Individual Aggregates Research Articles

Score filtering for contextualized noise suppression of Poisson‐distributed geophysical signals

AbstractGeophysical and remote sensing products that rely on Poisson‐distributed measurement signals, such as cosmic‐ray neutron sensing (CRNS) and gamma spectrometry, often face challenges due to inherent Poisson noise. Common techniques to enhance signal stability include data aggregation or smoothing (e.g., moving averages and interpolation). However, these methods typically reduce the ability to resolve detailed temporal (stationary data) and spatial (mobile data) features. In this study, we introduced a method for contextual noise suppression tailored to Poisson‐distributed data, utilizing a discrete score attribution system. This score filter evaluates each observation against eight different criteria to assess its consistency with surrounding values, assigning a score between 0 (very unlikely) and 8 (very likely) to indicate whether the observation is likely to act as noise. These scores can then be used to flag or remove data points based on user‐defined thresholds. We tested the score filter's effectiveness on both stationary and mobile CRNS data, as well as on gamma‐ray spectrometry and electromagnetic induction (EMI) recordings. In our examples, the score filter consistently outperformed established filters, for example Savitzky–Golay and Kalman, in direct competition when applied to CRNS time series data. Additionally, the score filter substantially reduced Poisson noise in mobile CRNS, gamma‐ray spectrometry and EMI data. The scoring system also provides a context‐sensitive evaluation of individual observations or aggregates, assessing their conformity within the dataset. Given its general applicability, customizable criteria and very low computational demands, the proposed filter is easy to implement and holds promise as a valuable tool for denoising geophysical data and applications in other fields.

Heidegger's argument for fascism

AbstractHeidegger's ontological theories, his observations about liberalism and fascism, and his evaluation of Being are three premises of an argument for fascism. The ontological premise is that integrated wholes and instruments or objects of will are ontologically superior, as Being and Time suggests in discussing Being‐a‐whole and using tools. The social premise is that fascist societies are wholes integrated by dictatorial will, while liberal societies are looser aggregates of free individuals, as Heidegger describes in his 1930s seminars. The evaluative premise, shared with the medieval tradition and expressed in his notebook remarks about war, is that ontological superiority makes things better. The conclusion that fascism is better than liberalism should be rejected along with the evaluative premise.

The effects of herding and dispersal behaviour on the evolution of cooperation on complete networks

Evolutionary graph theory has considerably advanced the process of modelling the evolution of structured populations, which models the interactions between individuals as pairwise contests. In recent years, these classical evolution models have been extended to incorporate more realistic features, e.g. multiplayer games. A recent series of papers have developed a new evolutionary framework including structure, multiplayer interactions, evolutionary dynamics, and movement. However, so far, the developed models have mainly considered independent movement without coordinated behaviour. Although the theory underlying the framework has been developed and explored in various directions, several movement mechanisms have been produced which characterise coordinated movement, for example, herding. By embedding these newly constructed movement distributions, within the evolutionary setting of the framework, we demonstrate that certain levels of aggregation and dispersal benefit specific types of individuals. Moreover, by extending existing parameters within the framework, we are not only able to develop a general process of embedding any of the considered movement distributions into the evolutionary setting on complete graphs but also analytically produce the probability of fixation of a mutant on a complete N-sized network, for the multiplayer Public Goods and Hawk–Dove games. Also, by applying weak selection methods, we extended existing previous analyses on the pairwise Hawk–Dove Game to encompass the multiplayer version considered in this paper. By producing neutrality and equilibrium conditions, we show that hawks generally do worse in our models due to the multiplayer nature of the interactions.

Biofabrication of engineered tissues by 3D bioprinting of tissue specific high cell-density bioinks.

Bioprinting of high cell-density bioinks is a promising technique for cellular condensation-based tissue engineering and regeneration medicine. However, it remains difficult to create precisely controlled complex structures and organization of tissues with high cell-density bioink-based bioprinting for tissue specific condensation. In this study, we present newly biofabricated tissues from directly assembled, tissue specific, high cell-density bioinks which have been three-dimensionally printed into a photocrosslinkable and biodegradable hydrogel microparticle supporting bath. Three types of tissue specific high cell-density bioinks have been prepared with individual stem cells or stem cell aggregates by incorporation of growth factor-loaded gelatin microparticles. The bioprinted tissue specific high cell-density bioinks in the photocrosslinked microgel supporting bath condense together and differentiate down tissue-specific lineages to form multi-phase tissues (e.g., osteochondral tissues). By changing the growth factors and cell types, these tissue specific high cell-density bioinks enable engineering of various functional tissues with controlled architecture and organization of cells.

A Hybrid Feature Selection through Ensemble Rank Aggregation to Improve Perdition and Classification Accuracy

Today, extending credit is a difficult operation since credit databases contain a large quantity of data as well as redundant and useless information. The surplus and unrelated data can lower the categorization and prediction accuracy. In this case, feature selection is crucial for managing massive data. Different rank aggregation (RA) methods are there to ensemble individual feature selection. However not every dataset will perform at its best when using a single RA technique, the combination of multiple RA techniques are needed to increase the perdition accuracy. This study proposes a hybrid rank aggregation model that select features that are significant across different rank aggregation methods like MC4, Kendall tau distance and Borda. This study observed that the performance of ensemble rank aggregation techniques is better than the existing individual rank aggregation methods.

Evaluation of a Multi-Component Phenotype Algorithm for Systemic Lupus Erythematosus across the PCORnet, OMOP, and i2b2 Common Data Models

The aim of this study was to evaluate the performance of a computable phenotype for systemic lupus erythematosus (SLE) patients when it is ported from a local data warehouse to the i2b2, OMOP, and PCORnet CDMs. We adapted the SLE phenotype to the Northwestern Medicine (NM) Enterprise Data Warehouse (EDW) and NU i2b2, OMOP, and PCORnet instances. Each of the phenotype’s 17 components were determined by a rules-based algorithm built on diagnosis, medication, lab, and procedure codes. We assessed the phenotype over 168 clinician-confirmed SLE patients and 100 healthy controls and calculated agreement between the EDW and CDMs for overall SLE classification, individual SLICC criteria membership, and individual code occurrence level aggregates - count, first and last date, lab values using Cohen’s kappa (Cκ) and intraclass correlation coefficients (ICC). For overall SLE classification, agreement of the OMOP and PCORnet datamarts with the EDW was high (Cκ 0.928, 0.802, respectively) while that of i2b2 was low (Cκ 0.328). For the panel of SLICC criteria, OMOP had high agreement for 14/17 SLICC criteria (Cκ 0.792-1.000). PCORnet had high agreement for 13/17 criteria (Cκ 0.708-1.000). i2b2 had high agreement for 10/17 criteria (Cκ 0.813-1.000) with the exception of lab-based criteria. While agreement between the EDW and CDMs at the level of individual codes was relatively poor, agreement at the levels of overall SLE classification and individual SLICC criteria were reasonably high for OMOP and PCORnet, suggesting that inconsistencies at a micro, code level become less apparent at the macro, phenotype level.

Beyond binary group categorization: towards a dynamic view of human groups

ABSTRACT Society is a composite of interacting people and groups. These groups play a significant role in maintaining social status, establishing group identity and social identity, and enforcing norms. As such, groups are essential for understanding human behavior. Nevertheless, the study of groups in everyday group life yields many diverse and sometimes contradicting theories of group behavior, and researchers tend to agree that we have yet to understand the emergence of groups out of aggregates of individuals. The current paper aims to shed new light on the convoluted interrelation between groups and individuals by focusing on individuals’ social identities and group categorization. It does so by exploring the dynamic nature of the self and its implications on identity and group membership, and introducing a framework recognizing the fluidity of groups and group categorization. Incorporating historical insights with contemporary theories, this paper argues for a flexible understanding of group dynamics that surpasses rigid in-group and out-group classifications, proposing instead that group affiliations exist along a continuum that reflects the ever-changing social landscape.

