The modification of GFP-CaaL sensor proteins by geranylgeranyl groups in plants requires an active plastidial mevalonate (MVA)-independent pathway. As a consequence, fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose (DX)-5 phosphate reductoisomerase/DXR, the second enzyme in this so-called methylerythritol phosphate (MEP) pathway, impedes protein prenylation, which results in GFP-labeling of nuclei instead of the plasma membrane. In tobacco cells, a visual screen of conditions that allowed membrane localization of GFP-CaaL proteins in the presence of fosmidomycin, pinpointed jasmonic acid methyl esther (Me-JA) as a chemical able to overcome the inhibition in a gradual manner. Using Arabidopsis protein prenyltransferase loss-of-function mutant lines expressing GFP-CaaL proteins, we demonstrated that Me-JA induces a modification in protein substrate recognition by protein farnesyltransferase (PFT). Similar to Me-JA, farnesol and MVA also alter the protein substrate specificity of PFT, whereas DX and geranylgeraniol have limited or no effect. Our data indicate that stimulation of the MVA pathway adjusts the protein substrate specificity of PFT, which is corroborated with metabolic cross-talk of the origin of the prenyl group used to modify the protein. To illustrate how activation of the MVA pathway impacting PFT substrate specificity benefits a plant under stress conditions, a model is proposed.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

It is well known that a sequence of two non-collinear Lorentz boosts (pure Lorentz transformations) does not correspond to a Lorentz boost, but involves a spatial rotation, the Wigner or Thomas-Wigner rotation. We visualize the interrelation between this rotation and the relativity of distant simultaneity by moving a Born-rigid object on a closed trajectory in several steps of uniform proper acceleration. Born-rigidity implies that the stern of the boosted object accelerates faster than its bow. It is shown that at least five boost steps are required to return the object's center to its starting position, if in each step the center is assumed to accelerate uniformly and for the same proper time duration. With these assumptions, the Thomas-Wigner rotation angle depends on a single parameter only. Furthermore, it is illustrated that accelerated motion implies the formation of an event horizon. The event horizons associated with the five boosts constitute a natural boundary to the rotated Born-rigid object and ensure its finite size.

We suggest progress regarding the following six physics opportunities. List all elementary particles. Describe dark matter. Explain ratios of dark matter to ordinary matter. Explain eras in the history of the universe. Link properties of objects. Interrelate physics models. We use models based on Diophantine equations.

We try to solve three decades-old physics challenges. List all elementary particles. Describe dark matter. Describe mechanisms that govern the rate of expansion of the universe. We propose new modeling. The modeling uses extensions to harmonic oscillator mathematics. The modeling points to all known elementary particles. The modeling suggests new particles. Based on those results, we do the following. We explain observed ratios of dark matter amounts to ordinary matter amounts. We suggest details about galaxy formation. We suggest details about inflation. We suggest aspects regarding changes in the rate of expansion of the universe. We interrelate the masses of some elementary particles. We interrelate the strengths of electromagnetism and gravity. Our work seems to offer new insight regarding applications of harmonic oscillator mathematics. Our work seems to offer new insight regarding three branches of physics. The branches are elementary particles, astrophysics, and cosmology.

We develop and apply new physics theory. The theory suggests specific unfound elementary particles. The theory suggests specific constituents of dark matter. We apply those results. We explain ratios of dark matter amounts to ordinary matter amounts. We suggest details about galaxy formation. We suggest details about inflation. We suggest aspects regarding changes in the rate of expansion of the universe. The theory points to relationships between masses of elementary particles. We show a relationship between the strength of electromagnetism and the strength of gravity. The mathematics basis for matching known and suggesting new elementary particles extends mathematics for harmonic oscillators.

Physics lacks a confirmed description of dark matter, has yet to develop an adequate understanding of dark energy, and includes unverified conjectures regarding new elementary particles. This essay features modeling that addresses those problems and explains otherwise unexplained data. Our modeling starts from five bases – multipole expansions for the electromagnetic and gravitational fields associated with an object, the list of known elementary particles, some aspects of mathematics for isotropic harmonic oscillators, concordance cosmology, and a conjecture that the universe includes six isomers of most elementary particles. The multipole expansions – which have use in conjunction with Newtonian kinematics modeling, special relativity, and general relativity – lead to a catalog of kinematics properties such as charge, magnetic moment, mass, and repulsive gravitational pressure. The multipole expansions also point to all known elementary particles, some properties of those particles, and properties of some would-be elementary bosons and elementary fermions. The harmonic-oscillator mathematics points to Gauge symmetries regarding some elementary bosons. The would-be elementary fermions lack charge and would measure as dark matter. The conjecture regarding six isomers of most elementary particles rounds out and dominates our specification for dark matter. Five of the isomers form the basis for most dark matter. Our modeling explains ranges of observed ratios of dark matter effects to ordinary matter effects – for the universe, galaxy clusters, two sets of galaxies observed at high redshifts, three sets of galaxies observed at modest redshifts, and one type of depletion of cosmic microwave background radiation. Our description of repulsive gravitational pressure points toward resolution for tensions – between data and modeling – regarding the recent rate of expansion of the universe, resolution for possible tensions regarding large-scale clumping, and resolution for possible tensions regarding interactions between neighboring galaxies. Our work regarding gravity, dark matter, and elementary particles suggests characterizations for eras that might precede the inflationary epoch, a mechanism that might have produced baryon asymmetry, mechanisms that govern the rate of expansion of the universe, and insight about galaxy formation and evolution.

Potassium 6-oxo-7,13,16,22-tetraazatetracyclo[12.6.2.18,12.017,21]tricosa-1(20),8(23),9,11,14,16,18,21-octaen-2-yne-15-carboxylate was synthesized through a multi-step pathway starting from commercially available 3-iodo-1,2-phenylenediamine. Structure characterization of this new substituted macrocyclic quinoxaline compound was achieved by using 1H NMR, 13C NMR, and HRMS spectral analysis. This new macrocyclic derivative demonstrated submicromolar potency on both Pim-1 and Pim-2 isoforms, with an interesting selectivity profile against a selected panel of human kinases.

This review seeks to explain four features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid response of outbreaks to weather, specifically temperature; (4) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called Temperature Dependent Viral Tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that “wild” respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the existence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. The TDVT hypothesis has important practical implications for preventing and treating respiratory illness including Covid-19. TVDT is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

Extracts of Cordyceps militaris which possess the bioactive capacity such as antimicrobial activity and DPPH-free radical scavenging capacity, are applied to the serum product. This finished serum product has been evaluated the in vitro bioactivity and the stability with expect to find out a good extract with a suitable percentage used for serum product as natural materials on preservatives and antioxidation.

Starting from acid chlorides, alkynes, tryptamines, and acroyl chloride, 21 densely substituted tetrahydro-beta-carbolines are prepared in a four-component one-pot reaction. In this study, the aza-Michael addition step to generate intermediate enaminones is optimized in the presence of ytterbium triflate. Moreover, apart from acroyl chloride, all reactants can be deployed in almost equimolar ratios, which increases the atom economy of the sequence. For mechanistic rationali-zation, the concluding aza-anellation was investigated by DFT calculations on potential inter-mediates and corresponding activation energies, revealing that the aza-anellation rather pro-ceeds via ene-reaction than via electrocyclization.

Introduction. Musculoskeletal disorders related to work might follow with a cumulative effect during working life. We aimed to develop a new model to allow to compare the accuracy of duration of work and intensity/frequency associations in application to severe knee pain. Methods. The CONSTANCES cohort is used with data from n=66553 subjects who were working at inclusion and coded. From a biomechanical job exposure matrix “JEM Constances”, intensity/frequency of heavy lifting and kneeling/squatting were used and applied to the work history in comparison to severe knee pain. An innovative model was developed and evaluated, allowing to compare the accuracy of duration of work and intensity/frequency associations. Results. The mean age is 49 years at inception with 46 percent of women. The G model developed was slightly better than regular models. In men, odds ratios of the highest quartile for the duration and low intensity were not significant for both exposures, whereas intensity/duration were for every duration. Results in women were less interpretable. Conclusion. Though increased duration increased strength of association with severe knee pain, intensity/frequency were important predictors among men. Exposure estimation along working history should have emphasis on such parameters, though other outcomes should be studied such as women.

