DOE Office of Scientific and Technical Information (OSTI.GOV)

Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.

The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structuresmore » of these segments, we designed two non-natural peptide inhibitors that block aggregation. Lastly, this work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.« less

Phthalocyanine tetrasulfonates affect the amyloid formation and cytotoxicity of alpha-synuclein.

PubMed

Lee, Eui-Nam; Cho, Hyun-Ju; Lee, Choong-Hwan; Lee, Daekyun; Chung, Kwang Chul; Paik, Seung R

2004-03-30

Alpha-synuclein is a pathological component of Parkinson's disease by constituting the filamentous component of Lewy bodies. Phthalocyanine (Pc) effects on the amyloidosis of alpha-synuclein have been examined. The copper complex of phthalocyanine tetrasulfonate (PcTS-Cu(2+)) caused the self-oligomerization of alpha-synuclein while Pc-Cu(2+) did not affect the protein, indicating that introduction of the sulfonate groups was critical for the selective protein interaction. The PcTS-Cu(2+) interaction with alpha-synuclein has occurred predominantly at the N-terminal region of the protein with a K(d) of 0.83 microM apart from the hydrophobic NAC (non-Abeta component of Alzheimer's disease amyloid) segment. Phthalocyanine tetrasulfonate (PcTS) lacking the intercalated copper ion also showed a considerable affinity toward alpha-synuclein with a K(d) of 3.12 microM, and its binding site, on the other hand, was located at the acidic C-terminus. These mutually exclusive interactions between PcTS and PcTS-Cu(2+) toward alpha-synuclein resulted in distinctive features on the kinetics of protein aggregation, morphologies of the final aggregates, and their in vitro cytotoxicities. The PcTS actually suppressed the fibrous amyloid formation of alpha-synuclein, but it produced the chopped-wood-looking protein aggregates. The aggregates showed rather low toxicity (9.5%) on human neuroblastoma cells (SH-SY5Y). In fact, the PcTS was shown to effectively rescue the cell death of alpha-synuclein overexpressing cells caused by the lactacystin treatment as a proteasome inhibitor. The anti-aggregative and anti-amyloidogenic properties of PcTS were also demonstrated with alcohol dehydrogenase, glutathione S-transferase, and amyloid beta/A4 protein under their aggregative conditions. The PcTS-Cu(2+), on the other hand, promoted the protein aggregation of alpha-synuclein, which gave rise to the fibrillar protein aggregates whose cytotoxicity became significant to 35.8%. Taken together, the data provided in this study indicate that PcTS/PcTS-Cu(2+) could be considered as possible candidates for the development of therapeutic or prophylactic strategies against the alpha-synuclein-related neurodegenerative disorders.

7 CFR 51.1564 - External defects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... percent of the surface in the aggregate. Growth Cracks When the growth crack(s) affects more than 1/2 the... growth crack(s) affects more than 3/4 the length of the potato in the aggregate or when the depth is... 25 percent of the surface in the aggregate is affected. Second Growth When materially detracting from...

Corn rootworms (Coleoptera: Chrysomelidae) in space and time

NASA Astrophysics Data System (ADS)

Park, Yong-Lak

Spatial dispersion is a main characteristic of insect populations. Dispersion pattern provides useful information for developing effective sampling and scouting programs because it affects sampling accuracy, efficiency, and precision. Insect dispersion, however, is dynamic in space and time and largely dependent upon interactions among insect, plant and environmental factors. This study investigated the spatial and temporal dynamics of corn rootworm dispersion at different spatial scales by using the global positioning system, the geographic information system, and geostatistics. Egg dispersion pattern was random or uniform in 8-ha cornfields, but could be aggregated at a smaller scale. Larval dispersion pattern was aggregated regardless of spatial scales used in this study. Soil moisture positively affected corn rootworm egg and larval dispersions. Adult dispersion tended to be aggregated during peak population period and random or uniform early and late in the season and corn plant phenology was a major factor to determine dispersion patterns. The dispersion pattern of root injury by corn rootworm larval feeding was aggregated and the degree of aggregation increased as the root injury increased within the range of root injury observed in microscale study. Between-year relationships in dispersion among eggs, larvae, adult, and environment provided a strategy that could predict potential root damage the subsequent year. The best prediction map for the subsequent year's potential root damage was the dispersion maps of adults during population peaked in the cornfield. The prediction map was used to develop site-specific pest management that can reduce chemical input and increase control efficiency by controlling pests only where management is needed. This study demonstrated the spatio-temporal dynamics of insect population and spatial interactions among insects, plants, and environment.

Liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide affect Aβ aggregation features and cross the blood-brain-barrier: implications for therapy of Alzheimer disease.

PubMed

Bana, Laura; Minniti, Stefania; Salvati, Elisa; Sesana, Silvia; Zambelli, Vanessa; Cagnotto, Alfredo; Orlando, Antonina; Cazzaniga, Emanuela; Zwart, Rob; Scheper, Wiep; Masserini, Massimo; Re, Francesca

2014-10-01

Targeting amyloid-β peptide (Aβ) within the brain is a strategy actively sought for therapy of Alzheimer's disease (AD). We investigated the ability of liposomes bi-functionalized with phosphatidic acid and with a modified ApoE-derived peptide (mApoE-PA-LIP) to affect Aβ aggregation/disaggregation features and to cross in vitro and in vivo the blood-brain barrier (BBB). Surface plasmon resonance showed that bi-functionalized liposomes strongly bind Aβ (kD=0.6 μM), while Thioflavin-T and SDS-PAGE/WB assays show that liposomes inhibit peptide aggregation (70% inhibition after 72 h) and trigger the disaggregation of preformed aggregates (60% decrease after 120 h incubation). Moreover, experiments with dually radiolabelled LIP suggest that bi-functionalization enhances the passage of radioactivity across the BBB either in vitro (permeability=2.5×10(-5) cm/min, 5-fold higher with respect to mono-functionalized liposomes) or in vivo in healthy mice. Taken together, our results suggest that mApoE-PA-LIP are valuable nanodevices with a potential applicability in vivo for the treatment of AD. From the clinical editor: Bi-functionalized liposomes with phosphatidic acid and a modified ApoE-derived peptide were demonstrated to influence Aβ aggregation/disaggregation as a potential treatment in an Alzheimer's model. The liposomes were able to cross the blood-brain barrier in vitro and in vivo. Similar liposomes may become clinically valuable nanodevices with a potential applicability for the treatment of Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of pH control in the formation of inclusion bodies during production of recombinant sphingomyelinase-D in Escherichia coli.

PubMed

Castellanos-Mendoza, Andrea; Castro-Acosta, Ricardo M; Olvera, Alejandro; Zavala, Guadalupe; Mendoza-Vera, Miguel; García-Hernández, Enrique; Alagón, Alejandro; Trujillo-Roldán, Mauricio A; Valdez-Cruz, Norma A

2014-09-12

Inclusion bodies (IBs) are aggregated proteins that form clusters when protein is overexpressed in heterologous expression systems. IBs have been considered as non-usable proteins, but recently they are being used as functional materials, catalytic particles, drug delivery agents, immunogenic structures, and as a raw material in recombinant therapeutic protein purification. However, few studies have been made to understand how culture conditions affect the protein aggregation and the physicochemical characteristics that lead them to cluster. The objective of our research was to understand how pH affects the physicochemical properties of IBs formed by the recombinant sphingomyelinase-D of tick expressed in E. coli BL21-Gold (DE3) by evaluating two pH culture strategies. Uncontrolled pH culture conditions favored recombinant sphingomyelinase-D aggregation and IB formation. The IBs of sphingomyelinase-D produced under controlled pH at 7.5 and after 24 h were smaller (<500 nm) than those produced under uncontrolled pH conditions (>500 nm). Furthermore, the composition, conformation and β-structure formation of the aggregates were different. Under controlled pH conditions in comparison to uncontrolled conditions, the produced IBs presented higher resistance to denaturants and proteinase-K degradation, presented β-structure, but apparently as time passes the IBs become compacted and less sensitive to amyloid dye binding. The manipulation of the pH has an impact on IB formation and their physicochemical characteristics. Particularly, uncontrolled pH conditions favored the protein aggregation and sphingomyelinase-D IB formation. The evidence may lead to find methodologies for bioprocesses to obtain biomaterials with particular characteristics, extending the application possibilities of the inclusion bodies.

Trehalose induced conformational changes in the amyloid-β peptide.

PubMed

Khan, Shagufta H; Kumar, Raj

2017-06-01

Alzheimer's disease is an irreversible and progressive brain disorder featured by the accumulation of Amyloid-β (Aβ) peptide, which forms insoluble assemblies that builds up into plaques resulting in cognitive decline and memory loss. The formation of fibrillar amyloid deposits is accompanied by conformational changes of the soluble Aβ peptide into β-sheet structures. Strategies to prevent or reduce Aβ aggregation using small molecules such as trehalose have shown beneficial effects under in vitro cell- and in vivo mouse- models. However, the role of trehalose in reducing Aβ peptide aggregation is still not clear. In the present study, using circular dichroism- and fluorescence emission- spectroscopies, we demonstrated that in the presence of trehalose, Aβ peptide adopts more helical content and undergoes a disorder/order conformational transition. Based on our findings, we conclude that trehalose affects the conformation of Aβ peptide to form α-helical structure, which may inhibit the formation of β-sheets and thereby aggregation. Copyright © 2017 Elsevier GmbH. All rights reserved.

The impact of anisotropy and interaction range on the self-assembly of Janus ellipsoids

NASA Astrophysics Data System (ADS)

Ruth, D. P.; Gunton, J. D.; Rickman, J. M.; Li, Wei

2014-12-01

We assess the roles of anisotropy and interaction range on the self-assembly of Janus colloidal particles. In particular, Monte Carlo simulation is employed to investigate the propensity for the formation of aggregates in a spheroidal model of a colloid having a relatively short-ranged interaction that is consistent with experimentally realizable systems. By monitoring the equilibrium distribution of aggregates as a function of temperature and density, we identify a "micelle" transition temperature and discuss its dependence on particle shape. We find that, unlike systems with longer ranged interactions, this system does not form micelles below a transition temperature at low density. Rather, larger clusters comprising 20-40 particles characterize the transition. We then examine the dependence of the second virial coefficient on particle shape and well width to determine how these important system parameters affect aggregation. Finally, we discuss possible strategies suggested by this work to promote self-assembly for the encapsulation of particles.

True and apparent inhibition of amyloid fibril formation.

PubMed

Martins, Pedro M

2013-01-01

A possible therapeutic strategy for amyloid diseases involves the use of small molecule compounds to inhibit protein assembly into insoluble aggregates. According to the recently proposed Crystallization-Like Model, the kinetics of amyloid fibrillization can be retarded by decreasing the frequency of new fibril formation or by decreasing the elongation rate of existing fibrils. To the compounds that affect the nucleation and/or the growth steps we call true inhibitors. An apparent inhibition mechanism may however result from the alteration of thermodynamic properties such as the solubility of the amyloidogenic protein. Apparent inhibitors markedly influence protein aggregation kinetics measured in vitro, yet they are likely to lead to disappointing results when tested in vivo. This is because cells and tissues media are in general much more buffered against small variations in composition than the solutions prepared in lab. Here we show how to discriminate between true and apparent inhibition mechanisms from experimental data on protein aggregation kinetics. The goal is to be able to identify false positives much earlier during the drug development process.

The temporal course and clinical correlates of subjective impulsivity in bipolar disorder as revealed through ecological momentary assessment.

PubMed

Depp, Colin A; Moore, Raeanne C; Dev, Sheena I; Mausbach, Brent T; Eyler, Lisa T; Granholm, Eric L

2016-03-15

Impulsivity is frequently linked with bipolar disorder and is associated with mania and negative outcomes. The temporal dynamics of subjective impulsivity are unclear, in particular whether impulsivity precedes or follows changes in positive or negative affect. A total of 41 outpatients with bipolar disorder (I or II) were provided with mobile devices for 11 weeks and completed twice-daily surveys about affective states and subjective impulsivity. We examined the association between aggregate subjective impulsivity with baseline global cognitive function, suicide risk ratings, and medication adherence, as well as concurrent and lagged associations with momentary positive and negative affect ratings. A total of 2902 ratings were available across study subjects. Higher aggregate mean ratings of impulsivity were associated with worse baseline global cognitive function, prior suicide attempts, and self-reported problems with medication adherence, as well as more severe manic (but not depressive) symptoms. Time-lagged models indicated that greater negative affect, but not positive affect, predicted subsequent increases in subjective impulsivity, which, in turn, predicted diminished positive affect. Other measures of impulsivity with which to validate subjective ratings were unavailable and the sample was restricted to generally clinically stable outpatients. Subjective impulsivity as measured by daily monitoring was associated with worse cognitive function and self-rated medication adherence, and higher suicide risk ratings. Impulsivity may be a maladaptive strategy to regulate negative affect in bipolar disorder. Copyright © 2016. Published by Elsevier B.V.

Abrupt strategy change underlies gradual performance change: Bayesian hierarchical models of component and aggregate strategy use.

PubMed

Wynton, Sarah K A; Anglim, Jeromy

2017-10-01

While researchers have often sought to understand the learning curve in terms of multiple component processes, few studies have measured and mathematically modeled these processes on a complex task. In particular, there remains a need to reconcile how abrupt changes in strategy use can co-occur with gradual changes in task completion time. Thus, the current study aimed to assess the degree to which strategy change was abrupt or gradual, and whether strategy aggregation could partially explain gradual performance change. It also aimed to show how Bayesian methods could be used to model the effect of practice on strategy use. To achieve these aims, 162 participants completed 15 blocks of practice on a complex computer-based task-the Wynton-Anglim booking (WAB) task. The task allowed for multiple component strategies (i.e., memory retrieval, information reduction, and insight) that could also be aggregated to a global measure of strategy use. Bayesian hierarchical models were used to compare abrupt and gradual functions of component and aggregate strategy use. Task completion time was well-modeled by a power function, and global strategy use explained substantial variance in performance. Change in component strategy use tended to be abrupt, whereas change in global strategy use was gradual and well-modeled by a power function. Thus, differential timing of component strategy shifts leads to gradual changes in overall strategy efficiency, and this provides one reason for why smooth learning curves can co-occur with abrupt changes in strategy use. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Maternal emotion regulation during child distress, child anxiety accommodation, and links between maternal and child anxiety.

PubMed

Kerns, Caroline E; Pincus, Donna B; McLaughlin, Katie A; Comer, Jonathan S

2017-08-01

Environmental contributions are thought to play a primary role in the familial aggregation of anxiety, but parenting influences remain poorly understood. We examined dynamic relations between maternal anxiety, maternal emotion regulation (ER) during child distress, maternal accommodation of child distress, and child anxiety. Mothers (N=45) of youth ages 3-8 years (M=4.8) participated in an experimental task during which they listened to a standardized audio recording of a child in anxious distress pleading for parental intervention. Measures of maternal and child anxiety, mothers' affective states, mothers' ER strategies during the child distress, and maternal accommodation of child anxiety were collected. Mothers' resting respiratory sinus arrhythmia (RSA) reactivity during the recording was also acquired. Higher maternal negative affect and greater maternal ER switching (i.e., using multiple ER strategies in a short time without positive regulatory results) during child distress were associated with child anxiety. Sequential mediation modeling showed that maternal anxiety predicted ineffective maternal ER during child distress exposure, which in turn predicted greater maternal accommodation, which in turn predicted higher child anxiety. Findings support the mediating roles of maternal ER and accommodation in linking maternal and child anxiety, and suggest that ineffective maternal ER and subsequent attempts to accommodate child distress may act as mechanisms underlying the familial aggregation of anxiety. Copyright © 2017 Elsevier Ltd. All rights reserved.

The invasion mode of GH(3) cells is conditioned by collagen subtype, and its efficiency depends on cell-cell adhesion.

PubMed

Azorín, Erika; