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Abstract Background Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer’s disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut. Methods To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC). Results Aβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%). Conclusion Thus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated. more...

Conserving bird populations is a key goal for management of the Sacramento–San Joaquin Delta ecosystem and is likely to have effects well beyond its boundaries. To inform bird- conservation strategies, we identified Priority Bird Conservation Areas for riparian landbirds and waterbirds in the Delta, defined as the most valuable 5% of the landscape for each group. We synthesized data from 2,547 surveys for riparian landbirds and 7,820 surveys for waterbirds to develop predictive distribution models, which then informed spatial prioritization analyses. We identified a total of 26,019 ha that are a high priority for conserving riparian landbirds, waterbirds, or both, representing the most important places in the Delta to protect and manage, as well as strategic areas where adjacent restoration could expand valuable habitat. These Priority Bird Conservation Areas include the Yolo Bypass Wildlife Area, Cosumnes River Preserve, Stone Lakes National Wildlife Refuge, and bufferlands that surround the Sacramento County Regional Sanitation District. However, we also found that over 60% of the Priority Bird Conservation Areas are not currently protected, indicating a vulnerability to changes in land cover or land use. We recommend advancing strategies for bird conservation in the Delta by developing more specific objectives and priorities, extending these analyses to include other bird species, and planning to mitigate the loss of Priority Bird Conservation Areas where they are most vulnerable to land cover change. The predictive models and analysis framework we developed represent the current state of the science on areas important to bird conservation, while also providing a foundation for an evolving bird-conservation strategy that reflects the Delta’s continuously evolving knowledge base and landscape. more...

This paper deals with the phenomenon of torsion oscillations in railway vehicle drive systems. The main goal is to reduce the risk of presence of torsional oscillations in wheelset drive, eventually to propose systems to effectively identify and eliminate torsional oscillations of wheelsets. Therefore, a simulation wheelset drive model including a detailed model of the asynchronous traction motor control was built. The results of computer simulations show that the torsional oscillations can be effectively eliminated by avoiding the resonance states between the excitation frequencies given by pulse width modulation of the inverter and the eigenfrequencies of the mechanical part of the drive. Furthermore, it was found that the presence of torsional oscillations of the wheels can be detected based on the traction motor current ripple. The wheelset drive model was subsequently implemented in a simulation model of a four-axle locomotive. A new algorithm of an anti-slip protection system that utilizes motor currents was implemented in the model. Simulations show that such an anti-slip protection system can prevent the occurrence of undesired large amplitude of wheelset torsional oscillations. The models and simulation results are presented in detail in the paper. more...

In December 2020, a major vaccination program against COVID-19 commenced in Europe with vaccines such as Pfizer’s mRNABNT162b2 (Comirnaty®). Subsequent reports of immediate and delayed skin reactions emerged. This study presents a case of a 64-year-old male who developed multiple keratoacanthomas approximately two weeks after receiving a second booster dose of the Pfizer vaccine. The patient, who had significant medical history of hypertension and diabetes, presented with erythematous, crateriform lesions on his limbs. A physical examination and histopathological analysis confirmed the diagnosis of Generalized Eruptive Keratoacanthoma (GEKA). Treatment involved cemiplimab I.v. 350 mg administered every three weeks. Within two months, the patient showed significant improvement, with the disappearance of all lesions. Dermoscopy and histopathological exams supported the GEKA diagnosis, which is a rare variant of multiple keratoacanthomas. This case suggests a potential immune-mediated mechanism triggered by the COVID-19 vaccine, leading to the rapid development of keratoacanthomas. Treatment with cemiplimab showed promise, highlighting the potential of immune checkpoint inhibitors in managing multiple keratoacanthomas. Further research is needed to explore the efficacy and safety of such treatments. more...

The rapid advancement of artificial intelligence (AI) and natural language processing (NLP) has profoundly impacted our understanding of emotions, decision-making, and opinions, particularly within the context of the Internet and social media [...] more...

