Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analyzed by nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R²=0.26, F(29,121)=2.80, p<0.001) in micro- and 12% (R²=0.12, F(29,124)=1.70, p=0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R²=0.13, F(3,143)=8.42, p<0.001) of micro and 8% (R²=0.08, F(3,145)=5.46, p=0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.

Most computer keyboard layouts (mappings of characters to keys) do not reflect the ergonomics of the human hand, resulting in preventable repetitive strain injuries. We present a set of ergonomics principles relevant to touch typing, introduce a scoring model that encodes these principles, and outline a systematic approach for developing optimized keyboard layouts in any language based on this scoring model coupled with character-pair frequencies. We then create a keyboard layout optimized for touch typing in English by constraining key assignments to reduce lateral finger movements and enforce easy access to high-frequency letters and letter pairs, applying open source software to generate millions of layouts, and evaluating them based on Google’s N-gram data. We use two independent scoring methods to compare the resulting Engram layout against 10 other prominent keyboard layouts based on a variety of publicly available text sources. The Engram layout scores consistently higher than other keyboard layouts.

After proving, in a purely categorial way, that the inclusion functor InAlg(Σ) from Alg(Σ), the category of many-sorted Σ-algebras, to PAlg(Σ), the category of many-sorted partial Σ-algebras, has a left adjoint FΣ, the (absolutely) free completion functor, we recall, in connection with the functor FΣ, the generalized recursion theorem of Schmidt, which we will also call the Schmidt construction. Next we define a category Cmpl(Σ), of Σ-completions, and prove that FΣ, labeled with its domain category and the unit of the adjunction of which it is a part, is a weakly initial object in it. Following this we associate to an ordered pair (α,f), where α=(K,γ,α) is a morphism of Σ-completions from F=(C,F,η) to G=(D,G,ρ) and f a homomorphism in D from the partial Σ-algebra A to the partial Σ-algebra B, a homomorphism ΥαG,0(f):Schα(f)B. We then prove that there exists an endofunctor, ΥαG,0, of Mortw(D), the twisted morphism category of D, thus showing the naturalness of the previous construction. Afterwards we prove that, for every Σ-completion G=(D,G,ρ), there exists a functor ΥG from the comma category (Cmpl(Σ)↓G) to End(Mortw(D)), the category of endofunctors of Mortw(D), such that ΥG,0, the object mapping of ΥG, sends a morphism of Σ-completion in Cmpl(Σ) with codomain G, to the endofunctor ΥαG,0.

In this work it is acknowledged that important attempts to devise an emergent quantum (gravity) theory require space-time to be discretized at the Planck scale. It is therefore conjectured that reality is identical to a sub-quantum dynamics of ontological micro-constituents that are connected by a single interaction law. To arrive at a complex system-based toy-model identification of these micro-constituents, two strategies are combined. First, by seeing gravity as an entropic phenomenon and generalizing the dimensional reduction of the associated holographic principle, the universal constants of free space are related to assumed attributes of the micro-constituents. Second, as the effective field dynamics of the micro-constituents must eventually obey Einstein’s field equations, a sub-quantum interaction law is derived from a solution of these equations. A Planck-scale origin for thermodynamic black hole characteristics and novel views on entropic gravity theory result from this approach, which eventually provides a different view on quantum gravity and its unification with the fundamental forces.

Secondary and tertiary prevention strategies targeting people with disabilities to improve their health and wellbeing is important. In Sweden, >95% of all children with cerebral palsy (CP) participate in a follow-up program, where one of the goals is the prevention of hip dislocations. We reviewed the incidence of hip dislocations from 2010 to 2019 and the number of children who underwent different types of hip surgeries. The number of hip dislocations was reduced from 8.8% before introduction of the program to 0.3-0.4% up to 2015, followed by a gradual increase to 0.8% in 2019. The proportion of children who underwent adductor-psoas lengthening as their primary preventive surgery decreased from 50% in 2017 to 37% in 2019 with a corresponding increase of children undergoing femoral osteotomy, indicating more children underwent surgery at a later stage. Reasons for the increased number of children with hip dislocation may be that more children have moved to Sweden in recent years without corresponding compensation in health care resources and increased waiting times for surgery due to, among other things, a shortage of nurses. The results highlight the importance of constantly monitoring follow-up programs.

Marula seed cake (MSC) is a nutritionally-rich natural feed resource that can enhance the healthiness of animal-derived foods (ADFs) for human consumption. This study compared the health-related fatty acid (FA) profiles of MSC products from South Africa and Eswatini. Composite samples monthly collected from both countries were analysed for FAs. MSC products from both countries were found to be dominated by oleic acid (>70%), followed by palmitic, linoleic and stearic acids. Consequently, both products had their FA totals dominated by ƩMUFA followed by ƩSFA, ƩPUFA, Ʃn-6 PUFA and Ʃn-3 PUFA. Both oleic and stearic acids were higher (P < 0.01) whilst linoleic (P < 0.001), α-linolenic (P < 0.05), margaric (P < 0.05), palmitoleic (P < 0.05) and eicosatrienoic (P < 0.05) acids were lower in South African in comparison to Eswatini MSC. Consequently, South African MSC had higher ƩMUFA (P < 0.01) but lower ƩPUFA (P < 0.001), Ʃn-6 PUFA (P < 0.001) and Ʃn-3 PUFA (P < 0.05). Also, Eswatini MSC had higher n-6 : n-3 PUFA, PUFA : SFA (P = 0.001) and PUFA : MUFA (P < 0.05) ratios. Further, MSC products from both countries had similarly (P > 0.05) low atherogenicity and high desaturase indices. In conclusion, both country products are rich particularly in oleic acid and their incorporation into farm animal diets would increase content of the MUFA in ADFs and, consequently, improve health benefits to human consumers.

Background: The dairy industry heavily relies on fermentation processes driven in high proportion by Lactococcus lactis. The fermentation process can be perturbed or even stopped by bacteriophage activity leading to complete loss of fermentation batch or decreased quality product. Monitoring of the phage diversity and dynamics in the process allows to implement protective measures (e.g. starter rotation) in order to maintain unperturbed production.; Methods: Universal primers were used to amplify sequences of the 936, c2, and P335 Lactococcus phage types. The amplicons were sequences with Sanger method and obtained degenerate sequences were analyzed using simple bioinformatic pipeline in R environment.; Results: The most prevalent phage type is 936, followed by P335, whereas c2 type is less frequent.; Conclusions: Curd cheeses prepared on non-pasteurized milk based on native milk microbiota had higher diversity of phages distinct of these found in dairy plants. Sanger sequencing of heterogenous amplicons generated on metagenome DNA can be used to asses low-complexity microbiota diversity.

Ongoing debates regarding the virtues and challenges of implementing open science for brain imaging research mirror those of the larger scientific community. The present commentary acknowledges the merits of arguments on both sides, as well as the underlying realities that have forced so many to feel the need to resist the implementation of an ideal. Potential sources of top-down reform are discussed, along with the factors that threaten to slow their progress. The potential roles of generational change and the individual are discussed, and a starter list of actionable steps that any researcher can take, big or small, is provided.

Using of the organic base tetramethylammonium hydroxides (TMAH) is a viable, cheap and fast route, for the MgZnAl-LDH type materials synthesis by both co-precipitation and mechano-chemical methods. TMAH provided several advantages as smaller quantity of water required in the washing step compared to the use of inorganic alkalis, prevention of LDH contamination with alkali cations, acting as template molecule in texture tailoring along with disadvantages as its presence in small quantities in the resulting layered materials. Regardless the use of organic / inorganic bases and co-precipitation / mechano-chemical methods, zincite stable phase was found in all the synthesized solids. The basicity of catalysts followed the trend: mixed oxides &gt; reconstructed &gt; parent LDH. The memory effect of LDH is supported only by the presence of Mg and Al cations, while Zn remains as zincite stable phase. The catalytic activities for Claisen-Schmidt condensation of benzaldehyde with cyclohexanone provided values higher than 90% after 2h, with a total selectivity in 2,6-dibenzylidenecyclohexanone, while in self-condensation of cyclohexanone no more than 7.29% after 5h. These behaviors depended on catalysts basicity as well as the planar rigidity of the compound.

Pain is a natural bioassay for detecting and quantifying biological activities of venoms. The painfulness of stings delivered by ants, wasps, and bees can be easily measured in the field or lab using the stinging insect pain scale that rates the pain intensity from 1 to 4, with 1 being minor pain, and 4 being extreme, debilitating, excruciating pain. The painfulness of stings of 96 species of stinging insects and the lethalities of the venoms of 90 species was determined and utilized for pinpointing future promising directions for investigating venoms having pharmaceutically active principles that could benefit humanity. The findings suggest several under- or unexplored insect venoms worthy of future investigations, including: those that have exceedingly painful venoms, yet with extremely low lethality – tarantula hawk wasps (Pepsis) and velvet ants (Mutillidae); those that have extremely lethal venoms, yet induce very little pain – the ants, Daceton and Tetraponera; and those that have venomous stings and are both painful and lethal – the ants Pogonomyrmex, Paraponera, Myrmecia, Neoponera, and the social wasps Synoeca, Agelaia, and Brachygastra. Taken together, and separately, sting pain and venom lethality point to promising directions for mining of pharmaceutically active components derived from insect venoms.

Disputes on authorships or the order of authors on publications are among the most common conflicts in science, particularly where multi-author papers have become the norm. Here, I propose an adaptable and generalizable method to rationalize and democratize decisions about authorships, which can be applied in diverse scientific areas. In the process, the authors of a manuscript collect, discuss, score, and weight their contributions to the final manuscript. The decision process is assisted by a simple spreadsheet-based “authorship matrix”, which helps to break down the complexity of different contributions and their importance. The matrix generates a score s describing the percentage of the author’s total contributions and can be used to determine authorship and their order. The transparency and simplicity score s can reduce conflicts and thus increase productivity in collaborations.

