Artificial Intelligence (AI) models are expected to have a great impact in the manufacturing industry, optimizing time and resource cost by enabling applications such as predictive maintenance (PM) of production machines. A necessary condition for this is the availability of high quality data collected as close as possible to the process in question. With the advent of 5G equipped multi sensor platforms (MSPs), high sampling rate data can be collected and transmitted for processing in real time. This poses a data security challenge, since this data may give valuable insight into confidential business information of companies. Federated learning (FL) enables the training of AI models with data from multiple sources without it leaving the shop floor, by utilizing distributed computing resources available on premise. This paper introduces an architecture of FL based on data collected from 5G MSPs for enabling PM in industrial environments and discusses its potential benefits and challenges.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

Text fields in electronic medical records (EMR) contain information on important factors that influence health outcomes, however, they are underutilized in clinical decision making due to their unstructured nature. We analyzed 6,497 inpatient surgical cases with 719,308 free text notes from Le Bonheur Children’s Hospital EMR. We used a text mining approach on preoperative notes to obtain the text-based risk score algorithm as predictive of death within 30 days of surgery. We studied the additional performance obtained by including text-based risk score as a predictor of death along with other structured data based clinical risk factors. The C-statistic of a logistic regression model with 5-fold cross-validation significantly improved from 0.76 to 0.92 when text-based risk scores were included in addition to structured data. We conclude that preoperative free text notes in EMR include significant information that can predict adverse surgery outcomes.

To show that underlying Schmitt's account of fascist politics lies a Gnostic-like metaphysical dualism separating the realms of value and power. Contrary to the normative political tradition of the West, which defends an ethical politics, Schmitt - jurist and theorist of the Nazis - aligns himself with Machiavelli and Hobbes to defend realpolitik: where sovereignty is ultimately a function of the Dictator's will alone. This paper shows the contradiction within such a position, which criticizes values in politics but by its advocacy, and its defense of the Dictator's willing, relies on valuation, choice, and hence the ethical.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

The complete-lattice approach to optimization problems with a vector- or even set-valued objective already produced a variety of new concepts and results and was successfully applied in finance, statistics and game theory. For example, the duality issue for multi-criteria and vector optimization problems could be solved using the complete-lattice approach, compare [11]. So far, it has been applied to set-valued dynamic risk measures (in the stochastic case), as discussed in Feinstein, Rudloff etc. (see [11], for example), but it has not been applied to deterministic calculus of variations and optimal control problems. In this paper, the following problem of set-valued optimization is considered: minimize the functional $$ \overline J_t[y]=\int_0^t \overline L(s,y(s),\dot y(s))\ ds + U_0(y(0)) $$ over all admissible arcs $y$, where $\overline L$ is the associated multifunction to a vector-valued Lagrangian $L$, the integral is in the Aumann sense and $U_0$ is the initial cost. A new concept of \emph{value function}, for which a Bellman's optimality principle holds, is introduced. Also the classical result of the Hopf-Lax formula holds for the generalized value function. Finally, a derivative with respect to the time $t$ and a directional derivative with respect to $x$ of the value function are defined, based on ideas close to the concepts in [12]. The value function is proved to be solution of a suitable Hamilton-Jacobi equation.

Post-acute COVID-19 vaccination syndrome (PACVS) is distinguished from the normal post-vaccination state by altered receptor antibodies (Semmler et al. Vaccines 2023, 11, 1642). Here, we explore the symptoms registry and standard serum markers acquired in the above study to delineate the disease phenotype of PACVS. Symptoms reported by the participants overlapped with established complex dysautonomia syndromes (ME/CFS, POTS, MCAS, SFN). However, many participants were qualified for several (131/191) or none (31/191) of these syndromes. Unbiased clustering (modified Jaccard index) revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (> 80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, vasomotor dysfunction, (ii) cardiovascular impairment, and (iii) cognitive impairment, headache, optic, oculo-motoric and acoustic dysfunctions were also frequently represented. Conspicuous serum markers encompassed increases in interleukins 6 and 8 and low fT3 levels (> 80%), IgG-subclass imbalances and impaired iron-storage (> 50%), and increases in sNFL (> 30%). Serum markers were not correlated to specific symptoms or symptom clusters. A single and unique cause (i. e. SARS-CoV-2 vaccination) is improbable to trigger several distinct etiologies. Therefore, the symptoms and serological features observed in our study cohort probably represent facets of a single complex syndrome.

The increased adoption of information and communication technology for smart grid applications will require innovative cyber-physical system (CPS) testbeds to support research and education in the field. The groundbreaking CPS testbeds with realistic and scalable platforms have progressively gained interest in recent years, with electric power flowing in the physical layer and information flowing in the network layer. However, CPSs are critical infrastructures and not designed for testing or direct training, as any misbehaving in an actual system operation could cause a catastrophic impact on its operation. Based on that, it is not easy to efficiently train professionals in CPSs. Aiming to support the advancement and encourage the training of industry professionals, this paper proposes and develops a complete testbed with commercial tools. The testbed can reliably replicate the performance of smart grid systems and the main potential cyber threats that electric grids may face. The complex interdependencies between the cyber and physical domains are discussed in detail, and different case scenarios are presented, providing insightful guidelines for key features and design decisions for future smart grid testbeds.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Lack of physical activity participation for adults with a disability remain a large public health concern. For those with existing, or newly acquired disability, increased sedentary behavior stemming from physical impairments often results in the development of secondary chronic health conditions (e.g., obesity or osteoarthritis) which leads to participation restrictions within major life roles. Without intervention these secondary conditions further increase physical impairment which, in turn, sets these populations up for continuous negative health trajectories over their remaining lifespan. Physical activity can attenuate the development of secondary health conditions and optimize health outcomes within these populations. However, those with disability often do not possess the necessary physical capacity to maintain physically active lifestyles. Therefore, exercise programs specifically designed to increase physical functioning have been identified as a necessary intermediate step to reduce physical limitations prior to adoption of physically active lifestyles. Adoption of exercise program participation remains a difficult task for both the general population and those with disability alike. Based on current rates of physical inactivity, it is clear that traditional health behavior change models do not adequately address the complexity of this issue. This paper highlights some of the limitations within the current health behavior change models as they relate to exercise behavior. Additionally, a novel conceptual framework is presented for the intent of its incorporation within research and health promotion interventions targeting exercise behavior within disability populations.

A model of space-time is presented, whose origin is set before the appearance of any universe. It uses concepts of previous work, a central one being that the information about the laws of nature is stored locally everywhere in space such that all physical processes obey them. Since information storage is bound to matter or energy, space is assumed to consist of dark energy (DE), which thus assumes an importance far beyond its function as a stopgap for an energy deficit in our universe ( U ). The primordial state (PS) is a timeless and relatively large space of 3 dimensions described by a Wheeler DeWitt (WDW) equation, whose solution is interpreted as an arrangement of very many space quanta and possesses properties that remind of the time-honored concept of the unmoved mover. The comparison of WDW solutions belonging to different mass densities of the DE favors one in which the space quanta are mini black holes. This allows the space quanta to be imagined as mass points which are kept at a distance compatible with the quantum volume by the Pauli principle or something equivalent. Triggered by a dramatic increase in probability, the PS is followed by a time-controlled sequence of quantized expansion states (ES i ). The concomitant emergence of time occurs in a lightning huge crash, consuming almost all DE of the PS. The subsequent quantized ES i emerge from a WDW equation, novelly derived from a solution of the modified cosmic momentum equation, which classically describes an exponential space expansion (CS). The huge volme of the ES i is also used as size of the PS. Information is assumed to be geometrically stored in arrangements of space quanta similar to how genetic information is stored in DNA molecules. During the CS information must be transferred from already existing "information quanta" to new ones. This requires time, slows down the expansion and is taken into account by a friction term in the cosmological momentum equation thus modified. Since the Friedmann-Lemaître (FL) equation remains fully valid, the model is widely based on recognized equations, so that some results may be understood as interpretations.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

A time-sequential working, spatially multiplexed autostereoscopic 3D display design consisting of a fast switchable RGB-color filter array is presented. The wavelength-selective filter barrier emits the light from a display over a larger active area than common autostereoscopic barrier displays. An optical modelling of wavelength-selective barriers has been used for instance to calculate the light ray distribution properties of that arrangement. To find well working display designs, automated searches by simulation and computational evaluation has been proceeded. Wavelength-selective filter barrier arrangements exhibit characteristics different from common barrier displays with similar barrier pitch and ascent. In particular, these constructions show strong angular luminance dependency under barrier inclination specified by correspondent slant angle. In time-sequential implementation it is important to avoid that quick eye or eyelid movement lead to visible color artifacts. In the millisecond regime tunable liquid crystal Fabry-Pérot color filters for the colors red, green and blue are presented. They consist of a sub-micrometer thick nematic layer sandwiched between dielectric mirrors and ITO-electrodes. These cells shall switch narrow-banding light of red, green or blue. An array for a glasses-free 3D display has to be equipped with several thousand switchable filter elements having different color apertures. The newly introduced design is usable as a multi user display as well as a single user system with user adaptive control.

Introducing the Moving Least-Squares Aided Finite Element Method (MLS-FEM), we present a robust computational technique that effectively evaluates the development of mixing in polymeric mixing devices. Our approach uses the Moving Least-Squares (MLS) interpolant to enhance the classic finite element shape functions. As a result, it becomes possible to treat fixed or moving components, such as rotors of a mixer, as discontinuities within the flow domain. This allows analysis of the flow field with a background mesh independent of the rotors' shape, orientation, and position. We compared the MLS-FEM results with the classical boundary-fitted mesh FEM, which comprises the mesh regeneration steps by the movement of the rotors. We then showed that the new method provides accurate results for the flow field parameters (i.e., the velocity components and the pressure values) and the mixing evolution without requiring mesh regeneration and without compromising accuracy.

In common model testing practise, the measured values of the self propulsion test are split into the characteristics of the hull, the propeller and into the interaction factors. These coefficients are scaled separately to the respective full scale values and subsequently reassembled to give the power prediction. The accuracy of this power prediction depends {\em inter alia} on the accuracy of the measured values and the scaling procedure. An inherent problem of this approach is, that it is virtually impossible to verify each single step, because of the complex nature of the underlying problem. In recent years the scaling of the open-water characteristics of propeller model tests attracted a renewed interest, fuelled by competitive tests, which became the norm due to requests of the customer. This paper will show the influence of different scaling procedures on the predicted power. The prediction is compared to the measured trials data and the quality of the prediction will be judged. The procedures examined are the standard ITTC~1978 procedure plus derivatives of it: the Meyne, the strip method and the βᵢ-method.

Experimental test facilities are generally characterised using linear transfer functions to relate the wavemaker forcing amplitude to wave elevation at a probe located in the wavetank. Second and third order correction methods are becoming available but are limited to certain ranges of waves in their applicability. Artificial intelligence has been shown to be a suitable tool to find even highly nonlinear functional relationships. This paper reports on a numerical wavetank implemented using the OpenFOAM software package which is characterised using artificial intelligence. The aim of the research is to train neural networks to represent non-linear transfer functions mapping a desired surface-elevation time-trace at a probe to the wavemaker input required to create it. These first results already demonstrate the viability of the approach and the suitability of a single setup to find solutions over a wide range of sea states and wave characteristics.

Recycling information can be complex and often confusing which may subsequently reduce the participations in any waste recycling schemes. As a result, this research explored the roles as well as the importance of a holistic approach in designing recycling information using 15 expert-based in-depth interviews. The rationale was to offer a better understanding of what constitutes waste, recycling, and how recycling information should be designed and presented to make recycling more attractive/convenient. Based on the research participants’ perceptions with supports from the existing studies, this research sub-categorised recycling information into three different themes, termed the “WWW” of recycling information components. As a result, these components (or attributes) were extensively described (using findings of semi-structured interviews) to elicit pragmatic guidance for practitioners, policy-makers, and other stakeholders in designing structured communication or information strategies that may simplify and subsequently increase waste-recycling practices. The policy implications of holistic information in enhancing recycling are further discussed.

Abstract: Yeast – especially Saccharomyces cerevisiae – have long been a preferred workhorse for the production of numerous recombinant proteins and other metabolites. S. cerevisiae is a noteworthy aroma compound producer, and has also been exploited to produce foreign bioflavour compounds. In the past few years, important strides have been made in unlocking the key elements in the biochemical pathways involved in the production of many aroma compounds. The expression of these biochemical pathways in yeast often involves the manipulation of the host strain to direct the flux towards certain precursors needed for the production of the given aroma compound. This review highlights recent advances in the bioengineering of yeast – including S. cerevisiae – to produce aroma compounds and bioflavours. To capitalise on recent advances in synthetic yeast genomics, this review presents yeast as a significant producer of bioflavours in a fresh context and proposes new directions for combining engineering and biology principles to improve the yield of targeted aroma compounds.

Although work events can be regarded as pivotal elements of organizational life, only a few studies have examined how positive and negative events relate to and combine to affect work engagement over time. Theory suggests that to better understand how current events affect work engagement (WE), we have to account for recent events that have preceded these current events. We present competing theoretical views on how recent and current work events may affect employees (e.g., getting used to a high frequency of negative events or becoming more sensitive to negative events). Although the occurrence of events implies discrete changes in the experience of work, prior research has not considered whether work events actually accumulate to sustained mid-term changes in WE. To address these gaps in the literature, we conducted a week-level longitudinal study across a period of 15 consecutive weeks among 135 employees, which yielded 849 weekly observations. While positive events were associated with higher levels of WE within the same week, negative events were not. Our results support neither satiation nor sensitization processes. However, high frequencies of negative events in the preceding week amplified the beneficial effects of positive events on WE in the current week. Growth curve analyses show that the benefits of positive events accumulate to sustain high levels of WE. WE dissipates in the absence of continuous experience of positive events. Our study adds a temporal component and informs research that has taken a feature-oriented perspective on the dynamic interplay of job demands and resources.

Interactions between mobile robots and human operators in common areas require a high safety especially in terms of trajectory planning, obstacle avoidance and mutual cooperation. In this connection the crossings of planned trajectories, their uncertainty based on model fluctuations, system noise and sensor noise,play an outstanding role. This paper discusses the calculation of expected areas of interactions du ring human-robot navigation with respect to fuzzy and noisy information. Expected crossing points of possible trajectories are nonlinearily associated with positions and orientations of robot and human. The nonlinear transformation of a noisy system input, such as directions of motion of human and robot, to a system output, the expected area of intersection of their trajectories, is done by two methods: statistical linearization and the sigma-point-transformation. For both approaches fuzzy approximations are presented and the inverse problem is discussed where the input distribution parameters are computed from given output distribution parameters.

With increasing concerns over environmental impact, and overall health of both the environment and its people, a need to quantify contaminants is of the utmost importance. Chemosensors with low detection limits and relative ease of application can address this challenge. Nitrite ions are known to be detrimental to both the environment and human health. A new colorimetric chemodosimeter has been prepared from a homolytic photochemical cleavage of a reaction between pyrrole and pyridine. The product, 4(pyrrol1-yl)pyridine, yields a limit of detection of 0.330 (±0.09) ppm for the detection of nitrite in aqueous solution, employing a colorimetric change from yellow to pink. It is also highly selective for nitrite when various competitive anions such as SO32- , NO3-, PO43-, SO4-2, Cl-, F-, I-, Br-, and CN- are present in great excess. The molecule’s especially high sensitivity to nitrite is apparently the result of a complex supramolecular mechanism, characterized by both dynamic light scattering of the aggregate and the Tyndall effect. Consequently, this new sensor provides a simple, low-cost way to rapidly detect nitrite anions in aqueous solution.

Pteridine reductase 1 is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of Dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of TbDHFR and TbPTR1 has implications in the exploitation of anti-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to Molecular dynamics to characterize their molecular interactions and energetics followed by in vitro testing. In this study, we identified five potential TbPTR1 inhibitors that showed low micromolar Trypanosome growth inhibition in in vitro experiments with no significant human cell cytotoxicity. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Our results provide a basis for scaffold optimization for further studies in the development of HAT antifolates.

Smart air filters are beneficial to provide highly efficient particle removal, treat multiple contaminants simultaneously and conserve energy during air filtration processes. Herein, a type of self-supporting smart air filter (SSSAF) was fabricated by sandwiching the VOC-responsive PZT/PVDF electrospun membrane with two metal mesh electrodes. Besides the high filtration efficiency for sub-micron particles, the SSSAF showed good responses to pressure drop in the range of 0 to 500 Pa via the electroactivity of PZT/PVDF membrane. In addition, the SSSAF achieved VOC sensing function via the swelling properties of PZT/PVDF membrane in organic vapors, demonstrated by its signal to 50 to 200 ppm ethanol gases. The SSSAF based nanogenerator was employed to harvest wind energy, which was further applied to inhibit bacterial growth without the need of additional power input. The results provide new insight into development of all-in-one smart air filters.

The role of Black Carbon (BC) as a contributor to glacial retreat is of particular interest to the scientific community and decision makers, due to its impact on snow albedo and glacier melt. In this study, a thermal-optical instrument (LAHM) was used to measure effective Black Carbon (eBC) in a series of surface snow samples collected from the Vallunaraju glacier, Cordillera Blanca, between April 2019 and May 2020. The time series obtained indicates a marked seasonal variability of eBC with maximum concentrations during the dry season and dramatic decrease during the wet season. The concentrations detected ranged between a minimum of 3.73 ng/g and 4.23 ng/g during the wet season and a maximum of 214.13 ng/g and 181.60 ng/g during the dry season, in the accumulation and ablation zone. Using SNICAR model, the reduction of albedo was estimated at 6.36% and 6.60% during the dry season and 0.68% and 0.95% during the wet season, which represents an average radiative forcing of 4.52 ± 1.84 W/m2 and 4.69 ± 1.59 W/m2 in the accumulation zone, and 0.49 ± 0.27 W/m2 and 0.68 ± 0.43 W/m2 in the ablation zone. The melting of snow due to the eBC translates into 80.18 ± 37.30 kg/m2 and 83.16 ± 32.75 kg/m2 during the dry season, and 7.91 ± 4.29 kg/m2 and 10.85 ± 6.62 kg/m2 during the wet season, in the accumulation and ablation zones, respectively. Finally, the HYSPLIT trajectory assessment shows that aerosols predominate in the Amazon rainforest, especially when forest fires are most abundant according to VIIRS images.

Abstract. Background: This paper investigates the propagation of behaviorally transmitted traits with negative effect on host fitness. Methods: We analyze equilibrium between genetically transmitted and behaviorally transmitted competing propagators and consider whether a behavioral propagator is linked to reproduction (e.g. vertical culture transmission), or not. We employ combined genetic and behavior-induced fitness components for hosts, while behavioral propagators have replication factors to distinguish from what’s good for the host (fitness). Results: A trait which spreads faster than its marginal host fitness contribution reduces population will establish itself. The often transient nature of laterally transmitted traits may be a defense against accumulation of deleterious traits. Laterally transmitted traits with high spreading rate often do not equalize with genetic traits, spreading outside natural selection of the hosts. Vertical transmission reduces replication rate and allows group selection against deleterious behaviorally transmitted traits. Competing mutually exclusive propagators contribute to inequality and altruism, but compete through adverse fitness since exclusivity assumes low conversion. Conclusion: Behaviorally transmitted traits, in some cases a tremendous advantage, may also be a significant problem in the development of societies.

Trends such as Industrial Internet of Things (IIoT) and Industry 4.0 have increased the need to use powerfull network technologies in industrial automation. The growing communication in industrial automation is harnessing the productivity and efficiency of manufacturing and process automation with minimum human intervention. Due to the ongoing evolution of industrial networks from Fieldbus technologies to Ethernet, the new opportunity has emerged to integrate the Software Defined Networking (SDN) technique. In this paper, we provide a brief overview of SDN in the domain of industrial automation. We propose a network architecture called Software Defined Industrial Automation Network (SDIAN), with the objective of improving network scalability and efficiency. To match the specific considerations and requirements of having a deterministic system in an industrial network, we propose two solutions for flow creation: Pro-active Flow Installation Scheme (PFIS) and Hybrid Flow-Installation Scheme (HFIS). We analytically quantify the proposed solutions in alleviating the overhead incurred from the flow setup cost. The analytical model is verified through monte carlo simulations. We also evaluate the SDIAN architecture and analyze the network performance of the modified topology using an emulator called Mininet. We further list and motivate SDIAN features and in particular report on an experimental food processing plant demonstration featuring Raspberry PIs (RPIs) instead of traditional Programmable Logic Controllers (PLCs). Our demonstration exemplifies the characteristics of SDIAN.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

We cultured Parmelina carporrhizans and P. quercina in Corn Meal Agar and 0.2% glucose Malt Yeast Agar for 160 days. Chemosyndrome of natural thalli and mycobiont cultures were analyzed by HPLC. Lecanoric acid, atranorin, chloratranorin and ergosterol were detected in P. carporrhizans thalli, while lecanoric acid, chloratranorin and aliphates were found in P. quercina thalli. The secondary methabolites pattern between thalli and mycobiont culture was completely different in both species. Both species secreted the phenalenone myeloconone C in culture media and was also detected in P. quercina mycobiont aggregates. Interestingly, the phenolic compounds produced by the mycobiont culture of P. carporrhizans are related to those produced by natural thallus by the same biosynthetic pathway, while the chemosyndrome of P. quercina mycobiont implies switch of biosynthetic pathway from acetate-polymalonate pathway to shikimic acid pathway, with pulvinic acid as major compound of mycobiont culture. The role of Myelochonone C, confluentic acid and pulvinic acid produced by mycobiont culture is discussed as possible adaptive vantage in field as photoprotective agent or as byproduct result of stressing artificial culture conditions.

The utilization of wind energy has become increasingly popular in the United States and many European countries due to its abundant natural source and optimized design. While existing wind turbines are predominantly large-scale and not suitable for standalone or distributed power production, Lubbock County in West Texas offers a diverse range of renewable energy options to meet its energy needs. The region relies heavily on utility-scale wind energy sources to supply power to the Texas Grid, replacing conventional fossil fuel-based systems. Currently, standalone solar PV systems are the preferred choice for renewable energy generation. However, West Texas possesses an ample supply of wind energy that can be harnessed to establish a microgrid and provide standalone power to rural communities. By employing the latest technology and optimizing efficiency, even in low-scale generation, a 6 kW permanent magnet alternator-based distributed wind turbine has been designed. This paper focuses on analyzing the techno-economic aspects of implementing this wind turbine in a real-world scenario, taking into account wind attributes such as velocity and available power at the specific location.

Fourier transform infrared (FTIR) absorption spectroscopy of cold molecules and clusters in supersonic slit jet expansions complements and extends more sensitive action spectroscopy techniques and provides important reference data for the latter. We describe how its major drawback, large substance and carrier gas consumption, can be alleviated by one to two orders of magnitude via direct and continuous recycling of the gas mixture. This is achieved by a combination of dry rotary lobe and screw pump compression. The signal-to-noise ratio is boosted by the established buffered giant gas pulse technique with full interferogram synchronization. The buildup of water impurities typically limits the recycling gain, but is turned into a feature for the study of hydrate complexes of volatile molecules. Continuous operation with a single gas filling over several days becomes practical and useful. Decadic absorbances in the low ppm range are detectable and the mid infrared range can be recorded simultaneously with the near infrared. The less straightforward hydration number assignment of spectral features in direct absorption spectroscopy is supported by a gradual water buildup at a rate of less than 0.5 mg/h. A recent reassignment proposal for the water dimer OH stretching spectrum is refuted and vibrational spectra of vacuum-isolated 18O-water clusters are presented for the first time. Methanol docking on asymmetric ketones is used to illustrate the advantages and limitations of the recycling concept. Previous assignments of the hydrate complex of 1-phenylethanol are confirmed. Additional features of the setup await testing and refinement, but the recycling technique already substantially widens the applicability of direct absorption spectroscopy of neutral molecular clusters. It may be attractive for other high-throughput jet spectrometers.

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env. To investigate the role of sulfation for this complex, we modeled the sulfation of Tyr100H and compared the dynamics and energetics of the modified and unmodified complex by atomistic molecular dynamics simulations. Our results show that sulfation does not affect the overall conformation of CDRH3, but still enhances gp120 interactions both at the site of mutation and for the neighboring residues. This stabilization affects not only protein-protein contacts, but also the interactions between PG16 and the gp120 glycan shield. Further, we also investigated whether PG16-CDRH3 is a suitable template for the development of peptide mimetics. For a peptide spanning residues 93-105 of PG16 we obtained an experimental EC50 value of 3nM for the binding of gp120 to the peptide. This affinity can be enhanced by almost one order of magnitude by artificial disulfide bonding between residues 99 and 100F. In contrast, any truncation results in significantly lower affinity, suggesting that the entire peptide segment is involved in gp120 recognition. Their high affinity makes PG16-derived peptides useful building blocks for further optimization to obtain a potent inhibitor that efficiently blocks HIV-1 infection.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

The optimization of photovoltaic (PV) systems is vital for enhancing efficiency and economic viability, especially under Partial Shading Conditions (PSCs). This study focuses on the development and comparison of traditional and advanced algorithms, including Perturb and Observe (P&O), Incremental Conductance (IC), Fuzzy Logic Control (FLC), Grey Wolf Optimization (GWO), Particle Swarm Optimization (PSO), and Artificial Neural Networks (ANN), for efficient Maximum Power Point Tracking (MPPT). Simulations conducted in MATLAB/SIMULINK evaluated these algorithms’ performance under various shading scenarios. The results indicate that while traditional methods like P&O and IC are effective under uniform conditions, advanced techniques, particularly ANN-based MPPT, exhibit superior efficiency and faster convergence under PSCs. The study concludes that integrating AI and ML into MPPT algorithms significantly enhances the reliability and efficiency of PV systems, paving the way for broader adoption of solar energy technologies in diverse environmental conditions. These findings contribute to advancing renewable energy technology and support the green energy transition.

Amazon tropical forest is actually subject to strong deforestation, generally originated from illegal logging, resulting in ecological, environmental and economic problems. Aiming stop deforestation and timber commercialization of illegal logging of tropical forest, new laws has been introduced in many countries. Here we investigated the utility of DNA fingerprinting of nuclear and cytoplasmatic SNPs to timber tracking the intensive logged and commercialized of the Amazonian Neotropical tree Jacaranda copaia. Samples of 832 individuals from 43 populations from Bolivia, Brazil, French Guiana, and Peru were used to investigate the power of 113 nuclear SNPs, 11 CpSNPs, and four MtSNP loci to determine the country and population origin. The genetic differentiation among all populations and contries was high (0.233–0.942), specialy for CpMtSNP (generally>0.6) loci, and there is a strong isolation by distance pathern among populations, favoring the group or individual samples tracking to correct site. For self-assignment tests, we were able to 100% correct determine country and population origin of all samples using all SNPs. Our results show that the use of 128 SNP markers is suitable to correct determination of country and population site of J. copaia timber origin and very useful tool for customs and local and international policies.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

Quantitative measurements of performance parameters has the potential to increase consistency and enhance performance of the surfaces as well as to contribute to the safety of horses and riders. This study investigates how factors known to influence the performance of the surface, incorpo-ration of a drainage package, control of the moisture control, and introduction of a geotextile reinforcement, affect quantitative measurements of arena materials. The measurements are made by using affordable lightweight testing tools which are readily available or easily constructed. Sixteen boxes with arena materials at a consistent depth were tested with the Going Stick (GS), both penetration resistance and shear, the impact test device (ITD), and the rotational peak shear device (RPS). Volumetric moisture content (VMC %) was also tested with time-domain reflectometry (TDR). Results obtained using GS, RPS, ITD, and TDR indicate that the presence of the drainage package, moisture content, and geotextile addition were detected. Alterations due to combinations of treatments could also be detected by GS, ITD, and TDR. While the testing showed some limi-tations of these devices, the potential exists to utilize them for quality control of new installations as well as for the monitoring of maintenance of the surfaces.

Computational Fluid Dynamics (CFD) simulations, based on Reynolds Averaged Navier Stokes (RANS) models, are a useful tool for a wide range of coastal and offshore applications, providing a high fidelity representation of the underlying hydrodynamic processes. Generating input waves in the CFD simulation is performed by a numerical wavemaker (NWM), with a variety of different NWM methods existing for this task. While NWMs, based on impulse source methods, have been widely applied for wave generation in depth averaged, shallow water models, they have not seen the same level of adoption in the more general RANS based CFD simulations, due to difficulties in relating the required impulse source function to the resulting free surface elevation for non-shallow water cases. This paper presents an implementation of an impulse source wavemaker, which is able to self-calibrate the impulse source function to produce a desired wave series in deep or shallow water at a specific point in time and space. Example applications are presented, for a numerical wave tank (NWT), based on the opensource CFD software OpenFOAM, for wave packets in deep and shallow water, highlighting the correct calibration of phase and amplitude. Also, the suitability for cases requiring very low reflection from NWT boundaries is demonstrated. Possible issues in the use of the method are discussed and guidance for good application is given.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Background: Recently some photon models of a Wigner's friend experiment have led investigators to suggest objective reality does not exist, and to publish non-academic articles with such claims. The public is not equipped to evaluate the severe limitations of these experiments. The separation of Wigner from the experiment and use of only reversible coherent processes for the friend allow operations that are not possible in ordinary reality according to the latest quantum research. Methods: We suggest directly testing the implied claim that objective reality, including incoherent objects with irreversible non-destructive memory, can be held in superposition. We suspect it will fail, but provide for a graduated approach that may discover something about the conditions for superposition collapse. To this end we design a thought experiment to model the objective world, investigating under what conditions experimenters in the same world (ensemble member) will be able to record a result and find it does not appear to change. An observer has a viewing apparatus and a memory apparatus. A second uncorrelated viewer of the same recorded result is employed to obtain objectivity. By hypothesis the uncorrelated second viewer obtains the same view of the measurement record as the first observer. There are not two measurements. This is not an investigation of hidden variables. Results: To model the objective world, incoherent and irreversible processes must be included. To test for superposition, coherence has to be established. These seem to present a contradiction. Conclusions: The thought experiment has suggested new places to look other than size for the origin of objective reality from the quantum world, casts doubt on the Many-Worlds interpretation, and provides a method of testing it.

The goal of this paper is to contribute the perspective of a systems engineer to the effort to fight pandemics. The availability of low latency case data and effectiveness of social distancing suggest there is sufficient control for successful smoothing and targeting almost any desired level of low or high cases and immunity. This control proceeds from spontaneous public reaction to caseloads and news as well as government mediated recommendations and orders. We simulate multi-step and intermittent-with-feedback partial unlock of social distancing for rapidly-spreading moderate-mortality epidemics and pandemics similar to COVID-19. Optimized scenarios reduce total cases and therefore deaths typically 8% and up to 30% by controlling overshoot as groups cross the herd immunity threshold, or lower thresholds to manage medical resources and provide economic relief. We analyze overshoot and provide guidance on how to damp it. However, we find overshoot damping, whether from expert planning or natural public self-isolation, increases the likelihood of transition to an endemic disease. An SIR model is used to evaluate scenarios that are intended to function over a wide variety of parameters. The end result is not a case trajectory prediction, but a prediction of which strategies produce near-optimal results over a wide range of epidemiological and social parameters. Overshoot damping perversely increases the chance a pathogen will transition to an endemic disease, so we briefly describe the undershoot conditions that promote transition to endemic status.

High-Intensity Functional Training (HIFT) is a novel exercise intervention that may test body systems in a balanced and integrated fashion by challenging individuals’ abilities to complete mechanical work. However, research has not previously determined if physical work capacity is unique to traditional physiologic measures of fitness. Twenty-five healthy men and women completed a six-week HIFT intervention with physical work capacity and various physiologic measures of fitness assessed pre- and post-intervention. At baseline, these physiologic measures of fitness (e.g., aerobic capacity) were significantly associated with physical work capacity and this relationship was even stronger at post-intervention assessment. Further, there were significant improvements across these physiologic measures in response to the delivered intervention. However, the change in these physiologic measures failed to predict the change in physical work capacity induced via HIFT. These findings point to the potential utility of HIFT as a unique challenge to individuals’ physiology beyond traditional resistance or aerobic training. Elucidating the translational impact of increasing work capacity via HIFT may be of great interest to health and fitness practitioners ranging from strength/conditioning coaches to physical therapists.

(1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about 2 million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e. distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01-0.146) but decreasing over time (HR 1.351-2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.

First, we examine how spin is treated in special relativity and the necessity of introducing spin supplementary conditions (SSC) and how they are related to the choice of a center-of-mass of a spinning particle. Next, we discuss quantum electrodynamics and the Foldy-Wouthuysen transformation which we note is a position operator identical to the Pryce-Newton-Wigner position operator. The classical version of the operators are shown to be essential for the treatment of classical relativistic particles in general relativity, of special interest being the case of binary systems (black holes/neutron stars) which emit gravitational radiation.

Considering the need to reduce greenhouse gas emissions, onshore wind energy is certain to play a major role in future energy systems. This topic has received significant attention from the research community, producing many estimations of Europe's onshore wind potential for capacity and generation. Despite this focus, previous estimates have relied on distribution assumptions and simulation schemes that summarily under predict both the amount of available future wind capacity as well as its performance. Foremost in this regard is the common use of contemporary, or at least near-future, turbine designs which are not fitting for a far-future context. To fulfill this role, an improved, transparent, and fully reproducible work flow is presented for determining European onshore wind potential. Within a scenario of turbine cost and design in 2050, 13.5 TWof capacity is found to be available, allowing for 34.4 PWh of generation. By sorting the explicitly-placed potential generation locations by their expected generation cost, national relations between turbine cost and performance versus a desired capacity are exposed. In this way, it is shown that all countries possess some potential for onshore wind energy generation below 4 €_ct kWh^-1. and, furthermore, that it is unlikely for these costs to exceed 6 €_ct kWh^-1.

Genome-scale engineering and custom synthetic genomes are reshaping the next generation of industrial yeast strains. The Cre-recombinase mediated chromosomal rearrangement mechanism of designer synthetic Saccharomyces cerevisiae chromosomes, known as SCRaMbLE, is a powerful tool which allows rapid genome evolution upon command. This system is able to generate millions of novel genomes with potential valuable phenotypes, but the excessive loss of essential genes often results in poor growth or even the death of cells with useful phenotypes. In this study we expanded the versatility of SCRaMbLE to industrial strains, and evaluated different control measures to optimise genomic rearrangement, whilst limiting cell death. To achieve this, we have developed RED (Rapid Evolution Detection), a simple colorimetric plate-assay procedure to rapidly quantify the degree of genomic rearrangements within a post-SCRaMbLE yeast population. RED-enabled semi-synthetic strains were mated with haploid progeny of industrial yeast strains to produce stress tolerant heterozygous diploid strains. Analysis of these heterozygous strains with the RED-assay, genome sequencing and custom bioinformatics scripts demonstrated a correlation between RED-assay frequencies and physical genomic rearrangements. Here we show that RED is a fast and effective method to evaluate optimal SCRaMbLE induction times of different Cre-recombinse expression systems for the development of industrial strains.

Electromagnetic interference (EMI) generated by switching operations within high voltage DC (HVDC) converter stations is an issue that has been addressed by CIGRE and methods to manage EMI should be considered in the design phase using electromagnetic modeling techniques. It is shown that method of moments-based techniques that have been used in many previous studies may not be sufficient. Here, the finite-difference time-domain method is used to study the properties of single switching events using a realistic model of an HVDC converter station with special emphasis on determining the impact of the valve hall on shielding EMI. It is shown that the valve hall does not confine high frequency electromagnetic fields to the valve hall; rather it delays them from exiting through bushings in the wall. Further, it is shown that incorporating electromagnetic absorbing material into the valve hall design can significantly reduce EMI outside the converter station.

The growing concerns about floods have highlighted the need for accurate and detailed precipitation data as extreme precipitation occurrences can lead to catastrophic floods, resulting in significant economic losses and casualties. Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement (GPM-IMERG) is a commonly used high-resolution gridded precipitation dataset and is recognized as trustworthy alternative sources of precipitation data. The aim of this study is to comprehensively evaluate the performance of GPM IMERG Early (IMERG-E), Late (IMERG-L), and Run Final (IMERG-F) in precipitation estimation and their capability in detecting extreme rainfall indices over southwestern Iran during 2001-2020. The Asfezari gridded precipitation data which are developed using a dense of ground-based observation were utilized as the reference dataset. The findings indicate that the IMERG-F performs reasonably well in capturing many extreme precipitation events (defined by various indices). All the three products showed a better performance in capturing fixed and non-threshold precipitation indices across the study region. The findings also revealed that both IMERG-E and IMERG-L have problems in rainfall estimation over elevated areas showing values of overestimations. Examining the effect of land cover type on the accuracy of the precipitation products suggest that both IMERG-E and IMERG-L show large and highly unrealistic overestimations over inland water bodies and permanent wetlands. The results of the current study highlight the potential of IMERG-F as a valuable source of data for precipitation monitoring in the region.

The described data set contains features from the machine control of a five-axis milling machine. The features were recorded during thirteen series productions. Each series production includes a changeover process in which the machine was set up for the production of a different product. In addition to the timestamps and the twenty recorded features derived from Numerical Control (NC) control variables, the data set also contains labels for the different production phases. For this purpose, up to 23 phases were assigned, which are based on a generalized milling process. The data set consists of thirteen .csv files, each representing a series production. The data set was recorded in a production company in the contract manufacturing sector for components with real series orders in ongoing industrial production.

This article presents a comprehensive study on enhancing grid resilience through advanced forecasting and optimization techniques in the context of power outages. Power outages pose significant challenges to modern societies, affecting various sectors such as industries, households, and critical infrastructures. The research combines statistical analysis, machine learning algorithms, and optimization methods to address this issue to develop a holistic approach for predicting and mitigating power outage events. The proposed methodology involves the use of Monte Carlo simulations in MATLAB for future outage prediction, Long Short-Term Memory (LSTM) networks for forecasting solar irradiance and load profiles, and a hybrid LSTM-Particle Swarm Optimization (PSO) model to improve accuracy. Furthermore, the role of Battery State of Charge (SoC) in enhancing system resilience is explored. The study also assesses the techno-economic advantages of a grid-tied microgrid integrated with solar panels and batteries over conventional grid systems. The results highlight the potential of the proposed approach in strengthening grid resilience, reducing downtime, and fostering sustainable energy utilization.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

For orthopaedic applications, additive manufactured (AM) porous scaffolds made of absorbable metals like magnesium, zinc or iron are of particular interest. They do not only offer the potential to design and fabricate bio-mimetic or rather bone equivalent mechanical properties, they also do not need to be removed in further surgery. Located in a physiological environment, scaffolds made of absorbable metals show a decreasing Young’s modulus over time, due to product dissolution. For WE43 scaffolds, during the first days an increase of the smeared Young's modulus can be observed, which is mainly attributed to a forming substrate layer of degradation products on the struts surfaces. In this study the influence of degradation products on the stiffness properties of metallic scaffolds is investigated. For this, analytical calculations and finite element simulations are performed to study the influence of the substrate layer thickness and Young's modulus for single struts and for a new scaffold geometry with adapted polar f2cc,z unit cells. The finite element model is further validated by compression tests on AM scaffolds made from Zn1Mg. The results show, that even low thicknesses and Young's moduli of the substrate layer increases significantly the smeared Young's modulus under axial compression.

This study introduces an innovative seeding method for cells on large scaffolds (1-100 sqcm) with an accuracy of 0.1mm, comparing the conventional drop-wise seeding technique with an automated seeding approach using an open sourced robotic liquid handling system (OpenLH). This automated system employs an algorithm in which the user inputs the desired droplet volume and seeding pattern dimensions such in number of rows, columns and distance between droplets, thus optimizing the distribution of cells on the scaffold. By adjusting these parameters, the method achieves greater accuracy and consistency over manual seeding and requires less operation space volume than dynamic seeding. Additionally, the system’s tip replacement feature can support the precise seeding of multiple cell types on a single scaffold and the dispensing of growth factors to foster patterns of cell differentiation and proliferation on the large 3D scaffold. This seeding method not only enhances the precision and efficiency of cell distribution on scaffolds but also shows significant potential for scalability in the cultured meat industry, where large scaffolds are essential. The adoption of such automated systems could promote efficient scaffold-based tissue engineering by promoting uniform cell distribution and enabling the creation of complex tissue constructs, thereby advancing both biomedical research and cultured meat production.

New information suggests female autistic spectrum disorder (ASD) is much more common than previously thought, with a likely prevalence of 6% and with 80% undiagnosed at the age of 18. ASD then becomes a common comorbidity of female mental illness with nearly one in five women who develop a mental illness being autistic. ASD has heretofore been regarded as a pediatric condition and though now thought to be life long it is still not well recognized by adult health services. Most mental illness first presents in the teens and early twenties. Comorbid ASD is more difficult to diagnose due to diagnostic overshadowing, and ASD comorbidity maks the mental illness more severe and mor difficult to treat. Recognized ASD is readily treatable with an approach sympathetic to neurodiversity. Improving the pathway from adolescence to adulthood by increasing knowledge of autism in adult health services would dramatically improve female mental health at surprisingly little extra cost. It is low hanging fruit in a very fraught area of healthcare. This paper will examine the extent of the problem. It will explore solutions and quantify the gains of appropriate therapy.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

This new study revised interlinked issues of global soil organic carbon (SOC), annual net primary productivity (NPP) and atmospheric CO₂ turnover time (τ). Soil is confirmed as both the greatest sink and source for excess atmospheric CO₂. Most terrestrial NPP (~218 Gt C/yr) is ultimately processed in topsoil and SOC stocks now total >10,000–12,000 Gt. More excess carbon is released into the air and water from SOC loss (>20 Gt C/yr) due to land clearance for pasture/crops, fires, agrichemical poisoning and erosion, than from fossil fuels (~10 Gt C/yr). NOAA’s Barrow bounce and isotopic analyses support high terrestrial flux up to ~800 Gt C/yr and CO₂ turnover time of ~1–4 years. Earth’s re-humification via compost offers the best and only practical/time-critical fix for climate, strategy for species extinction plus remedy for human health.

Shutdown for just six days enables land plants to entirely fix CO₂ excess of +4 Gt C per yr. Rebuilding soil organic carbon (SOC) in worm-worked humus is the only practical carbon capture and storage (CCS) capable of freely offsetting annual anthropogenic emissions. A case is made to redirect all available resources towards proven, earthworm-based, organic husbandry. Priority is to safely combat mounting global threats due to irreversible species extinction, perilous climate change and deteriorating human wellbeing (mental/physical health). All three interlinked risks are underpinned by a relentless, yet largely ignored, critical loss of precious topsoil. A first step to topsoil recovery is vermi-composting all vegetable and animal ‘wastes’ for return to the field.

Corynebacterium glutamicum is prominent for the industrial production of secreted amino acids. Notably, it naturally accumulates the carotenoid pigment decaprenoxanthin in its membranes. Metabolic engineering enabled production of astaxanthin. Here, a bioprocess for astaxanthin production in lab-scale stirred bioreactors was established by a DoE-guided approach to optimize the basic process parameters pH, rDOS, aeration rate as well as inoculation cell density. The DoE-guided approach from 2 L scale cultivation revealed that the pH showed the strongest effect on the product formation. Subsequently, an optimum at pH 8, an aeration rate of 0.25 vvm, 30 % rDOS and an initial optical density of 1 was established that allowed production of 7.6±0.6mg L-1 astaxanthin in batch mode. These process conditions were successfully transferred to a fed-batch process resulting in a high cell density cultivation with up to 60 g CDW L-1 biomass and 64 mg L-1 astaxanthin and thus demonstrating an about 9-fold improvement compared to optimal batch conditions. Moreover, pH shifts experiments indicate that the cells can quickly adapt to a change from pH 6 to 8 and start producing astaxanthin showing the possibility of a biphasic bioprocesses for astaxanthin production.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

Two conundrums have puzzled COVID-19 investigators: 1) morbidity and mortality is rare among Infants and young children and 2) rates of morbidity and mortality exhibit very large variances across nations, locals and even within cities. These differences correlate with rates of Haemophilus influenzae type B (Hib) and pneumococcal vaccination, which are almost universal among infants and vary widely by geography among adults and the elderly. The higher the rate of vaccination, the lower the COVID-19 morbidity and mortality. Vaccination rates with other vaccines, including BCG and poliovirus, do not correlate with COVID-19 risks. Notably, both Hib and pneumoccoci are common co-infections with influenza and coronaviruses and are associated with more severe disease and risk of death. Whether the vaccines simply protect against COVID-19 complications, directly protect against COVID-19 infection by inducing cross-reactive immunity, or are markers for some other types of protection such as availability of better healthcare, is not yet known. What is known is that improving coverage rates of Hib and pneumococcal vaccination has significantly lowered severe morbidity and mortality in influenza epidemics and might have similar efficacy for mitigating coronavirus outbreaks. If infants and children are valid indicators, the beneficial effects might be very significant. The possibility that anti-viral proteins in milk (e.g., lactoferrin) protect against COVID-19 is also explored.

Stellar NGC 6853, also known as the Dumbbell Nebula, is a remarkable example of an elliptical morphological type 1 multiple shell planetary nebula, which is now in one of its last evolutionary stages. This project focuses on examining the distinct varieties of the nebula temperatures and densities using observation data from the Issac Newton Group of Telescopes and comparing them with the observation data from Observatoire de Haute Provence from 14th to 18th of October 2019, with a primary focus on the data from the Issac Newton Telescope (INT). The densities ranged from diffused regions of 376.63 ± 228.97 atoms per cm³ to dense regions of 6441.11 ± 228.90 atoms per cm³; these values are slightly lower approximately by 2000 than the values from the Observatoire de Haute Provence. The radial velocity and the expansion velocity were also calculated using the spectroscopic data and were found to be 29.50 ± 0.38 km⁻¹ and 37.40 ± 0.38 km⁻¹ respectively. This result is expected from a multi-shell nebula that consists of the main body and surrounding halo

Background: A large percentage of deaths in an epidemic or pandemic can be due to overshoot of population (herd) immunity, either from the initial peak or from planned or unplanned exit from lockdown or social distancing conditions. Objectives: We study partial unlock or reopening interaction with seasonal effects in a managed epidemic to quantify overshoot effects on small and large unlock steps and discover robust strategies for reducing overshoot. Methods: We simulate partial unlock of social distancing for epidemics over a range of replication factor, immunity duration and seasonality factor for strategies targeting immunity thresholds using overshoot optimization. Results: Seasonality change must be taken into account as one of the steps in an easing sequence, and a two step unlock, including seasonal effects, minimizes overshoot and deaths. It may cause undershoot, which causes rebounds and assists survival of the pathogen. Conclusions: Partial easing levels, even low levels for economic relief while waiting on a vaccine, have population immunity thresholds based on the reduced replication rates and may experience overshoot as well. We further find a two step strategy remains highly sensitive to variations in case ratio, replication factor, seasonality and timing. We demonstrate a three or more step strategy is more robust, and conclude that the best possible approach minimizes deaths under a range of likely actual conditions which include public response.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

Rainfall, or more generally the precipitation process (flux), is a clear example of chaotic variables resulting from a highly nonlinear dynamical system, the atmosphere, represented by a set of physical equations such as the Navier-Stokes equations, energy balances and hydrological cycle among others. As a generalization of the Euclidean (ordinary) measurements, chaotic solutions of these equations are characterized by fractal dimensions, which are non-integer values that represent the complexity of variables like the precipitation. However, observed precipitation is measured as an aggregate variable over time, thus physical analysis of the observed fluxes is very limited. Therefore, this review aims to go through the different approaches used in the identification and analysis of the complexity of the observed precipitation, taking advantage of its geometry footprint. To address the review, it ranges from classical perspectives of fractal-based techniques to new perspectives at temporal and spatial scales as well as for classification of climatic features, including monofractal dimension, multifractal approaches, Hurst exponent, Shannon entropy and time scaling in intensity-duration-frequency curves.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Earth’s land surface area is raised from conventionally flat 15 to 64 Gha to account for hilly undulation and soil relief detail. Three main aspects are: topography, rugosity/tortuosity and micro-relief/porosity of vegetation-free ground. Recalibration is arrived at from four approaches: first, direct empirical estimates from the few compiled satellite or LiDAR data with means of +2.5–26% progressively overlain by +94% at cm² scale for soil ruggedness then +108% for mm² micro-relief; second, from digital elevation models with 1.6–2.0 times flat areas; third, by ‘reverse engineering’ global soil bulk densities and carbon reserves requiring x 2–6 land. Finally, a Fermi estimation conveniently sets the World’s new surface area – that exposed to Sun, air and rain – at 100 Gha (with 36 Gha flat ocean). Soil organic carbon (SOC) is thence raised to 8,580 Gt mainly in SOM/humus with its biotic complexity plus roots, VAM-fungi and leaf-litter, that itself = 17,800 Gt. Although four to six times IPCC’s or NASA/NOAA’s calculations of just 1,500–2,300 Gt SOC, this is likely an underestimation. Global biomass and biodiversity are at least doubled (x 2–3.5) and net primary productivity (NPP) similarly increased on land to >270 Gt C yr^-1 due to terrain.

Introduction. Strontium-82/Rubidium-82 (⁸²Sr/⁸²Rb) generators are used widely for positron emission tomography (PET) imaging of myocardial perfusion. In this study, the ⁸²Rb isotope yield and production efficiency of two FDA-approved ⁸²Sr/⁸²Rb generators were compared.Methods. N=515 sequential daily quality assurance (QA) reports from 9 CardioGen-82® and 9 RUBY-FILL® generators were reviewed over a period of 2 years. A series of test elutions was performed at different flow-rates on the RUBY-FILL® system to determine an empirical correction-factor used to convert CardioGen-82® daily QA values of ⁸²Rb activity (dose-calibrator ‘maximum’ of 50 mL elution at 50 mL/min) to RUBY-FILL® equivalent values (integrated ‘total’ of 35 mL elution at 20 mL/min). The generator yield (⁸²Rb) and production efficiency (⁸²Rb yield / ⁸²Sr parent activity) were measured and compared after this conversion to a common scale. Results. At the start of clinical use, the system reported ⁸²Rb activity from daily QA was lower for CardioGen-82® vs RUBY-FILL® (2.3 ± 0.2 vs 3.0 ± 0.2 GBq, p<0.001) despite having similar ⁸²Sr activity. Dose-calibrator ‘maximum’ (CardioGen-82®) values were found to under-estimate the integrated ‘total’ (RUBY-FILL®) activity by ~24% at 50 mL/min. When these data were used to convert the CardioGen-82 values to a common measurement scale (integrated total activity) the CardioGen-82® efficiency remained slightly lower than the RUBY-FILL® system on average (88 ± 4% vs 95 ± 4%, p<0.001). The efficiency of ⁸²Rb production improved for both systems over the respective periods of clinical use.Conclusions. ⁸²Rb generator yield was significantly under-estimated using the CardioGen-82® vs RUBY-FILL® daily QA procedure. When generator yield was expressed as the integrated total activity for both systems, the estimated ⁸²Rb production efficiency of the CardioGen-82® system was ~7% lower than RUBY-FILL® over the full period of clinical use.

Some of the key features of inclusive and equitable teaching approaches encourage prompt feedback, student cooperation in communities of learning, active learning, and promotes diverse ways of knowing in the classroom. In my article, I present step-bystep tips to help instructors create guided microlearning inquiry questions within an inclusive and equitable general biology classroom setting. Microlearning is a special approach that helps students complete a specific task linked to a specific learning objective that would be completed in a short time window around five minutes. The step-by-step tips presented in my article helps instructors to develop questions aligned to specific learning objective to help clarify unclear or confusing topics in general biology using the Kahoot e-Learning platform. This guided microlearning inquiry toolkit provides a blueprint for helping instructors to infuse student-centered approaches to help clarify difficult concepts in general biology and further develop avenues refine students’ critical thinking and experimental design in biology research.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

Porcelain tile manufacturing is an energy-intensive industry that is in dire need of increasing productivity, minimizing costs, and reducing CO2 emissions, while keeping the product quality intact to remain competitive in today’s environment. In this contribution, alternative processing parameters for the porcelain tile production sequence were proposed based on simulation-based process optimization. Flowsheet simulations in the Dyssol framework were used to study the impact of milling and firing process parameters on the electrical and thermal energy consumption, final product quality, and productivity of the entire processing sequence. For this, a new model of gas flow consumption in the sintering stage was proposed and implemented. During optimization, the primary condition was to maintain the product quality by keeping the final open porosity of the tile within the specified industrial range. The proposed simulation methodology proved to be effective in predicting the influence of processing parameters on the intermediate and final products of the manufacturing sequence, as well as in estimating production costs for the Brazilian and Spanish economic conditions. This approach has shown great potential to promote digitalization and establish digital twins in ceramic tile manufacturing for further in-line process control.

Heart Rate Monitors (HRMs) are an indispensable tool for controlling training parameters of healthy athletes. They became a source of information about stress heart rhythm disturbances, recognized as unexpected increases in heart rate (HR), which can be life-threatening for athletes. Most HRMs do not recognize the type of arrhythmia, confusing them with artifacts. The aim of the study was to assess the usefulness of ECG recording functions by sports HRMs among endurance athletes, coaches, and physicians in comparison with other basic and hypothetical functions. We conducted 3 surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), as well as 10 coaches and 10 sports doctors to obtain information on how important ECG recording is, and what functions of HRMs should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as preference for HRM type (optical/strap). For athletes, the 4 most important functions were distance traveled, pace, instant heart rate, and information about reaching the oxygen threshold. ECG recording was the 8th and 9th most important for momentary and continuous, respectively. Coaches opined more importance to ECG recording. Doctors placed ECG recording as most important. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions shows slightly different preferences of athletes compared to coaches and doctors. Suspected arrhythmia increases the value of the HRM’s ability to record ECGs during training by athletes and coaches. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups continuous ECG recording during training will significantly improve the safety of athletes.

The motivations for the move to electrified vehicles are discussed with reference to their improved energy efficiency, their potential for lower CO2 emissions (if the electricity system is decarbonized), their lower (or zero) NOx/particulate matter (PM) tailpipe emissions, and the lower overall costs for owners. Some of the assumptions made in life-cycle CO2 emissions calculations are discussed and the effect of these assumptions on the CO2 benefits of electric vehicles are made clear. A number of new tribological challenges have emerged, particularly for hybrid vehicles that have both a conventional internal combustion engine and a battery, such as the need to protect against the much greater number of stop-starts that the engine will have during its lifetime. In addition, new lubricants are required for electric vehicle transmissions systems. Although full battery electric vehicles (BEVs) will not require engine oils (as there is no engine) they will require a system to cool the batteries – alternative cooling systems are discussed, and where these are fluid based, the specific fluid requirements are outlined.

ABSTRACT: The idea of a Common Mucosal Immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway, has been poorly understood. The consequent failure of current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and can not be achieved by systemic and mucosal vaccination for prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome, is demonstrated through review of randomised controlled trials (RCT’s) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced.

It appears that up to 80% of females with autistic spectrum disorder (ASD) have not been diagnosed by 18 years of age. This translates to a prevalence of about 5-6%, and if true has serious implications for female mental health. One way of finding the true value is to use Bayes’ Theorem with a comorbid condition as a more easily recognizable flag. An obvious choice is anorexia nervosa (AN), but it transpires that the proportion of women with ASD who develop AN is unknown. This study uses published data in novel ways to provide two methods of estimating a range for this variable, and gives a median value of 8.3% for AN in ASD and with four other methods a median prevalence of 6% for female ASD. The clinical implications for diagnosis and management of ASD and comorbidities are discussed and a solution is provided for the rate of ASD in generalized joint hypermobility.

This article evaluates the reliability and consistency of nutrition- and supplementation-related advice for pregnant women provided by ten selected health-related Internet portals. The portals were chosen based on their perceived reliability and prominence in Google searches, with representation from both English and Polish language sources. The evaluation criteria included the adherence of the presented information to official recommendations and its evidence-based character based on specific items representing dietary aspects important in pregnancy. While the overall reliability was deemed acceptable, significant variations existed both among the portals and specific evaluated items. Notably, HealthLine, Medline Plus, and NCEZ emerged as the most evidence-based, while WebMD and Medycyna Praktyczna were identified as less reliable. Despite a number of issues, the analysed portals remain valuable sources of nutritional information for pregnant women, offering user-friendly accessibility superior to alternatives such as social media, on the one hand, and scientific articles, on the other. Improved consistency and attention to detail, especially in relation to vitamin intake and supplementation, would improve the overall quality of health portals.

Functional osseoconductive coatings based on hydroxylapatite (HAp) and applied preferentially by atmospheric plasma spraying to medical implant surfaces are a mainstay of modern implantology. During contact with the hot plasma jet, HAp particles melt incongruently and undergo complex dehydration and decomposition reactions that alter their phase composition and crystallographic symmetry, and thus, the physical and biological properties of the coatings. Surface analytical methods such as laser-Raman and nuclear magnetic resonance (NMR) spectroscopies are useful tools to assess the structural changes of HAp imposed by heat treatment during their flight along the hot plasma jet. In this contribution, the controversial information on the existence or non-existence of oxyapatite, i.e. fully dehydrated HAp as a thermodynamically stable compound is highlighted.

Transportation of goods is as old as human civilizations : past networks and their evolution shed light on long term trends. Transportation impact on climate change is measured as major, as well as the impact on spreading a pandemic. These two reasons motivate the importance of providing relevant and reliable historical geographic datasets of these networks. This paper focuses on reconstructing the railway network in France at its maximal extent, a century ago. The active stations and lines are well documented by the French SNCF, in open public data. However, that information ignores past stations (ante 1980), which represent probably more than what is recorded in public data. Additional open data, individual or collaborative (eg. Wikipedia) are particularly valuable, but they are not always geo-coded, and two more sources are necessary to completing that geo-coding: ancient maps and aerial photography. Therefore, remote sensing and volunteer geographic information are the two pillars of past railway reconstruction. The methods developed are adapted to the extraction of information from these sources: automated parsing of Wikipedia Infoboxes, data extraction from simple tables, even from simple text. That series of sparse procedures can be merged into a comprehensive computer-assisted process. Beyond this, a huge effort in quality control is necessary when merging these data: automated wherever possible, or finally visually controlled by observation of remote sensing information. The main output is a reliable dataset, under ODbl, of more than 9100 stations, which can be combined with the information about the 35000 communes of France, for a large variety of studies. This work demonstrates two thesis: (a) it is possible to reconstruct transport network data from the past, and generic computer assisted methods can be developed; (b) the value of remote sensing and volunteered geo info is considerable (what archeologists already know).