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from ethyl acetate soluble fraction of Acacia auriculiformis stem bark. Column chromatography, gel filtration and NMR spectroscopy were used to purified and characterized betulin from the extract. Betulin which is a known inducer of apoptosis was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1epsilon (CK1epsilon), glycogen synthase kinase 3alpha/β (GSK-3alpha/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6) and vascular endothelial growth factor receptor 2 kinase (VEGFR2) and with activity in µM range. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to underline its putative use as anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway similarly to imatinib mesylate, a well-known inhibitor of ABL1 kinase. The interaction of betulin and ABL1 was studied by molecular docking showing an interaction of the inhibitor with the ATP binding pocket. Altogether, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and notably for treatment of leukemia.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

The two-component compound formed by codeine and cyclopentobarbital was produced by grinding techniques and by evaporation from alcoholic solutions. The cocrystal nature of this phase was established unequivocally by single crystal X-ray structure determination. The asym-metric unit contains one formula unit. In the cyclopentobarbital molecule, the cyclopentenyl ring is disordered over two positions related by a rotation of approximately 180° about its C‒C bond to the pyrimidine ring. The two NH groups of the cyclopentobarbital molecule form N—H···N and N—H···O bonds to piperidine and hydroxyl groups, respectively, belonging to different codeine molecules. In addition, the hydroxyl and methoxy groups of neighboring codeine molecules are linked by O—H···O interactions, resulting H-bonded framework structure of codeine and cyclo-pentobarbital molecules. The cocrystal was also characterized by thermal analysis, X-ray powder diffraction and IR spectroscopy.

Background and Aims. Most research on Parkinson's disease (PD) focuses on describing symp-toms and movement characteristics. Studies rarely focus on the early detection of PD and the search for suitable markers of a prodromal stage. Early detection is important, so treatments that may potentially change the course of the disease can be attempted early on. While gait disturb-ances are less pronounced in the early stages of the disease, the prevalence, and severity increase with disease progression. Therefore, postural instability and gait difficulties could be identified as sensitive biomarkers. The aim was to evaluate the discriminatory power of the Trail-Walking Test (Schott, 2015) as a potential diagnostic instrument to improve the predictive power of the clinical evaluation concerning the severity of the disease and record the different aspects of walking. Methods. 20 older healthy (M = 72.4 years, SD = 5.53) adults and 46 older adults with PD and the motor phenotypes postural instability/gait difficulty (PIGD; M = 69.7 years, SD = 8.68) and tremor dominant (TD; M = 68.2 years, SD = 8.94) participated in the study. The participants performed a motor-cognitive dual task (DT) of increasing cognitive difficulty in which they had to walk a given path (condition 1), walk to numbers in ascending order (condition 2), and walk to numbers and letters alternately and in ascending order (condition 3). Results. With an increase in the cognitive load, the time to complete the tasks (seconds) become longer in all groups, F(1.23, 73.5) = 121, p < .001, ɳ2p = .670. PD-PIGD shows the longest times in all conditions of the TWT, F(2, 60) = 8.15, p < .001, ɳ2p = .214. Mutual interferences in the cognitive and motor domain can be observed. How-ever, clear group-specific patterns cannot be identified. A differentiation between the motor phenotypes of PD is especially feasible with the purely motor condition (TWT-M; AUC = . 685, p = 0.44). Conclusions. PD patients with PIGD must be identified by valid, well-evaluated clinical tests that allow a precise assessment of the disease's individual fall risk, the severity of the dis-ease, and the prognosis of progression. The TWT covers various aspects of mobility, examines the relationship between cognitive functions and walking, and enables differentiation of the motor phenotypes of PD.

The extensive use of rare earth elements (REEs) in a number of technologies is expected to impact on human health, including occupational REE exposures. A body of experimental evidence on REE-associated toxicity has been accumulated in recent decades. Unlike experimental studies, the consequences of REE exposures to human health have been subjected to relatively fewer investigations. Geographical studies have been conducted on residents in the Chinese REE mining districts, reporting on REE bioaccumulation, and associations between REE residential exposures and adverse health effects. A more limited series of studies has been focused on occupational REE exposures, such as movie operator (with occurrence of cerium aerosol) with the observation of pneumoconiosis and lung fibrosis. Similar effects have been reported in case reports for other workers, such as a lens grinder and a printer exposed to carbon-arc lamp emission. As for the occupations related to REE mining and processing, REE bioaccumulation in scalp hair and excess REE urine levels were reported. A study was devoted to workers employed in e-waste separation, showing alterations of several plasma markers. As for other REE occupational exposures, mention should be made of: a) mechanical workshops, with exposures to diesel exhaust microparticulate (containing nanoCeO₂ as a catalytic additive) and, b) production and manufacture of REE supermagnets for hybrid engines and wind turbines. Diesel exhaust microparticulate has been studied in animal models, leading to evidence of several pathological effects in animals exposed by respiratory or systemic routes. As for supermagnet production and manufacture, a body of literature is reviewed of experimental studies, and of human exposure studies showing several pathological effects of static magnetic fields, warranting further investigations.

Up to forty percent of dairy cows develop metritis or endometritis when pathogenic bacteria infect the uterus after parturition. However, resilient cows remain healthy even when exposed to the same pathogens. Here, we provide a perspective on the mechanisms that dairy cows use to prevent postpartum uterine disease. We suggest that resilient cows prevent the development of uterine disease using the three complimentary defensive strategies of avoiding, tolerating and resisting infection with pathogenic bacteria. Avoidance maintains health by limiting the exposure to pathogens. Avoidance mechanisms include intrinsic behaviors to reduce the risk of infection by avoiding pathogens or infected animals, perhaps signaled by the fetid odor of uterine disease. Tolerance improves health by limiting the tissue damage caused by the pathogens. Tolerance mechanisms include neutralizing bacterial toxins, protecting cells against damage, enhancing tissue repair, and reprogramming metabolism. Resistance improves health by limiting the pathogen burden. Resistance mechanisms include inflammation driven by innate immunity and adaptive immunity, with the aim of killing and eliminating pathogenic bacteria. Farmers can also help cows prevent the development of postpartum uterine disease by avoiding trauma to the genital tract, reducing stress, and feeding animals appropriately during the transition period. Understanding the mechanisms of avoidance, tolerance and resistance to pathogens will inform strategies to generate resilient animals and prevent uterine disease.

Saltwater intrusion in the rapidly developing city of Da Nang in central Vietnam is currently causing various water-related challenges, including inadequate water supply and water pollution. An integrated SWAT-MODFLOW numerical model was used to investigate the origin and mechanism of saltwater in Holocene and Pleistocene aquifers. Geophysical and isotopic approaches were used to validate the SEAWAT model applied for simulating saltwater intrusion. The results suggest that the ebb and flow of tides, as well as water levels in rivers primarily impact coastal aquifers. However, effective water resource planning and management, along with maintaining the natural recharge of fresh water from local rain during the rainy season, could enable the rational and efficient utilization of groundwater, reducing saltwater intrusion in many areas. During the dry season, groundwater is recharged from higher altitude areas. The current saltwater intrusion mainly occurs along the rivers up to the hydraulic dam. Simulated models, using scenarios of stop abstracting groundwater, but changing to the use of surface water for drinking water, show that the area of saline water shrinks quickly after 30 years, reducing from 59.6 km2 to 39.5 km2 and from 40.2 km2 to 28.6 km2 in Holocene and Pleistocene, respectively.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

Lead Acid Batteries (LABs) are used for starting, lighting, and igniting, as well as in air conditioning systems and to supply power to electric engines in transport vehicles (TVs). However, the application of LABs for TVs has faced a number of market challenges, mounted by the upcoming high energy density and long lifespan batteries, such as lithium ion. LABs, on the other hand, are inexpensive. The key research question is, how can the lifespan of LABs used in automotive industries be increased, while still ensuring a low cost solution? Thus, integrating LABs with the supercapacitor (known as an electric double layer capacitor—EDLC) is likely to outperform the competing alternative batteries for TVs. This paper proposes a multiple stage approach to hybrid lead acid batteries and a supercapacitor system for TVs that is capable of maintaining the battery state-of-charge (SOC) at statistically high limits, ranging between 90% and 95%. This SOC target will likely ensure that the lifespan of the hybrid battery system can be elongated (extended) more than its competitors. In this study, the multiple stage approach of concatenated converters has been designed in order to satisfy all energy storage requirements for different characteristics of LABs and the supercapacitor. The designed hybrid system has been simulated using Matrix Laboratory (MATLAB/Simulink (version R2016a, MathWorks, Natick, MA, USA)). The simulated results show that high transient currents from the direct current (DC) bus of LABs, caused by the regenerative braking or deceleration of the TVs, reduce the battery lifespan and induce mechanical stress. The supercapacitor reduces the stress on the LAB by absorbing high transient currents. This, in turn, keeps the LABs’ SOC between 90% and 96% and the voltage at 12 V. As indicated by the simulated results, the hybrid battery SOC is maintained at 90–96% and the terminal voltage is approximately 12 V.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