In this paper, dual-rotor counter-rotating (CR) configurations of vertical axis wind turbines (VAWT) are briefly inspected and divided into three types. This investigation was focused on one of these types – the CR-VAWT with co-axial rotors, in which two equal rotors are placed on the same shaft, displaced from each other along it and rotate in opposite directions. For this CR-VAWT with three-blade H-Darrieus rotors, the properties of the design in terms of aerodynamics, mechanical transmission and electric generator, as well as control system are analyzed. A new direct-driven dual-rotor (DR) permanent magnet synchronous generator (PMSG) was proposed, in which two built-in low-power PM electric machines have been added. They perform two functions – start-up and overclocking of the rotors to the angular velocity at which the lifting force of the blades is generated and stabilizing the CR-VAWT work as wind gusts act on the two rotors. Detailed in this paper is the evaluation of aerodynamic performance of the CR-VAWT via 3D computational fluid dynamics (CFD) simulations. The evaluation was conducted using the CONVERGE CFD software with the inclusion of the actuator line model for the rotor aerodynamics, which significantly reduces the computational effort. Obtained results show that both rotors, while they rotate in opposite directions, had a positive impact on each other: the power coefficients of the upper and lower rotors in the CR-VAWT increased by 5.5% and 13.3% respectively compared to the single-rotor VAWT at the optimal distance between the rotors of 0.3 from a rotor height.

AGI could arise within the next decades, promising a decisive strategic advantage. This paper discusses risks, associated with the development of AGI: destabilizing effects on strategic balance, underestimating risks in the interest of victory in the race, egoistically exploiting the huge benefits by a tiny minority. Further: Developed AGI could be beyond human control. Human goals could not be implemented and an intelligence explosion to superintelligence could take place leading to a total loss of control and power. If competition for AGI is non-transparent, secret, uncontrolled and not regulated, it’s possible that risks could not be managed and would lead to catastrophic consequences. The danger corresponds to that of nuclear weapons. It is crucial that the key actors of a possible AI Race agree at an early stage on the prevention and transparent regulation of a possible AI Race - similar to measures to secure strategic stability, on arms control measures, disarmament, and prevention of the proliferation of nuclear weapons. The realization that an uncontrolled AI race can lead to the extinction of humanity - this time even independent of human will – requires analogous measures to contain, prevent, regulate and secure an AI race within the framework of AGI development.

The increasingly used approach of combining different simulation software in testing of automated driving systems (ADS) increases the need for potential and convenient software designs. Recently developed co-simulation platforms (CSP) provide the possibility to cover the high demand on testing kilometers for ADS by combining vehicle simulation software (VSS) with traffic flow simulation software (TFSS) environments. The emphasis on the demand of testing kilometers is not enough to choose a suitable CSP. The complexity level of the used vehicle, object, sensors and environment models is essential for valid and representative simulation results. Choosing a suitable CSP raises the question of how the test procedures should be defined and constructed and what the relevant test scenarios are. Parameters of the ADS, the environments, objects, sensors in VSS as well as traffic parameters in TFSS can be used to define and generate test scenarios. In order to generate a large number of scenarios in a systematic and automated way, suitable and appropriate software designs are required. In this paper we present a software design for CSP based on the Model-View-Controller (MVC) design pattern and implementation of a complex CSP for virtual testing of ADS. Based on this design, an implementation of a CSP is presented using the VSS from IPG Automotive called CarMaker and the TFSS from PTV Group called Vissim. The results have shown that the presented CSP design and the implementation of the co-simulation can be used to generate relevant scenarios for testing of ADS.

Printed oral splints are a therapeutic alternative in the treatment of functional disorders. Their mechanical properties are crucial to their clinical success and their performance can vary depending on cleaning, post-polymerization, or build orientation. This in vitro study aimed to compare the biaxial flexural strength of the chosen materials depending on the aforementioned parameters. 720 discs (n = 15 per group, 16 mm x 2 mm) were printed from splint materials. Printing was performed under 90°, 45°, or 0° orientation to the building platform with supporting structures. Specimens were either automatically or manually cleaned with isopropanol. Post-polymerization was performed with LED- or Xenon-light. Biaxial flexural strength (BFS) was determined with a piston-on-3-ball test after 24 hours or 60 days water storage (37°C). Test specimens were preloaded with 0.5 N and the load was applied by a piston of 1.6 mm in diameter at 1 mm/min crosshead speed. Statistics were performed by using descriptive statistics, ANOVA, and Levene-tests. Mean BFS after 24 hours of storage varied between 79 MPa and 157 MPa. After 60 hours the BFS significantly decreased and revealed values ranging from 72-127 MPa (mean24 113 MPa, mean60 97 MPa; p&lt;0.001). No significant differences could be determined between the materials (p=0.103) or between the different cleaning procedures (p=0.321). Post-polymerization yielded higher means with LED- (P1: 115 MPa) than with Xenon-light (P2: 95 MPa; p&lt;0.001). Regarding position, the mean values ranged from 101 MPa for 0°, 102 MPa for 45°, and 115 MPa for 90°, which was significantly different (p&lt;0.001). Build orientation of 90° and post-polymerization with LED-light provided significantly higher biaxial flexural strength and should be used to guarantee optimal strength of splint materials. Aging decreased the biaxial flexural strength of the tested specimens.

Cognitive impairment is a condition which affects aging patient populations and is becoming more prevalent as the geriatric population expands. It is categorized by the extent of cognitive decline, memory loss, functional abilities, and the capability to perform daily tasks. Based on the degree of impairment, it is classified as mild cognitive impairment or dementia. Considering the debilitating nature of cognitive decline and its impact on quality of life, prevention is key. In addition, given the gradual progression of the underlying causes of cognitive decline, early diagnosis and appropriate management has the potential to offer clinical advantages and better patient outcomes. Management options discussed vary from pharmaceutical regimens to neurosurgical interventions, with differing outcomes based on etiology of cognitive impairment.

Lateral vehicle control is a high importance in automated vehicles as it directly influences the vehicle’s performance and safety during operation. The Linear Quadratic Regulator (LQR) controller stands out due to its high-performance characteristics and is used in the open source for self driving functions. However, a notable limitation of the current approach is the manual calibration of LQR controllers based on the experience and intuition of the designers, leading to empirical uncertainties. To address this issue and enhance the lateral control performance, this paper concentrates on refining the LQR by employing three optimization algorithms: Artificial Bee Colony Optimization (ABC), Genetic Algorithm (GA), and Particle Swarm Optimization (PSO). These algorithms aim to overcome the reliance on empirical methods and enable a data-driven approach to LQR calibration. By comparing the outcomes of these optimization algorithms to the manual LQR controller within an offline multibody simulation as testing platform, the study highlights the superiority of the best-performing optimization approach. Following this, the optimal algorithm is implemented on a real-time system for the full vehicle level, revealing the Model-in-the-Loop and the Hardware-in-the-Loop gap up to 78,89% with lateral velocity when we use Relative Error Criterion (REC) method to validate and 2.35m with lateral displacement when considering by maximum absolute value method.

The pandemic is fast moving, accelerating rapid changes that lead to new challenges and making organizations suffer an impact. A big mark has been left on the workplaces - places where we do business, because an ongoing change to remote work challenges the role of the office. It is highly possible that as the change is progressing, it is not only the workplace that will change its design, but also the way in which work will be planned, organized, done and controlled. However, as the restrictions ease up questions appear: What is the potential of office sustainability? How has the perception of flexible office space changed due to the COVID-19 pandemic? This paper used an online survey as a quantitative research method. In this paper, we looked at the employer’s vision of the office. We investigated employers’ perspectives of where and in what settings the work will be done in the post-pandemic time. Specifically, we discussed the changes employers will apply in terms of work environment and office layout. The findings suggest that an increasing mobile workforce and expansion of the new workstyle will not mean an office exodus, but will certainly have an impact on office utilization.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

Gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between response to the anti-PD-1 therapy and the baseline gut microbiome in the Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy and 10 healthy subjects were recruited. Response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis, and metataxonomics of the microbiota. The Bacteroidota to Firmicutes ratio was higher, and the richness was decreased in the responders. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas non-responder gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis, and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption, but also gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota alongside diet were found associated with response to the therapy in the Polish population of melanoma patients.

The naturally occurring dipeptide carnosine (β alanyl L histidine) specifically attenuates tumor growth. Here, we asked whether other small imidazole containing compounds also affect viability of tumor cells without affecting non-malignant cells, and whether formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L alanyl L histidine (LA-LH), ß alanyl L alanine, L histidine, histamine, imidazole, β alanine and L alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L histidine and formation of histamine was investigated by High Performance Liquid Chromatography coupled Mass Spectrometry. Whereas carnosine and LA LH inhibited tumor cell growth with minor effects on fibroblasts, L-histidine, histamine and imidazole affected viability in both cell types. Compounds without imidazole moiety did not diminish viability. In the presence of LA LH but not in the presence of carnosine a significant rise of intracellular amounts of histidine was detected in all cells. Formation of histamine was not detectable in the presence of carnosine, LA LH or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA LH. Despite histamine had a strong effect on cell viability, formation of histamine is not responsible for the effects on cell viability of carnosine, LA LH and histidine.

In order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, BiI3 has been reacted with two equivalents of MeOC(=S)N(H)Ph in MeCN solution to afford the dinuclear title compound complexes [{I2Bi(μ2-I)2BiI2}{1-MeOC(=S)N(H)Ph}4] 1. Compound 1 has been characterized by IR, UV and NMR spectroscopy, the dinuclear framework has be ascertained by a single-crystal X-ray diffraction study performed at 100 K.

