming regions have been analyzed using thermodynamic calculations. [ABSTRACT FROM AUTHOR]

Adoptive transfer of allogeneic natural killer (NK) cells is becoming a credible immunotherapy for hematological malignancies. In the present work, using an optimized expansion/activation protocol of human NK cells, we generate expanded NK cells (eNK) with increased expression of CD56 and NKp44, while maintaining that of CD16. These eNK cells exerted significant cytotoxicity against cells from 34 B-CLL patients, with only 1 sample exhibiting resistance. This sporadic resistance did not correlate with match between KIR ligands expressed by the eNK cells and the leukemic cells, while cells with match resulted sensitive to eNK cells. This suggests that KIR mismatch is not relevant when expanded NK cells are used as effectors. In addition, we found two examples of de novo resistance to eNK cell cytotoxicity during the clinical course of the disease. Resistance correlated with KIR-ligand match in one of the patients, but not in the other, and was associated with a significant increase in PD-L1 expression in the cells from both patients. Treatment of one of these patients with idelalisib correlated with the loss of PD-L1 expression and with re-sensitization to eNK cytotoxicity. We confirmed the idelalisib-induced decrease in PD-L1 expression in the B-CLL cell line Mec1 and in cultured cells from B-CLL patients. As a main conclusion, our results reinforce the feasibility of using expanded and activated allogeneic NK cells in the treatment of B-CLL. [ABSTRACT FROM AUTHOR]

Ultrafast optical reflectivity measurements of silicon, germanium, and gallium arsenide have been carried out using an advanced set-up providing intense subpicosecond pulses (35 fs FWHM, λ = 400 nm) as a pump and broadband 340–780 nm ultrafast pulses as a white supercontinuum probe. Measurements have been performed for selected pump fluence conditions below the damage thresholds, that were carefully characterized. The obtained fluence damage thresholds are 30, 20.8, 9.6 mJ/ cm 2 for Si, Ge and GaAs respectively. Ultrafast reflectivity patterns show clear differences in the Si, Ge, and GaAs trends both for the wavelength and time dependences. Important changes were observed near the wavelength regions corresponding to the E 1 , E 1 + Δ singularities in the joint density of states, so related to the peculiar band structure of the three systems. For Ge, ultrafast reflectivity spectra were also collected at low temperature (down to 80 K) showing a shift of the characteristic doublet peak around 2.23 eV and a reduction of the recovery times. [ABSTRACT FROM AUTHOR]

Understanding of the processes of petroleum source rock (SR) accumulation in lacustrine rift basins and the behavior of lake systems as long-term carbon sinks is fragmentary. Investigation of an 800 m thick (500 m core and ~ 300 m outcrop), deep-lacustrine, Oligocene section in Vietnam, provides a rare insight into the controls and deposition of organic carbon (OC) and SR formation in continental rift basins. A multidisciplinary dataset, combining elemental data, inorganic and organic geochemistry with sedimentology, shows that the richest alginite-prone, sapropelic SR developed during periods of relative tectonic quiescence characterized by moderate primary productivity in a mainly dysoxic lacustrine basin. Increased rift activity and further development of graben morphology intensified water column stratification and anoxia, which hindered nutrient recycling. Sapropelic organic matter (OM) continued to accumulate, but with increasing amorphous OM content and decreasing total OC values. Periods of increased seasonality were characterized by thermocline weakening, enhanced mixing of water columns, increased primary productivity and diatom blooming. The results suggest that a change from dysoxia towards anoxia or extreme primary productivity does not necessarily enhance OC burial and SR quality. External nutrient input from a phosphate-rich hinterland is sufficient for sapropel formation, whereas the main limiting factor is methanogenesis. [ABSTRACT FROM AUTHOR]

Earlier we introduced the concept of 'nanochemoprevention' i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome. [ABSTRACT FROM AUTHOR]

The Fermi level position in (Ga,Mn)N has been determined from the period-analysis of GaN-related Franz-Keldysh oscillation obtained by contactless electroreflectance in a series of carefully prepared by molecular beam epitaxy GaN/Ga1−xMnxN/GaN(template) bilayers of various Mn concentration x. It is shown that the Fermi level in (Ga,Mn)N is strongly pinned in the middle of the band gap and the thickness of the depletion layer is negligibly small. For x > 0.1% the Fermi level is located about 1.25-1.55 eV above the valence band, that is very close to, but visibly below the Mn-related Mn2+/Mn3+ impurity band. The accumulated data allows us to estimate the Mn-related band offsets at the (Ga,Mn)N/GaN interface. It is found that most of the band gap change in (Ga,Mn)N takes place in the valence band on the absolute scale and amounts to −0.028 ± 0.008 eV/% Mn. The strong Fermi level pinning in the middle of the band gap, no carrier conductivity within the Mn-related impurity band, and a good homogeneity enable a novel functionality of (Ga,Mn)N as a semi-insulating buffer layers for applications in GaN-based heterostuctures. [ABSTRACT FROM AUTHOR]

We report on an operando XPS investigation of a GaN diode, by recording the Ga2p3/2 peak position under both forward and reverse bias. Areal maps of the peak positions under reverse bias are completely decoupled with respect to doped regions and allow a novel chemical visualization of the p-n junction in a 2-D fashion. Other electrical properties of the device, such as leakage current, resistivity of the domains are also tapped via recording line-scan spectra. Application of a triangular voltage excitation enables probing photoresponse of the device. [ABSTRACT FROM AUTHOR]

PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on PD4. This finding was confirmed by in vitro studies showing that RAX knockdown impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated migration required its third motif and was independent of PKR. PACT/RAX interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the FAK phosphorylation in CGNs. These findings demonstrated a novel function of PACT/RAX in the regulation of neuronal migration. [ABSTRACT FROM AUTHOR]