Background: Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (Dio3) is present in immune cells but there is no description of its presence in this patients. Here we aimed to determine the prognostic impact of thyroid hormones levels (TH) measured on ICU admission on mortality and on evolution to chronic critical illness (CCI) and the presence of D3 in white cells. Methods: Prospective cohort study with a follow-up for 28 days or deceased. Results: Low T3 levels at admission were present in 86.5% of the patients. Dio3 was 55% induced in immune cells. The cut-off value of 60 pg/mL for T3 displayed a sensitivity and specificity of 81% and 64% for predicting death, odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 and 0.75 for mortality and evolution to CCI, respectively, thus displaying better performance than commonly used prognostic scores. Conclusions: We advance in the pathophysiology of low T3 showing induced D3 in immune cells during sepsis. Low T3 levels independently predicted a progression to CCI and mortality within 28 days in sepsis and septic shock.

Levan is a fructan-type exopolysaccharide, which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to which extent levan is functionally diverse in dependence of its size. The aim of our study was to get deeper insights into the size-dependent, functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but significantly differ in their molecular size and rheological properties among each other. The smallest levan (< 107 Da) produced without adjustment of the pH exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). On the contrary, larger levans (> 108 Da) produced at pH ≥ 4.5 were shear-thinning and showed a gel like behavior at ≥ 5% (w/v). A third (intermediate) levan variant was obtained via production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid at ≥ 5% (w/v). Our study reveals that the variable size and composition of levan are controllable and more decisive for its functionality than the amount of exerted levan.

The phylogeny of Neoaves, the largest clade of extant birds, has remained unclear despite intense study. The difficulty associated with resolving the early branches in Neoaves is likely driven by the rapid radiation of this group. However, conflicts among studies may be exacerbated by the hypothesis that relationships are sensitive to the data type analyzed. For example, analyses of coding exons typically yield trees that place Strisores (nightjars and allies) sister to the remaining Neoaves, while analyses of non-coding data typically yield trees where Mirandornites (flamingos and grebes) is the sister of the remaining Neoaves. Our understanding of data type effects is hampered by the fact that previous analyses have used different taxa, loci, and types of non-coding data. Herein, we provide strong corroboration of the data type effects hypothesis for Neoaves by comparing trees based on coding and non-coding data derived from the same taxa and gene regions. A simple analytical method known to minimize biases due to base composition (coding nucleotides as purines and pyrimidines) resulted in coding exon data with increased congruence to the non-coding topology using concatenated analyses. These results improve our understanding of the resolution of neoavian phylogeny and point to a challenge - data type effects - that is likely to be an important factor in phylogenetic analyses of birds (and many other taxonomic groups). Using our results, we provide a summary phylogeny that identifies well-corroborated relationships and highlights specific nodes where future efforts should focus.

Both the use of plastic and its decomposition products lead to the distribution of plastic all over the earth and finally to the uptake by all kind of living beings including humans. Still, it is widely unknown what risks harbor the widespread uptake of plastics for human health, espe-cially regarding contributing factors like size, shape and surface composition. We assessed the uptake of polymethylmethacrylate (PMMA)-nano- and microbeads for HEK293-, A549- and MRC5 cells. Via confocal microscopy, we localized multiple PMMA-beads inside the cytosol of cells. Uptake of PMMA-beads did not alter cell growth and cell division, implying no short-term toxicity towards human cells. Further, we used a cAMP response element binding protein (CREB)-mediated reporter assay to assess whether internalized PMMA-nanobeads alter cell-signaling pathways. In contrast to the in vitro transcription, where the addition of PMMA-nanobeads abolished the transcription, no changes regarding CREB-mediated cell sig-naling are given in HEK293-cells. Our data led to the assumption that PMMA-nano-and mi-crobeads are internalized via endocytosis and end up as lysosomes within the cells cytosol. Therefore, we concluded differences regarding the surface composition of the PMMA-nanobeads mainly affect its potential to alter cell signaling. These findings emphasize the key role the sur-face composition plays regarding microplastic and its risks for human health.

Despite the long history of using protein sequences to infer the tree of life the potential for different parts of protein structures to retain historical signal remains unclear. We propose that it might be possible to improve analyses of phylogenomic datasets by incorporating information about protein structure; we test this idea using the position of the root of Metazoa (animals) as a model system. We examined the distribution of “strongly decisive” sites (alignment positions that support a specific tree topology) in a dataset comprising &gt;1,500 proteins and almost 100 taxa. The proportion of each class of strongly decisive sites in different structural environments was very sensitive to the model used to analyze the data when a limited number of taxa were used but they were stable when taxa were added. As long as enough taxa were analyzed, sites in all structural environments supported the same topology (ctenophores sister to other animals) regardless of whether standard tree searches or decisive sites were used to select the optimal tree. However, the use of decisive sites revealed a difference between the support for minority topologies for sites in different structural environments; buried sites and sites in sheet and coil environments exhibited equal support for the minority topologies whereas solvent exposed and helix sites had unequal numbers of sites supporting the minority topologies. Given the plausible trees equal support for minority topologies is consistent with discordance among gene trees, making it possible the relatively slowly evolving buried (and sheet and coil) sites are giving an accurate picture of the true species tree as well as the amount of conflict among gene trees. Alternatively, the apparent support could reflect currently uncharacterized processes of molecular evolution. Regardless, it is clear that analyses of the deepest branches in the animal tree of life using sites in different structural environments are associated with a subtle data type effect that results in distinct phylogenetic signals.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

Any photon, regardless of its origin, carries the same optical field profile. This feature and the quantum Rayleigh emissions generate temporally discrete groups of several photons in a resonant cavity incorporating one single quantum dot. A periodic stream of single photons is distorted by high-finesse optical cavities and the quantum Rayleigh spontaneous emission in a beam splitter. Groups of photons emerge from interferometric filters because of multiple internal reflections.

Three physical elements are missing from the conventional formalism of quantum photonics: 1) the quantum Rayleigh spontaneous and stimulated emissions; 2) the unavoidable parametric amplification; and 3) the mixed time-frequency spectral structure of a photonic field which specifies its duration or spatial extent. As a single photon enters a dielectric medium, the quantum Rayleigh scattering prevents it from propagating in a straight-line, thereby destroying any possible entanglement. A pure dynamic and coherent state composed of two consecutive number states, delivers the correct expectation values for the number of photons carried by a photonic wave front, its complex optical field, and phase quadratures. The intrinsic longitudinal and lateral field profiles associated with a group of photons for any instantaneous number of photons are independent of the source. These photonic properties enable a step-by-step analysis of the correlation functions characterizing counting of coincident numbers of photons or intensities with unity visibility interference, spanning the classical and quantum optic regimes

The presence of the quantum Rayleigh scattering, or spontaneous emission, inside a dielectric medium such as a beam splitter or an interferometric filter, prevents a single-photon from propagating in a straight-line. Modelling a beam splitter by means of a unitary transformation is physically meaningless because of the loss of photons. Additional missing elements from the conventional theory are: 1) the quantum Rayleigh stimulated emission which can form groups of photons of the same frequencies, and 2) the unavoidable parametric amplification of single-photons in the original parametric crystal. An interference filter disturbs, through multiple internal reflections, the original stream of single-photons, thereby confirming the existence of groups of photons being spread out to lengthen the coherence time. The approach of modelling individual, single measurements with statistical ensemble probability amplitudes leads to the counterintuitive explanations of the experimental outcomes and should be replaced with pure states describing instantaneous measurements which are afterwards averaged.

The locality condition of probabilities underpinning the derivation of Bell inequalities can be violated classically. The wave function collapse results in the factorization of quantum probabilities. It is possible to differentiate, locally, between ensemble probabilities of single detections with and without wave function collapse for the alleged quantum nonlocality. The theoretical concept of photonic quantum nonlocality cannot be implemented physically because of the quantum Rayleigh scattering of single photons. A distinction needs to be made between the correlation of individual, single measurements of pure states and the correlation of the ensemble states of the mixed states. The correlation operator of Pauli vector operators delivers the same probabilities of correlated detections of photons for both independent and multi-photon states as for ‘entangled’ states of photons. As single-photon sources are not needed, the design and implementation of quantum computing operations and other devices will be significantly streamlined.

Leukemia cutis (LC) is defined as leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and in T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis and treatment of leukemic skin involvement in different types of leukemia

The usage of biotechnological molecules and processes is an indispensable part of the resource technology research. The development of novel biomolecules therefore needs to be adapted to the existing applicational conditions and biological processes are to be examined. Novel biosorbents may not only contribute to future applications but can be of further used, e.g. to better understand the interaction of known metal- and metalloid-interacting biological molecules and materials. This review highlights biotechnological approaches published so far for bioremediation as well as metal recovery with a special spotlight on cobalt, nickel and arsenic.

Phylogenomics, the use of large datasets to examine phylogeny, has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life; this could reflect, at least in part, the poor-fit of the models used to analyze heterogeneous datasets. Some of the heterogeneity may reflect the different patterns of selection on proteins based on their structures. To test that hypothesis, we developed a pipeline to divide phylogenomic protein datasets into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had distinct signals for the topology of the deepest branches in the metazoan tree. The most striking difference in phylogenetic signal reflected relative solvent accessibility; analyses of exposed sites (on the surface of proteins) yielded a tree that placed ctenophores sister to all other animals whereas sites buried inside proteins yielded a tree with a sponge-ctenophore clade. These differences in phylogenetic signal were not ameliorated when we repeated our analyses using the CAT model, a mixture model that is often used for analyses of protein datasets. In fact, the heterogeneous CAT model resulted in several rearrangements that are unlikely to represent evolutionary history. However, analyses conducted after recoding amino acids to limit the impact of deviations from compositional stationarity increased the congruence in the estimates of phylogeny for exposed and buried sites; after recoding amino acids both trees supported placement of ctenophores sister to all other animals. These results provide striking evidence that it is necessary to achieve a better understanding of the constraints due to protein structure to improve phylogenetic estimation.