Insufficient physical activity (PA) is associated with low cardiorespiratory fitness, which favors cardiovascular and other non-communicable diseases. Besides, it evidentially affects mental health. Considering the WHO PA guidelines, CrossFit® represents a versatile exercise program, combining aerobic and resistance training with mobility and could help lowering disease incidences among sedentary people. Yet, long-term CrossFit research is sparse. We conducted a nine-months intervention (≥ 2 CrossFit workouts/week) in sixteen beginners (14 males, 35  6.8 years, 180  8.6 cm, 85. 5  19.1 kg). As primary endpoint, VO2max was assessed at baseline, after four, and nine months. A repeated-measures ANOVA and pearson correlation were conducted. Well-being was investigated by WHO-5-index pre- and post-intervention. For exploratory purpose, body composition was tracked. Main outcome was an 11.5 % VO2max improvement with large effect (p < .01, η_p^2 = .27). Strong negative correlations between baseline VO2max and its progression after nine months (p = .006, r = -.654) were found. Well-being increased by 8.7 % (p = .024, d = .51). Body composition improved without statistical significance. Resting metabolic rate increased by 2.2 % (p = .042). This study reveals the potential of CrossFit to enhance physiological and psychological health in beginners. For more robust results, bigger sample sizes with higher proportion of women are needed.

The adoption of Machine Learning (ML) for building emulators for complex physical processes has seen an exponential rise in the recent years. While neural networks are good function approximators, optimizing the hyper-parameters of the network to reach a global minimum is not trivial, and often needs human knowl- edge and expertise. In this light, automatic ML or autoML methods have gained large interest as they automate the process of network hyper-parameter tuning. In addition, Neural Architecture Search (NAS) has shown promising outcomes for improving model performance. While autoML methods have grown in popularity for image, text and other applications, their effectiveness for high-dimensional, complex scientific datasets remains to be investigated. In this work, a data driven emulator for turbulence closure terms in the context of Large Eddy Simulation (LES) models is trained using Artificial Neural Networks and an autoML frame- work based on Bayesian Optimization, incorporating priors to jointly optimize the hyper-parameters as well as conduct a full neural network architecture search to converge to a global minima, is proposed. Additionally, we compare the effect of using different network weight initializations and optimizers such as ADAM, SGDM and RMSProp, to explore the best performing setting. Weight and function space similarities during the optimization trajectory are investigated, and critical differences in the learning process evolution are noted and compared to theory. We observe ADAM optimizer and Glorot initialization consistently performs better, while RMSProp outperforms SGDM as the latter appears to have been stuck at a local minima. Therefore, this autoML BayesOpt framework provides a means to choose the best hyper-parameter settings for a given dataset.

The formation of solid solution series Cs_1-xM_xGaQ₂-mC64 (M = K, Rb; Q = S, Se; x = 0–1) was studied by X-ray diffraction and spectroscopic methods, revealing a complete miscibility of CsGaQ₂-mC64 with RbGaQ₂ and KGaSe₂, and a large miscibility gap with KGaS₂. All solid solution members exhibit similar Raman spectra, indicating the covalent Ga-Q bonding character. The similar optical band gaps likewise further contribute to this conclusion. Up to a degree of substitution, these solid solutions undergo a phase transition similar to CsGaQ₂-mC64. The influence of the substitution parameter x on phase transition process was investigated in situ using high-temperature X-ray powder diffraction experiments. Phase-pure solid solutions of the high-temperature polymorphs Cs_1-xM_xGaQ₂-mC16 were obtained up to x_max(K) = 0.1 and x_max(Rb) = 0.3. The crystal structures of these new CsGaQ₂-mC16 analogous high-temperature phases were refined from synchrotron diffraction data by Rietveld-refinement.

Trypanosome brucei, the causative agent of African sleeping sickness, harbours a highly ordered, subpellicular microtubule cytoskeleton that defines many aspects of morphology, motility and virulence. This array of microtubules is associated with a large number of proteins involved in its regulation. Employing proximity-dependent biotinylation assay (BioID) using the well characterized cytoskeleton-associated protein CAP5.5 as a probe we identified CAP50 (Tb927.11.2610). This protein colocalizes with the subpellicular cytoskeleton microtubules but not with the flagellum. Depletion by RNAi results in defects in cytokinesis, morphology and partial disorganization of microtubule arrays. Published proteomics data indicate a possible association of CAP50 with two other, yet uncharacterized, cytoskeletal proteins, CAP52 (Tb927.6.5070) and CAP42 (Tb927.4.1300), which were therefore included in our analysis. We show that their depletion causes phenotypes similar to those described for CAP50 and that they are essential for cellular integrity.

The improvement of energy efficiency of hydraulic systems remains to be an essential challenge for the industry, and the demand for more sustainable solutions is increasing. A main focus in this endeavor is the ability to eliminate or strongly reduce the use of throttle control valves which have been the preferred control element in industrial hydraulic systems for decades. Components have been subject to continuous evolution, and current industrial grade hydraulic pumps and motors are both efficient and reliable. Even though few percentages of energy efficiency can still be achieved, the main achievements in terms of efficiency is associated with novel system designs rather than further development of components. An area subject to increasing attention is the field of variable-speed displacement control, allowing to avoid the main control valve throttle losses. Systems using this technology are, however, mainly developed as standalone drive systems, necessitating maximum force, speed and power installed in each axis, with limited hydraulic power distribution capability as compared to valve controlled systems. An emerging field addressing this challenge is so-called electro-hydraulic variable-speed drive networks which allow to completely eliminate the use of control valves and enables power sharing both electrically and hydraulically, potentially reducing the necessary installed power in many cases. The idea of such a technology was first proposed in 2022, and so far developments reported in literature have mainly been of theoretical nature. This article presents the first ever experimental results for a dual cylinder electro-hydraulic variable-speed drive network prototype. The prototype has been developed for an industrial application, but has initially been implemented in a laboratory testbench. Extensive data acquisition has been conducted while subject to the associated industrial motion cycle, under different load conditions. The data is further used in combination with models to predict the total efficiency of the drive network prototype under higher loads than what could be achieved in the laboratory, suggesting a total efficiency from the electric supply to the cylinder pistons of 68 %. Re-configuring the prototype to a known standalone drive system structure implies comparable efficiencies. Finally, the drive network is theoretically compared to a valve drive solution, generally suggesting the prototype drive network to provide efficiency improvements of at least 40 % in comparison.

Reduced nutrient mineralization rates under minimum tillage are usually compensated by mineral fertilizer application. These cannot be applied in organic farming systems, however. We hypothesized that organic minimum tillage based on frequent cover cropping and application of dead mulch will improve soil fertility and can compensate for the potential negative effects of minimum tillage. Two long-term field experiments were set up in 2010 and 2011 comparing plough versus minimum tillage including application of transferred mulch. As second factor, the application of compost versus mineral potassium and phosphorus was compared. In 2019, soils were analyzed for soil pH, organic carbon, macro-, micronutrients, microbial biomass, microbial activity and total nematode abundance. In addition, performance of pea in the same soils was determined under greenhouse conditions. Across both experiments, macronutrients (+52%), micronutrients (+11%), microbial biomass (+51%), microbial activity (+86%), and bacterivorous nematodes (+112%) increased in minimum tillage compared with the plough-based system. In the greenhouse, pea biomass was 45% higher in the soil that had been subjected to minimum tillage compared to the plough. In conclusion, soil fertility can be improved in organic minimum tillage systems by intensive cover cropping and application of dead mulch to levels higher than in a plough-based system.

NF-B signalling is crucial for cellular responses to inflammation but has also been associated with the hypoxia response. NF-B and HIF transcription factors possess an intense molecular crosstalk. Although it is known that HIF-1beta modulates NF-kappaB transcriptional response, very little is understood regarding how HIF-1beta contributes to NF-kappaB signalling. Here, we demonstrate that HIF-1beta is required for full NF-kappaB activation in cells following canonical and non-canonical stimuli. We found that HIF-1beta specifically controls TRAF6 expression in human cells but also in Drosophila melanogaster. HIF-1beta binds to the TRAF6 gene and controls its expression independently of HIF-1alpha. Furthermore, exogenous TRAF6 expression is able to rescue all of the cellular phenotypes observed in the absence of HIF-1beta. These results indicate that HIF-1beta is an important regulator of NF-kappaB with consequences for homeostasis and human disease.

In the transition towards sustainable energy sources, hydrogen has emerged as the predominant alternative after fossil fuels. This comprehensive literature review delves into the evolving landscape of hydrogen launching strategies within the energy market. Numerous countries have strategically initiated efforts to introduce products based on hydrogen, underscoring the global acknowledgment of the potential inherent in hydrogen. Despite witnessing significant growth in the adoption of hydrogen energy worldwide, impediments to its widespread commercialization persist. This review identifies key barriers, including cost structures, technical complexities, and marketing challenges, hindering the establishment of a robust hydrogen energy market. The article critically examines the actions already undertaken to harness hydrogen energy for commercial purposes, leveraging scientific insights and statistical data. By carefully examining the current state of hydrogen energy initiatives, the review highlights gaps in existing strategies that require thoughtful consideration. Insights derived from scientific and statistical analyses inform the identification of barriers and contribute to a nuanced understanding of the challenges faced in the journey towards hydrogen energy commercialization. Ultimately, the article presents a strategic proposal outlining marketing actions geared towards expediting the commercialization and widespread adoption of hydrogen energy. Grounded in a thorough review of existing literature and supported by scientific and statistical evidence, this comprehensive analysis offers valuable insights for stakeholders seeking to navigate the intricate landscape of hydrogen energy in the global energy market.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called (super-)chaotropic effect, arises from the partial dehydration of both, the nano-ion and the solute, leading to a high gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403- on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques reveals that (i) below the micellization temperature of P84, PW12O403- exclusively binds to the propylene oxide moiety of P84 unimers and (ii) above the micellization temperature, PW12O403- mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403- to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and reinforced by the hydrophobic effect. At higher temperatures, the copolymer micellization leads to the displacement of PW12O403- from the PPO chain to the PEO chains. This study deepens the understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

In MBSE there is yet no converged terminology. The term ’system model’ is used in different contexts in literature. In this study we elaborated the definitions and usages of the term ’system model’, to find a common definition. 104 publications have been analyzed in depth for their usage and definition as well as their meta-data e.g., the publication year and publication background to find some common patterns. While the term is gaining more interest in recent years it is used in a broad range of contexts for both analytical and synthetic use cases. Based on this three categories of system models have been defined and integrated into a more precise definition.