Effect of Microwave Radiation on the Properties of Hydrogel, Cork, Perlite, and Ceramsite.

The present work analyzes the effect of releasing physically bound water from hydrogel, cork, perlite, and ceramsite on materials exposed to microwave radiation and subsequently investigates possible changes in the physical properties of these materials (water absorption and thermal conductivity coefficient). The release of physically bound water from individual materials has potential practical applications in materials engineering, for example, in the internal curing of concrete, where individual aggregates could, under the influence of microwave radiation, release water into the structure of the concrete and thus further cure it. Experimental analysis was carried out with samples of the above-mentioned materials, which were first weighed and then immersed in water for 24 h. Then, they were weighed again and exposed to microwave radiation. After exposure, the samples were weighed again, left immersed in water for 24 h, and weighed again. The focus of the study was on the ability of the aggregates to release water due to microwave radiation and on the changes in the properties (water absorption, thermal conductivity coefficient) of these materials when exposed to microwave radiation. The samples were further monitored by digital microscopy for possible changes in the surface layer of the materials. The hydrogels show the highest water absorption (1000%) and the fastest water release (45 min to complete desiccation). After the release of water due to microwave radiation, their ability to absorb water is maintained. Of interest, however, is that in the case of almost complete removal of water from the soaked hydrogel, the original powdered state of the hydrogel is not obtained, but the outcome has rather a solid structure. In the case of cork, the water absorption depends on the fraction of the material.

Performance Prediction of Centrifugal Norm Pumps Operating as Turbines

Pump-as-turbines (PAT) has been widely used during the last decade as one of the most interesting technologies in the field of energy recovery. Many studies and papers have been published in which the performance of the pumps in the turbine operating regime were analysed. Since horizontal single stage centrifugal norm pumps are most commonly used as PATs, their performances are analysed in this paper. Most of the research was related to individual pump aggregates or smaller groups and to obtaining their performance curves in turbine random mode. In this work, extensive experimental, numerical, and theoretical investigations were conducted to obtain complete dimensionless performance characteristics of single stage centrifugal norm pumps operating as turbines. One of the goals was to form a simple analytical expression that will, for this type of aggregate, map the pump operating characteristic to the appropriate turbine operating regime. By using the expressions obtained and presented in the paperwork, engineers are enabled to make the appropriate choice of pump aggregate for operation in turbine random mode for potential locations. For this purpose, the procedure for choosing the appropriate PAT aggregate or parallel operation of aggregates and the analysis of their operation on the existing system are presented in the paper. This innovative procedure allows us to select quickly PAT aggregates for a potential location and carry out appropriate techno-economic analyses and analyses of possible energy savings.

Hierarchical assembly of thermoresponsive helical dendronized poly(phenylacetylene)s through photo-crosslinking of the thermal aggregates

Supramolecular assembly of helical homopolymers to form stable chiral entities in water is highly valuable for creating chiral nanostructures and fabricating chiral biomaterials. Here we report on thermally induced supramolecular assembly of helical dendronized poly(phenylacetylene)s (PPAs) in aqueous solutions, and their in-situ photo-crosslinking at elevated temperatures to afford crosslinked nano-assemblies with hierarchical structures and stabilized helicities. These helical dendronized homopolymers carry cinnamate-cored dendritic oligoethylene glycol (OEG) pendants, which exhibit characteristic thermoresponsive behavior. Their thermal aggregation confers hexagonal packing of the polymer chains, and simultaneously resulting in enhancement of their chiralities. Assisted by radial amphiphilicity and worm-like molecular geometry, these dendronized PPAs form supramolecular twisted fibers, spheroid particles or toroids via thermal aggregation. Through UV photoirradiation above their cloud points (Tcps), cycloaddition of cinnamate moieties from the dendritic pendants promotes intermolecular crosslinking of dendronized PPA chains within the thermal aggregates, and simultaneously, the dynamic morphologies and supramolecular chirality from the dendronized PPAs through thermally induced aggregation can be fixed. In addition, photo-crosslinking can be occurred solely within individual aggregates due to the protection of densely packed dendritic OEGs. Therefore, various crosslinked assemblies from the dendronized homopolymers with tailorable morphologies and stabilized chirality are fabricated by tuning their thermally induced dynamic aggregations followed by in-situ photo-crosslinking. We believe that this work paves a convenient route to fabricate chiral assemblies with stabilized morphologies and fixed chiralities from dynamic helical homopolymers through intermolecular crosslinking, which can be promising for various chiral applications.

Supramolecular chemistry in cyclodextrin inclusion complexes: The formation rules of terpenes/β-cyclodextrin inclusion complexes

Supramolecular chemistry of cyclodextrins (CDs) inclusion complexes is a hot research topic at present, but current studies often focus on the host-guest interaction between CDs and hydrophobic substances, while ignoring the self-assembly behavior of the host and guest during the inclusion process. Based on the spatial structures, six representative terpenes were selected in this study, and the stoichiometric ratio between terpenes and β-cyclodextrin (β-CD) was investigated by isothermal titration calorimetry (ITC) method. Meanwhile, the constructed inclusion complexes (ICs) were characterized by nuclear magnetic resonance, X-ray diffraction, scanning electron microscope, etc. On this basis, the assembly process of β-CD and terpenes was investigated firstly by molecular simulation method, and the inclusion process between β-CD and terpenes was further studied in terms of the formation of individual ICs and ICs aggregates. Results showed that hydrophobic interaction and van der Waals force were the main driving forces of the reaction between terpenes and β-CD, and the formation of ICs, β-CD molecule aggregation, terpene aggregation, and ICs aggregation occurred simultaneously during the inclusion process of terpenes and β-CD. To sum up, this study may provide certain thinking and reference for the subsequent supramolecular chemical research on CDs.

Effects of group entitativity on young English-speaking children's interpretation of inclusive We.

The pronoun we can be used to refer to various collections of people depending on various pragmatic factors. This article reports the results of two online experiments that investigated children's interpretation of inclusive we, in which the child-listener is part of the intended referent of we. 128 2- and 4-year-olds collaborated with three partners in a coloring task. Before they played together, one partner informed participants that, e.g., "we can color!" Participants had their own markers and had to choose to how many partners to distribute (virtual) markers. In the first experiment, the partners appeared more like an aggregation of individuals than a collaborative group. The second experiment flipped this so that the partners appeared more like a collaborative group. Contrary to expectations, there was relatively little evidence for development in children's interpretation of we. Additionally, participants did not sharply distinguish their interpretations of we from those of we both or we all. Rather, participants were more likely to choose group interpretations when contextual cues indicated that their partners were a collaborative group than an aggregation of individuals. Interestingly, this interpretational distinction was sharpest for the pragmatically ambiguous we, compared to the relatively unambiguous we both and we all. These results are informative about the kinds of cues that shape young children's interpretation of pragmatically ambiguous pronominal reference.

Description of ASTAVIT, a rapid assessment method of soil structural stability based on image recognition

Measuring soil structure stability has always been a challenge, and various approaches have been proposed, mainly related to measuring soil aggregate stability upon wetting. This paper presents a rapid and cost-effective tool for evaluating soil structural stability named ASTAVIT, which stands for Aggregate STability Assessment using VIdeo Tests. The ASTAVIT principle involves visually monitoring the spreading of aggregates. This has already been implemented in the SLAKES smartphone application (now renamed Moulder), which simplifies the measurement of soil aggregates with minimal equipment. The aim of this work was to develop a robust, adaptable, and representative enough method that can be widely used in soil science laboratories. The protocol has been modified to use a 3D-printed plate, which source file is provided with this paper, to record the immersion of up to 96 individual aggregates in water. The increase in the projected area of the aggregates during slaking is tracked using image recognition software, ImageJ. The final stability index is determined based on this area increase. Soil structural stability can be assessed within an hour using a procedure that involves placing aggregates on a plate, filming, and analyzing. This method provides an objective evaluation of soil stability in a timely manner. The amount of soil used per test is similar to that used in Le Bissonnais tests (ISO 10930), ensuring representative results. The ASTAVIT index demonstrates expected behaviors of aggregate stability, as evidenced by its correlation with other soil characteristics and its ability to differentiate between soils that have undergone different tillage practices. An indicative classification of the ASTAVIT index into four categories of soil stability, similar to the Le Bissonnais tests, is proposed. ASTAVIT is expected to facilitate a broader implementation of structural stability studies.