The dynamic behaviour and dynamic phenomena in traction drives of railway vehicle has been studied for decades. Generally, in these days the motivation for this research is to look for answers related with service problems, which has been risen, e.g. an overloading of mechanical components as wheelsets or an intention to improve control systems of traction drives of railway vehicles. This problematic has also motivated the research at the Faculty of Mechanical Engineering at the Czech Technical University (CTU) in Prague. Nowadays it is also usual, that the main research tool has been a simulation based on a mathematical model of a railway vehicle or its specific components, as testing on real vehicles is very demanding regarding costs. However, there is an alternative – a roller rig. At the CTU in Prague there has been modernized the second roller rig for purposes of measurement regarding the torsion dynamics research, to support PhD students for their theses and possibly to extend the education for students oriented on the railway vehicle’s design. This contribution brings results of measurements just from the problematics of torsion oscillations and dynamics. Specifically, further presented measurements are on the loss of the adhesion in the contact of the wheelset and rollers, as the substitution for the railway, its impact on the reaction rod overloading and study of the axle load influence on the transition phenomena. more...

Pigmentary disorders of the face present a significant challenge in dermatology, impacting the confidence and well-being of affected individuals. Various approaches have been developed to address these concerns, including microneedling and topical vitamin C products. This study involved 15 participants undergoing three treatment sessions over 12 weeks, assessing the efficacy of a combined microneedling and CE Ferulic® serum approach. Clinical evaluation and statistical analysis were conducted before and after the intervention. Significant improvement of akin hyperpigmentation was observed, particularly on the side treated with microneedling and CE Ferulic® serum compared to microneedling alone. The integrated treatment protocol demonstrated a synergistic effect in improving skin texture and appearance. Integrated treatment protocols, such as combining microneedling with CE Ferulic® serum, show promise in managing facial hyperpigmentation disorders. Further research with larger cohorts is warranted to validate these findings and optimize treatment strategies, highlighting the potential of combined therapeutic modalities for achieving optimal clinical outcomes in pigmentary disorder management. more...

Wide adoption of social media has caused an explosion of information stored online, with the majority of that information containing subjective, opinionated, and emotional content produced daily by users. The field of emotion analysis has helped effectively process such human emotional expressions expressed in daily social media posts. Unfortunately, one of the greatest limitations of popular word-based emotion analysis systems has been the limited emotion vocabulary. This paper presents an attempt to extensively expand one such word-based emotion analysis system by integrating multiple emotion dictionaries and implementing an automatic extraction mechanism for emotive expressions. We first leverage diverse emotive expression dictionaries to expand the emotion lexicon of the system. To do that, we solve numerous problems with the integration of various dictionaries collected using different standards. We demonstrate the performance improvement of the system with improved accuracy and granularity of emotion classification. Furthermore, our automatic extraction mechanism facilitates the identification of novel emotive expressions in an emotion dataset, thereby enriching the depth and breadth of emotion analysis capabilities. In particular, the automatic extraction method shows promising results for applicability in further expansion of the dictionary base in the future, thus advancing the field of emotion analysis and offering new avenues for research in sentiment analysis, affective computing, and human–computer interaction. more...

The Sacramento–San Joaquin Delta is an important region for bird conservation in California, particularly as part of a large, productive estuary on the Pacific Flyway. The Delta currently provides habitat to an abundant, diverse community of birds, but it is likely only a small fraction of what the Delta’s bird community once was. Meeting the goal of restoring a healthy Delta ecosystem is legislatively required to include providing habitat for birds among the conservation goals and strategies in the Delta Plan, yet birds and their habitat needs are often not addressed in science syntheses, conservation planning, and large-scale restoration initiatives in the Delta. In this essay, we provide an avian perspective on the Delta, synthesizing recent scientific work to describe factors that contribute to the Delta’s current importance for birds, and the conservation needs of the diverse array of bird species that call the Delta home. We also evaluate the potential for the Delta to become even more important for birds in the future, incorporating climate change effects, species range shifts, and changes to the composition and configuration of the Delta’s landscape. Finally, recognizing the uncertainties about the Delta’s future landscape and the complexity of this social-ecological system, we provide recommendations—aimed at a higher- level policy and planning audience—for integrating bird conservation with other goals in the Delta. To improve ecosystem integrity, conserve biodiversity, and provide benefits to local communities of people, we urge a focus on creating a more resilient Delta and employing a diversified portfolio of conservation strategies, both old and new. more...

An increasing number of studies have demonstrated that disease states of the endocrine or exocrine pancreas aggravate one another, which implies bidirectional blood flow between islets and exocrine cells. However, this is inconsistent with the current model of unidirectional blood flow, which is strictly from islets to exocrine tissues. This conventional model was first proposed in 1932, and it has never to our knowledge been revisited to date. Here, large-scale image capture was used to examine the spatial relationship between islets and blood vessels in the following species: human, monkey, pig, rabbit, ferret, and mouse. While some arterioles passed by or traveled through islets, the majority of islets had no association with them. Islets with direct contact with the arteriole were significantly larger in size and fewer in number than those without contact. Unique to the pancreas, capillaries directly branched out from the arterioles and have been labeled as “small arterioles” in past studies. Overall, the arterioles emerged to feed the pancreas regionally, not specifically targeting individual islets. Vascularizing the pancreas in this way may allow an entire downstream region of islets and acinar cells to be simultaneously exposed to changes in the blood levels of glucose, hormones, and other circulating factors. more...

Water scarcity and related climate volatility are growing constraints on agricultural production landscapes around the world. While the adaptation options available are often dictated by system context, in many places broad-scale transformations are occurring in response to water-related pressures. We sought contributions from across regions, agricultural system types, and scientific disciplines to examine agricultural land use transitions driven by water scarcity, including the tradeoffs associated with alternative land uses; impacts on food production, environment, and society; innovations that can buffer risk; and considerations for planning and implementation. The research presented in this collection highlights the spectrum of policy and practice changes that are needed to facilitate beneficial land use transitions and system transformations, from quantifying risks, to evaluating multidimensional tradeoffs, to developing socio-technical policy bundles to maximize co-benefits. more...

Abstract The pathological hallmark of neurodegenerative diseases is the formation of toxic oligomers by proteins such as alpha-synuclein (aSyn) or microtubule-associated protein tau (Tau). Consequently, such oligomers are promising biomarker candidates for diagnostics as well as drug development. However, measuring oligomers and other aggregates in human biofluids is still challenging as extreme sensitivity and specificity are required. We previously developed surface-based fluorescence intensity distribution analysis (sFIDA) featuring single-particle sensitivity and absolute specificity for aggregates. In this work, we measured aSyn and Tau aggregate concentrations of 237 cerebrospinal fluid (CSF) samples from five cohorts: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and a neurologically-normal control group. aSyn aggregate concentration discriminates PD and DLB patients from normal controls (sensitivity 73%, specificity 65%, area under the receiver operating curve (AUC) 0.68). Tau aggregates were significantly elevated in PSP patients compared to all other groups (sensitivity 87%, specificity 70%, AUC 0.76). Further, we found a tight correlation between aSyn and Tau aggregate titers among all patient cohorts (Pearson coefficient of correlation r = 0.81). Our results demonstrate that aSyn and Tau aggregate concentrations measured by sFIDA differentiate neurodegenerative disease diagnostic groups. Moreover, sFIDA-based Tau aggregate measurements might be particularly useful in distinguishing PSP from other parkinsonisms. Finally, our findings suggest that sFIDA can improve pre-clinical and clinical studies by identifying those individuals that will most likely respond to compounds designed to eliminate specific oligomers or to prevent their formation. more...

Within the research of electromagnetically excited torsion oscillations in the mechanical part of traction drive systems of modern railway vehicles, which has been realized at the Faculty of mechanical engineering at the CTU in Prague, there are two separate simulation models in use. The basic calculation model, which is utilized to gain basic characteristics of the torsion system as natural frequencies and natural modes of oscillations. And the complex simulation model, which simulates a drive of the vehicle. This contribution is focused on the basic calculation model, which has been built in MATLAB. This model in its first version did not apply the contact between wheels and rails. It was necessary to find out, if this simplification is relevant with respect to subsequent simulations within the complex simulation model and its results. Therefore, the contact interaction as a traction force in longitudinal direction in the wheel-rail contact was realized via the Kalker’s linear theory. This article deals with the comparison between models with and without the implementation of the wheel-rail contact and its influence on the damping within the torsion system and retuning of the torsion system. more...

Biaryl monophosphines are important precursors to active catalysts of palladium-mediated cross-coupling reactions. The efficiency of the phosphine-based transition metal complex catalyst has its origin in the electronic structure of the complex used and the sterical hindrance created by the ligand at an active catalyst site. The aim of this paper is to shed some light on the multiverse of coordination modes of biaryl monophosphine ligands. Here, we present the analysis of the X-ray single crystal structures of palladium(II) complexes of a family of biaryl monophosphine ligands and the first crystallographic report on a related phosphine sulfide. Despite the common biaryl monophosphine ligand motif, they show diverse coordination modes (i) starting from the activation of aromatic C atoms and producing a C,P metallacycle, through (ii) the O,P chelation to Pd(II) ions with a simultaneous demethylation reaction of one of the methoxy groups, ending up with (iii) the monodentate coordination to metal cations via P atoms or (iv) via S atoms in the case of phosphine sulfide. We relate our results to the crystal structures found in the Cambridge Structural Database to show the multiverse of coordination modes in the group of biaryl monophosphine ligands. more...

The importance of the railway transport of both goods and passengers continuously grows as it is in many points of view more ecological and economical solution in comparison with road transport. Just the importance has been supporting efforts to design more powerful and faster trains reaching traction powers more than 1.6 MW per a wheel-set or service top speed much more than 300 km/h till these days. To reach design which has enabled such a kind of performances it was necessary to research dynamic behaviour of railway vehicles. Both via laboratory measurements and simulations. The laboratory experiments have been carried out on a specially designed laboratory equipment called roller rigs. A laboratory equipped by roller rig for testing of the railway vehicle dynamic behaviour has been built at the Faculty of Mechanical Engineering at CTU in Prague, also within PhD study programs and SGS grants. Another powerful tool within research activities is a simulation. Kind of a such simulation will be presented by this contribution with the focus on the torsion dynamics of high-power fully-suspended drive of a railway vehicle, which has been developed also by PhD students under financial support of The Faculty of Mechanical Engineering and related grants. more...

Background: Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer’s disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut. Methods: To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC). Results: Aβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%). Conclusion: Thus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated. [ABSTRACT FROM AUTHOR] more...

An extensive network of managed wetlands and flooded agriculture provides habitat for migrating and wintering shorebirds in California’s Central Valley. Yet with over 90% of historical wetlands in the region lost, Central Valley shorebird populations are likely diminished and limited by available habitat. To identify the timing and magnitude of any habitat limitations during the non-breeding season, we developed a bioenergetics model that examined whether currently available shorebird foraging habitat is sufficient to meet the daily energy requirements of the shorebird community, at either the baseline population size surveyed from 1992 to 1995 or double this size, which we defined as our long-term (100-year) population objectives. Using recent estimates of the extent of managed wetlands and flooded agriculture, satellite imagery of surface water, energy content of benthic invertebrates, and shorebird metabolic rates, we estimated that shorebird foraging habitat in the Central Valley is currently limited during the fall. If the population sizes were doubled, we estimated substantial energy shortfalls in the fall (late July–September) and spring (mid-March–April) totaling 4.02 billion kJ (95% CI: 2.23–5.83) and 7.79 billion kJ (2.00–14.14), respectively. We then estimated long-term habitat objectives as the minimum additional shorebird foraging habitat required to eliminate these energy shortfalls; the corresponding short-term (10-year) habitat objectives are to maintain an additional 2,160 ha (5,337 ac) of shallow ( more...

In California’s Central Valley, grassland and oak savannah ecosystems provide multiple economic and social benefits, ecosystem services, and vital bird habitat. There is a growing interest in protecting, restoring, and managing these ecosystems, and the Central Valley Joint Venture (CVJV) provides leadership in the formulation of conservation goals and objectives. We defined a long-term goal of protecting, restoring, and managing Central Valley grassland and oak savannah ecosystems so that they are capable of supporting genetically robust, self-sustaining, and resilient wildlife populations. To measure progress toward this goal, we selected a suite of 12 landbird focal species that primarily breed in grasslands and oak savannahs as indicators of the state of these ecosystems on the Central Valley floor (primary focus area) and in the Central Valley’s surrounding foothills (secondary focus area). Using data on current densities and habitat extent, we estimated that at least three of the focal species populations in the primary focus area and at least two of the focal species populations in the secondary focus area are currently small ( more...

The Central Valley of California provides important breeding habitat to numerous species of wetland-dependent birds, despite the loss of over 90% of naturally occurring wetlands. A majority of shorebirds breeding in this region rely on shallow-flooded habitat adjacent to sparsely vegetated uplands as provided by rice (Oryza sativa), managed wetlands, and other habitats. We estimated the current extent of potential breeding shorebird habitat provided by rice and managed permanent and semi-permanent wetlands in each of four major planning regions of the Central Valley, and estimated the average breeding densities and current population sizes of two species of shorebirds: the Black-Necked Stilt (Himantopus mexicanus) and American Avocet (Recurvirostra americana). Using a population status framework based on principles of conservation biology, we estimated that stilt populations are small ( more...

Riparian ecosystems provide important ecosystem services and recreational opportunities for people, and habitat for wildlife. In California’s Central Valley, government agencies and private organizations are working together to protect and restore riparian ecosystems, and the Central Valley Joint Venture provides leadership in the formulation of goals and objectives for avian conservation in riparian ecosystems. We defined a long-term conservation goal as the establishment of riparian ecosystems that provide sufficient habitat to support genetically robust, self-sustaining, and resilient bird populations. To achieve this goal, we selected a suite of 12 breeding riparian landbird focal species as indicators of the state of riparian ecosystems in each of four major Central Valley planning regions. Using recent bird survey data, we estimated that over half of the regional focal species populations are currently small (< 10,000) and may be vulnerable to extirpation, and two species have steeply declining population trends. For each focal species in each region, we defined long-term (100-year) population objectives that are intended to be conservation endpoints that we expect to meet the goal of genetically robust, self-sustaining, and resilient populations. We then estimated the long-term species density and riparian restoration objectives required to achieve the long-term population objectives. To track progress toward the long-term objectives, we propose short-term (10- year) objectives, including the addition of 12,919 ha (31,923 ac) of riparian vegetation in the Central Valley (by planning region: 3,390 ha in Sacramento, 2,390 ha in Yolo–Delta, 3,386 ha in San Joaquin, and 3,753 ha in Tulare). We expect that reaching these population, density, and habitat objectives through threat abatement, habitat restoration, and habitat enhancement will result in improvements to riparian ecosystem function and resilience that will benefit other wildlife populations and the people of the Central Valley and beyond. more...

Quantitative population objectives are necessary to successfully achieve conservation goals of secure or robust wildlife populations. However, existing methods for setting quantitative population objectives commonly require extensive species-specific population viability data, which are often unavailable or are based on estimates of historical population sizes, which may no longer represent feasible objectives. Conservation practitioners require an alternative, science-based method for setting long-term quantitative population objectives. We reviewed conservation biology literature to develop a general conceptual framework that represents conservation biology principles and identifies key milestones a population would be expected to pass in the process of becoming a recovered or robust population. We then synthesized recent research to propose general hypotheses for the orders of magnitude at which most populations would be expected to reach each milestone. The framework is structured as a hierarchy of four population sizes, ranging from very small populations at increased risk of inbreeding depression and extirpation (< 1,000 adults) to large populations with minimized risk of extirpation (> 50,000 adults), along with additional modifiers describing steeply declining and resilient populations. We also discuss the temporal and geographic scales at which this framework should be applied. To illustrate the application of this framework to conservation planning, we outline our use of the framework to set long-term population objectives for a multi-species regional conservation plan, and discuss additional considerations in applying this framework to other systems. This general framework provides a transparent, science-based method by which conservation practitioners and stakeholders can agree on long-term population objectives of an appropriate magnitude, particularly when the alternative approaches are not feasible. With initial population objectives determined, long-term conservation planning and implementation can get underway, while further refinement of the objectives still remains possible as the population’s response to conservation effort is monitored and new data become available. more...

Birds associated with wetlands have declined historically across North America from extensive habitat loss and degradation. Among the regions most affected is California’s Central Valley, where over 90% of the wetland base has been lost. Still, this region remains of continental importance to waterbirds. On-the-ground conservation efforts for all bird groups are the focus of the Central Valley Joint Venture, guided by a periodically updated implementation plan. To track progress toward goal attainment, that plan sets time-bound, quantitative conservation goals. Lacking robust data on the size and trends of populations of most species of waterbirds in the Central Valley, we set conservation goals for this group by selecting 10 focal species. These species are of heightened conservation concern or are otherwise representative of the habitat needs of Central Valley waterbirds. Given the great loss of historical habitat, we assumed focal species populations have declined by ≥ 50%. Hence, we defined population objectives for most focal species as increasing their current populations by 10% over 10 years and doubling them in 100 years. The corresponding habitat objectives are to increase wetlands or enhance suitable crops for waterbirds in proportion to the population objectives. These include an increase over 10 years of 7,948 ha (19,641 acres) of winter seasonal wetlands, 921 ha (2,276 acres) each of semi-permanent and summer seasonal wetlands, and 573 ha (1,416 acres) of strategically placed riparian forest. Agricultural needs include additional winter flooding of 15,160 ha (37,461 acres) of rice and 2,137 ha (5,281 acres) of corn. We distributed the habitat objectives across five planning regions, in some cases favoring proportionally larger increases in those regions with the greatest need. To maximize success, however, conservationists must take into account the specific needs of individual waterbird species, as a one-size-fits-all approach will not support the highest diversity of waterbirds. more...

Protein misfolding and aggregation are pathological hallmarks of various neurodegenerative diseases. In Alzheimer’s disease (AD), soluble and toxic amyloid-β (Aβ) oligomers are biomarker candidates for diagnostics and drug development. However, accurate quantification of Aβ oligomers in bodily fluids is challenging because extreme sensitivity and specificity are required. We previously introduced surface-based fluorescence intensity distribution analysis (sFIDA) with single-particle sensitivity. In this report, a preparation protocol for a synthetic Aβ oligomer sample was developed. This sample was used for internal quality control (IQC) to improve standardization, quality assurance, and routine application of oligomer-based diagnostic methods. We established an aggregation protocol for Aβ1–42, characterized the oligomers by atomic force microscopy (AFM), and assessed their application in sFIDA. Globular-shaped oligomers with a median size of 2.67 nm were detected by AFM, and sFIDA analysis of the Aβ1–42 oligomers yielded a femtomolar detection limit with high assay selectivity and dilution linearity over 5 log units. Lastly, we implemented a Shewhart chart for monitoring IQC performance over time, which is another important step toward quality assurance of oligomer-based diagnostic methods. more...