Selective Paste Intrusion (SPI) is an additive manufacturing (AM) process in which thin layers of aggregates are selectively bonded by cement paste only where the structure is to be produced. In this way, concrete elements with complex geometries and structures can be created. Reinforcement is required to increase the flexural strength of the concrete elements and, thus, enable their applicability in practice. Integrating the reinforcement is a difficult task, particularly in the case of SPI due to the layer-wise printing method. Especially with respect to possible complex structures, the production of the reinforcement needs to be adapted to SPI, thereby offering a high degree of freedom. One concept for a reinforcement integration is combining the two additive manufacturing processes SPI and Wire and Arc Additive Manufacturing (WAAM). However, since the two processes serve different fields of application, their compatibility is not necessarily given. Ongoing investigations show that the temperatures caused by WAAM adversely affect both, the cement paste rheology required for sufficient paste penetration into the particle bed and the overall concrete strength. This paper provides an overview of ongoing research focusing on different cooling strategies and their effects on the compressive strength of SPI-printed concrete parts.

Driver drowsiness is one of the leading causes of traffic accidents. This paper proposes a new method for classifying driver drowsiness using deep convolution neural networks trained by wavelet scalogram images of electrocardiogram (ECG) signals. Three different classes were de-fined for drowsiness based on video observation of driving tests performed in a simulator for manual and automated modes. The Bayesian optimization method is employed to optimize the hyperparameters of the designed neural networks, such as the learning rate and the number of neurons in every layer. To assess the results of the deep network method, Heart Rate Variability (HRV) data is derived from the ECG signals, some features are extracted from this data, and finally, random forest and k-nearest neighbors (KNN) classifiers are used as two traditional methods to classify the drowsiness levels. Results show that the trained deep network achieves balanced accuracies of about 77% and 79% in the manual and automated modes, respectively. However, the best obtained balanced accuracies using traditional methods are about 62% and 64%. We conclude that designed deep networks working with wavelet scalogram images of ECG signals significantly outperform KNN and random forest classifiers which are trained on HRV-based features.

Cesiumtrifluoroacetate (CsTFA) is a key chemical for RNA-based stable isotope analyses to link the structure and function of microbial communities. We report a protocol to easily synthesize CsTFA from Cesiumcarbonate (Cs₂CO₃₎ and Trifluoroacetate (TFA) and show that self-synthesized CsTFA behaves similar to commercial CsTFA in the separation of isotopically labelled and unlabelled E. coli RNA.

Vehicle safety promises to be one of the Advanced Driver Assistance System (ADAS) biggest benefits. Higher levels of automation remove the human driver from the chain of events that can lead to a crash. Sensors play an influential role in vehicle driving as well as in ADAS by helping the driver to watch the vehicle’s surroundings for safe driving. Thus, the driving load is drastically reduced from steering as well as accelerating and braking for long-term driving. The baseline for the development of future intelligent vehicles relies even more on the fusion of data from surrounding sensors such as Camera, Lidar and Radar. These sensors not only need to perceive in clear weather but also need to detect accurately adverse weather and illumination conditions. Otherwise, a small error could have an incalculable impact on ADAS. As most of the current study is based on indoor or static testing. In order to solve this problem, this paper designs a series of dynamic test cases with the help of outdoor rain and intelligent lightning simulation facilities to make the sensor application scenarios more realistic. As a result, the effect of rainfall and illumination on sensor perception performance is investigated. As speculated, the performance of all automotive sensors is degraded by adverse environmental factors, but their behaviour is not identical. Future work on sensor model development and sensor information fusion should therefore take this into account.

Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin. During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), SEC-HPLC and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX-heme interactions to approximate physiological conditions (from extremely low to more than 2-fold heme excess). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggests more than one binding site in both plasma and rhHPX. Further, our study provides a useful analytical platform for detailed characterization of HPX-heme interactions and potentially, novel HPX fusion constructs.

Since the first published genome sequence of Trypanosoma cruzi in 2005, there has been tremendous technological advance in genomics, reverse genetics, and assay development for this elusive pathogen. However, there is still an unmet need for new and better drugs to treat Chagas disease. Here we introduce a T. cruzi assay strain that is useful for drug research as well as basic studies in host-pathogen interaction. Trypanosoma cruzi STIB980 is a strain of discrete typing unit TcI that grows well in culture as axenic epimastigotes or intracellular amastigotes. We have evaluated the optimal parameters for genetic transfection and constructed derivatives of T. cruzi STIB980 that express reporter genes for fluorescence- or bioluminescence-based drug efficacy testing, as well as a Cas9-expressing line for CRISPR/Cas9-mediated gene editing. The genome of T. cruzi STIB980 was sequenced by combining short-read Illumina with long-read Oxford Nanopore technologies. The latter served for the primary assembly, the former to correct mistakes and fill the gaps. This resulted in a high-quality nuclear haplotype assembly of 28 Mb in 400 contigs, containing 10,043 open-reading frames with a median length of 1077 bp. We believe that T. cruzi STIB980 is a useful addition to the antichagasic toolbox, and propose that it can serve as a DTU TcI reference strain for drug efficacy testing.

As part of our research for new leads against human African trypanosomiasis (HAT), we report on a 3D-QSAR study for antitrypanosomal activity and cytotoxicity of aminosteroid-type alkaloids recently isolated from the African medicinal plant Holarrhena africana A. DC. (Apocynaceae), some of which are strong trypanocides against Trypanosoma brucei rhodesiense (Tbr) with low toxicity against mammalian cells. Fully optimized 3D molecular models of seventeen congeneric Holarrhena alkaloids were subjected to a comparative molecular field analysis (CoMFA). CoMFA models were obtained for both, the anti-Tbr and cytotoxic activity data. Model performance was assessed in terms of statistical characteristics (R², Q² and P² for partial least squares (PLS) regression, internal cross-validation (leave-one-out) and external predictions (test set), respectively, as well as the corresponding SDEP and F-values). With R²=0.99, Q²=0.83 and P²=0.79 for anti-Tbr activity and R²=0.94, Q²=0.64, P²=0.59 for cytotoxicity against L6 rat skeletal myoblasts, both models were of good internal and external predictive power. The regression coefficients of the models representing the most prominent steric and electrostatic effects on anti-Tbr and for L6 cytotoxic activity were translated into contour maps and analyzed visually, allowing suggestions for possible modification of the aminosteroids to further increase the antitrypanosomal potency and selectivity. Very interestingly, the 3D-QSAR model established with the Holarrhena alkaloids also applied to the antitrypanosomal activity of two aminocycloartane-type compounds recently isolated by our group from Buxus sempervirens L. (Buxaceae), which indicates that these structurally similar natural products share a common SAR and, possibly, mechanism of action with the Holarrhena steroids. This 3D-QSAR study has thus resulted in plausible structural explanations of the antitrypanosomal activity and selectivity of aminosteroid- and aminocycloartane-type alkaloids as an interesting new class of trypanocides and may represent a starting point for lead optimization.

Residual stresses in fiber metal laminates (FML) inevitably develop during the manufacturing process. The main contributor to these stresses is the difference in the coefficients of thermal expansion (CTE) between fibers and metal in combination with high process temperatures. To quantify these stresses, the use of specimens with an asymmetric layup is an easily adaptable method. The curvature that develops after the manufacturing of flat laminates with an asymmetrical layer stack is a measure of the level of residual stresses evolving during cure. However, the accuracy of the curvature evaluation is highly dependent on specimen design and other influencing parameters. In this work a large set of FML specimens is investigated to identify relevant influencing parameters and derive conclusions about specimen design and evaluation techniques. For certain layups and process parameters, there is a good correlation between the curvature and the stress-free temperature, which is further covered by analytical solutions for bimetals. This correlation is the basis to transfer curvature into a stress-free temperature that can consequently be used for the quantification of residual stress levels in more complex FMLs. The transfer is validated by in-situ strain measurements during cure using a strain gage technique. Based on the results, the application of asymmetric specimens for residual stress characterization in more complex laminates is presented in the form of a workflow.

Background: The thoracolumbar fascia (TLF) is thought to play a role in the development of LBP, but it is not yet clear which factor of TLF changes is a cause and which is an effect. Therefore, some studies used the cross-correlation function (CCR) to reveal time-dependent relationships between biomechanical and neuromotor factors. Methods: Ten patients with acute low back pain (aLBP) were matched to healthy controls. Simultaneous recording of surface electromyography (sEMG) of the erector spinae muscle (ES) and dynamic ultrasound (US) images of TLF deformation were performed during trunk extension. CCR functions and Granger causality were used to describe the relationship between the two measures. Results: CCR time lags were significant higher in the aLBP group (p = 0.04). Granger causality (GC) showed a direct effect of TLF deformation on ES activation only in the aLBP group (p &lt; 0.03). Conclusions: The results suggest that in aLBP, ES activity is significantly affected by TLF, whereas this relation-ship is completely random in healthy subjects studied with CCR and GC comparisons of dynamic US imaging and sEMG data signals. Fascia-related disturbances in neuromotor control, particularly due to altered muscle spindle functions, are suspected as a possible mechanism behind this.

Heavy and light quarks produced in high-pT partonic collisions radiate differently. Heavy quarks regenerate their color field, stripped-off in the hard reaction, much faster than the light ones and radiate a significantly smaller fraction of the initial quark energy. This peculiar feature of heavy-quark jets leads to a specific shape of the fragmentation functions observed in e+e− annihilation. Differently from light flavors, the heavy quark fragmentation function strongly peaks at large fractional momentum z, i.e. the produced heavy-light mesons, B or D, carry the main fraction of the jet momentum. This is a clear evidence of the dead-cone effect, and of a short production time of a heavy-light mesons. Contrary to propagation of a small qq¯ dipole, which survives in the medium due to color transparency, a heavy-light Qq¯ dipole promptly expands to a large size. Such a big dipole has no chance to remain intact in a dense medium produced in relativistic heavy ion collisions. On the other hand, a breakup of such a dipole does not affect much the production rate of Qq¯ mesons, differently from the case of light qq¯ meson production.