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Abstract: Doppler renal resistive index (RRI) has been used for several decades as a potential indi-cator for renal disease and progression. In recent years, RRI has emerged as a useful prognostic indicator for a range of co-morbidities in patients who are acutely unwell and as a potential marker for sub-clinical acute kidney injury (AKI) and post procedural AKI risk. Despite this, the clinical and theoretical determinants of RRI are poorly understood and remain contentious. Method: A narrative review of studies exploring the theoretical, experimental, and clinical evidence for factors affecting RRI. No date restrictions were set. Findings: Both experimental and clinical data confirm that RRI is markedly affected by a range of systemic and renal determinants and is influenced closely by the underlying risk factors and sys-temic vascular changes that lead to progressive renal damage. Discussion: This paper provides an overview of the key haemodynamic determinants of renal re-sistive index and aims to clarify their relative importance. With reference to a simplified theoretical model, evidence from experimental and clinical studies is reviewed. Pathophysiological factors and patient characteristics that influence RRI are explored to provide a better understanding of why RRI values change in the presence of common or complex pathologies. Conclusion: By gaining a better understanding of the complex systemic and renal factors that influ-ence RRI, ultrasound users will be better prepared to understand and interpret changes in RRI across a range of patient presentations.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.

There has been a recent revival of interest in the notion of a `trajectory' of a quantum particle. In this paper we detail the relationship between Dirac's ideas, Feynman paths and the Bohm approach. The key to the relationship is the weak value of the momentum which Feynman calls a transition probability amplitude. With this identification we are able to conclude that a Bohm `trajectory' is the average of an ensemble of actual individual stochastic Feynman paths. This implies that they can be interpreted as the mean momentum flow of a set of individual quantum processes and not the path of an individual particle. This enables us to give a clearer account of the experimental two-slit results of Kocsis {\em et al.}}

We report herein the synthesis of siloxane-functionalized CBP molecules (4,4’-bis(carbazole)-1,1′-biphenyl) for liquid optoelectronic applications. The room-temperature liquid state is obtained through a convenient functionalization of the molecules with heptamethyltrisiloxane chains via hydrosilylation of alkenyl spacers. The synthesis comprises screening of metal-catalyzed methodologies to introduce alkenyl linkers into carbazoles (Stille and Suzuki Miyaura cross-couplings), incorporate the alkenylcarbazoles to dihalobiphenyls (Ullmann coupling), and finally introduce the siloxane chains. The used conditions allowed the synthesis of the target compounds, despite the high reactivity of the alkenyl moieties bound to π-conjugated systems toward undesired side reactions such as polymerization, isomerization, and hydrogenation. The features of these solvent-free liquid CBP derivatives make them potentially interesting for fluidic optoelectronic applications.

Transgender youth experience elevated levels of victimization and may therefore report greater drug use than their cisgender peers, yet little is known about protective factors like school belonging that may mediate this relationship. Further, scant research has explored the experiences of youth at the intersection of transgender identity and youth of color status or low socioeconomic status, especially with respect to these multiple minority statuses’ associations with peer victimization, drug use, and school belonging. Using data from the California Healthy Kids Survey, the current study employs structural equation modeling to explore the relationships among school belonging, peer victimization, and drug use for transgender youth. Findings indicate that school belonging does mediate the pathway between peer victimization and drug use for transgender youth and that although youth of color experience greater victimization, they do not engage in greater drug use than their white transgender peers. Based on these results, those concerned with the healthy futures of transgender youth should advocate for more open and affirming school climates that engender a sense of belonging and treat transgender youth with dignity and fairness.

Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTC), or extracellular vesicles (EV) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.

The purpose of the present study was to compare heart rate (HR), blood lactate and training load between different CrossFit® workouts, with equalized total volume in men and women. The study included 23 individuals (13 men and 10 women) experienced in CrossFit® training, who performed two workouts with different training types (as many reps as possible - AMRAP and for time) but equalized volume. Measurements of lactate, HR and rating of perceived exertion (RPE) were performed. The results showed that there was no HR interaction between workout time and sex (p = 0.822; η2 = 0.006] and between workout type and sex (p = 0.064, η2 = 0.803). HR significantly differed during each workout type (p <0.001, η2 = 0.621), but not between the two workout types (p = 0.552, η2 = 0.017). Lactate showed no difference between the workout types (p = 0.474, η2 = 0.768), although the training load was higher (p = 0.033, η2 = 0.199) in women when they performed AMRAP. Altogether, HR was not significantly different between training types or sex, while RPE, lactate and training load showed small differences depending on the group (women or men) or workout type (AMRAP or 'for time').

Developmental, clinical, and epidemiological research have demonstrated the salience of perceived racial discrimination (PRD) as a contributor to negative mental health outcomes in adolescence. This article summarizes secondary analyses of cross-sectional data from a large-scale youth survey within a predominantly rural state to estimate the prevalence and strength of association between PRD and serious psychological distress, suicidal ideation, and prior suicidal attempts. Data from 93,812 students enrolled in Grades 6, 8, 10, and 12 within 129 school districts across Kentucky were examined to determine prevalence rates for subgroups within the cohort. Logistic regression analyses assessed differences and established comparative strength of association among these variables for racial/ethnic subgroups. PRD was self-reported at high rates across several demographic subgroups and was most evident among Black (24.5%) and Asian (22.1%) students. Multiracial students experienced the highest rates of both SPD and suicidality. Both for the entire cohort and for each racial/ethnic subgroup, PRD was significantly associated with increased likelihood of negative mental health outcomes, although the strength of these associations varied across subgroups and developmental levels. Implications for early intervention and prevention are discussed.

Displacement mapping is a computer graphics technique that enables the design of components with regularly or randomly textured surfaces that can be quickly materialized on a three-dimensional (3D) printer when needed. This approach is in principle more flexible, faster and more economical compared to conventional texturing methods, but the accuracy of the texture depends heavily on the parameters used. The purpose of this study is to demonstrate how to produce a surface-textured part using polygonal (mesh) modeling software and a photopolymerizable resin, and to develop a universal methodology to predict the dimensional accuracy of the model file log combined with a resin 3D printer. The printed components were characterized on a scanning confocal microscope. In the setup used in this study, the mesh size had to be reduced to 10% of the smallest feature size and the textured layer had to be heavily (x4) overexposed to achieve the desired accuracy. As a practical application, two functional stamps with a regular (honeycomb) and a random texture, respectively, were successfully manufactured. The insights gained will be of great benefit in quickly and cost-effectively producing components with innovative patterns and textures for a variety of hobby, industrial and biomedical applications.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

MnSi has played a major role since the late 1970s in developing the theory of helical magnets in non-centro symmetric materials showing Dzyaloshinsky-Moriya interaction (DMI). With a long helimagnetic pitch of 175 \AA~as compared to the lattice d-spacing of 4.55\AA, it was ideal for performing neutron studies especially as large single crystals could be grown. In these studies under the application of a field of 180 mT perpendicular to Q, a so-called A-phase in the B-T phase diagram was found and interpreted as a rotation of the alignment of the magnetic helix away from the pinning axis. After the surprising discovery of the skyrmion lattice in the A-phase in 2009 much interest arose as it could be shown that the magnetic skyrmion lattice is topologically protected. Due to the rigidity of the skyrmionic lattice it is only loosely bound to the crystal lattice and therefore only relatively small current densities can already induce a motion of this lattice. Another very interesting aspect are the excitations in the spin system of MnSi. As the helimagnetic state is characterized by a long pitch of about 175 \AA, the associated characteristic excitations form a band structure due to Umklapp scattering and can only be observed at very small q with energies below 1 meV. We have investigated the the magnons in MnSi in the whole (B,T)-phase diagram starting in the single-k helimagnetic state by applying a small magnetic field B = 100 mT. This way, the complexity of the magnon spectrum is significantly reduced allowing a detailed comparison of the data with theory resulting in a full theoretical understanding of the spin system of MnSi in all its different magnetic phases.