Velké krystaly nitridu titanu (osbornitu) v metalurgické strusce z kladenských oceláren

Large crystals of titanium nitride (mineral osbornite) from metallurgical slag were studied by EMPA, XRD and Raman spectroscopy. The sample was collected at metallurgical dump in Kladno in the early 1970s and briefly described by Žáček and Ondruš (2003). The sample has a size of about 40 × 30 × 30 mm and is notable for its high density and conspicuous cubes of copper-like red to gold colour with metallic lustre (Fig. 1–2). The material consists of dominant gehlenite (~ 65% of the sample, all vol. %), osbornite (~ 20%), metallic iron (~ 8%), oldhamite (~ 5%), spinel (~1%) and anorthite (~1%), see Fig 3. All these phases were analyzed with the Cameca SX100 electron microprobe, and osbornite by Raman spectroscopy. Gehlenite and osbornite were also confirmed by XRD (Žáček – Ondruš 2003). Gehlenite contains a low concentration of MgO (0.8–1.1 wt.%) and traces of Na2O (0.06–0.16 wt.%) and Fe2O3 (0.4 wt.%). Aggregates of metallic iron embedded in gehlenite contain low titanium (up to 0.06 wt.% Ti) and elevated phosphorus concentrations (0.53–1.59 wt.% P), whereas tiny iron inclusions embedded in osbornite are richer in titanium (1.31 wt.%) and poorer in P (0.37 wt.%). Oldhamite, a cubic CaS, forms rounded inclusions 20–150 µm in size embedded in massive gehlenite. It is characterized by elevated concentration of Mn (2.7 wt.%) and low Fe (0.3 wt.%) and Mg (0.15 wt.%). Spinel has empirical formula Mg0.98Al1.99O4, and plagioclase is pure anorthite. Compositional data of osbornite are given in Table 1, those of associated minerals in Table 2 and 3. Osbornite forms aggregates of cubic crystals in a small slag cavity. Individual and crystal aggregates, usually up to 5 mm in size, are embedded in massive gehlenite. The largest aggregate of osbornite crystals reaching about 15 × 8 mm in size (Fig. 2). Osbornite contains 76.30–78.21 wt.% Ti, 21.31–23.82 wt.% N, and 0.02–0.46 wt. % Fe and displays stoichiometric composition Ti0.97–1.03N0.96–1.03 with only 0.005 apfu Fe (see Table 1). Lattice parameter is: a = 4.2536(3) A (Žáček – Ondruš 2003). The Raman spectrum of osbornite (Fig. 4) measured on the unpolished surface of cubic crystals showed the following vibrational bands: 1498, 201, 226, 271, 316, 345, 395, 439, 520, 559, 609, 649, 765, 836, and 1075 (all in cm–1). Raman spectra of TiN and other Ti nitrides have been studied by a number of authors (e.g. Spengler et al. 1978, Subramanian et al. 2011, Judek et al. 2021). The spectra can be divided into acoustic (A) and optical (O) part and further to the combination A O, 2A and 2O modes (Spengler et al. 1978; see Fig. 4). In addition to the vibrational bands typical of osbornite (201, 271, 316, 345, 395, 520, 559, 649, 765, 836 and 1075 cm–1), there are also vibrational bands corresponding to rutile and to the TiON phase (149, 226, 395, 439, 520, 609 and 649 cm–1, Spengler et al. 1978, Judek et al. 2021). The position of the vibrational band of osbornite at 201 cm–1 indicates a stoichiometric Ti : N ratio of 1 : 1, which is in agreement with the results of WDS chemical analysis (Spengler et al. 1978). The detected presence of TiON and TiO2 phases on the surface of osbornite crystals indicates oxidation of osbornite, probably at elevated temperatures. A similar effect was achieved during laboratory annealing of TiN layers at temperatures above 250 °C (Glaser et al. 2007) or above 500 °C (Chen et al. 2005). Osbornite had long been considered as an exclusively extraterrestrial mineral (Ramdohr 1973, Casanova 1992), and only a few natural terrestrial localities have been identified so far. It was first detected in heavy mineral concentrates from volcanic breccias at the contact of the Priazov Massif with the Donbas Basin in Ukraine (Tataritsev et al. 1987).