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from e.g. diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19-54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyra^fit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps,obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability.

To understand forest dynamics under today’s changing environmental conditions, it is important to analyze the state of forests at large scales. Forest inventories are not available for all regions, so it is important to use other additional sources of information, e.g. remote sensing observations. Increasingly, remotely sensed data based on optical instruments and airborne LIDAR are becoming widely available for forests. There is great potential in analyzing these measurements and gaining an understanding of forests state. In this work, we combine the new generation radiative transfer model mScope with the individual-based forest model FORMIND to generate reflectance spectra for forests. Combining the two models allows us to account for species diversity at different height layers in the forest. We compare the generated reflectances for forest stands in Finland, in the region of North Karelia, with Sentinel-2 measurements. We investigate which level of forest representation gives the best results. For the majority of the forest stands, we generated good reflectances with all levels forest representation compared to the measured reflectance. Good correlations were also found for the vegetation indices (especially NDVI with R²=0.62). This work provides a forward modelling tool for relating forest reflectance to forest characteristics. With this tool it is possible to generate a large set of forest stands with corresponding reflectances. This opens the possibility to understand how reflectance is related to succession and different forest conditions.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

Cellular biomolecular condensates termed ribonucleoprotein (RNP) granules often are enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules is not well understood. In this study, we performed single molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SG) and processing bodies (PB), which are distinct in their molecular composition and function. We developed a photobleaching- and noise-corrected colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule’s boundaries. We found that mRNAs are often localized at granule boundaries, an observation consistent with recently published data. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid-liquid interfaces, which is observed in various technological and biological processes. We also suggest that this confinement could be due to a combination of intermolecular interactions associated with, first, the screening of a portion of the RNP granule interface by the polymer and, second, electrostatic interactions due to a strong electric field induced by a Donnan potential generated across the thin interface.

To fully appreciate genetics, one must understand the link between genotype (DNA sequence) and phenotype (observable characteristics). Advances in high-throughput genomic sequencing technologies and applications, so-called “-omics”, have made genetic sequencing readily available across fields in biology from applications in non-traditional study organisms to precision medicine. Thus, understanding these tools is critical for any biologist, especially those early in their career. This comprehensive review discusses the chronological development of different sequencing methods, the bioinformatics steps to analyzing this data, and social and ethical issues raised by these techniques that must be discussed and evaluated.

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.

The chemical graph theory is a subfield of mathematical chemistry which applies classic graph theory to chemical entities and phenomena. Chemical graphs are main data structures to represent chemical structures in cheminformatics. Computable properties of graphs lay the foundation for (quantitative) structure activity and structure property predictions - a core discipline of cheminformatics. It has a historic relevance for natural sciences, such as chemistry, biochemistry and biology, and is in the heart of modern disciplines, such as cheminformatics and bioinformatics. This review first covers the history of chemical graph theory, then provides an overview of its various techniques and applications for CASE, and finally summarises modern tools using chemical graph theory for CASE.

Airborne wind energy (AWE) systems use tethered flying devices to harvest higher-altitude winds to produce electricity. For a successful deployment of these systems, it is crucial to understand how the public perceives them. If public concerns about the technology are not taken seriously, implementation could be delayed or, in some cases, prevented, resulting in increased costs for project developers and a lower contribution of the sector to renewable energy targets. This literature review assessed the current state of knowledge on public responses to AWE. An exhaustive literature search led to the identification of 40 relevant publications that were reviewed. The literature assumed that the safety, visibility, acoustic emissions, ecological impacts, and the siting of AWE systems shape public responses to the technology. The reviewed literature views people’s responses to AWE very optimistically but lacks scientific evidence to back up its claims. It seems to overlook that the influence of AWE’s characteristics (e.g., visibility) on public responses will also depend on a range of situational and psychological factors (e.g., people’s general attitude towards AWE, the public’s trust in project developers). Therefore, empirical social scientific research is needed to increase the field’s understanding of public responses to AWE and thereby facilitate deployment.

We developed and applied a method for characterizing bacterial promoters genome-wide by in vitro transcription coupled to transcriptome sequencing specific for native 5’-ends of transcripts. This method called ROSE (Run-Off transcription/RNA-SEquencing), only requires chromosomal DNA, ribonucleotides, RNA polymerase (RNAP) core enzyme, and a specific sigma factor, recognizing the corresponding promoters, which have to be analyzed. ROSE was performed on E. coli K-12 MG1655 genomic DNA using E. coli RNAP holoenzyme (including σ70) and yielded 3,226 transcription start sites, 2,167 of which were also identified in in vivo studies, and 598 were new. Many new promoters not yet identified by in vivo experiments might be repressed under the tested conditions. Complementary in vivo experiments with E. coli K-12 strain BW25113 and isogenic transcription factor gene knockout mutants of fis, fur, and hns were used to test this hypothesis. Comparative transcriptome analysis demonstrated that ROSE could identify bona fide promoters that were apparently repressed in vivo. In this sense, ROSE is well-suited as a bottom-up approach for characterizing transcriptional networks in bacteria and ideally complementary to top-down in vivo transcriptome studies.

Knowledge of the temperature evolution is crucial to understand and control laser beam welding of low-melting materials. Existing temperature determination approaches are restricted to i) one-dimensional temperature information (e.g. ratio-pyrometers), ii) a priori knowledge of the emissivity (e.g. thermography) and iii) high temperature regions (e.g. two-wavelength imaging). In this paper, a ratio-based two-color-thermography approach is developed that allows for two-dimensional temperature determination in low-melting temperature ranges (< 1200 K). For static measurement situations it is demonstrated, that temperature can be determined despite variation in signal intensity and emissivity with high accuracy. The two-color-thermography set-up is further transferred into a commercial laser beam welding machine and experiments are conducted for varying process parameters. The direct application of the developed two-color-thermography system in dynamic process situations is limited as image artifacts presumably caused by internal reflections inside the optical beam path are present.

The rowing technique is a key factor in the overall rowing performance. Nowadays the athletes’ performance is so advanced that even small differences in technique can have an impact on sport competitions. To further improve the athletes’ performance, individualized rowing is necessary. This can be achieved by intelligent measurement technology that provides direct feedback. To address this issue, we developed a novel wireless rowing measurement system (WiRMS) that acquires rowing movement and measures muscle activity using electromyography (EMG). Our measurement system is able to measure several parameters simultaneously: the rowing forces, the pressure distribution on the scull, the oar angles, the seat displacement and the boat acceleration. WiRMS was evaluated in a proof-of-concept study with seven experienced athletes performing a training on water. Evaluation results showed that WiRMS is able to assess the rower’s performance by recording the rower’s movement and force applied to the scull. We found significant correlations (p&lt;0.001) between stroke rate and drive-to-recovery ratio. By incorporating EMG data, a precise temporal assignment of the activated muscles and their contribution to the rowing motion was possible. Furthermore, we were able to show that the rower applies the force to the scull mainly with the index and middle fingers.

Due to the high specific surface area of titanium aluminide powders, significant and unavoidable surface oxidation takes place during processing. The resulting oxides disrupt the conventional powder metallurgical process route (pressing and sintering) by reducing green strength and sintered properties. Oxide-free particle surfaces offer the potential to significantly increase particle bond strength and enable the processing of difficult-to-press material powders. In this work, the effect of milling titanium aluminide powder in a silane-doped atmosphere on the component properties after pressing and subsequent sintering was investigated. Ball milling was used to break up the oxide layers and create bare metal surfaces on the particles. With the help of silane-doped inert gas, the oxygen partial pressure was greatly reduced during machining. It was investigated whether oxide-free surfaces could be produced and maintained by milling in silane-doped at-mospheres. Furthermore, the resulting material properties after pressing and sintering were an-alyzed using density measurements, hardness tests, EDX-measurements and micrographs. It was concluded, that ball milling in a silane-doped atmosphere produces and maintains oxide-free particle surfaces. These oxide-free surfaces and smaller particle sizes improve the component properties after pressing and sintering.

Education outside the classroom (EOtC) can be beneficial for students. The relationship between biological stress markers and sedentary behavior (SB) plus physical activity (PA) is insufficiently evaluated in school settings. This exploratory study aims to evaluate the association between students’ cortisol, plus circulating cell-free deoxyribonucleic acid (cfDNA) levels, and their SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) during outdoor and indoor classes in different seasons. We assessed data from an education outside the classroom (EOtC) program (n = 48; intervention group [IG], n = 37; control group [CG], n = 11). We sampled data on 3 school-days in three seasons (fall, spring, and summer) in normal teaching indoors (CG) and outdoor lessons (IG) in the forest. SB and PA were evaluated by accelerometry, and cortisol and cfDNA levels by saliva samples. The compositional data analysis approach analyzed SB and PA. Fitted Bayesian hierarchical linear models evaluated the association between cortisol and cfDNA, and SB/LPA/MVPA. A steady decline of cortisol in the outdoor setting is associated with relatively high levels of LPA. SB and MVPA tended to exhibit a similar effect in the indoor setting. CfDNA is positively associated with a relatively high amount of SB in the IG, the same association is likely for LPA and MVPA in both groups. LPA seems to support a healthy cortisol decrease in children during outdoor lessons. The relevance of SB/PA as a composition in relation to students stress response in school should be emphasized. This study facilitates the formulation of straightforward and directed hypotheses for further research.