Deterioration of concrete subjected to freezing and thawing climatic conditions is one of most important factors affecting the durability of concrete infrastructure in cold climates. The freeze-thaw resistance of cementitious materials like concrete and mortar can be determined by the CDF test (Capillary Suction of De-icing chemicals and Freeze-Thaw Test). Here, concrete specimens are subjected to repeated freeze-thaw cycles with simultaneous addition of de-icing salt and the amount of material weathered near the surface is determined. For concretes with adequate freeze-thaw resistance, this test method works very well. However, specimens with inadequate or unknown performance often experience increased edge weathering, which is caused by the detachment of the lateral isolation tape. The increasing edge influence thus leads to a falsification of the results and consequently to an underestimation of the actual freeze-thaw resistance of the material. In materials research in particular, however, concretes with high levels of weathering are studied in order to be able to investigate various factors of influence on the freeze-thaw resistance of concretes in a targeted manner. This paper presents a novel methodology that delivers new information regarding the weathering of CDF test samples and the associated distribution function of the height decrease using high resolution 3D scan data. The results indicate a correlation between the progression of the distribution function and the sample's maximum aggregate size. The change of the sample volume can be used to support the weathering results of the standard CDF methodology. The increase of the surface area is used to estimate the tortuosity of the sample surface. It indicates an asymptotic curve approaching a specific maximum value, which is dependent on the the weathering depth of the sample.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

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

The RNA-guided endonuclease system CRISPR-Cas9 has been extensively modified since its discovery, allowing its capabilities to be extending far beyond double-stranded cleavage to high fidelity insertions, deletions, and single base edits. Such innovations have been possible due to the modular architecture of CRISPR-Cas9 and the robustness of its component parts to modifications and the fusion of new functional elements. Here, we review the broad toolkit of CRISPR-Cas9-based systems now available for diverse genome editing tasks. We provide an overview of their core molecular structure and mechanism and distil the design principles used to engineer their diverse functionalities. We end by looking beyond the biochemistry and towards the societal and ethical challenges that these CRISPR-Cas9 systems face if their transformative capabilities are to be deployed in a safe and acceptable manner.

Novel effluent treatment solutions for dangerous organic pollutants are crucial worldwide. In recent years, chemical reduction using noble metal-based nanocatalysts and NaBH4, a reducing agent, has become common practice for eliminating organic contaminants from aquatic environments. We suggest a straightforward approach to synthesizing magnetic cellulose nanocrystals (CNC) modified with magnetite (Fe3O4) and silver nanoparticles (Ag NPs) as a catalyst for organic contamination removal. Especially, Ag NPs were decorated on the CNC surface without reducing agents or stabilizers by reducing AgNO3. XRD, FE-SEM, TEM, EDX, VSM, BET, and zeta potential tests characterized the Ag/Fe3O4/CNC nanocomposite. The nanocomposite's catalytic activity was tested by eliminating 4-nitrophenol (4-NP) and organic dyes methylene blue (MB) and methyl orange (MO) in an aqueous solution at 25 oC. The Ag/Fe3O4/CNC nanocomposite reduced 4-NP and decolored these hazardous organic dyes in short time (2 to 5 min) using a tiny amount of catalyst (2.5 mg for 4-NP and 15 mg for MO and MB). The magnetic catalyst was removed and reused three times without losing catalytic activity. This work shows that the Ag/Fe3O4/CNC nanocomposite can chemically reduce harmful pollutants in effluent for environmental applications.

Background (1) In the time of the 4th Industrial Revolution or Industry 4.0, a conglomerate of technical and social inventions, political contexts, socio-cultural circumstances, environmental policies, business models, and economic policies has emerged. Sustainability policy in theory and practice aims to deal with the effects of all these factors and to try to make decisions that ensure both social and economic development sustainably. The question is how to familiarize oneself with the current knowledge about the relationship between Industry 4.0 and sustainability?; (2) Methods: This research utilizes an automated content analysis method to analyses scientific journals, newspapers and magazines. The comparison of results of both research group shows that the scientific literature focuses more on changes in business models, production processes and technologies that enable sustainable development; (3) We found that the scientific literature focuses more on changes in business models, production processes and technologies that enable sustainable development. Newspapers and magazines articles write more about sustainable or green investment, sustainable standards and sustainable reporting. Newspapers and magazines articles write more about sustainable or green investment, sustainable standards and sustainable reporting. Newspapers, as well as some latest research journals, include articles of the COVID-19 outbreak and its effect on the economy and the environment. Indeed, the outbreak of the virus brings a new thought to the reorganization of the complex relationships between consumers, businesses and the state; (4) Conclusions: According to the comparison of the analyses of the results, it can is that the analyses of both types of literature, both scientific and professional, shows that there are common topics they write about, which are related to the field of clean production, emissions, renewable energy, climate change, sustainable investments and corporate sustainability. An urgent global issue that extends all over the world is the promotion of energy-saving technologies and reduction of carbon dioxide emissions.

In the realm of digital transformation, effective leadership and motivation are pivotal for organisations navigating the complexities of today’s systems. This study explores the intersection of intrinsic motivation and mental well-being among mature students—an analogy that sheds light on strategies applicable to organisational contexts. In developed nations like the UK, mental health for mature students is increasingly recognised as a crucial component of their educational journey. Mature students, who typically enrol in higher education after an educational gap and upon turning 21, often face specific challenges that can impact their mental well-being while pursuing academic goals. The primary objective of our study was to assess the relationship between intrinsic motivation and the mental well-being of mature students. Our research revealed a significant positive correlation between these two variables. Confirmatory factor analysis (CFA) results supported a one-factor solution for the sample data from mature students. Additionally, we found that intrinsic motivation is a significant predictor of the mental well-being of mature students. Recognising and addressing the unique difficulties individuals encounter and providing appropriate support can enhance their well-being and contribute to the overall success of the higher education community.

Background. Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. Awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. Methods. CBSIs occurring from 2006-2016 among patients in a large children’s hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to antifungal agent use. Results. The overall incidence rate of CBSI among this complex patient population was 1.97/1,000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in Neonatal Intensive Care Unit (NICU) patients. Antifungal resistance was minimal: 96.7% of isolates were fluconazole-, 99% were micafungin-, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed antifungal agent including for NICU patients. Overall CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Conclusions. Pediatric CBSI characteristics differ substantially from those in adults. Improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI while continuing to maintain low resistance rates among Candida isolates.

Introduction: The choice of Cardiac Preservation Solution (CPS) for myocardial protection at the time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm Heart Transplantation (HTx) outcomes. Thus, we retrospectively analyzed our adult HTx performed with two different CPS, during a period of 12 years, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. Methods: From January 2009 to December 2020, 154 adult HT were performed in our hospital. Patients were divided in two groups according to the CPS used: St. Thomas (n=75, group P 1) and HTK-Custodiol (n=79, group P 2). The choice of CPS was related to an institutional policy; from 2009 to 2015, St. Thomas solution was exclusively used, and after that, HTK-Custodiol alone. Results: There was no significant difference between the two groups in terms of preoperative and intraoperative features. Postoperatively, the Custodiol group showed significantly lower inotropic score (p&lt;0.0001), mean rejection score (p= 0.036) and 30 days mortality (p=0.0068). The use of HTK-Custodiol was the only variable that improved midterm survival (HTK-Custodiol vs St Thomas, HR= 0.20 (95% CI: 0.069 -0.6) p=0.0039). Conclusion: In our single center experience, using HTK-Custodiol as myocardial protection during heart procurement leads to improved outcomes after HTx, including postoperative inotropic score, rejection score, 30-days mortality and midterm survival.