A dendrochronological investigation was undertaken on subfossil Scots pine (Pinus sylvestris L.) stumps following their discovered during conservation management activities at Wem Moss, a small (28ha) former raised mire in Shropshire, UK. Two ring-width chronologies were constructed from 14 of the 17 trees investigated spanning 198 and 208 years respectively. Whilst absolute dating was not possible, radiocarbon assays provided an estimated age for this mire-rooting woodland of between 3015 – 2505 years Cal BC, coinciding with the age traditionally associated with the widespread mortality of pine trees throughout much of the UK and Ireland, The Pine Decline (circa 4 ka radiocarbon years BP). Placed in a wider geographical context, the Wem Moss pines are located within the wider lowland area of the Meres and Mosses Region, where previous studies on subfossil pine have demonstrated protracted declines in mire-rooting trees. These have included tree mortality significantly post-dating The Pine Decline, notably at larger peatland sites exceeding 5.5 km2. This macrofossil evidence for the presence of Scots pine into the late Holocene is supported by continuous Pinus pollen representation at peatland sites in the Welsh Marches (English-Welsh border) suggesting the possible survival of native Scots pine trees in this area up to the present-day. This research highlights the incomplete and patchy nature of palaeo-vegetational records and also the potential for genetic research on living Scots pine in possible refugial areas in the UK and Ireland.

The factors that determine the relative rates of amino acid substitution during protein evolution are complex and they are known to vary among taxa. We estimated relative exchangeabilities for pairs of amino acids from clades spread across the tree of life and assessed the historical signal in the distances among these clade-specific models. We trained these models separately on collections of arbitrarily selected protein alignments and on ribosomal protein alignments. In both cases we found a clear separation between the models trained using multiple sequence alignments from bacterial clades and the models trained on archaeal and eukaryotic data. We assessed the predictive power of our novel clade-specific models of sequence evolution by asking whether fit to the models could be used to identify the source of multiple sequence alignments. Model fit was generally able to classify protein alignments correctly at the level of domain (bacterial versus archaeal), but the accuracy of classification at finer scales was much lower. The only exceptions to this were the relatively high classification accuracy for two archaeal lineages: Halobacteriaceae and Thermoprotei. Genomic GC content had a modest impact on relative exchangeabilities despite having a large impact on amino acid frequencies. Relative exchangeabilities involving aromatic residues exhibited the largest differences among models. There were a small number of exchangeabilities that exhibited large differences in comparisons among major clades and between generalized models and ribosomal protein models. Taken as a whole, these results reveal that a small number of relative exchangeabilities are responsible for much of the structure of the “model space” for protein sequence evolution. If we look beyond the information that these clade-specific models reveal about protein evolution the models themselves are likely to be useful tools for phylogenomic inference across the tree of life.

Avian sex chromosomes evolved after the divergence birds and crocodilians from their common ancestor, so they are much younger than the better-studied chromosomes of mammals. It has long been recognized that there may have been several stages to the evolution of avian sex chromosomes. For example, the CHD1 undergoes recombination in paleognaths but not neognaths. Genome assemblies have suggested there may be variation in the timing of barriers to recombination among Neognathae, but there remains little understanding of the extent of this variability. Here, we look at partial sequences of ATP5F1A, which is on the avian Z and W chromosomes. It is known that recombination of this gene has independently ceased in Galliformes, Anseriformes, and at least five neoavian orders, but whether there are other independent cessations of recombination among Neoaves is not understood. We used a combination of data extracted from published chromosomal-level genomes with data collected using PCR and cloning to identify Z and W copies in 22 orders. Our results suggest there may be at least 19 independent cessations of recombination within Neognathae, and 3 clades that may still be undergoing recombination (or have only recently ceased recombination). Analyses of ATP5F1A protein sequences revealed an increased amino acid substitution rate for W chromosome gametologs, suggesting relaxed purifying selection on the W chromosome. Supporting this hypothesis, we found that the increased substitution rate was particularly pronounced for buried residues, which are expected to be more strongly constrained by purifying selection. This highlights the dynamic nature of avian sex chromosomes, and that this level of variation among clades means they should be a good system to understand sex chromosome evolution.

Emulsion stabilisation of base layers surfaced with chip seals often proves problematic with chips punching into the base and early distress. This can be aggravated by the use of modified binders that restricts the evaporation of moisture from pavement layers. The introduction of New-age (Nano) Modified Emulsion (NME) stabilisation has the advantage that water is chemically repelled from the stabilised layer resulting in an accelerated development of strength. A need was identified to evaluate the early life performance of selected chip seals, together with identified binders. Three different chip seal surfacings with unconventional modified binders were constructed and evaluated using Accelerated Pavement Testing (APT) with the MMLS3. The objectives of the experimental design and testing were to evaluate binder performance, early loss of chips before chip orientation at low temperatures, punching of the chips into the NME stabilised base, deformation characteristics of a Cape seal and the effect of the use of a standard normal modified binder. This paper contains details of the NME base layer, the binder and seal selection and the test results. It is shown that a cost-effective thin chip seal in combination with a suitable binder can be used on a NME stabilised base with confidence.

Maximal quantum correlations of unity do not violate the CSHS-Bell inequalities because the remaining two correlations vanish. The probability of coincident detections should not be confused with the correlation of mixed states. The theoretical requirements for implementing the quantum nonlocality theory are not present in the experimental configurations purporting to prove Bohr’s or Bell’s nonlocality because of the quantum Rayleigh scattering of single photons. By means of a normalization factor corresponding to the total number of initiated events, the detection probabilities obtained experimentally are too small to enable any violation of a Bell inequality. Correlations between independent states of qubits can easily outperform those calculated with entangled photons. Additionally, the quantum joint probability for a Bell state can be factorized enabling a local detection of the alleged quantum nonlocality, if it existed. © The Author 2023

A physical scrutiny of experimental results published in Physical Review Letters (December 2015, M. Giustina, et al., Phys. Rev. Lett. 115, 250401, and L. K. Shalm et al., Phys. Rev. Lett. 115, 250402) is undertaken. These articles reported that measured outcomes were fitted with quantum states possessing a dominant component of non-entangled photons, thereby contradicting their own claim of quantum nonlocality. With probabilities of photon detections lower than 0.1 %, the alleged quantum nonlocality cannot be classified as a resource for developing quantum computing devices, despite recent publicity. Experimental evidence of a feasible process for quantum-strong correlations has been identified (M. Iannuzzi, et al., Phys. Lett. A, 384 (9), 126200, 2020) in terms of correlations between independent and multi-photon states evaluated as Stokes vectors on the Poincaré sphere. As single-photon sources are not needed, the design and implementation of quantum computing operations will be significantly streamlined.

In a recent article we showed that the analog of the cosmological constant in two spacetime dimensions for a wide variety of integrable quantum field theories has the form ρvac = −m2/2g where m is a physical mass and g is a generalized coupling, where in the free field limit g → 0, ρvac diverges. We speculated that in four spacetime dimensions ρvac takes a similar form ρvac = −m4/2g, but did not support this idea in any specific model. In this article we study this problem for λφ4theory in d spacetime dimensions. We show how to obtain the exact ρvac for the sinh-Gordon theory in the weak coupling limit by using a saddle point approximation. This calculation indicates that the cosmological constant can be well-defined, positive or negative, without spontaneous symmetry breaking. We also show that ρvac satisfies a Callan-Symanzik type of renormalization group equation. For the most interesting case physically, ρvac is positive and can arise from a marginally relevant negative coupling g and the cosmological constant flows to zero at low energies.

Controllable, quantum-strong correlations of polarization states can be implemented with multi-photon independent states. Polarization-based photonic quantum correlations can be traced back to the overlap of the polarization Stokes vectors on the Poincaré sphere between two polarization filters. The quantum Rayleigh scattering prevents a single photon from propagating in a straight line inside a dielectric medium, and it also provides a mechanism for the projective measurement of polarization. Complexities associated with single-photon sources and detectors can be eliminated because the quantum Rayleigh scattering in a dielectric medium destroys entangled photons. Entanglement-free, identical sources and processing devices give rise to correlations rather than these being caused by “quantum nonlocality”. These analytic developments were prompted by the vanishing expectation values of the Pauli spin vector for a single photon of maximally entangled photonic Bell states.

Despite multiple classical outcomes arising from the quantum Rayleigh conversions of photons underlying the propagation of optical waves through dielectric media and the ensuing light-matter interactions, this quantum process has been largely ignored. Several of its outcomes are considered in this article from a physical perspective, e.g., inter-quadrature coupling of photons, phase-dependent amplification in optical directional couplers and related polarization rotation, phase-shifting of weak signals in the optically linear regime, location-dependent coupling coefficient for refractive index gratings, etc. A correct identification of these effects will enable useful design and operation of integrated photonic functional devices.

The interpretation of published experimental results intended to prove the existence of a quantum phenomenon of non-locality involving photonic entangled states did not take into consideration the existence of the quantum Rayleigh conversion of photons in dielectric media. This phenomenon leads to the existence of high levels of correlations between two independent photonic and linearly polarized quantum states generated after the entangled photons have been absorbed through the quantum Rayleigh conversion. Both pure and mixed individual states of polarization result in expressions normally associated with entangled photonic states, providing support for the view that the physical reality of quantum non-locality is highly questionable.

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acids exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution dataset for transmembrane helices from a variety of sampled set of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

We present a summary of the main results within the Scale Invariant Vacuum (SIV) paradigm as related to the Weyl Integrable Geometry. After a brief review of the mathematical framework, we will highlight the main results related to inflation within the SIV [9], the growth of the density fluctuations [8], and the application of the SIV to scale-invariant dynamics of Galaxies, MOND, Dark Matter, and the Dwarf Spheroidals [7]. The connection of the weak-field SIV results to the un-proper time parametrization within the reparametrization paradigm is also discussed [14].

Despite a rapid rise in NBS development in recent years, the methods for evaluating NBS still have certain gaps. We propose an approach based on a combination of remote sensing data and meteorological variables to reconstruct the spatio-temporal variation of net ecosystem exchange from eddy-covariance stations. Lagrangian particle dispersion model was used for upscaling of satellite images and flux towers. We trained data-driven models based on kernel methods separately for each selected land cover class. The results suggest that the proposed approach to quantifying carbon exchange on a medium-to-large scale by blending eddy covariance flux data with moderate resolution satellite and weather data provides a set of key advantages over previously deployed methods: (1) scalability, achieved via the validation design based on a separate set of eddy covariance stations; (2) high spatial and temporal resolution due to use of the Landsat imagery; (3) robust and accurate predictions due to improved data quality control, advanced machine learning techniques, and rigorous validation. The machine learning models yielded high cross-validation results. Overall we present here globally scaled technology for the land sector based on high resolution remote sensing imagery, meteorological variables, and direct carbon flux measurements of eddy covariance flux stations.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

We present a summary of the main results within the Scale Invariant Vacuum (SIV) paradigm based on the Weyl Integrable Geometry (WIG) as an extension to the standard Einstein General Relativity (EGR). After a brief review of the mathematical framework, where we also highlight the connection between the weak-field SIV equations and the notion of un-proper time parametrization within the reparametrization paradigm, we continue with the main results related to early Universe; that is, applications to inflation, Big Bang Nucleosynthesis, and the growth of the density fluctuations within the SIV. In the late time Universe the applications of the SIV paradigm are related to scale-invariant dynamics of galaxies, MOND, dark matter, and the dwarf spheroidals where one can find MOND to be a peculiar case of the SIV theory. Finally, within the recent time epoch, we highlight that some of the change in the length-of-the-day (LOD), about 0.92 cm/yr, can be accounted for by SIV effects in the Earth-Moon system.

HIV/AIDS and COVID-19 discourses are often compared; however, theorizing them together in terms of political efficacy and possibility is more novel. The collective of academics, activists, artists, and others–What Would an HIV Doula Do? (WWHIVDD) which for years has responded to the HIV/AIDS pandemic, has turned their attention to experiences of living with COVID-19. Through a qualitative analysis of two texts–a zine and a guide for authors writing about these pandemics–that specifically address experiences of/with COVID-19 by WWHIVDD, we examine how HIV/AIDS and COVID-19 discourses can productively be considered as chronic illness/COVID discourses that have the potential for more fruitful collective/political action and scholarly theorization of people living with pandemics.

Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pretransplant serum concentrations of Cav-1 and the occurrence of rejection during follow up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute rejection episodes. Moreover, Cav-1 could be therapeutically useful for attenuating graft rejection.

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring under different physical activity levels in a postprandial state in healthy and active subjects without diabetes. Ten healthy, active subjects (26±4 years, 67±11 kg bodyweight (BW), 11±3 h) were included in the study. Within 14 days, they underwent six tests consisting of a) resting fasted (R/Fast), b) resting after intake of 1 g glucose/kg BW (R/Glc) and c) running for 60 minutes at moderate (65/Glc) and d) high (85/Glc) intensity after intake of 1 g glucose/kg BW. Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to simultaneous capillary blood glucose concentrations. Pearson’s r correlation coefficient was highest for R/Glc (.92, p<.001) compared to R/Fast (.45, p<.001), 65/Glc (.60, p<.001) and 85/Glc (.70, p<.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (R/Fast: 8±6%, R/Glc: 17±12%, 65/Glc: 22 ± 24%, 85/Glc: 18±17%). However, Bland-Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. However, further data in healthy subjects need to be gathered considering physical activity and nutrition status.

Quantum Rayleigh scattering of single photons rules out coincident detections of the originally entangled, paired photons Correlations between independent states of qubits can easily outperform those calculated with entangled photons. The quantum joint probability for a Bell state can be factorized enabling a local detection of the alleged quantum nonlocality, if it existed.

A Gem-quality rubies and sapphires are often commercially heat treated at about 800°C or higher temperatures to enhance their colour and clarity, and hence quality. For this study, selected corundum samples containing diaspore- and goethite inclusions were heated step-by-step to a maximum of 1000 °C with the aim to monitor the dehydration and phase transformation of these oxyhydroxides to corundum and hematite during heating. Based on our experiments and in agreement with literature, the dehydration of diaspore in corundum occurs between 525 to 550 °C, whereas goethite transforms to hematite already between 300 and 325 °C. As both, diaspore and goethite are common inclusions in rubies, sapphires, and other corundum varieties, these dehydration reactions and phase transformations can be considered important criteria to separate unheated stones from heated ones, specifically in cases in which other methods (e.g. microscopy, FTIR) are unsuccessful.

Classical and optimal control architectures for motion mechanics with fusion of noisy sensors use different algorithms and calculations to perform and control any number of physical demands, to varying degrees of accuracy, precision, and cost. Their performances are tested for the purpose of comparison through the means of a Monte Carlo simulation that simulates how different parameters might vary under noise, representing real-world imperfect sensors. We find that improvements in one figure of merit often come at a cost in the performance in the others, especially depending on the presence of noise in the system sensors. If sensor noise is negligible, open-loop optimal control performs the best. However, in the overpowering presence of sensor noise, using a control law inversion patching filter performs as the best replacement, but has significant computational strain.

: Solar sails use radiation from the sun to generate thrust without any fuel or propellant. Since this is a form of propulsion that has theoretically infinite use, we would like to test its capability on long-term missions by simulating a spacecraft equipped with solar sails to the Sun-Earth L5 Lagrange point. To control the sail angle, which is the main form of control we have over the sail’s performance, we will devise a form of optimal control based on Pontryagin’s Minimum Principle. Simulating the dynamics in MATLAB SIMULINK, we find that such a control method relies on iterating over initial conditions for the co-states to find the necessary parameters for the trajectory to reach the desired point. Therefore, an autonomous control scheme that uses this form of optimal control will need a way to numerically find said initial conditions in order to find the control angle needed at any point in time, which may be computationally intensive.

Scale invariance is expected in empty Universe models, while the presence of matter tends to suppress it. As shown recently, scale invariance is certainly absent in cosmological models with densities equal to or above the critical value ρ_c = 3(H₀)²/(8πG). For models with densities below ρc, the possibility of limited effects remains open. If present, scale invariance would be a global cosmological property. Some traces could be observable locally. For the Earth-Moon two-body system, the predicted additional lunar recession would be increased by 0.92 cm/yr, while the tidal interaction would also be slightly increased. The Earth-Moon distance is the most systematically measured distance in the Solar System, thanks to the Lunar Laser Ranging (LLR) experiment active since 1970. The observed lunar recession from LLR amounts to 3.83 (±0.009) cm/yr; implying a tidal change of the length-of-the-day (LOD) by 2.395 ms/cy. However, the observed change of the LOD since the Babylonian Antiquity is only 1.78 ms/cy, a result supported by paleontological data, and implying a lunar recession of 2.85 cm/yr. The significant difference of (3.83-2.85) cm/yr = 0.98 cm/yr, already pointed out by several authors over the last two decades, corresponds well to the predictions of the scale-invariant theory, which is also supported by several other astrophysical tests.

The formation and propagation of cracks occurs through irreversible dislocation movements at notches, material defects and grain boundaries. Since this process is partly thermally controlled, the resistance to dislocation movements at low temperatures increases. This slows both fatigue initiation and fatigue crack propagation. From recent experimental data, it can be seen that fatigue crack growth is accelerated below the fatigue transition temperature (FTT) that correlates with the ductile-brittle transition temperature (DBTT) found by well-known fracture mechanics tests, i.e., Charpy impact, fracture toughness, and CTOD. Hence, this study investigates the relation between FTT and DBTT in S500 high-strength steel base material and welded joints at low temperatures using fatigue crack growth, fracture toughness tests as well as scanning electron microscopy. From the tests, an almost constant decrease in fatigue crack propagation rate is determined with decreasing test temperature even below the DBTT.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

The Open Access (OA) publishing model that is based on article processing charges (APC) is often associated with the potential for more transparency regarding the expenditures for publications. However, the extent to which transparency can be achieved depends not least on the completeness of data in APC monitoring systems. This article investigates two blind spots of the largest collection of APC payment information, OpenAPC. It aims to identify likely APC-liable publications for German universities that contribute to this system and for those that do not provide data to it. The calculation combines data from Web of Science, the ISSN-Gold-OA-list and OpenAPC. The results show that for the group of universities contributing to the monitoring system, more than half of the APC payments are not covered by it and the average payments for non-covered APCs is higher than for APCs covered by the system. In addition, the group of universities that does not contribute to OpenAPC accounts for two thirds of the number of APC-liable publications recorded for contributing universities. Regarding the size of these blind spots, the value of the monitoring system is limited at present.

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy. This treatment is profoundly underutilized in the palliative care of these patients. The objective of this review is to discuss the pharmacology, pharmacokinetics, side effects, available evidence of effectiveness of pancreatic enzyme use for patients with pancreatic cancer, and challenges along with proposed solutions regarding its use. Pancrelipase is an expensive drug, and it is inactive if not taken correctly. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use of pancreatic enzyme replacement therapy. Pancreatic enzyme replacement therapy (PERT) is a key strategy in managing symptoms of EPI and can improve quality of life, which is a central focus in palliative care.

Abstract: Interface risks are inherent in every construction project from start to finish. Identifying and managing these risks effectively in every project phase is crucial for actualising project objectives. This paper shows a comprehensive framework showing several relationships between project stakeholders and how the interface risks between them that influence project execution are identified and managed for the overall construction project success. Firstly, literature review on interfaces and interface risks were car-ried out and how organisations managed interface risks were discussed and secondly, the collection of quantitative data was conducted by means of structured online questionnaires. The sample consisted of 205 construction project professionals who were selected randomly. This group included individuals with various roles in the construction industry, The data was analysed using descriptive statistical methods, including factor analysis, reliability assessment, and calculations of frequencies and percentages. Finally, the results showed all the factors, work culture and organisational approaches that influence interface risk management and ways to identify and manage interface risks effectively.

Prescriptions for fuels management are universally applied across forest types in British Columbia, Canada, to reduce fire behaviour potential in the wildland-urban interface. Fuel thinning treatments are assumed to reduce the potential for sustained ignition and crown fire initiation by reducing surface fuel loading. We hypothesized that these prescriptions are not appropriate for the coastal wet forests in the Whistler region of the province. Our study measured the efficacy of fuel thinning treatments in four stands located in the Whistler community forest. We examined several in-stand microclimate variables during snow melt in the spring and at the height of fire danger in late summer, at thinned and unthinned locations paired using GIS- analysis. We found that thinning increased the wildfire risk based on the differences between unthinned and thinned areas in the same forest stand.

Preliminaries Convolutional Neural Network (CNN) applications have recently emerged in Structural Health Monitoring (SHM) systems focusing mostly on vibration analysis. However, the SHM literature shows clearly that there is a lack of application regarding the combination of PZT (Lead Zirconate Titanate) based method and CNN. Likewise, applications using CNN along with the Electromechanical Impedance (EMI) technique applied to SHM systems are rare. To encourage this combination, an innovative SHM solution through the combination of the EMI-PZT and CNN is presented here. To accomplish this, the EMI signature is split into several parts followed by computing the Euclidean distances among them to form a RGB (red, green and blue) frame. As a result, we introduce a dataset formed from the EMI-PZT signals of 720 frames, encompassing a total of 4 types of structural conditions for each PZT. In a case study, the CNN-based method was experimentally evaluated using three PZTs glued onto an aluminum plate. The results reveal an effective pattern classification; yielding a 100% hit rate which outperforms other SHM approaches. Furthermore, the method needs only a small dataset for training the CNN, providing several advantages for industrial applications.

BACKGROUND: Stable-phase schizophrenia may comprise two distinct nosological entities namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with the deficit syndrome) and simple NP (SNP), which are defined by neuroimmune and neurocognitive abnormalities. Furthermore, cognitive impairments and PHEM (psychotic, hostility, excitation, mannerism) and negative symptoms load on the same dimension.METHODS: The current study aimed to investigate associations of psychomotor retardation (PMR) and clinical as well as biomarker characteristics of schizophrenia. We recruited 40 healthy controls and 79 schizophrenia patients and measured IgA responses to tryptophan catabolites (TRYCATs), IgM to malondialdehyde and nitroso (NO)-cysteinyl, macrophage inflammatory protein-1 (MIP-1), soluble interleukin (IL)-1 receptor antagonist (sIL-1RA), IL-10, CCL-11 as well as PMR items of different rating scales and motor screening task (MOT). RESULTS: PMR differentiated schizophrenia from controls and MNP from SNP. In addition, PMR was strongly associated with executive functions, deficits in episodic and semantic memory, PHEM and negative (PHEMN) symptoms. Around 50% of the variance in PMR was predicted by the cumulative effects of immune activation, CCL-11, TRYCATs and NO-Cysteinyl levels, and lowered natural IgM. PRM may be reliably combined with PHEMN symptoms and memory and executive impairments into one latent vector reflecting overall psychopathology.CONCLUSIONS: Current findings indicate that PMR may be a key psychopathological feature of schizophrenia and mainly MNP. In addition, PMR and associated impairments in memory and executive functions, and PHEMN symptoms may be driven by deficits in the compensatory immune regulatory system (natural IgM) combined with increased production of neurotoxic immune products, namely TRYCATs and IgM to NO-cysteinyl, and an endogenous cognition deteriorating chemokine, namely CCL-11.

Modern anesthesia continues to be impacted in new and unforeseen ways by digital technology. Combining portability and versatility, mobile applications or “apps” provide a multitude of ways to enhance anesthetic and peri-operative care. Research suggests that uptake of apps into anesthetic practice is becoming increasingly routine, especially amongst younger anesthetists brought up in the digital age. Despite this enthusiasm, there remains no consensus in how apps are safely and efficiently integrated into anesthetic practice. This review summarizes the most popular forms of app usage in anesthesia currently and explores the challenges and opportunities inherent in implementing app use in anesthesia, with an emphasis on a practical approach for the modern anesthetist.

The purpose of this work is to study the mechanism of running-in during the friction and to determine the informative parameters characterizing the degree of its completion. During the friction, contact interaction of rough surfaces causes various wave phenomena covering a wide range of frequencies, the subsequent frequency analysis can provide information about the sizes of wave sources and thereby clarify the mechanism of interaction between surface roughness. The using of the wavelet transform for processing of the signals of audible acoustic emission made it possible to determine the beginning and the end of the change in the frequency ranges of the interaction of roughness. The code developed by the authors was used to analyze the acoustic emission signals by using wavelet energy and entropy criteria. The mother wavelet was chosen by carefully evaluating the effectiveness of 54 preliminary candidates for the mother wavelet from 7 wavelet families, ac-cording to three criteria: 1) maximum wavelet energy; 2) Shannon entropy minimum; 3) maximum energy-to-Shannon entropy ratio.

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO₂) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO₂-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO₂-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO₂-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

Optical sensor data can be used to determine changes in anthocyanins, chlorophyll and soluble solids content (SSC) in apple production. In this study, visible and near-infrared spectra (729 to 975 nm) were transformed to SSC values by advanced multivariate calibration models i.e. partial least square regression (PLSR) in order to test the substitution of destructive chemical analyses through non-destructive optical measurements. Spectral field scans were carried out from 2016 to 2018 on marked ’Braeburn’ apples in Southwest Germany. The study combines an in-depth statistical analyses of longitudinal SSC values with horticultural knowledge to set guidelines for further applied use of SSC predictions in the orchard to gain insights into apple carbohydrate physiology. The PLSR models were investigated with respect to sample size, seasonal variation, laboratory errors and the explanatory power of PLSR models when applied to independent samples. As a result of Monte Carlo simulations, PLSR modelled SSC only depended to a minor extent on the absolute number and accuracy of the wet chemistry laboratory calibration measurements. The comparison between non-destructive SSC determinations in the orchard with standard destructive lab testing at harvest on an independent sample showed mean differences of 0.5 % SSC over all study years. SSC modelling with longitudinal linear mixed-effect (LME) models linked high crop loads to lower SSC values at harvest and higher SSC values for fruit from the top part of a tree.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we have studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1 and HPAFII, we show that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73 - but not the isoform - interfered with cell migration as shown by xCELLigence technology. Our findings highlight the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identify direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism.

H-adaptivity is an effective tool to introduce local mesh refinement in FEM-based numerical simulation of crack propagation. The implementation of h-adaptivity could benefit the numerical simulation of fatigue or accidental load scenarios involving large structures such as ship hulls. In engineering applications, the element deletion method is frequently used to represent cracks. However, the element deletion method has some drawbacks such as strong mesh dependency and loss of mass or energy. In order to mitigate this problem, the element splitting method could be applied. In this study, a numerical method called ‘h-adaptive element splitting’ (h-AES) is introduced. The h-AES method is applied in FEM programs by combining h-adaptivity with the element splitting method. Two examples using the h-AES method to simulate cracks in large structures under linear-elastic fracture mechanics scenario are presented. The numerical results are verified against analytical solutions. Based on the examples, the h-AES method is proven to be able to introduce mesh refinement in large-scale numerical models that consist of structured coarse meshes. By employing the mesh refinement introduced in this paper, very small cracks are well represented in large structures.

An approximation-free and fully quantum optic formalism for parametric processes is presented. Phase-dependent gain coefficients and related phase-pulling effects are identified for quantum Rayleigh emission and the electro-optic conversion of photons providing parametric amplification in small scale integration of photonic devices. These mechanisms can be manipulated to deliver, simultaneously, sub-Poissonian distributions of photons as well as phase-dependent amplification in the same optical quadrature of a signal field.

Africa spans the hemispheres from temperate region to temperate region, has a long history of hominin evolution and yet has a relatively poorly understood Quaternary climate history. Speleothems, as archives of terrestrial hydroclimate variability, can help reveal this history, and here we review the progress made to date, with a focus on the first version of the Speleothem Isotopes Synthesis & Analysis (SISAL) database. The geology of Africa has limited development of large karst regions to four areas - the northern and eastern coasts bordering the Mediterranean and the Indian Ocean, west Africa and southern Africa. Exploitation of the speleothem palaeoclimate archives in these regions is uneven, with long histories of research in South Africa and Morocco but no investigations elsewhere e.g. West Africa. Consequently, the evidence of past climate change reviewed here is irregularly sampled in both time and space. Nevertheless, we show evidence of migration of the monsoon belt, with enhanced rainfall during interglacials observed in northeast Africa, southern Arabia and the northern part of southern Africa. Evidence from East Africa also indicates significant centennial scale rainfall variability. In northwestern and southern Africa precession and eccentricity influence speleothem growth, largely through changing synoptic storm activity.

Objective: To examine associations between chemokines and menstrual cycle associated symptoms (MCAS). Methods: Forty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days of the menstrual cycle. MCAS is diagnosed when the total daily DRSP score during the menstrual cycle is > 0.666 percentile. We assayed plasma CCL2, CCL5, CCL11, CXCL8, CXCL10, EGF, IGF-1, and PAI-1 at days 7, 14, 21 and 28 of the menstrual cycle. Results: CCL2, CCL5, CCL11 and EGF are significantly higher in women with MCAS than in those without. Increased CCL2, CXCL10, CXCL8, CCL11 and CCL5 levels are significantly associated with DRSP scores while CCL2 is the most significant predictor explaining 39.6% of the variance. The sum of the neurotoxic chemokines CCL2, CCL11 and CCL5 is significantly associated with the DRSP score and depression, physiosomatic, breast-craving and anxiety symptoms. The impact of chemokines on MCAS symptoms may differ between consecutive weeks of the menstrual cycle with CCL2 being the most important predictor of increased DRSP levels during the first two weeks, and CXCL10 or a combination of CCL2, CCL11 and CCL5 being the best predictors during week 3 and 4, respectively. Discussion: The novel case definition “MCAS” is externally validated by increased levels of uterus-associated chemokines and EGF. Those chemokines are involved in MCAS and are regulated by sex hormones and modulate endometrium functions and brain neuro-immune responses, which may underpin MCAS symptoms. As such, uterine-related chemokines may link the uterus with brain functions via a putative uterine-chemokine-brain axis.

The compound, C27H23N3 (1), crystallizes in the triclinic system of the P-1 space group. The unit cell comprises a dimer of 1, in which the monomers are linked by two complementary hydrogen bonds between N1 and H1-C1 of another molecule. The dimers form chains along the a-axis through intermolecular interactions between the N2 acceptor atoms and C17 donors from molecules in the nearest neighbouring dimer. These interactions form extended sheets of the dimers of 1, along the ab plane. The quinolinylmeth-2-yl groups of 1 lie in almost orthogonal planes and their N1/2(q) donor atoms being away from the apical amino N3 atom.

Increased gut permeability (leaky gut) with increased translocation of Gram-negative bacteria plays a role in the gut-brain axis through effects on systemic immune-inflammatory processes. Deficit schizophrenia is characterized by an immune-inflammatory response combined with a deficit in natural IgM antibodies to oxidative specific epitopes (OSEs), which are a first line defense against bacterial infections. This study measured plasma IgA/IgM responses to 5 Gram-negative bacteria in association with IgM responses to malondialdehyde (MDA) and azelaic acid in 80 schizophrenia patients (40 with the deficit syndrome and 40 without) and in 38 healthy controls.Deficit schizophrenia was characterized by significantly increased IgA responses to Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii and Klebsiella pneumoniae as compared with non-deficit schizophrenia. The presence of deficit schizophrenia was highly predicted by increased IgA responses to Pseudomonas putida and IgM responses to all 5 Gram-negative bacteria and lowered natural IgM to MDA and azelaic acid with a bootstrap area under the ROC curve of 0.960 (2000 random curves). A large proportion of the variance (41.5%) in the PANSS negative score was explained by the regression on IgA responses to K. pneumoniae and IgM responses to the 5 enterobacteria coupled with lowered IgM antibodies to azelaic acid. There were significant associations between IgA levels to Gram-negative bacteria and Mini Mental State Examination, Boston naming test, Verbal Fluency and Word List Memory test scores.These findings provide further evidence that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by an increased impact of Gram-negative commensal bacteria coupled with a deficit in natural IgM, pointing to aberrations in B1 cells. It is concluded that increased bacterial translocation and deficits in the compensatory immune-regulatory system (CIRS) may drive negative symptoms and neurocognitive impairments, which are hallmarks of deficit schizophrenia.

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters, and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to baseline. Downstream effects of these catecholamines and corticosterone appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to baseline by the final measurement. DHEA, used as a ratio with corticosterone, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to understanding crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

Background: It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle could be associated with the presence and severity of premenstrual syndrome (PMS).Objective: To examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS severity considering different diagnostic criteria for PMS.Methods: Forty women aged 18-45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21 and 28 to assay oestradiol and progesterone. Results: We developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e. depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including the one presented by the American College of Obstetricians and Gynecologists. Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone. Conclusion: A significant increase in menstrual-cycle related symptoms can best be conceptualized as “peri-menstrual syndrome” and may result from “corpus luteum insufficiency”, which may result from suboptimal pre-ovulatory follicular development. Future research should trial Clomiphene citrate (given the first 5 days of the cycle) and a mid-cycle injection of human Chorionic Gonadotrophin in subjects with peri-menstrual syndrome.

The local reactive power control in distribution grids with a high penetration of distributed energy resources (DERs) is essential in future power system operation. Appropriate control characteristic curves for DERs support stable and efficient distribution grid operation. However, the current practice is to configure local controllers collectively with constant characteristic curves that may not be efficient for volatile grid conditions or the desired targets of grid operators. To address this issue, this paper proposes a time series optimization-based method to calculate control parameters, which enables each DER to be independently controlled by an exclusive characteristic curve for optimizing its reactive power provision. To realize time series optimizations, the open-source tools pandapower and PowerModels are interconnected functionally. Based on the optimization results, Q(V)- and Q(P)-characteristic curves can be individually calculated using the linear decision tree regression to support voltage stability and provide reactive power flexibility and potentially reduce grid losses and component loadings. In this paper, the newly calculated characteristic curves are applied in two representative case studies, and the results demonstrate that the proposed method outperforms the reference ones suggested by grid codes.

The increasing complexity of the design and operation evaluation process of multi-energy grids (MEGs) requires tools for the coupled simulation of power, gas and district heating grids. Most tools analyzed in this paper either do not allow coupling of infrastructures, simplify the grid model or are not publicly available. We introduce the open source piping grid simulation tool pandapipes that – in interaction with pandapower - fulfills three crucial criteria: clear data structure, adaptable MEG model setup and performance. In an introduction to pandapipes we illustrate how it fulfills these criteria through its internal structure and demonstrate how it performs in comparison to STANET®. Then we show two case studies that have been performed with pandapipes already. The first case study demonstrates a peak shaving strategy as interaction of a local electricity and district heating grid in a small settlement. The second case study analyzes the potential of a power-to-gas device to serve as flexibility in a power grid under consideration of gas grid constraints. They both show the importance of a clear database, a simple simulation setup and good performance to set up different large and complex studies on grid infrastructure design and operation.

Thermal and catalytic pyrolysis of virgin low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP) and mixtures of LDPE/PP were carried out in a 200 ml laboratory scale batch reactor at 460 °C in a nitrogen atmosphere. Thermogravimetric analysis (TGA) was carried out to study the thermal and catalytic degradation of the polymers at a heating rate of 10 °C/min. The amount of PP was varied in the LDPE/PP mixture to explore its effect on the reaction. In thermal degradation (TGA) of LDPE/PP blends, a lower decomposition temperature was observed for LDPE/PP mixtures compared to pure LDPE, indicating interaction between the two polymer types. In the presence of a catalyst (CAT-2), the degradation temperatures for the pure polymers were reduced. The TGA results were validated in a batch reactor using PP and LDPE respectively. Thermal cracking results showed that the oil product contains a significant amount of gasoline (C7 − C12) and diesel (C13 − C20) hydrocarbon fractions. The catalyst enhanced cracking at lower temperatures and narrowed the hydrocarbon distribution in the oil towards the gasoline range fraction (C7 – C12). The result suggests that the oil produced from catalytic pyrolysis of waste plastics has a potential as an alternative fuel.

Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.

Fluxgate magnetometers require calibration methods appropriate to their application levels and particularities; however the development of fully controlled calibration procedures presents a particular challenge regarding the inevitable influence of the local geomagnetic field and other external interferences when a laboratory with magnetically shielded walls is not available. In that context, we discussed the development of an automated calibration method for fluxgate magnetometers, considering those limitations in time and space, and avoiding some of the problems commonly found in other proposed solutions for the same challenge. For this task, we designed and built a new set of high level procedures, electronic systems and software, which perform active testing and automated calibration of fluxgate magnetometers, considering some resource constraints and employing instruments commonly found in electronic calibration laboratories.

Vitamin D is crucial for athletes' health and performance. Although the exact vitamin D requirements for athletes have not been established, maintaining 25(OH)D levels of at least 40 ng/ml is considered beneficial. This study aimed to determine whether an individual loading dose formula for vitamin D supplementation is suitable to meet a target value of 40 ng/ml and is more effective than standardized supplementation. In a 10-week supplementation study during the winter months in Germany, 90 athletes with insufficient vitamin D levels (25(OH)D<30ng/ml) were randomly assigned to receive either a universal dose of 2000 IU/day of vitamin D or a loading dose of 4000 IU/day, followed by a maintenance dose of 1000 IU/day. Total 25(OH)D concentration was measured from dried blood spots at three time points: at baseline, at the computed date of 40ng/ml, and after the 10-week period. Additionally, a vitamin D-specific questionnaire was issued. On the day when 25(OH)D blood concentrations of 40 ng/ml were calculated to prevail, the individualized group had a significantly higher 25(OH)D level than the standardized group (41.1+-10.9 ng/ml vs. 32.5+-6.4 ng/ml, p<0.001). This study demonstrated that the examined formula is suitable for athletes to achieve a 25(OH)D concentration of 40 ng/ml. This indicates that a personalized approach is more effective than a one-size-fits-all approach in restoring adequate vitamin D levels in athletes.

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

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is the desmoplastic reaction of the tumor stroma, the formation of which is orchestrated by transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that the TGF-β pathway is controlled by transcriptionally active p73 (TAp73) through secretion of biglycan (Bgn) via intermittent expression of the TGF-β signaling intermediates, Smad3 and Smad4. Genetic knockout of TP73, and, as a consequence, deficient induction of Smad3/Dpc4 and secretion of Bgn led to activation of TGF-β signaling through a (Smad-independent) ERK pathway, favoring epithelial-mesenchymal transition (EMT) and cell motility. Except for BGN, these functions of TAp73 have recently been shown to also operate in human PDAC cells and are reminiscent of what we previously observed for the small GTPase, RAC1b. This prompted us to hypothesize that TAp73 and RAC1b are part of the same tumor-suppressive pathway in human PDAC cells. The two objectives of this study, therefore, were to reveal i) if the regulatory interactions between TAp73 and Bgn previously discovered in murine PDAC-derived cells also operate in their human counterparts, and ii) if RAC1b collaborates with TAp73 in these tumor-suppressive activities in human PDAC cells. Using a variety of experimental approaches, including mutual rescue experiments, we were able to show that the previously proposed tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human cells and that RAC1b is as an upstream activator of this pathway. Our findings highlight the complex role of TGF-β in pancreatic tumorigenesis and might have implications for therapeutic approaches targeting this growth factor for inhibition.

The increasing demand for sustainable products and services has become a constant requirement by the different stakeholders in an organization. Higher Education Institutions (HEI) have a crucial role in training conscious and competent professionals to lead these changes. Chemical analyses laboratories bring together the proper mix, where the adoption of mature and efficient management systems proves to be crucial not only to better train the institutions´ human resources but also to cooperate in recruiting research projects and other services to benefit society. Maturity models assist in the needed stages for sustainable growth to take place. This paper proposes a Maturity Model based on standardized norms to guide adjustments related to quality, risks, safety, and environment of chemical analyses laboratories in public higher education institutions. This research was done in four stages: theoretical research about Maturity Models, sustainability, and integrated management systems; survey with laboratories; case study at a chemical analyses laboratory of an HEI; and structuring and validating a maturity model. As a result of this, the model includes eight dimensions (Strategy, Leadership, Management, Operations, Continuous Improvement, Sustainability, Culture, and Integration), 31 subdimensions, and 204 management practices to assess and guide chemical analyses laboratories to sustainable maturity levels.

At present European buildings typically consume two to five times more energy than predicted at the design stage. An important cause of this performance gap is the discrepancies between the design specification and the As-Built condition. Such discrepancies are mainly due to the gaps in knowhow between design, production and construction professionals. Design is more and more contained into a virtual environment and loses touch with the physical production and construction sites. As the construction sector enters the Industry 4.0 era, Building Information Modelling (BIM) based Mixed Reality can intertwine virtual and real worlds to bridge the knowhow gaps.

Context: CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia cases (CAH), a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provides critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Objective: Analyze the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of the CYP21A2. Methods: SNVs of the CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of the CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. Results: SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). Conclusion: From our analysis, we identified four predictors of CYP21A2 pathogenicity with good performance. These results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP21A2.

The multidrug-resistant fungal pathogens belonging to the Candida haemulonii complex and the phylogenetically related species Candida auris are well-known for causing infections that are difficult to treat due to their multidrug-resistance profile. C. auris is even more worrisome due to its ability to cause outbreaks in healthcare settings. These emerging yeasts produce a wide range of virulence factors that facilitate the development of the infectious process. In recent years, the aggregative phenotype has been receiving attention, as it is mainly associated with defects in cellular division and its possible involvement in helping the fungus to escape from host immune responses. In this study, we initially investigated the aggregation ability of 18 clinical isolates belonging to the C. haemulonii species complex and C. auris. Subsequently, we evaluated the effects of physicochemical factors on the fungal aggregation competence. The results demonstrated that cell aggregation was a typically time-dependent event, in which almost all studied fungal isolates exhibited high aggregation after 2 h of incubation at 37°C. The aggregation was not impacted by pH, temperature, -mercaptoethanol (a protein-denaturing agent) and EDTA (a chelator agent). Conversely, proteinase K, trypsin and sodium dodecyl sulfate significantly diminished the aggregation. Collectively, our results demonstrated that the aggregation ability in these opportunistic yeast pathogens is time-dependent, and surface proteins and hydrophobic interactions seem to mediate cell aggregation, since the presence of proteases and anionic detergent affected the aggregation ability. However, further studies are necessary to better elucidate this phenomenon.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

Sewage sludge is an organic waste generated in waste-water treatment plants with certain content of nutrients, what may potentially be used as a source of slow release fertilizer, especially as phosphorus (P) source, but it demands some pre-treatment and the content of P is much lower compared to soluble mineral fertilizers. For these reasons, composted sewage sludge was used to manufacture pelletized organomineral fertilizers, mixing it with the inorganic sources monoammonium phosphate (MAP) and AshDec® (ASD) (thermochemically incinerated sewage sludge). The fertilizers were physiochemically characterized and evaluated as to the dynamics of soil P solubilization, and the forms of P remaining according to its lability. The sources evaluated were: organic compost of sewage sludge powder (SSC), pelletized SSC (SCP), pelletized organominerals SSC+MAP (S+MAP) and SSC+ASD (S+ASD), ASD alone, all compared to a soluble mineral fertilizer (MAP), and a control without P fertilizer. A test was conducted in leaching columns with 50 g of soil (Oxisol), where the fertilizers were applied at a dose of 100 mg P/column, and 30 mL of water or 2% citric acid were added daily for 30 consecutive days. The collected leachates had pH measured and P content determined. Pelletizing process resulted in denser products and promoted more gradual P release. The organomineral S+MAP was the most water-soluble recycled source, solubilizing about 70% of the total P, while the others presented much lower solubilization (&lt;20%). In contrast, all fertilizers showed high solubility in 2% citric acid (except for S+ASD). After leaching, the greatest amount of P remaining in the soil as labile and moderately labile. Composting and the AshDec process produced materials with slow P solubilization, which would be favoured to solubilize in acidic soils and acidic rhizosphere conditions. In turn, the organomineral mixture of SSC with a highly soluble mineral fertilizer (MAP) resulted in a promising product with intermediate nutrient solubility, better synchronized with crop demand, thus increasing efficiency in P use.

Artificial intelligence (AI) systems are poised to become deeply integrated into society. If developed responsibly, AI has potential to benefit humanity immensely. However, it also poses a range of risks, including risks of catastrophic accidents. It is crucial that we develop oversight mechanisms that prevent harm. This article outlines a framework for evaluating and auditing AI to provide assurance of responsible development and deployment, focusing on catastrophic risks. We argue that responsible AI development requires comprehensive auditing that is proportional to AI systems’ capabilities and available affordances. This framework offers recommendations toward that goal and may be useful in the design of AI auditing and governance regimes.

Communicating about sex is important in generating positive perceptions about one’s sexual and romantic life. The last decade has provided insight into the theoretical applications on sex communication research. While the focus on extant research focuses on the psychological processes’ individuals employ to talk about sex, no theoretical framework exists that identifies key constructs that provides a parsimonious understanding about the communicative processes of sex and sexuality. This review sought to identified key constructs that are suitable to develop a sex talk theory. In the current project, we reviewed 24 studies including 8,698 participants (Mage = 24.98) that applied a theoretical framework to sex research. This review identified three salient constructs (e.g., disclosure, cognitive, and relational and behavioral) that are important for a sex talk theory. Last, this review indicated that scholarship should explain the relationships between the key constructs. We provided several recommendations that scholars should take when developing a theory in sex communication research.

Spent coffee grounds (SCG) have great potential as a useful, value-added biological material. In this context, activated carbon (AC) was prepared from SCG by an activation process using H3PO4 at 600°C in air and used as an adsorbent for the azo dye AO7, a model molecule for dye colorants found in textile industry effluents. X-ray diffraction, SEM and BET revealed that the AC was predominantly amorphous, consisting of a powder of 20-100 µm particles with mesopores averaging 5.5 nm in pore size. Adsorption kinetics followed a pseudo-second-order law, while the Langmuir model best fitted experimental isotherm data (maximum capacity of 119.5 mg AO7 per AC g). Thermodynamic parameters revealed that adsorption was endothermic and spontaneous. All the characterizations indicated that adsorption occurred by physisorption via mainly - interactions. The best experimental removal efficiency optimized by means of a Box-Behnken design and response surface methodology was 98% for an initial AO7 concentration of 20 mg.L-1 at pH 7.5 with a dose of 0.285 g.L-1 of AC and a contact time of 40 min. These results clearly show that activated carbon prepared from SCG can be a useful material for efficiently removing organic matter from aqueous solutions.

The description of stellar interiors remains as a big challenge for the nuclear astrophysics community. The consolidated knowledge is restricted to density regions around the saturation of hadronic matter $\rho _{0} = 2.8\times 10^{14} {\rm\ g\ cm^{-3}}$, regimes where our nuclear models are successfully applied. As one moves towards higher densities and extreme conditions up to five to twenty times $\rho_{0}$, little can be said about the microphysics of such obejects. Here, we employ an MCMC strategy in order to access the variability of polytropic three-pircewised models for neutron star equation of states. With a fixed description of the hadronic matter we explore a variety of models for the high density regimes leading to stellar masses up to 2.5 $M_{\odot}$. In addition, we also discuss the use of a Bayesian power regression model with heteroscedastic error. The set of EoS from LIGO was used as inputs and treated as data set for testing case.

Selective laser melting (SLM) is a commonly used laser powder bed technique where the final properties are influenced by many different powder related properties, such as particle size distribution, chemical composition and flowability. In applications where high hardness, wear resistance, strength and good heat properties are required, high speed steels (HSS) are widely used today. HSS has high carbon content and are therefore considered as unweldable. The rapidly growing implementation of AM technologies has led to a growing range of new applications and demands for new alloys and properties. The interest in being able to manufacture HSS by SLM without cracking is therefore increasing. In SLM, it is possible to preheat the base plate to a few hundred degrees Celsius which has been used for HSS and proved successful due to reduced thermal gradients. In this study, the properties of SLM produced high speed steel PEARL Micro®2012 with a carbon content of 0.61 wt.-% have been investigated and compared to those of a forged and rolled PM-HIP counterpart ASP®2012.

Purposely slow velocity resistance exercise (i.e., 10 s concentric and eccentric phases) is a popular training method, but limits the loads that can be lifted (e.g., <50% 1 RM). This study compared the biomechanical properties of purposely slow velocity (SLOW) and traditional resistance exercise (TRAD) that uses maximal lifting velocities. Healthy resistance-trained men (n=5) performed two testing sessions (barbell squat and bench press) in random-order; a SLOW session (1 set x 10 repetitions at 28% 1 RM, 10 s concentric & eccentric), and a TRAD session (3 x 10 at 70% 1 RM, controlled eccentric and maximal concentric). A force plate and linear position transducer were used to collect kinetic and kinematic data for every repetition of both protocols (α = 0.05). For both exercises, both concentric and eccentric mean force (N) and power (W) for each repetition was greater for TRAD. When the entire training session (squat + bench press) was examined, SLOW exhibited greater time under tension, while TRAD produced greater work (J) and impulse (N·s). Contrary to suggestions in both the lay and scientific literature, purposely slow resistance exercise produced less force, power, and work than traditional velocity resistance exercise.

With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) currently being developed and deployed to bolster access to personal protective equipment (PPE), patient treatment and diagnostics.

In the last decades droughts, deforestation and wildfires have become recurring phenomena that have affected both human activities and natural ecosystems in Amazonia. The time an ecosystem requires to recover from carbon losses is a crucial metric to evaluate disturbance impacts on forests. However, the factors influencing and controlling the recovery time and its spatiotemporal patterns at the regional scale are still poorly understood. In this study, we combined forest growth model, remote sensing and field plots, to map Amazonia-wide (300-ha resolution) impact and recovery time of aboveground biomass (AGB) after drought, fire and a combination of logging and fire. Our simulated results indicate that AGB decreases by 4%, 19% and 46% in forests disturbed by drought, fire and logging + fire, respectively, with an average AGB recovery time of 27 years for drought, 44 years for burned and 63 years for logged + burned areas and with maximum values reaching 184 years in areas of high fire intensity. Our findings provide two major insights in the spatial and temporal patterns of drought and wildfire in the Amazon: 1) the recovery time of the forests takes longer in the southeastern part of the basin, and, 2) as droughts and wildfires become more frequent – since the intervals between the disturbances is getting shorter than forest regeneration – potentially causing a long-lasting damage in these fragile ecosystems and a permanent degradation.

A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase of saturated fatty acids in the membrane. The C. elegans homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated 13C stable isotopes into the diet of nematodes and quantified the 13C-labelled fatty acid by GC-MS and HPLC/MS-MS to track the metabolic response to various concentrations of glucose. Previous work has analyzed membrane composition of C. elegans when responding to mild glucose stress and showed few alterations in overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction of oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid me-tabolism to increasing levels of glucose stress has been characterized, revealing a funneling of monounsaturated fatty acids to preserve polyunsaturated fatty acid abundance. Taken together, higher levels of glucose unveil a specific reduction of oleic and linolenic acid in the metabolic re-wiring required to survive glucose stress.

Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.

Access and Benefit Sharing (ABS) is a framework which refers to a relatively recent type of legal requirements for access to and/or use of “genetic resources”. They are based on diverse national and regional laws and regulations, which mostly result from the implementation of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary agreement, the Nagoya Protocol. Their ambition is to achieve fair and equitable sharing of benefits arising out of the use of genetic resources as an incentive to conserve and sustainably use them. This paper describes the experiences, practical constraints and complexities encountered by users of genetic resources when dealing with ABS legislation, with a focus on users from the private sector. We provide insights on how ABS laws have fundamentally changed the way of working with genetic resources in the hope that it inspires re-thinking of the ABS framework, to better support the overall objectives of the CBD.

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are well defined phenotypes of chronic inflammatory bowel diseases (IBD). A mechanism of inflammation in these diseases is partially controlled by intestinal dendritic cell (DC). In this study we observed a mature CD83+DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: There were 219 subjects included in the study: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with primary antibody Anti-CD83. Intraepithelial CD83+DC were counted per 100 enterocytes. Presence of CD83+DC was analysed according type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83+DCs (0, ≥1) significantly differed among disease types of IBD (p=0.001), histologic inflammation activity (p=0.049) and applied therapy (p=0.001). The odds for CD83+DC presence was 5.2 times higher in CD group than in control/UC group. The odds for CD83+DC presence was 2.6 times higher in subjects without inflammation or chronic inflammation than in acute inflammation. It was also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83+DC (Rock analysis area=0.699; SE 0,046;p<0.001;95%CI:0.609-0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83+DC could be used as a possible parameter in distinction between UC and CD, as well as predictor of inflammation activity and treatment outcome.

The German government's ambitious goal of achieving CO2-neutrality by 2045 has prompted a focus on improving building insulation as a vital step toward energy efficiency. However, in this process, existing radiators and boilers are often left unchanged, leading to inefficiencies due to oversized heating systems. This paper presents various approaches to reduce the required radiator inlet temperature, drawing on data from 100 multifamily buildings. The approaches include heat reserve reduction, heat power shifting, uniform radiator usage, and heat requirement analysis. These approaches collectively aim to lower flow temperatures and decrease peak heat loads, reducing energy consumption, and minimizing waste in compliance with the user comfort temperature. The findings reveal that the application of these methods can lead to substantial temperature reductions, with an average decrease of 20.82 K and 7.28 K for the highest necessary flow temperature in the provided example. Furthermore, peak load reductions of 21.07% and 13.65% were achieved, demonstrating the potential to enhance energy efficiency. While each approach can be applied individually, their synergistic implementation can highly increase the efficiency of water to x heat pumps, due to the lower required flow temperatures.

The capacity and the mechanism of the adsorption of aqueous barium (Ba), cobalt (Co), strontium (Sr) and zinc (Zn) by Ecuadorian (NatAllo) and synthetic (SynAllo-1 and SynAllo-2) allophanes were studied as a function of contact time, pH and metal ion concentration using kinetic and equilibrium experiments. The mineralogy, nano-structure and chemical composition of the allophanes were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and specific surface area analyses. The evolution of adsorption fitted to a pseudo-first-order reaction kinetics, where equilibrium between aqueous metal ions and allophane was reached within < 10 min. The metal ion removal efficiencies varied from 0.7 to 99.7 % at pH 4.0 to 8.5. At equilibrium, the adsorption behavior is better described by the Langmuir model than by the Dubinin-Radushkevich model, yielding sorption capacities of 10.6, 17.2 and 38.6 mg/g for Ba^(2+), 12.4, 19.3 and 29.0 mg/g for HCoO_2^-, 7.2, 15.9 and 34.4 mg/g for Sr^(2+) and 20.9, 26.9 and 36.9 mg/g for Zn^(2+), respectively, by NatAllo, SynAllo-2 and SynAllo-1. The uptake mechanism is based on a physical adsorption process. Allophane holds great potential to remove aqueous metal ions and could be used instead of zeolites, montmorillonite, carbonates and phosphates for wastewater treatment.

Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered, but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider effects of ice loading and its stochastic nature on fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3–4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008-2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3–4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children’s reciprocal social and repetitive behaviors and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no association between plasma PCB concentrations and autistic behavior, However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest quartile of plasma PCB concentrations compared with the lowest quartile; for instance, an average increase of 1.1 [95%PCI: −0.5, 2.6] in the mean SRS (exposure contrast 4^th versus 1^st quartile) for PCB138 translated to an odds ratio of 1.6 [95%PCI: 1.0, 2.5]. Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.

Titanium dioxide (TiO2) thin films have been widely used in transparent optoelectronic devices owing to their excellent optical properties also is used in photocatalysis, cosmetics, and many other biomedical applications. However, a lack of studies was published on microstructure and adherence comparison of the TiO2 deposited on both AISI substrates. In this work, TiO2 thin films were deposited onto AISI 304 and AISI 316L stainless steel (SS) substrates via atomic layer deposition. Its heterostructure, morphology, and adhesion were compared in both substrates looking for synergistic and multifunctional properties. Raman spectroscopy mapping and X-ray diffraction using the Rietveld refinement method showed that the films are composed of anatase and rutile phases in different percentages. Scratching tests were used to analyze the film adher-ence and friction between a diamond tip and TiO2 film, showing well adhered in both substrates.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Flooding and overflows are recurring problems in several Brazilian cities, which usually undergo disorderly development. Their causes vary from increased impervious surface areas, deficiency/inefficiency of drainage structures and their maintenance, siltation of rivers, channel obstructions, and climatic factors. This situation is aggravated in the major cities. The Anhangabau watershed lies in the central portion of the city of Sao Paulo – Brazil and covers a drainage area of 5.4 km². The region is highly urbanized and crossed by a major north-south road connection. During heavy rain events, portions of this interconnection passage become compromised, disrupting the flow of vehicles, creating a chaotic situation for the population, as well as losses to the national economy. Observed rainfall records and an existing IDF (intensity duration frequency) curve for the region are used to obtain design storms. To account for climate change, a well know procedure, the equidistance quantile matching method for updating IDF curves under climate change, was applied to the existing historical data. Several different global climate models (GCM) and one regional model were applied to obtain and update rainfall design storm. The GCMs and future scenarios used were from the IPCC Assessment Report 5 (AR5) and two future projections: RCP (representative concentration pathway) 4.5 and 8.5. Alternatives previously proposed to solve to flooding issue are briefly reviewed. On one of the latest studies [1], a few modern concepts of water resources management are presented, and the linear retention measure was found to offer higher potential to mitigate the flooding problem in the lower valley of the watershed. Therefore, this alternative was used to evaluate different design storms scenarios combined with return periods of 25 and 100-years as well as the updated IDF under climate change for RCP 4.5 and RCP 8.5. To model the complex network, representing both road and drainage systems and their interconnections, PCSWMM/SWMM software was applied. Results are presented as flooding maps and show the impacts of the proposed linear retention measure based on the existing IDF curves and the updated IDF curves under climate change for two different drainage system conditions, current and improved with the use of linear retention reservoirs. Results show that the prosed changes on the drainage system help reduce the risk and damage to flooding. The climate change scenarios, however, impose a significant threat and need immediate attention from city planners and stakeholders.

The Cl- transporting proteins CFTR, SLC26A9, and anoctamin (ANO1; ANO6) appear to have more in common than anticipated initially. They all participate in the pathogenic process and clinical outcome of renal and airway diseases. In the present review we will therefore concentrate on recent findings concerning electrolyte transport in airways and kidney, and the role of CFTR, SLC26A9, and anoctamins (ANO1 and ANO6). A particular focus will be on the airway diseases cystic fibrosis and asthma, as well as renal alkalosis and polycystic kidney disease. In essence, latest findings are summarized that demonstrate CFTR as the only relevant secretory Cl- channel in airways under basal (non-stimulated) conditions and after stimulation by secretagogues. For proper CFTR function, expression of ANO1 and ANO6 appears to be a prerequisite. Evidence is summarized suggesting that the Cl- transporter SLC26A9 may have a reabsorptive rather than a Cl- secretory function in the airways. In renal collecting ducts bicarbonate secretion takes place due to synergistic tasks of CFTR and the Cl-/HCO3- transporter SLC26A4 (pendrin), which is likely to be supported by ANO1. Finally, in autosomal dominant polycystic kidney disease (ADPKD), the secretory function of CFTR in renal cyst formation might have been overestimated, while ANO1 as well as ANO6 turned out to be crucial in ADPKD, and therefore represent novel pharmacological targets for the treatment of polycystic kidney disease.

Hydrogen peroxide (H2O2) is an essential analyte for detecting neurodegenerative diseases and in-flammatory processes and plays a crucial role in pharmaceutical, food industry, and environmental monitoring. However, conventional H2O2 detection methods have drawbacks such as lengthy analysis time, high costs, and bulky equipment. Non-enzymatic sensors have emerged as promising alternatives to overcome these limitations. In this study, we introduce a simple, portable, and cost-effective non-enzymatic electrochemical sensor based on carbon black (CB) and silver nano-particle-modified δ-FeOOH (Ag/δ-FeOOH), integrated into a disposable electrochemical cell (DCell). Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and electrochemical impedance spectroscopy (EIS), confirmed successful CB and Ag/δ-FeOOH immo-bilization on the DCell working electrode. Electrochemical investigations revealed that the DCell-CB//Ag/δ-FeOOH sensor exhibited an approximately twofold higher apparent heterogene-ous electron transfer rate constant than the DCell–Ag/δ-FeOOH sensor, capitalizing on CB ad-vantages. Moreover, the sensor displayed excellent electrochemical response for H2O2 reduction, boasting a low detection limit of 22 µM and a high analytical sensitivity of 214 μA mM-1 cm-2. Notably, the DCell-CB//Ag/δ-FeOOH sensor exhibited outstanding selectivity for H2O2 detection, even in potential interferents such as dopamine, uric acid, and ascorbic acid. Furthermore, the sensor demonstrated its suitability for monitoring H2O2 in complex biological samples, as evidenced by H2O2 recoveries ranging from 92% to 103% in 10% fetal bovine serum. These findings underscore the considerable potential of the DCell-CB//Ag/δ-FeOOH sensor for precise and reliable H2O2 monitoring in diverse biomedical and environmental applications.

This study examines the effects of the δ phase and annealing twins on the hardness, Charpy impact toughness, and tensile properties of Inconel 718 fabricated using L-PBF. Two heat treatment methods, involving solid solution and precipitation hardening, were utilized. The δ phase was formed through solid solution heat treatment at 980C for 1 hour while annealing twins were generated at 1100C for 3 hours. After precipitation hardening, specimens with a higher concentration of  precipitates exhibited increased ultimate tensile strength (13%), yield strength (27%), and hardness (12%) compared to those with annealing twins. This can be attributed to the smaller grain size, subgrains, and δ precipitates, which contribute to the differences in mechanical strength. On the contrary, specimens with annealing twins showed significantly higher impact toughness (4 times) and ductility (twice) than those with δ precipitates. This is caused by the formation of  precipitates, which serve as sites for void formation and crack propagation, leading to a decrease in plasticity due to lattice mismatches with the matrix. Microstructural, compositional, phase, crystallographic, and fractographic analyzes were performed using OM, SEM, TEM and XRD techniques to identify the factors responsible for the variations in the measurements. The results demonstrate that the heat treatment method involving annealing twins significantly improves the ductility of Inconel 718 while maintaining the required mechanical strength.

Deficiency of Cytochrome P450 Steroid 21-hydroxylase (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction along with functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in the Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of 21OH deficiency.

The production and quality of Phaseolus vulgaris (snap bean) have been negatively impacted by leaf crumple disease caused by two whitefly-transmitted begomoviruses; cucurbit leaf crumple virus (CuLCrV) and sida golden mosaic Florida virus (SiGMFV), which often appear as a mixed infection in Georgia. Host resistance is the most economical management strategy against whitefly-transmitted viruses. Currently, information is not available with respect to resistance to these two viruses in commercial cultivars. In two field seasons (2018 and 2019), we screened Phaseolus sp. genotypes (n = 84 in 2018; n = 80 in 2019; most of the genotypes were common in both years with a few exceptions) for resistance against CuLCrV and/or SiGMFV. Twenty genotypes with high- to moderate-levels of resistance (disease severity ranging from 5-50%) to CuLCrV and/or SiGMFV were identified. Twenty-one genotypes were found to be highly susceptible with a disease severity of ≥66%. Adult whitefly counts differed significantly among snap bean genotypes for both years. The whole genome of these Phaseolus sp. (n=82) genotypes was sequenced and genetic variability among them was identified. Over 900 giga-base (Gb) of filtered data were generated and >88% of the resulting data were mapped to the reference genome, and SNP and Indel variants in Phaseolus genotypes were obtained. A total of 645,729 SNPs and 68,713 Indels including 30,169 insertions and 38,543 deletions were identified, which were distributed in 11 chromosomes with chromosome 02 harboring the maximum number of variants. These phenotypic and genotypic information will be helpful in genome-wide association studies that will aid in identifying genetic basis of resistance to these begomoviruses in Phaseolus sp.

The zoonotic disease anthrax caused by the endospore-forming bacterium Bacillus anthracis is very rare in Germany. In the state of Bavaria, the last case occurred in July of 2009 resulting in four dead cows. In August of 2021, the disease reemerged after heavy rains, killing one gestating cow. Notably, both outbreaks affected the same pasture, suggesting a close epidemiological connection. B. anthracis could be grown from blood culture and the presence of both virulence plasmids (pXO1 and pXO2) were confirmed by PCR. Also, recently developed diagnostic tools enabled rapid detection of B. anthracis cells and nucleic acids directly in clinical samples. The complete genome of the strain isolated from blood, designated BF-5, was DNA-sequenced and phylogenetically grouped within the B.Br.CNEVA clade that is typical for European B. anthracis strains. The genome was almost identical to BF-1, the isolate of 2009, separated only by three single nucleotide polymorphisms on the chromosome, one on plasmid pXO2 and three indel-regions. Further, B. anthracis DNA was detected by PCR from soil-samples taken from spots, where the cow had fallen onto the pasture. New tools based on phage receptor binding proteins enabled the microscopic detection and isolation of B. anthracis directly from soil-samples. These environmental isolates were genotyped and found to be SNP-identical to BF-1. Therefore, it seems that the BF-5 genotype is currently the prevalent one at the affected premises. The contaminated area was subsequently disinfected with formaldehyde.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

In this paper we propose a novel theoretical framework, which was previously developed for major depression and bipolar disorder, namely the compensatory immune-regulatory reflex system (CIRS), as applied to the neuro-immune pathophysiology of schizophrenia and its phenotypes, including first episode psychosis (FEP), acute relapses, chronic and treatment resistant schizophrenia (TRS), comorbid depression, and deficit schizophrenia. These schizophrenia phenotypes and manifestations are accompanied by increased production of positive acute phase proteins, including haptoglobin and α2-macroglobulin, complement factors, and macrophagic M1 (IL-1β, IL-6 and TNF-α), T helper (Th)-1 (interferon-γ and IL-2R), Th-2 (IL-4, IL-5), Th-17 (IL-17) and T regulatory (Treg; IL-10 and transforming growth factor (TGF)-β1) cytokines, cytokine-induced activation of the tryptophan catabolite (TRYCAT) pathway as well as chemokines, including CCL-11 (eotaxin), CCL-2, CCL-3 and CXCL-8. While the immune profiles in the different schizophrenia phenotypes indicate activation of the immune-inflammatory response system (IRS), there are simultaneous signs of CIRS activation, including increased levels of the IL-1 receptor antagonist (sIL-1RA), sIL-2R and tumor necrosis factor-a receptors, Th-2 and Treg phenotypes with increased IL-4 and IL-10 production, and increased levels of TRYCATs and haptoglobin, α2-macroglobulin and other acute phase reactants, which have immune-regulatory and anti-inflammatory effects. Signs of activated IRS and CIRS pathways are also detected in TRS, chronic and deficit schizophrenia indicating that these conditions are accompanied by a new homeostatic setpoint between upregulated IRS and CIRS components. In FEP, increased baseline CIRS activity is a protective factor which may predict favorable clinical outcomes. Moreover, impairments in the CIRS are associated with deficit schizophrenia and greater impairments in semantic and episodic memory. It is concluded that CIRS plays a key role in the pathophysiology of schizophrenia by negatively regulating the primary IRS and contributing to recovery from the acute phase of illness. Components of the CIRS may offer promising therapeutic targets for schizophrenia.

A single farmed fish species assimilates about 20% of the nutrients in the supplied diet. This study evaluated if the culture of complementary ecological-function species can recover nutrients dispersed into the water and transform them into high-valued biomass. A completely randomized experiment was designed with three treatments and four replications of each production system: monoculture of lambari (Astyanax lacustris); integrated aquaculture of lambari and Amazon river prawn (Macrobrachium amazonicum); and integrated aquaculture of lambari, Amazon river prawn, and curimbatá (Prochilodus lineatus). Fingerlings of lambari (0.8 ± 0.8 g) were stocked in twelve earthen-ponds (0.015 ha) at the density of 50 fish m^-2. Eight ponds, were stocked with juveniles of Amazon river prawn (1.1 ± 0.2 g) at the density of 25 prawn m⁻². Four of these eight ponds were stocked with curimbatá fingerlings (0.2 ± 0.1 g) at a density of 13 fish m^-². Only lambari was fed twice a day with an extruded commercial diet. The experiment lasted 60 days when lambari attained commercial size. The inclusion of prawn increased the total species yield from 1.8 to 2.4 t ha^-1 cycle^-1 and reduced the feed conversion ratio (FCR) from 2.5 to 1.8. The inclusion of prawn and curimbatá increased the total yield to 3.2 t ha^-1 cycle^-1 and reduced the FCR to 1.4. Therefore, the integrated culture of lambari, prawn, and curimbatá improves the use of space, water, feed, and benthic species can recover the large quantity of nutrients accumulated in the bottom of lambari pond production, converting them into high-nutritional and monetary-valued biomass.