Technical components should be produced sustainably and are subject to growing demands in terms of durability and reliability. To meet these expectations, the development of thermochemical processes is auspicious. Titanium alloys, which have a comparatively high gas solubility, allow temporary hydrogen (H) loading, often called thermo hydrogen treatment (THT). THT causes lattice deformation and reduces the β transformation temperature. These effects enable an adjustment of the microstructure, which improves the mechanical properties as compared to those produced conventionally. Furthermore, the process is applicable to complex geometries that cannot be surface hardened by mechanical surface treatment techniques. The investigation presented intends to realize a local microstructure gradient in additively via laser-powder bed fusion (L-PBF) manufactured cylindrical Ti–6Al–4V specimens by changing the distribution and morphology of strengthening precipitates as well as the β grain size depending on the distance to the surface, which should improve the material fatigue properties. To evaluate the mechanical properties of such THT-induced microstructure gradients, the resulting change in fatigue life in the LCF and HCF range was determined by stress-controlled cyclic deformation tests. Besides, the resulting microstructure was characterized by means of XRD and TEM. In addition to the additively manufactured and thermo hydrogen treated cylindrical specimens, conventionally produced tube-like specimens were thermo hydrogen treated and examined. For the THT-induced microstructure gradients, numerically simulated H concentration profiles as well as experimentally determined hardness profiles were used for the evaluation of the THT process. The study shows that H-loading at 500°C and H-degassing at 750°C, followed by aging at 550°C, allows the establishment of a microstructure gradient that shows an 8% improvement in fatigue properties compared to a reference condition without THT. The reason for this improvement is an increased volume fraction secondary alpha phase in the near-surface area of the specimens. Moreover, the results show that the process is applicable a tube-like specimen with varying wall thicknesses.

Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.

New innovative green concepts in electrified vertical take-off and landing vehicles currently emerge as a revolution to urban mobility going into the third dimension (vertically). The high population density of cities makes the market share highly attractive while posing an extraordinary challenge for community acceptance due to the increasing and possibly noisier commuter traffic. In addition to passenger transport, package deliveries to customers by drones may enter the market. The new challenges associated with this increasing transportation need in urban, rural and populated areas pose challenges for established companies and startups to deliver low-noise emission products. The article's objective is to revisit the benefits and drawbacks of an affordable acoustic measurement campaign focused on early prototyping. In the very early phase of product development, often considerably limited resources are available. With this in mind, the article discusses the sound power results using the enveloping surface method in a typically available low-reflection room with a reflecting floor according to DIN EN ISO 3744:2011-02. The method is applied to a subsonic electric ducted fan (EDF) unit of a 1:2 scaled electrified vertical take-off and landing vehicle. The results show that considerable information at low costs can be gained for the early prototyping stage, despite this easy-to-use, easy-to-realize, and not fine-tuned measurement setup. Furthermore, the limitations and improvements to a possible experimental setup are presented to discuss a potentially more ideal measurement environment. Measurements at discrete operating points and transient measurements across the total operating range were conducted to provide complete information on the EDF's acoustic behavior. The rotor-self noise and the rotor-stator interaction were identified as primary tonal sound sources, along with the highest broadband noise sources located on the rotor. Based on engineering experience, a first acoustic improvement treatment is also quantified with a sound power level reduction of 4dB(A). In conclusion, the presented method is a beneficial first measurement campaign to quantify the acoustic properties of an electric ducted fan unit at minimal resources in a reasonable time of several weeks when starting from scratch.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and elderly individuals. DM may accelerate the aging process, and the age-related declines in the estimated Glomerular Filtration Rate (eGFR), can pose a challenge to diagnose diabetic kidney disease (DKD) using standard diagnostic criteria especially with absence of severe albuminuria among the elderly. In the presence of CKD and DM, elderly patients may need multidisciplinary care due to susceptibility to various health issues e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to the elderly. We review the evidence that the benefits from these newer therapies apply equally to elderly and non-elderly patients and propose a framework for the management of DKD by discussing the nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), Sodium Glucose Co-Transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and Glucagon Like Peptide 1 Receptor Agonists (GLP1-RAs).

Abiogenic hydrocarbons are fundamentally important for understanding the deep microbial communities and the origin of life. The generation of abiogenic hydrocarbons was proposed to be limited to ultramafic-hosted hydrothermal systems, fueled by the serpentinization product H₂. Here, we present the discharge of short-chain alkanes from an andesitic rock-hosted Lutao geothermal field in the north Luzon arc, carrying abiotic chemical and isotopic signals. These abiogenic hydrocarbons were generated from CO₂-H₂O-rich fluid inclusions, where the long-term storage since Lutao volcanism (~ 1.3 Ma) allowed overcoming the sluggish kinetics of CO₂ to CH₄ reduction at temperatures of 174 - 206 ^oC. Natural abiogenic production of hydrocarbons, therefore, can be more ubiquitous than previously thought. The hypothesis regarding the origin of methane in Earth’s early atmosphere and its implication to the origin of life may require reconsideration.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

Plant diseases cause losses of approximately 16% globally. Thus, management measures must be implemented to mitigate losses and guarantee food production. In addition to traditional management measures, resistance induction and biological control have gained ground in agriculture due to their enormous potential. Endophytic fungi colonize plant tissues internally and have the potential to act as biological control agents, as elicitors in the process of resistance induction and in attenuating abiotic stresses. In this review, we list the action of this group of microorganisms as potential agents which can act in controlling plant diseases and describe several examples in which endophytes were able to reduce the damage caused by pathogens and adverse conditions. This is due to their arsenal of molecules generated during the interaction by which they form a kind of biological shield in the plant. Studies on these microorganisms have grown due to the existing diversity and the multiple benefits they can offer. Finally, considering that endophytic fungi can be an important tool in managing diseases due to the large amount of biologically active substances produced, bioprospecting this class of microorganisms is tending to increase and generate valuable products.

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

Among hearing aid (HA) users, there is a considerable variability in word-recognition scores (WRS). This variability is most pronounced among individuals with moderately severe to severe hearing loss. The variability cannot be adequately explained by factors such as the pure-tone audiogram, audiogram type, or age. This prospective study was designed to investigate the relationship between tone decay (TD) and WRS in a group of HA users with corresponding pure-tone hearing loss. The study population included 22 patients with hearing loss between 50 and 80 dB HL. Aided WRS, unaided WRS and TD were assessed for both ears. TD was found to be frequency-dependent. TD and WRS were correlated, with up to R=–0.66. The TD test was revealed as a feasible method for explaining the variability in WRS among HA users with hearing loss below 80 dB. This may contribute to improved differential diagnostics. The TD test may thus offer a better understanding of the limitations of HA use in the context of cochlear implant candidacy assessment for HA users.

Transportation tasks in nursing are common and shorten the time for direct patient care in times of nursing shortage and an aging society. There is a lack of research on transportation needs, with most studies focusing on overall nursing task analysis without a deeper analysis of transportation tasks. In July and September 2023, we conducted weekly observations of nurses to assess clinical transportation needs. We aim to understand the economic impact and the methods nurses use for transportation tasks. We conducted a participant observation using a standardized app-based form over a seven-day observation period in two rural clinics. N=1,830 transports were made by nurses and examined by descriptive analysis. Non-medical supplies account for 27.05 % (n=495) of all transports, followed by medical supplies at 17.32 % (n=317), pharmacotherapy at 14.10 % (n=258) and other other categories like meals or drinks contributing 12.68 % (n=232). Most transports had a factual transport time of under a minute, with patient transport and lab samples displaying more variability. In total, 77.15 % of all transports were made by hand. Requirements to collect items or connect transports with patient care were included in 5 % of all transports. Our economic evaluation spotlighted meals as the most costly transport, with 9,596.16€ p.a. in the observed clinics. Budget-friendly robots would amortize over one year by transporting meals. We support understanding nurses’ transportation needs via further research on assistive robots to validate our findings and determine the feasibility of transport robots.

Road marking recognition is of great importance for the deployment of automated driving systems and for already existing driver line-keeping assistance systems. For proper and reliable function of machine vision systems that include LiDAR and camera, road markings must be visible to them to facilitate planning of driving trajectory. In this study, LiDAR intensity and the number of LiDAR points collected from a field analysis of two road markings systems reflectorised with premium and standard glass beads were analysed. In the lateral direction, it was demonstrated that the use of premium glass beads for road markings lead to 56% higher LiDAR intensity and 14% more LiDAR points captured than in case of standard road markings. In the longitudinal direction, premium road markings showed less distance attenuation, which is seen as advantageous for trajectory planning by machine version systems. The outcomes of this study offer insights for road infrastructure decision-makers, developers of automated driving systems, and researchers in the field of transportation technology.

Immunity against respiratory pathogens is often short-term, and consequently there is an unmet need for effective prevention of such infections. One such infectious disease is COVID-19, which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on March 11, 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, con-tained the pandemic's expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus transmission is warrant-ed. In this review, we present the status of the systemic vaccines, of the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell pep-tide-based vaccination applied by prime-boost schedule for eliciting both systemic and mucosal immunity.

Background: Instrument-assisted soft tissue mobilization (IASTM) is thought to alter fluid dynamics in human soft tissue. The aim of this study was to investigate the influence of IASTM on the thoracolumbar fascia (TLF) on the water content of the lumbar myofascial tissue. Methods: 21 healthy volunteers were treated with IASTM. Before and after the procedure and 5 and 10 minutes later, lumbar bioimpedance was measured by bioimpedance analysis (BIA) and TLF stiffness by indentometry. Tissue temperature was recorded at the measurement time points using an infrared thermometer. Results: Bioimpedance increased significantly from 58.3 to 60.4 Ω (p < 0.001) at 10-minute follow-up after the treatment. Temperature increased significantly from 36.3 to 36.6° Celsius from 5 to 10 minutes after treatment (p = 0.029), while lumbar myofascial stiffness did not change significantly (p = 0.84). Conclusions: After the IASTM intervention, there was a significant increase in bioimpedance, likely due to a decrease in water content in myofascial lumbar tissue. Further studies in a randomized control trial design are needed to extrapolate the results in healthy subjects to a symptomatic population as well and to confirm the reliability of BIA in myofascial tissue.

We are witnessing a dramatic transformation in the way we do science. In recent years, significant flaws with existing scientific methods have come to light, including lack of transparency, insufficient involvement of stakeholders, disconnection from the public, and limited reproducibility of research findings. These concerns have sparked a global movement to revolutionize scientific practice and the emergence of Open Science. This new approach to science extends principles of openness to the entire research cycle, from hypothesis generation to data collection, analysis, replication, and translation from research to practice. Open Science seeks to remove all barriers to conducting high quality, rigorous, and impactful scientific research by ensuring that the data, methods, and opportunities for collaboration are open to all. Emerging digital technologies and "big data" (see "Ten simple rules for responsible big data research") have further accelerated the Open Science movement by affording new approaches to data sharing, connecting researcher networks, and facilitating the dissemination of research findings. Open scientific practices are also having a profound impact on the health sciences and medical research, and specifically how we conduct clinical research with human participants. Human health research necessitates careful considerations for practicing science in an ethical manner. There is also a particular urgency to human health research since the goal is to help people, so doing good science takes on a different meaning than simply doing science well. It also implores the scientist to reassess the conventional view of human health research as a pursuit conducted by scientists on human subjects, and lays a greater emphasis on inclusive and ethical practices to ensure that the research takes into account the interests of those who would be most impacted by the research. Openness in the context of human health research also raises greater concerns about privacy and security and presents more opportunities for people, including participants of research studies, to contribute in every capacity. At the core of open health research, scientific discoveries are not only the product of collaboration across disciplines, but must also be owned by the community that is inclusive of researchers, health workers, and patients and their families. To guide successful open health research practices, it is essential to carefully consider and delineate its guiding principles. This editorial is aimed at individuals participating in health science in any capacity, including but not limited to people living with medical conditions, health professionals, study participants, and researchers spanning all types of disciplines. We present ten simple rules that, while not comprehensive, offer guidance for conducting health research with human participants in an open, ethical, and rigorous manner. These rules can be difficult, resource-intensive, and can conflict with one another. They are aspirational and are intended to accelerate and improve the quality of human health research. Work that fails to follow these rules is not necessarily an indication of poor quality research, especially if the reasons for breaking the rules are considered and articulated (see rule 6: document everything). While most of the responsibility of following these rules falls on researchers, anyone involved in human health research in any capacity can apply them.

In eukaryotes, the Dph1•Dph2 dimer is a non-canonical radical SAM enzyme. Using iron-sulfur (FeS) clusters, it cleaves the cosubstrate S-adenosyl-methionine (SAM) to form a 3-amino-3-carboxy-propyl (ACP) radical for synthesis of diphthamide. The latter decorates a histidine residue on elongation factor 2 (EF2) conserved from archaea to yeast and humans and is important for accurate mRNA translation and protein synthesis. Guided by evidence from archaeal orthologues, we searched for a putative SAM binding pocket in Dph1•Dph2 from Saccharomyces cerevisiae. We predict a SAM binding pocket near the FeS cluster domain that is conserved across eukaryotes in Dph1 but not Dph2. Site-directed DPH1 mutagenesis and functional characterization by assays diagnostic for loss of diphthamide reveal the SAM pocket is essential for synthesis of the décor on EF2 in vivo. Further evidence from structural modeling suggests particularly critical residues close to the methionine moiety of SAM. Presumably, they facilitate a geometry specific for SAM cleavage and ACP radical formation that distinguishes Dph1•Dph2 from classical radical SAM enzymes, which generate canonical 5′-deoxyadenosyl (dAdo) radicals.

The separation of microparticles with respect to different properties such as size and material is a research field of great interest. Dielectrophoresis, a phenomenon which is capable of addressing multiple particle properties at once, can be used to perform a chromatographic separation. However, the selectivity of current dielectrophoretic particle chromatography (DPC) techniques is limited. Here we show a new approach for DPC based on differences in the dielectrophoretic mobilities and the crossover frequencies of polystyrene particles. Both differences are addressed by modulating the frequency of the electric field to generate positive and negative dielectrophoretic movement to achieve multiple trap and release cycles of the particles. A chromatographic separation of different particle sizes revealed a voltage dependency of this method. Additionally, we showed the frequency bandwidth influence on separation using one example. The DPC method developed was tested with model particles but offers possibilities to separate a broad range of plastic and metal microparticles or cells and to overcome currently existing limitations in selectivity.

Long-range interactions are relevant for a large variety of quantum systems in quantum optics and condensed matter physics. In particular, the control of quantum-optical platforms promises to gain deep insights in quantum-critical properties induced by the long-range nature of interactions. From a theoretical perspective, long-range interactions are notoriously complicated to treat. Here, we give an overview of recent advancements to investigate quantum magnets with long-range interactions focusing on two techniques based on Monte Carlo integration. First, the method of perturbative continuous unitary transformations where classical Monte Carlo integration is applied within the embedding scheme of white graphs. This linked-cluster expansion allows to extract high-order series expansions of energies and observables in the thermodynamic limit. Second, stochastic series expansion quantum Monte Carlo which enables calculations on large finite systems. Finite-size scaling can then be used to determine physical properties of the infinite system. In recent years, both techniques have been applied successfully to one- and two-dimensional quantum magnets involving long-range Ising, XY, and Heisenberg interactions on various bipartite and non-bipartite lattices. Here, we summarise the obtained quantum-critical properties including critical exponents for all these systems in a coherent way. Further, we review how long-range interactions are used to study quantum phase transitions above the upper critical dimension and the scaling techniques to extract these quantum critical properties from the numerical calculations.

We examined whether the ambient illuminance during extended wakefulness modulates the homeostatic increase in human deep sleep [i.e. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA)] in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e. sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800K), and once under either white light (WL: 250 lux, 2800K) or blue-enriched white light (BL: 250 lux, 9000K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.

Forest management aims to preserve ecosystem integrity, maintaining resilience thresholds. For this, conservation and invasion patterns must be determined in managed landscapes. The objective was to identify proxies (landscape and environmental patterns) that allowed the plant species invasion and define thresholds of human impacts to improve management practices. We also want to identify indicator species for the different kinds of impacts and environments. 165 plots were measured in Nothofagus antarctica forests and associated open-lands (dry and wet grasslands) in Tierra del Fuego (Argentina). We found differences in the studied variables across landscape and among different uses and impact types. Human impacts influenced over land types, emphasizing the importance of managing intensities. Indicator plant species allowed to identify potential ecological thresholds related to human impacts and the establishment of species linked to ecological and economic degradation, e.g. Bolax gummifera and Azorella trifurcata were associated with high grazing pressure in grasslands and fire in forested areas, while Rumex acetosella and Achillea millefolium, typically associated with forested areas, were related to high harvesting pressure and fire impacts. These findings contribute to understanding the long-term effects of some impacts, and allow us to define variables of monitoring and indicator species for each impact type.

The genus Dirphys Howard is synonymized with Encarsia Förster syn. n. and treated as a species-group of Encarsia, referred to henceforth as the Encarsia mexicana species-group. The monophyly of Encarsia is discussed in relation to Dirphys. The new synonymy is based on phylogenetic analyses of the nuclear ribosomal 28S-D2 gene region (43 taxa, 510 bp). The Encarsia mexicana species-group is recovered as strongly monophyletic within Encarsia. All species of the Encarsia mexicana species-group are revised. The group includes six previously described species, and fourteen newly described species. All species are described (or redescribed) and illustrated. Detailed distributional data, and, where available, plant associate and host records are provided for all species. Encarsia myartsevae Kresslein &amp; Polaszek nom. nov. is here proposed as a replacement name for Encarsia mexicana Myartseva, now preoccupied by Encarsia mexicana (Howard). A dichotomous identification key, supplemented by an online multiple-entry key, is provided for all species.

Background: The intrauterine and early extrauterine development represents a “window of opportunity” in the immunological development. The underlying mechanisms are still poorly understood. The aim of this study was to provide reference values B cell subpopulations in cord blood of term newborns, juveniles and in adults to find the spectrum of their physiological age-related variation. Methods: In this study, we used flow cytometry to evaluate human B lymphocytes and subpopulations in cord blood (n = 10), in peripheral blood from healthy juveniles aged 1 to 17 years (n=20) and from donors aged 24 to 62 years (n = 10). Results: Our findings showed increasing frequencies of IgM memory B cells, class-switched memory B cells, marginal zone B cells and plasmablasts, from cord blood to peripheral blood of juveniles and adults. In con-trast, the percentage of naïve B cells was higher in newborns than in juveniles and adults. The frequencies of were similar in cord blood and peripheral blood of adults. Interestingly, transitional B cells frequencies were similar in cord blood and adults but significantly lower in juveniles. Conclusions: The frequencies of circulating B cell subpopulation are subject to considerable changes during on-togeny, reflecting overlying effects of maturation and of the acquisition of an adaptive immune memory.

Accurate retroperitoneal lymph node metastasis (LNM) prediction in early-stage testicular germ cell tumours (TGCT) harbours the potential to significantly reduce over- or undertreatment and treatment-related morbidity in this group of young patients as an important survivorship imperative. We investigated the role of computed tomography (CT) radiomics models integrating clinical predictors for the individualized prediction of LNM in early-stage TGCT. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. Dedicated radiomics software was used to segment 273 retroperitoneal lymph nodes and extract features. After feature selection, radiomics-based machine learning models were developed to predict LN metastasis. The robustness of the procedure was controlled by 10-fold cross-validation. Using multivariable logistic regression modelling, we developed three prediction models: A radiomics-only model, a clinical-only model and a combined radiomics-clinical model. The models' performance was evaluated using the area under the receiver operating characteristic curve (AUC). Finally, decision curve analysis was performed to estimate the clinical usefulness of the predictive model. The radiomics-only model for predicting lymph node metastasis reached a greater discrimination power than the clinical-only model, with an AUC of 0.84 (± 0.17; 95% CI ) vs 0.60 (± 0.22; 95% CI) in our study cohort. The combined model integrating clinical risk factors and selected radiomics features outperformed the clinical-only and the radiomics-only prediction models and showed good discrimination with an area under the curve of 0.94 ( ± 0.10; 95% CI). The decision curve analysis demonstrated the clinical usefulness of our proposed combined model. The presented combined CT-based radiomics-clinical model represents an exciting non-invasive prediction tool for individualized prediction of LN metastasis in testicular germ cell tumours. Multi-centre validation is required to generate high-quality evidence for its clinical application.

Infertility affects millions worldwide, posing a significant global health challenge. The proteomic analysis of follicular fluid provides a comprehensive view of the complex molecular landscape within ovarian follicles, offering valuable information on the factors influencing oocyte development and on the overall reproductive health. The follicular fluid is derived from the plasma and contains various proteins that can have different roles in oocyte health and infertility and this fluid is a critical microenvironment for the developing oocytes as well. Using HPLC/MS method we investigated the protein composition of the follicular fluid and after classification we did relative quantification of the identified proteins in the pregnant (P) and non-pregnant (NP) groups. Based on the protein-protein interaction analysis ALB and ApoA1 was found to be hub proteins and the quantitative comparison of the P and NP groups resulted significantly lower concentration of ApoA1 and HDL-cholesterol in the P group. As both molecules are involved in the cholesterol transport, we also investigated their role in the development of oocytes and in the prediction of fertility.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern part of the hemisphere, its use has moved and flourished in the Western Nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. Passing the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Bioglasses are highly adoptable bone substitute materials, which can be combined with so-called therapeutic ions. These ions have shown to influence underlying molecular processes of the bone regeneration cascade. Moreover, it is known that bone substitutes induce an immune reaction within their implantation area involving macrophages and their pro- and anti-inflammatory subtypes dependent on their chemical composition. However, only poor knowledge exists regarding the influence of therapeutic ions onto the immune reactions and the associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglasses on the induction of M1- and M2-macrophages as well as the implant bed vascularization. (2) Methods: For this study, two alkali glasses were produced on basis of ICIE-16 bioglass via the melt-quench route with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglasses were used as control materials. The bioactivity (ion release), chemical composition and the surface pattern were investigated, as well as an in vivo experiment was performed using the subcutaneous implantation model in rats. (3) Results: SEM imaging showed different formations of hydroxyapatite on the surfaces of the bioglass systems after submersion in simulated body fluid. EDX analysis confirmed the doping process by showing the release kinetics. Copper-doped bioglass exhibited a higher ion release than strontium-doped bioglass. Copper induced both a low immune cell migration and triggered a low number of M1- and M2-macrophages but also of blood vessels. The strontium-containing bioactive glass induced higher numbers of M1-macrophages after 30 days. Both copper- and strontium-doped bioglasses induced comparable numbers of M2-macrophages as found in the control groups. (4) Conclusions: Bioglass doping with copper and strontium did not exhibit significant influence on the foreign body response or the implantation bed vascularization in vivo. However, the prepared bioglass systems seemed to be biocompatible.

Notwithstanding the fact that there is some improvement for an earlier detection of patients with lung cancer, the majority of them still present with a late-stage disease at the time of diagnosis. Next to the most frequently used factors affecting the prognosis of lung cancer patients (stage, performance and age) the recent application of biomarkers obtained by liquid profiling gained more acceptance. In our study we aimed to answer these questions: i) is the quantification of free-circulating methylated PTGER4 and SHOX2 plasma DNA an useful method for the therapy monitoring and is this also possible for patients treated with different therapy regimens?, and ii) is this approach possible when blood drawing tubes are used which allow for a delayed processing of blood samples? Baseline values for mPTGER4 and mSHOX2 do not allow for a clear discrimination between different response groups. In contrast the combination of the methylation values for both genes show a clear difference between responders vs non-responders at the time of re-staging. Additionally, blood drawing into tubes stabilizing the sample give researchers more flexibility.

Among others, UWB-based multi anchor localization systems have been established for industrial indoor localization systems. However, multi anchor systems have high costs and installation effort. By exploiting the multipath propagation of the UWB signal, the infrastructure and thus the costs of conventional systems can be reduced. Our UWB Single Anchor Localization System (SALOS) successfully pursues this approach. The idea behind SALOS is to create a localization system with a sophisticated signal modeling. Therefore, neither measured reference like fingerprinting nor training is required for position estimation. Although SALOS has been implemented and tested successfully already in an outdoor scenario with multipath propagation, it has not yet been evaluated in indoor environment with challenging and hardly predictable multipath propagation. For this purpose, we have developed new algorithms for the existing hardware mainly a three-dimensional statistical multipath propagation model for arbitrary spatial geometries. The signal propagation between the anchor and predefined candidate points for the tag position is modeled in path length and complex-valued receive amplitudes. For position estimation, these modeled signals are combined to multiple sets and compared to UWB measurements via a similarity metric. In the end, a majority decision of multiple position estimates is performed. For evaluation, we implement SALOS in a modular fashion and install the system in a building. For a fixed grid of 20 positions, SALOS is evaluated in terms of position accuracy. The system results in correct position estimations for more than 73% of the measurements.

Human papillomavirus (HPV) self-sampling (Self-HPV) is a promising strategy to improve cervical cancer screening coverage in low-income countries. However, issues associated with women who prefer conventional HPV clinical-sampling over HPV self-sampling may affect screening participation. To address this issue, our study assessed factors associated with women’s preferences related to Self-HPV. This study was embedded in a large clinical trial recruiting women aged 30–49 years in a primary HPV-based study termed “3T-Approach” (for Test-Triage-Treatment), launched in 2018 at Dschang District Hospital, West Cameroon. Participants were invited to perform a Self-HPV. After the sampling and before receiving the results, participants completed a questionnaire about cervical cancer screening and their preferences and perceptions around Self-HPV. The median age of the 2201 participants was 40.6 (IQR 35–45) years. Most (1693 (76.9%)) preferred HPV self-sampling or had no preference for either method and 508 (23.1%) preferred clinician-sampling. Factors associated with an increased likelihood of reporting a clinician-sampling preference were tertiary educational level (14.4% CI: 12.8–16.1 vs 29.5% CI: 25.6–33.6) and being an employee with higher grade professional or managerial occupations (5.5% CI: 3.8–7.9 vs 2.6% CI: 2.3–2.8). The main reported reason for women preferring clinician-sampling was a lack of “self-expertise”. Most women (&gt;99%) would agree to repeat HPV self-sampling and would recommend it to their relatives. HPV self-sampling in the cultural context of central Africa was well accepted by participants, but some participants would prefer to undergo clinician sampling. Health systems should support well-educated women to increase self-confidence in using HPV self-sampling.

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.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

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.

Total-body PET/CT scanners provide increased sensitivity, enabling the adjustment of imaging parameters by reducing injected activity or shortening acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectabil-ity, and quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min. scan time) were included in this analysis. PET raw data was rebinned for shorter frame durations to simulate 5 min. scans with lower activities in high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n=82) were assessed using a 5-point Likert scale. The co-efficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Sub-jective image ratings were generally superior in UHS compared to HS mode. At 0.5 MBq/kg, le-sion detectability decreased to 95% (HS) and 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7±0.6) and 0.5 MBq/kg in UHS (5.5±0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a total-body PET/CT provides diagnostic image quality without statistical-ly significant changes in uptake parameters. UHS mode improves image quality, noise, and le-sion detectability compared to HS mode.

An inter- and transdisciplinary concept has been developed, focusing on the scaling of industrial circular construction using innovative compacted mineral mixtures (CMM) derived from various soil types (sand, silt, clay) and recycled mineral waste. The concept aims to accelerate the systemic transformation of the construction industry towards carbon neutrality by promoting the large-scale adoption and automation of CMM-based construction materials, which incorporate natural mineral components and recycled aggregates or industrial by-products. In close collaboration with international and domestic stakeholders in the construction sector, the concept explores the integration of various CMM-based construction methods for producing wall elements in conventional building construction. Leveraging a digital urban mining platform, the concept aims to standardize the production process and enable mass-scale production. The ultimate goal is to fully harness the potential of automated CMM-based wall elements as a fast, competitive, emission-free, and recyclable alternative to traditional masonry and concrete construction techniques. To achieve this objective, the concept draws upon the latest advances in soil mechanics, rheology, and automation and incorporates open-source digital platform technologies to enhance data accessibility, processing, and knowledge acquisition. This will bolster confidence in CMM-based technologies and facilitate their widespread adoption. The extraordinary transfer potential of this approach necessitates both basic and applied research. As such, the proposed transformative, inter- and transdisciplinary concept will be conducted and synthesized using a comprehensive, holistic, and transfer-oriented methodology.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Radiomics refers to the extraction and analysis of a wide range of medical imaging features in a non-invasive and cost-effective manner to comprehensively characterise tumours. In this study, machine learning models combining radiomics and clinical factors were developed to predict retroperitoneal lymph node metastasis in testicular germ cell tumours (TGCTs), with the aim of reducing unnecessary treatment in this group of young patients. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. After segmenting 273 retroperitoneal lymph nodes using dedicated radiomics software, we developed machine-learning prediction models using Random Forest (RF), Light Gradient Boosting Machine (LGBM), Support Vector Machine Classifier (SVC), and K-Nearest Neighbours (KNN). For each classifier, we developed a radiomics-only, clinical-only, and combined radiomics-clinical prediction model. The models’ performances were evaluated using the area under the receiver operating characteristic curves (AUCs). The RF-based combined clinical and radiomic model showed the most robust performance in predicting LNM with an area under the curve (AUC) of 0.95 (±0.03; 95% CI), accuracy 87%, precision 89%, recall 86% and F1 score 87%, followed by the LGBM model with an area under the curve (AUC) of 0.93 (±0.05; 95% CI), accuracy 83%, precision 87%, recall 80% and F1 score 82%. Decision curve analysis demonstrated the clinical utility of our proposed RF-based combined clinical–radiomics model. Our study has identified reliable and predictive machine-learning techniques for predicting lymph node metastasis in early-stage testicular cancer. Identifying the most effective machine-learning approaches for predictive analysis based on radiomics integrating clinical risk factors can expand the applicability of radiomics in precision oncology and cancer treatment. Multi-centre validation is required to provide high-quality evidence for clinical application.