(1) Background: The importance of this article is to analyze the technological developments in the field of the Internet and Internet technologies and to determine their significance for the sustainable development which will result in the emergence of the Society 5.0; (2) The authors used automated content analysis for the analysis of 552 articles published in 306 scientific journals indexed by SCII and/or SCI - EXPANDED (Web of Science (WOS) platform) between the years 1996 and 4/2020. The goal of the research was to present the relationship between the internet and sustainable development. (3) Results: The results of the analysis show that the top four most important themes in the selected journals were “development”, “information”, “data”, and “business and services”. (4) Conclusions: Our research approach emphasizes the importance of the culmination of scientific innovation with the conceptual, technological and contextual frameworks of the internet and internet technology usage and its impact on sustainable development and emergence of the Society 5.0

MicroRNA-155 (miR-155) expression promotes inflammatory responses in macrophages. Activation of macrophages with lipopolysaccharide (LPS) elevates miR-155, while the anti-inflammatory cytokine interleukin-10 (IL10) reduces miR-155 levels. MiR-155 exists in two forms, miR-155-5p and miR-155-3p, produced from the precursor of miR-155 (pre-miR-155). MiR-155-5p is the most abundant strand in activated macrophages, but in response to LPS, the miR-155-3p level is upregulated first, followed by miR-155-5p later. We have previously identified CELF2 protein which interacts with pre-miR-155 and impairs miR-155-5p expression. We now show that CELF2 only regulates the miR-155-5p expression and that another protein FUBP1 controls miR-155-3p levels in response to LPS and IL10.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

The Global Human Settlement Layer (GHSL) produces new global spatial information, evidence-based analytics and knowledge describing the human presence on the planet based mainly on two quantitative factors: i) the spatial distribution (density) of built-up structures and ii) the spatial distribution (density) of resident people. Both factors are observed in the long-term temporal domain and per uniform surface units in order to support trends and indicators for monitoring the implementation of international framework agreements. The GHSL uses various input data including global, multi-temporal archives of fine-scale satellite imagery, census data, and volunteered geographic information. In this paper, we present the characteristics of GHSL information to demonstrate how original frameworks of data and tools rooted on Earth Observation could support Sustainable Development Goals monitoring. In particular, we demonstrate the reach of gridded, open and free, local yet globally consistent, multi-temporal data in filling the data gap for the Sustainable Development Goal 11. Our experiments produce a global estimate for the Land Use Efficiency indicator (SDG 11.3.1) for 10,000 urban centers, calculating the ratio of land consumption to population growth rate that took place between 1990 and 2015. The results of our research demonstrate that there is a potential to lift SDG 11.3.1 from a tier 2 as GHSL provides a global baseline for the essential variables called by the SDG 11.3.1 metadata.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Rapidly and repeatedly ascertaining the health status of coral reefs is an ever more pressing issue as part of activities to understand and monitor the damaging impacts of climate change. A combination of increasing ocean temperatures, acidity and frequency of extreme storm events continues to alter the marine environment beyond what sensitive organisms, such as coral, can cope with. It is therefore vital to establish technologies and validated methods to provide a metric or indication into the health of these organisms. There are currently many surveys and techniques used by coral scientists to uncover insights into the status and assessment of coral reefs, from colour wheels to multispectral satellite surveys. Here we outline an array of current techniques and methods focused specifically on coral monitoring and health diagnosis, ranging across the length scales from simple diver-based surveyance to satellite remote sensing. The technique of using hyperspectral fluorescence imaging is also introduced as a viable novel addition to aid and extend the current toolbox of available technologies.

The development of a novel and simple inhibition biosensor array for detection of water pollutants based on immobilized bacteria is the main goal of this work. A series of electrochemical measurements (i.e. cyclic voltammograms) were carried out on screen-printed gold electrodes with three types of bacteria, namely Escherichia coli, Shewanella oneidensis, and Methylococcus capsulatus, immobilized via poly L-lysine. For comparison purposes, similar measurements were carried out on bacteria samples in solutions,; also optical measurements (fluorescence microscopy, optical density, and flow cytometry) were performed on the same bacteria in both liquid and immobilized forms. The study of the effect of heavy metal ions (lead), pesticides (atrazine) and petrochemicals (hexane) on DC electrochemical characteristics of immobilized bacteria revealed a possibility of pattern recognition of the above inhibition agents in aquatic environment.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

For many engineering applications it is sufficient to use the concept of simple materials. However, higher gradients of the kinematic variables are taken into account to model materials with internal length scales as well as to describe localization effects using gradient theories in finite plasticity or fluid mechanics. In many approaches length scale parameter have been introduced that are related to a specific micro structure. An alternative approach is possible, if a thermodynamically consistent framework is used for material modelling as shown in the present contribution. However, even if sophisticated and thermodynamically consistent material models can be established there are still not yet standard experiments to determine higher order material constants. In order to contribute to this ongoing discussion system identification based on the method of self-adaptive filtering is proposed in this paper. To evaluate the effectiveness of this approach it has been applied to second-order gradient materials considering longitudinal vibrations. Based on thermodynamically consistent models that have been solved numerically it has been possible to prove that system identification based on self-adaptive filtering can be used effectively for both narrow-band and broadband signals in the field of second-order gradient materials. It has also been found that the differences identified for simple materials and gradient materials allow for condition monitoring and detection of gradient effects in the material behavior.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Retrospective information about the climate system and plant ecophysiology are key inputs in climate and Earth system modelling. Dendrochronology provides such information with large spatiotemporal coverage, and stable carbon isotope (¹³C/¹²C) analysis across tree-ring series is among the most advanced dendrochronological tools. For the past seventy years, this analysis was performed on whole molecules, and, to this day, ¹³C/¹²C variation is attributed to ¹³C discrimination during CO₂ diffusion into leaves and assimilation by rubisco. By contrast, ¹³C discrimination by post-rubisco processes is presumed constant. Here, recently reported results on the first dataset of intramolecular ¹³C discrimination in tree rings were synthesised by variance component analysis. The emerging picture is not consistent with the classical (DR-discrimination-centred) concepts and practices of carbon-isotope dendrochronology. Specifically, leaf and stem post-rubisco discrimination each account for more variation in the data than diffusion-rubisco discrimination, i.e., post-rubisco discrimination is not constant. Furthermore, diffusion-rubisco discrimination is used widely as proxy of leaf intrinsic water-use efficiency (iWUE), a key determinant in the responses of global biogeochemical cycles to climate change. However, since diffusion-rubisco discrimination is a small component of the total data variance, whole-molecule analysis yields confounded iWUE estimates, yet intramolecular analysis will likely offer solutions. Lastly, all currently observed ¹³C/¹²C-climate relationships are attributed to diffusion-rubisco discrimination. However, here, relationships with temperature and radiation derive from leaf-level post-rubisco discrimination while relationships with precipitation derive from stem-level post-rubisco discrimination. That said, advances in mass spectrometry may soon make intramolecular ¹³C/¹²C analysis broadly available taking carbon-isotope dendrochronology to the next level.

Florida geologic units and soils contain a wide range in concentrations of naturally-occurring arsenic. The average range of bulk rock concentrations is 1 to 13.1 mg/kg with concentrations in accessary minerals being over 1,000 mg/kg. Soils contain natural arsenic concentrations of between 0.18 and 2.06 mg/kg with organic-rich soils having the highest concentrations. Anthropogenic sources of arsenic have added about 610,000 metric tons of arsenic into the Florida environment since 1970, thereby increasing background concentrations in soils. The anthropogenic sources of arsenic in soils include: pesticides (used in Florida beginning in the 1890’s), fertilizers, chromated copper arsenate (CCA)-treated wood, soil amendments, cattle-dipping vats, chicken litter, sludges from water treatment plants, and others. The default Soil Cleanup Target Level (SCTL) in Florida for arsenic in residential soils is 2.1 mg/kg which is below some naturally-occurring background concentrations in soils and anthropogenic concentrations in agricultural soils. A review of risk considerations shows that adverse health impacts associated with exposure to arsenic is dependent on many factors and that the Florida cleanup levels are very conservative. Exposure to arsenic in soils at concentrations that exceed the Florida residential cleanup level in residential environments does not necessarily pose a meaningful public health risk.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

TThe following three objectives were tested in this study: (1) investigate the utility of low-altitude remote sensing using UAS technology to compare the effects of different N application systems in rice production; (2) use spatial extrapolation to scale up plot-level generated to farmer field rice yield data based on crop spectral signatures, and (3) predict and map out rice productivity as a function of N placement systems. Images were captured on a UAV platform at midseason of the rice crop. Orthomosaics were developed for selected fields in rice-producing zones. Grain yields were assessed from low, medium, and high crop health plots delineated based on NDVI values. On the plot scale, UDP outyielded non-UDP by 0.84%. Individual plot yield data were scaled up to the farmer field level through Jenks natural breaks classification and es-tablishing an empirical relationship between OSAVI and plot yields. Assessment of the scaled-up field levelfield-level data also confirmed the superiority of UDP N man-agement over the non-UDP systems in promoting rice yields. Scaling up plot scale da-ta to whole field levels also facilitated generating and mapping expected yield maps for individual farmer fields in the three zones studied. This study has established a tangible simple but tangible protocol protocol for predicting and mapping rice yields in small-scale farmer fields using UAS data.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Psychiatric patients are particularly vulnerable to strong weather stimuli, such as foehn, a hot wind that occurs in the alps. However, there is a dearth of research regarding its impact on mental health. This study investigated the impact of foehn wind among patients of a psychiatric hospital located in a foehn area in the Swiss Alps. Analysis was based on anonymized datasets obtained from routine records on admission and discharge, including the Brief Symptom Checklist (BSCL) questionnaire, as well as sociodemographic parameters (age, sex, and diagnosis). Between 2013 and 2020 a total of 10,456 admission days and 10,575 discharge days were recorded. All meteorological data were extracted from the database of the Federal Office of Meteorology and Climatology of Switzerland. We estimated the effect of foehn on the BSCL items using a distributed lag model. Significant differences were found between foehn and non-foehn admissions in obsession-compulsion, Interpersonal Sensitivity, depression, Anxiety, Phobic Anxiety, Paranoid Ideation, and General Severity Index (GSI) (p &lt;.05). Our findings suggest that foehn wind events may negatively affect specific mental health parameters in patients. More research is needed to fully understand the impact of foehn’s events on mental health.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identifies a novel ‘protagonist-antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.

In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted, and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x10^4 – 2x10^7 CFU per ml and has a sensitivity of S = 1.655x10^5 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10^-9 grams (g), which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Monitoring the health of coral reefs is essential to understand the damaging impacts of anthropo-genic climate change. Non-invasive methods to survey coral reefs are the most desirable and op-tics-based surveys, ranging from simple photography to multispectral satellite imaging are well es-tablished. Herein, we review these techniques, focusing on their value for coral monitoring and health diagnosis. A new, low-cost hyperspectral imaging technique using linear variable filters is also described. This system is capable of simultaneously producing hyperspectral and photogrammetric outputs, which provides integrated information of reef structure and physiology.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

By using a systems biological perspective and available literature on human social interaction, grouping, and cohesiveness, a new coherent model is proposed that integrates existing social integration and neurobiological research into a theoretical neurobiological framework of personality and social interaction. This model allows for the coherent analysis of complex social systems and interactions within them, and proposes a framework for estimating group cohesiveness and evaluating group structures in order to build and organize optimized social groups. This „Neurobiological-Associative“ model proposes two primary feedback loops, with environmental conditioning (learning) being sorted into an associative model that modulates interaction with the social environment, and which impacts the second feedback loop involving the individuals' neurobiological capacity. In this paper, the concept of neurobiological capacity is developed and based upon contemporary research on intelligence, personality, and social behavior with a focus on the oxytocin, serotonin, and dopamine systems. The basis of social exclusion and group structure is thus, expressed in the very most simple terms, neurobiological compatibility and risk assessment modulated by an internal associative model.

Mass hauling operations play central roles in construction projects. They typically use many haulers that consume large amounts of energy and emit significant quantities of CO₂. However, practical methods for estimating the energy consumption and CO₂ emissions of such operations during project planning are lacking. This paper presents a detailed model for estimating the energy consumption and CO₂ emissions of mass haulers that integrates the mass hauling plan with a set of predictive equations. The mass hauling plan is generated using a planning program such as DynaRoad in conjunction with data on the productivity of selected haulers and the amount of material to be hauled during cutting, filling, borrowing, and disposal operations. This plan is then used as input for estimating the energy consumption and CO₂ emissions of the selected hauling fleet. The proposed model will help planners to assess the energy and environmental performance of mass hauling plans, and to select hauler and fleet configurations that will minimize these quantities. The model was applied in a case study, demonstrating that it can reliably predict energy consumption, CO₂ emissions, and hauler productivity as functions of the hauling distance for individual haulers and entire hauling fleets.

Mapping settlement extents at the annual time step has a wide variety of applications in demography, public health, sustainable development, and many other fields. Recently, while more multitemporal urban feature or human settlement datasets have become available, issues still exist in remotely-sensed imagery due to coverage, adverse atmospheric conditions, and expenses involved in producing such feature sets. These challenges make it difficult to increase temporal coverage while maintaining high fidelity in the spatial resolution. Here we demonstrate an interpolative and flexible modeling framework for producing annual built-settlement extents. We use a combined technique of random forest and spatio-temporal dasymetric modeling with open source subnational data to produce annual 100m x 100m resolution binary settlement maps in four test countries of varying environmental and developmental contexts for test periods of five-year gaps. We find that in the majority of years, across all study areas, the model correctly identified between 85-99% of pixels that transition to built-settlement. Additionally, with few exceptions, the model substantially out performed a model that gave every pixel equal chance of transitioning to the category “built” in each year. This modelling framework shows strong promise for filling gaps in cross-sectional urban feature datasets derived from remotely-sensed imagery, provide a base upon which to create future built/settlement extent projections, and further explore the relationships between built area and population dynamics.

This article explores the significant parallels between big tobacco companies and major social networking sites regarding their influence on public health and society. While acknowledging the fundamental differences in their products and services, the paper scrutinises both industries through five primary lenses: addiction, misinformation, lack of regulation, harm to public health, and youth targeting. Both industries exhibit addictive characteristics, have faced criticism for the spread of misinformation, operate with limited regulation and transparency, and have raised concerns about targeting young demographics. Moreover, the potential harm to public health is a significant concern, with tobacco leading to well-established physical health issues. At the same time, excessive social media use has been linked to psychological harm, particularly among young users. The comparison underscores the necessity for greater regulation and oversight of social media companies, highlighting the urgent need for more comprehensive policies to mitigate potential harm and safeguard public health in the digital age.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

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

Abstract: Theoretical and non-dimensional investigations have been performed to study the vibration control potential of approaches that can be based on viscoelastic but also on endochronic elements. The latter are known from the endochronic theory of plasticity and provide the possibility to establish rate-independent schemes for vibration control. The main question that has to be answered is: Can rate-independent damping be efficiently used to reduce mechanical vibrations? To answer this question non-dimensional models for dynamical systems are derived and analyzed numerically in time-domain as well as in frequency-domain. The results are used to compare the performance of an optimally tuned endochronic absorber to the performance of an optimally tuned dynamic absorber with viscoelastic damping. Based on a novel closed form representation for non-linear systems with endochronic elements, it has been possible to prove that rate-independent control of vibration results in an overall control profit that is close to the control profit obtained by the application of well-established approaches. It has also been found that the new concept is advantageous if anti-resonances have to be considered in broadband vibration control. Based on these novel findings, a practical realization in the context of active vibration control is proposed in which the rate-independent control law is implemented on an appropriate signal processing hardware.

The structures of a number of dimers of sulphur dioxide and ozone have been optimized by means of a series of ab initio calculations. The dimer species have been classified as either genuine energy minima or transition states of first or higher order, and the most probable structures consistent with the experimental data have been confirmed. The molecular orbitals engaged in the interactions resulting in adduct formation have been identified and relations between the orbitals of the dimers of the valence isoelectronic monomer species examined. The vibrational spectra of the most probable structures have been computed, and compared with those reported in the literature, particularly with spectra observed in cryogenic matrices. The calculations have been extended to predict the properties of a number of possible heterodimers formed between sulphur dioxide and ozone.

Twice-exceptional learners face a unique set of challenges arising from the intersection of extraordinary talent and disability. Neurobiology research has the capacity to complement pedagogical research and provide support for twice-exceptional learners. Very few studies have attempted to specifically address the neurobiological underpinnings of twice-exceptionality. However, neurobiologists have built a broad base of knowledge in nervous system function spanning from the level of neural circuits to the molecular basis of behavior. It is known that distinct neural circuits mediate different neural functions, which suggests that 2e learning may result from enhancement in one circuit and disruption in another. Neural circuits are known to adapt and change in response to experience, a cellular process known as neuroplasticity. Plasticity is controlled by a bidirectional connection between the synapse, where neural signals are received, and the nucleus, where regulated gene expression can return to alter synaptic function. Complex molecular mechanisms compose this connection in distinct neural circuits, and genetic alterations in these mechanisms are associated with both memory enhancements and psychiatric disorder. Understanding the consequences of these changes at the molecular, cellular, and circuit levels will provide critical insights into the neurobiological bases of twice-exceptional learning.

Responding to changing value creation processes in the sheet metal working sec-tor, where the complexity and interchangeability of products challenge traditional dif-ferentiation strategies, this empirical analysis explores integrating service-oriented and data-driven business models as new paths to ensure competitiveness, especially for small and medium-sized enterprises (SMEs). This study aims to capture the current state and challenges associated with the implementation of these business models in this sector. The research was conducted through semi-structured interviews with SMEs in the industry. The findings indicate that service-oriented and data-driven business models are not yet widely adopted and that manufacturing companies re-quire support in their implementation. Fields of action were identified for the industry. These are "Creating awareness and understanding", "Recognizing added value", "In-creasing company maturity" and "Understanding the change process". Cooperation between science and industry is essential in tackling these fields of action to ensure the successful integration of such business models in manufacturing companies. This pa-per identifies challenges in the fields of action that companies must address through a structured approach promoting awareness, recognizing value, improving organiza-tional maturity, and understanding the change process to successfully implement ser-vice-oriented and data-driven business models.

Objectives Independent validation of risk scores after hip fracture is uncommon, particularly for evaluation of outcomes other than death. We aimed to assess the Nottingham Hip Fracture Score (NHFS) for prediction of mortality, physical function, length of stay and postoperative complications. Design Analysis of routinely collected prospective data partly collected by follow-up interviews. Setting and Participants Consecutive hip fracture patients were identified from the Northumbria hip fracture database between 2014-2018. Patients were excluded if they were not surgically managed or if scores for predictive variables were missing. Methods C-statistics were calculated to test the discriminant ability of the NHFS, Abbreviated Mental Test Score (AMTS), and ASA grade for in-hospital, 30- and 120-day mortality, functional independence at discharge, 30-days and 120-days, length of stay, and postoperative complications. Results We analysed data from 3208 individuals, mean age 82.6 (SD 8.6). 2192 (70.9%) were female. 194 (6.3%) died during the first 30-days, 1686 (54.5%) were discharged to their own home, 211 (6.8%) had no mobility at 120-days, 141 (4.6%) experienced a postoperative complication. The median length of stay was 18 days (IQR 8-28). For mortality, c-statistics for the NHFS ranged from 0.68-0.69, similar to ASA and AMTS. For postoperative mobility, the c-statistics for the NHFS ranged from 0.74-0.83, similar to AMTS (0.61-0.82) and better than the ASA grade (0.68-0.71). Length of stay was significantly correlated with each score (p<0.001 by Jonckheere-Terpstra test); NHFS and AMTS showed inverted U-shaped relationships with length of stay. For postoperative complications, c-statistics for NHFS (0.54-0.59) were similar to ASA grade (0.53-0.61) and AMTS (0.50-0.58). Conclusions and Implications The NHFS performed consistently well in predicting functional outcomes, moderately in predicting mortality, but less well in predicting length of stay and complications. There remains room for improvement by adding further predictors such as measures of physical performance in future analyses.

Duke University was founded in 1930 primarily due to funds generated from James B. Duke’s tobacco business. Duke achieved great financial wealth primarily due to the early application of machine rolled cigarettes, as opposed to hand rolled. This early adoption of technology allowed Duke Tobacco to out-produce other companies still selling hand rolled cigarettes. By making smoking more inexpensive and easier than pipe smoking, the cigarette formed the foundation for nicotine addiction in the 1900s, generating huge profits for the tobacco industry. At the time Duke University was founded, little was known about the connection between nicotine, cigarettes, and respiratory diseases such as emphysema and lung cancer. Through James Duke’s philanthropy, the devastating harm from cigarettes has been mitigated in part through the founding of one of the world’s most prominent medical centers and research universities.

Ecology is working to face its colonial roots and institutional inequities. As we build more diverse, equitable, and inclusive (DEI) institutions we must work to support new ecologists by empowering them with the knowledge and tools to succeed. Undergraduate research experiences (UREs) are critical for a student’s professional and interpersonal skill development and key for recruiting more diverse groups of students to ecology. Here, we highlight DEI dimensions of a URE in ecology, acknowledge safety considerations for field ecology, including harassment and assault, and provide tools to support the URE. This is written primarily for all URE students and secondarily for their advisors. We welcome students from underrepresented groups and encourage allyship from students from non-underrepresented groups. After reading this paper, we hope that all students feel more confident and excited about their URE and that advisors see how to improve DEI in their lab.

Some physicists surmise that gravity lies outside of quantum mechanics. Thus theories like the standard semiclassical theory of quantum to gravity coupling (that of Rosenfeld and Møller) are possible real models of interaction, rather than a mere approximation of a theory of quantum gravity. Unfortunately, semiclassical gravity creates inconsistencies such as superluminal communication. Alternatives by authors such as Diósi, Martin, Penrose, and Wang often use the term 'stochastic' to set themselves apart from the standard semiclassical theory. These theories couple to fluctuations caused by for instance continuous spontaneous localization, hence the term 'stochastic'. This paper looks at stochastic gravity in the framework of a class of emergent or ontological quantum theories, such as those by Bohm, Cetto, and de Broglie. It is found that much or all of the trouble in connecting gravity with a microscopic system falls away, as Einstein's general relativity is free to react directly with the microscopic beables. The resulting continuous gravitational wave radiation by atomic and nuclear systems does not, in contrast to Einstein's speculation, cause catastrophic problems. The small amount of energy exchanged by gravitational waves may have measurable experimental consequences. A very recent experiment by Vinante et al. performed on a small cantilever at mK temperatures shows a surprising non-thermal noise component, the magnitude of which is consistent with the stochastic gravity coupling explored here.

Milk is a complex liquid, and the concentrations of many of its components are under genetic control. Many genes and pathways are known to regulate milk compositon, and the purpose of this review is to highlight how the discoveries of quantitative trait loci (QTL) for milk phenotypes can elucidate these pathways. The main body of this review focusses primarily on QTL discovered in cattle (Bos taurus) as a model species for lactation biology, with occasional references to other ruminant species, and some comparisons with human milk composition are also presented. The following section describes a range of techniques that can be used to help identify the causative genes underlying QTL when the underlying mechanism involves the regulation of gene expression. As genotype and phenotype data bases continue to grow and diversify, new QTL will continue to be discovered, and, although proving the causality of underlying genes and variants remains difficult, these new data sets will further enhance our understanding of lactation biology.

Physics theory has yet to settle on specific descriptions for new elementary particles, for dark matter, and for dark energy forces. Our work extrapolates from the known elementary particles. The work suggests well-specified candidate descriptions for new elementary particles, dark matter, and dark energy forces. This part of the work does not depend on theories of motion. This work embraces symmetries that correlate with motion-centric conservation laws. The candidate descriptions seem to explain data that prior physics theory seems not to explain. Some of that data pertains to elementary particles. Our theory suggests relationships between masses of elementary particles. Our theory suggests a relationship between the strengths of electromagnetism and gravity. Some of that data pertains to astrophysics. Our theory seems to explain ratios of dark matter effects to ordinary matter effects. Our theory seems to explain aspects of galaxy formation. Some of that data pertains to cosmology. Our theory suggests bases for inflation and for changes in the rate of expansion of the universe. Generally, our work proposes extensions to theory in three fields. The fields are elementary particles, astrophysics, and cosmology. Our work suggests new elementary particles and seems to explain otherwise unexplained data.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Cross-institutional secondary use of medical data benefits from structured semantic annotation, which, ideally, enables matching and merging semantically related data items from different sources and sites. While numerous medical terminologies and ontologies, as well as some tooling, exist to support such annotation, cross-institutional data usage based on independently annotated datasets is challenging for multiple reasons: the annotation process is resource intensive and requires a combination of medical and technical expertise since it often requires judgment calls to resolve ambiguities resulting from non-uniqueness of potential mappings to various levels of ontological hierarchies and relational and representational systems. Divergent resolution of such ambiguities can inhibit joint cross-institutional data usage based on semantic annotation since data items with related content from different sites will not be identifiable based on their respective annotations if different choices were made without further steps such as ontological inference, which is still an active area of research. We hypothesize that a collaborative approach to semantic annotation of medical data can contribute to more resource efficient and high-quality annotation by utilizing prior annotational choices of others to inform the annotation process, thus both speeding up the annotation itself and fostering a consensus approach to resolving annotational ambiguities by enabling annotators to discover and follow pre-existing annotational choices. Therefore, we have implemented a prototypical Collaborative Annotation Tool (CoAT), evaluated its usability, and present first inter-institutional experiences with this novel approach to promoting practically relevant interoperability driven by use of standardized ontologies.

Quantum chaos is presented as a paradigm of information processing by dynamical systems at the bottom of the range of phase-space scales. Starting with a brief review of classical chaos as entropy flow from micro- to macro-scales, I argue that quantum chaos came as an indispensable rectification, removing inconsistencies related to entropy in classical chaos: Bottom-up information currents require an inexhaustible entropy production and a diverging information density in phase space, reminiscent of Gibbs' paradox in Statistical Mechanics. It is shown how a mere discretization of the state space of classical models already entails phenomena similar to hallmarks of quantum chaos, and how the unitary time evolution in a closed system directly implies the “quantum death” of classical chaos. As complementary evidence, I discuss quantum chaos under continuous measurement. Here, the two-way exchange of information with a macroscopic apparatus opens an inexhaustible source of entropy and lifts the limitations implied by unitary quantum dynamics in closed systems. The infiltration of fresh entropy restores permanent chaotic dynamics in observed quantum systems. Could other instances of stochasticity in quantum mechanics be interpreted in a similar guise? Where observed quantum systems generate randomness, that is, produce entropy without discernible source, could it have infiltrated from the macroscopic meter? This speculation is worked out for the case of spin measurement.

Loneliness is becoming prevalent across Japan in spite of its a dense population and communal culture. Surveys show 40% of adults report isolation across demographics. The contradiction emerges due to deteriorating social structure with modernization, economic parity, urbanization, and fading conventional setup. The continually social withdrawals, called “hikikomori." Relief seekers have embraced AI based emotive robots, digital avatars, and immersive VR as low-stakes social surrogates despite limited capacity to cultivate human intimacy. To stabilise government attempts awareness through reforms, scheme and support services. But a concrete transformation can be brough in with work-life balance, gender equality and rewire the metrics for self-esteem. Even a perfectly personalized AI cannot replace the human affection lacking in the society. Lasting solutions demand technological aids be balanced by confronting and reinventing community purpose and bring in structural change. Overall Japan’s endemic isolation reveals the societal fraying when modernization privileges independence over interdependence. The path forward rests on restoring cultural foundations to reverse loneliness and social isolation.

In several mammalian species including humans, complex stimulation patterns such as cognitive challenge and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. The hypothesis is presented here that activity-dependent transcriptional programs, induced by these environmental stimuli, temporarily and lightly de-differentiate somatic cells such as neurons and muscle cells into a state that resembles functionally younger cells to allow cellular remodeling and adaptation of the organism to environmental change. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell-cell communication, intracellular signaling and epigenetic information processing and leads to functional improvements in these areas. I reverse engineer these activity-dependent gene programs, identify critical molecular nexus points such as CREB, MEF2 and cFos and speculate as to how one might leverage them to prevent and attenuate human aging-related decline of body function, enhance human performance and restore more youthful levels of function and morphology. The findings presented here can serve as a basis for the study and development of effective longevity efforts as the underlying gene programs could be used as markers for treatment success and as targets for therapy development.

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

Japanese encephalitis virus is a mosquito-borne member of the Flaviviridae family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO®) has been approved by the US Food & Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of introduction of JEV in the US, the need to integrate planning for such an event in public health policy and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.

The topic of this paper is the airborne evaluation of ICESat-2 Advanced Topographic Laser Altimeter System (ATLAS) measurement capabilities and surface-height-determination over crevassed glacial terrain, with a focus on the geodetical accuracy of geophysical data collected from a helicopter. To obtain surface heights over crevassed and otherwise complex ice surface, ICESat-2 data are analyzed using the density-dimension algorithm for ice surfaces (DDA-ice), which yields surface heights at the nominal 0.7~m along-track spacing of ATLAS data. As the result of an ongoing surge, Negribreen, Svalbard, provided an ideal situation for the validation objectives in 2018 and 2019, because many different crevasse types and morphologically complex ice surfaces existed in close proximity. Airborne geophysical data, including laser altimeter data (profilometer data at 905~nm frequency), differential Global Positioning System (GPS), Inertial Measurement Unit (IMU) data, on-board-time-lapse imagery and photographs, were collected during two campaigns in summers of 2018 and 2019. Airborne experiment setup, geodetical correction and data processing steps are described here. To date, there is relatively little knowledge of the geodetical accuracy that can be obtained from kinematic data collection from a helicopter. Our study finds that (1)~Kinematic GPS data collection with correction in post-processing yields higher accuracies than Real-Time-Kinematic (RTK) data collection. (2)~Processing of only the rover data using the Natural Resources Canada Spatial Reference System Precise Point Positioning (CSRS-PPP) software is sufficiently accurate for the sub-satellite validation purpose. (3)~Distances between ICESat-2 ground tracks and airborne ground tracks were generally better than 25~m, while distance between predicted and actual ICESat-2 ground track was on the order of 9~m, which allows direct comparison of ice-surface heights and spatial statistical characteristics of crevasses from the satellite and airborne measurements. (4)~The Lasertech Universal Laser System (ULS), operated at up to 300~m above ground level, yields full return frequency (400~Hz) and 0.06-0.08~m on-ice along-track spacing of height measurements. (5)~Cross-over differences of airborne laser altimeter data are 0.1918 $\pm$ 2.385~m along straight paths over generally crevassed terrain, which implies a precision of approximately 2.4~m for ICESat-2 validation experiments. (6)~In summary, the comparatively light-weight experiment setup of a suite of small survey equipment mounted on a Eurocopter (Helicopter AS-350) and kinematic GPS data analyzed in post-processing using CSRS-PPP leads to high accuracy repeats of the ICESat-2 tracks. The technical results (1)-(6) indicate that direct comparison of ice-surface heights and crevasse depths from the ICESat-2 and airborne laser altimeter data is warranted. The final result of the validation is that ICESat-2 ATLAS data, analyzed with the DDA-ice, facilitate surface-height determination over crevassed terrain, in good agreement with airborne data, including spatial characteristics, such as surface roughness, crevasse spacing and depth, which are key informants on the deformation and dynamics of a glacier during surge.

Cell division control 37 (CDC37) increases the stability of HSP90 client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SCAN transcription factor family- MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1 / ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc-fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in CDC37 gene, negatively regulated CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.

The gauge field equation for fluid mechanics established in Part 1 is developed into a first-order scattering theory in the simplified case of a two-dimensional incompressible flow over a flat plate. This is used to present a model for the origin of Tollmien-Schlichting (TS) waves based on scattering between fluid particles. As a result, analytical formulae for the maximum amplification factor and the transition point from laminar to turbulent flow in the boundary layer are obtained. The mathematical transformations from the stationary field equations in Part 1 to a scattering theory with time evolution along the flow axis using Wick rotation are elaborated in detail.

As the embedded device and internet of things (IoTs) concept prevalent in today's world, there is an increasing demand for the security and performance requirements on deploying these devices to private and public sectors. The crucial part of it is to protect privacy, confidentiality and integrity, meanwhile, maintain an adequate level of performance during transmission, storage and access of critical information. While the conventional cryptography methods, such as the Advanced Encryption Standard (AES), SHA$-$2 hashing method and RSA and Diffie Hellman for message authentication and identification, work well on systems which have reasonable processing power and memory capabilities. These do not scale well into a world with embedded systems and sensor networks, in conjunction with their nature of smaller size and lower cost. Thus, in the context of resource constrained device, lightweight cryptography methods are proposed to overcome many of the problems of conventional cryptography possessed. This includes constraints related to physical size, processing requirement, memory limitation, energy drain and production cost. This paper provides a survey of the architectures that are defined as replacements for conventional ciphers within an IoTs space and discuss some trends in the design of future lightweight algorithms. The performance metrics are carefully chosen to reflect and assess the suitability for embedded devices. The aim of this research is to identify the various performance metrics applied on different types of symmetric block ciphers especially lightweight ciphers and compare the results on versatile platforms with stream ciphers and public key methods. The comparative analysis on efficient LW cipher will be tested against other similar block ciphers on both MacBook Pro with Intel core and resource constrained device Raspberry Pi with ARM processor.

The rapid expansion of social media and instant messaging applications, such as WhatsApp, has transformed how individuals and organizations communicate and engage. This think piece explores the potential of integrating WhatsApp as a customer relationship management (w-CRM) tool within the education sector to foster and sustain long-term relationships among students, teaching staff, and non-teaching staff. By leveraging real-time features and the widespread use of WhatsApp, educational institutions can create a more interactive and dynamic learning environment, benefiting all stakeholders involved. The literature highlights the importance of establishing clear frameworks for mutual engagement and interaction and the potential of w-CRM to improve communication between students' families and educational institutions. There are potential risks associated with the pervasive use of WhatsApp, and call for future research to explore strategies for mitigating these risks while maximizing the benefits of w-CRM in the education sector. Longitudinal studies are recommended to evaluate the long-term impact of w-CRM on stakeholder relationships, student outcomes, and overall institutional performance.

Local food has continued to become more popular in both the home and as featured ingredients in all segments of food service. Numerous studies have explored the motivating factors for consumer purchasing motivators. However, no known study has explored if there is a correlation between ego and intent to buy local foods. This study adopted a modified version of the Theory of Trying and surveyed a sample of 237 food service buying agents in South Carolina to examine their perceptions of buying local. Results suggest that ego is a predictor of trying to purchase local foods for restaurants. It was also found that the modified model is an acceptable model for predicting buyer intent. These findings support the majority of the studies looking at ego-centric behaviors with green purchases and could potentially help local food suppliers to better market their products to foodservice establishments. This study could also act as the foundation for future studies to explore the full extent of ego’s motivational effect on purchasing intentions in the food service industry.

Managing a portfolio whose value closely tracks an index by trading only in a subset of the index constituents involves an NP-hard optimisation problem. In the prior literature, it has been suggested to solve this problem using sequential Monte Carlo (SMC, a.k.a. particle filter) methods. However, this literature does not take transaction costs into account, although transaction costs are the primary motivation for attempting to replicate the index by trading in a subset, rather than the full set of index constituents. This paper extends the SMC approach to index tracking to allow for proportional transaction costs and implements this extended method on empirical data for a variety stock indices. In addition to providing a more practically useful tracking strategy by allowing for transaction costs, we find that including a penalty for transaction costs in the optimisation objective can actually lead to better tracking performance.

Contaminants of Emerging Concern (CECs), a new category of contaminants in limelight, is a major issue of global concern. The pervasive nature of CECs and its harmful effects, such as cancer, reproductive disorders, neurotoxicity etc., make the situation alarming. The perilous nature of CECs lies in the fact that even very small concentration of CECs can cause great impacts on living beings. It also has a nature of bioaccumulation. Thus, it is the ultimate need to have efficient sensors for detection of CECs to ensure safe living environment. Electrochemical sensors are an efficient platform for CEC detection as they are highly selective, sensitive, stable, reproducible, and prompt, and can detect very low concentrations of analyte. Major classes of CECs are pharmaceuticals, illicit drugs, personal care products, endocrine disruptors, newly registered pesticides, and disinfection by-products. This review focusses on CECs, including their sources and pathways, health effects caused by them, and electrochemical sensors as reported in literatures under each category for the detection of major CECs.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

High-throughput screening technologies continues to produce large amounts of multiomics data from different populations and cell types for various diseases, such as cancer. However, analysis of such data encounters difficulties due to cancer heterogeneity, further exacerbated by human biological complexity and genomic variability. There is a need to redefine the drug discovery development pipeline, bringing an Artificial Intelligence (AI)-powered informational view that integrates relevant biological information and explores new ways to develop effective anticancer approaches. Here, we show SynPred, an interdisciplinary approach that leverages specifically designed ensembles of AI-algorithms, links omics and biophysical traits to predict synergistic anticancer drug synergy. SynPred exhibits state-of-the-art performance metrics: accuracy – 0.85, precision – 0.77, recall – 0.75, AUROC – 0.82, and F1-score - 0.76 in an independent test set. Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application available online at http://www.moreiralab.com/resources/synpred/ was constructed to predict synergistic anticancer drug combinations requiring only the upload of the two drug SMILES to be tested, allowing easy access by non-expert researchers.

Antibiotic Resistance (ABR) is increasing the mortality and morbidity associated with infectious diseases, besides increasing the cost of healthcare, saturating health-system capacity, and adversely affecting food security. Framing an appropriate narrative and engaging local communities through ‘One Health’ approach is essential to complement the top down measures. However, the absence of objective criteria to measure the performance of ABR interventions at community settings make it difficult to mobilize interest and investment for such interventions. An exercise was therefore done to develop an indicator framework for this purpose. An exhaustive list of indicators was developed from experiences gathered through community engagement work in a local panchayat (small administrative area) in Kerala, India, and a consultative process with health, veterinary, environment, and development experts. A prioritization exercise was done, looking at appropriateness, feasibility and validity, by global experts on ABR. A 15-point indicator framework was designed based on the prioritization process. The final set of indicators covers human health, animal health, environment management and Water Sanitation and hygiene (WASH) domains. The indicator framework was piloted in the panchayat(located in Kerala), which attained a score of 34 (maximum 45). The score increased when interventions were implemented to mitigate the ABR drives, indicating the framework is sensitive to change. Simultaneously, the indicator framework was tested in four sites from three other Indian states with different socioeconomic and health profiles, yielding different scores. Those collecting the field data were able to use it with minimal training. To conclude, this indicator framework can help policymakers broadly understand the factors contributing to ABR and measure the performance of interventions they choose to implement in the community

There is a long-standing association between exceptional cognitive abilities, of various sorts, and neuropsychiatric illness, but it has historically largely been investigated in an exploratory and non-systematic way. One group in which this association has been investigated with more rigor is in subjects who have been identified as twice exceptional; an educational term describing subjects who are both gifted and diagnosed with a neuropsychiatric disability. This term covers multiple conditions, but is of specific interest in particular in the study of autism spectrum disorder. Recent findings have led to the development of a hypothesis that a certain degree of the neurobiology associated with autism might even be advantageous for individuals and could lead to high giftedness, while becoming disadvantageous, once a certain threshold is surpassed. In this model, the same neurobiological mechanisms confer an increasing advantage up to a certain threshold, but become pathological past that point. Twice-exceptional individuals would be exactly at the inflection point, being highly gifted, but also symptomatic at the same time. Here, we review how existing neuroimaging literature on autism spectrum disorder can inform research on twice exceptionality specifically. We propose to study key neural networks with a robust implication in ASD to identify the neurobiology underlying twice-exceptionality. A better understanding of the neural mechanisms of twice exceptionality should help to better understand resilience and vulnerability to neurodevelopmental disorders and tofurther support affected individuals.

QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern, with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neo-nates. Further research in this age category is needed to improve primary screening practices, earlier detection of risk factors and precision pharmacovigilance.

The objective of this study was to evaluate the efficacy of fungal treatment (Pleurotus ostreatus) of urea-treated rice stubble on growth performance in slow-growing goats. Eighteen crossbred Thai native x Anglo-Nubian male goats (average body weight: 20.4 ± 2.0 kg) were randomly assigned to three experimental total mixed rations containing 35% rice stubble (RS) that was either untreated (URS), urea treated (UTRS) or treated with urea and fungi (UFTRS). URS and UTRS were cultivated and harvested from aseptically fungal spawn, incubated at 25-30 °C for 25 days. Indicators of growth performance were monitored and faeces were collected quantitatively to assess nutrient digestibility, during a 12-week feeding trial. All goats remained healthy throughout experiment. The goats fed UFTRS had a lower feed conversion ratio (kg feed/kg growth) compared to goats fed URS or UTRS. Compared to URS, dietary UFTRS increased nutrient digestibility of slow-growing goats, such as OM (+8.5%), CP (+5.5%), NDF (+39.2%), and ADF (+27.4%). Likewise, dietary UFTRS tended to increase rumen ammonia concentrations but rumen pH and volatile fatty acids were not affected by UFTRS. In conclusion, the present study indicates that the fungal treatment of RS is an effective tool to improve the growth performance of slow-growing goats.

Advanced ceramics are recognized as key enabling materials possessing combinations of properties not achievable in other material classes. They are characterized by very high thermal, chemical and mechanical resistance and also usually have a lower density than metals. These properties predestine ceramics for many different applications, especially space applications.In the aerospace sector aerospike nozzles promise performance and application advantages compared to classic bell nozzles but are also inherently more complex to manufacture due to their shape. AM methods drastically simplify or even enable the fabrication of those complex structures while minimising the number of individual parts. The applicability of ceramic AM (“CerAMfacturing”) on rocket engines and especially nozzles is consequently investigated in the frame of the “MACARONIS” project, a cooperation of the Institute of Aerospace Engineering at Technische Universität Dresden and the Fraunhofer Institute for Ceramic Technologies and Systems (IKTS) in Dresden. The goal is to develop novel large size aerospike thrust nozzles including areas of highest resolution and fineness. Finding a suitable AM process that enables the realisation of both aspects is extremely challenging. One possibility could be the hybridization of shaping methods, in that case CerAM VPP (ceramic additive manufacturing via vat photopolymerization) and CerAM FFF (ceramic additive manufacturing via fused filament fabrication) in combination with sinter joining. This contribution focuses on the high resolution CerAM VPP process, in particular the development, characterization and testing of a new photoreactive Al₂O₃ suspension validated by AM of novel aerospike nozzles.