Enhancing social cohesion with cooperative bots in societies of greedy, mobile individuals.

Addressing collective issues in social development requires a high level of social cohesion, characterized by cooperation and close social connections. However, social cohesion is challenged by selfish, greedy individuals. With the advancement of artificial intelligence (AI), the dynamics of human-machine hybrid interactions introduce new complexities in fostering social cohesion. This study explores the impact of simple bots on social cohesion from the perspective of human-machine hybrid populations within network. By investigating collective self-organizing movement during migration, results indicate that cooperative bots can promote cooperation, facilitate individual aggregation, and thereby enhance social cohesion. The random exploration movement of bots can break the frozen state of greedy population, help to separate defectors in cooperative clusters, and promote the establishment of cooperative clusters. However, the presence of defective bots can weaken social cohesion, underscoring the importance of carefully designing bot behavior. Our research reveals the potential of bots in guiding social self-organization and provides insights for enhancing social cohesion in the era of human-machine interaction within social networks.

Multiple Enrollment Policy: Clustering Dropout and Graduation Constellations in Psychology and Sociology Bachelor’s Programs

In Austria, it is possible to enroll in an unlimited number of programs simultaneously and consecutively. Study duration and student performance are important performance indicators of the university system. The disciplines of psychology and sociology share similarities in their curriculum structures but are different in selectiveness due to their admission rules. They show differences in their motivations to enroll and their trajectories through higher education, leading to different constellations of “dropout” and “graduation.” The aim was to identify and compare groups of students’ outcomes in bachelor’s programs of psychology and sociology along the dimensions of workload and duration, incorporating the possibility of enrolling in multiple programs. The sample consisted of 6498 students between the academic years of 2010/11 and 2022/23 who either graduated or dropped out of one or more programs. Cluster analyses using four algorithms per individual outcome constellation, categorization, and aggregation of the results suggest a longer overall study duration for students with more than one program. In graduation–graduation and graduation–dropout clusters, groups with less overall workload could be identified. The transferability of passed exams may be an important component for students in multiple programs. Implications for policy and practice are discussed.

Ejection and dynamics of aggregates in the coma of comet 67P/Churyumov-Gerasimenko

The process of gas-driven ejection of refractory materials from cometary surfaces continues to pose a challenging question in cometary science. The activity modeling of comet 67P/Churyumov-Gerasimenko, based on data from the Rosetta mission, has significantly enhanced our comprehension of cometary activity. But thermophysical models have difficulties in simultaneously explaining the production rates of various gas species and dust. It has been suggested that different gas species might be responsible for the ejection of refractory material in distinct size ranges. This work focuses on investigating the abundance and the ejection mechanisms of large aggregates (gtrsim 1 cm) from the comet nucleus. We aim to determine their properties and map the distribution of their source regions across the comet surface. This can place constraints on activity models for comets. We examined 189 images acquired at five epochs by the OSIRIS/NAC instrument on board the Rosetta spacecraft. Our goal was to identify bright tracks produced by individual aggregates as they traversed the camera field of view. In parallel, we generated synthetic images based on the output of dynamical simulations involving various types of aggregates. By comparing these synthetic images with the observations, we determined the characteristics of the simulated aggregates that most closely resemble the observations. We have identified over 30000 tracks present in the OSIRIS images, derived constraints on the characteristics of the aggregates, and mapped their origins on the nucleus surface. The aggregates have an average radius of $ cm and a bulk density consistent with that of the comet's nucleus. Due to their size, gas drag exerts only a minor influence on their dynamical behavior, so an initial velocity is needed to bring them into the camera field of view. The source regions of these aggregates are predominantly located near the boundaries of distinct terrains on the surface.

Mechanical behavior and microstructure evolution of slag-fly ash based geopolymer stabilized sand

Geopolymers made from ground granulated blast-furnace slag and fly ash could effectively address the issues of high energy consumption and emissions associated with Portland cement, which is commonly used as a soil curing agent. In this study, the unconfined compressive strength and microstructure of geopolymer-solidified sand were presented and analyzed. The study focused on effect of the type and ratio of activator, the ratio of slag to fly ash, and the ratio of water to (activator and cementitious materials) (W/(A + C)) on the behavior of geopolymer stabilized sand. The results of computed tomography (CT), and scanning electron microscope (SEM) indicate that the variation in initial water content significantly affects the porosity of the specimen, which increased as initial water content increased. The cracks were mainly found at the joints between the individual aggregates and at the edges of the individual aggregates. The pore size distribution of the specimens was concentrated in the range 0.0761–5 μm, while the polymer particle distribution was concentrated in the range 0.0761–10 μm, with a concentration of over 90 %. A significant amount of cementing material was densely distributed around both the aggregates and the pores. CT and SEM testing techniques enable a thorough analysis and mutual verification of the self-compacting process, pore distribution, and size, as well as the distribution of cementing material within the specimens. The optimum ratio for B-S19 has been determined.

Single-molecule characterization of salivary protein aggregates from Parkinson's disease patients: a pilot study.

Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of α-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary α-synuclein and amyloid-β peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary α-synuclein aggregate/amyloid-β aggregate ratio is increased almost 2-fold in patients with Parkinson's disease (n = 20) compared with controls (n = 20, P < 0.05). Morphological information also provides insight, with saliva from patients with Parkinson's disease containing a greater proportion of larger and more fibrillar amyloid-β aggregates than control saliva (P < 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson's disease (n = 17) and controls (n = 18) with a high degree of accuracy (area under the curve = 0.87, P < 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods.

Single‐Molecule Characterization and Super‐Resolution Imaging of Alzheimer's Disease‐Relevant Tau Aggregates in Human Samples

AbstractHyperphosphorylation and aggregation of the protein tau play key roles in the development of Alzheimer's disease (AD). While the molecular structure of the filamentous tau aggregates has been determined to atomic resolution, there is far less information available about the smaller, soluble aggregates, which are believed to be more toxic. Traditional techniques are limited to bulk measures and struggle to identify individual aggregates in complex biological samples. To address this, we developed a novel single‐molecule pull‐down‐based assay (MAPTau) to detect and characterize individual tau aggregates in AD and control post‐mortem brain and biofluids. Using MAPTau, we report the quantity, as well as the size and circularity of tau aggregates measured using super‐resolution microscopy, revealing AD‐specific differences in tau aggregate morphology. By adapting MAPTau to detect multiple phosphorylation markers in individual aggregates using two‐color coincidence detection, we derived compositional profiles of the individual aggregates. We find an AD‐specific phosphorylation profile of tau aggregates with more than 80 % containing multiple phosphorylations, compared to 5 % in age‐matched non‐AD controls. Our results show that MAPTau is able to identify disease‐specific subpopulations of tau aggregates phosphorylated at different sites, that are invisible to other methods and enable the study of disease mechanisms and diagnosis.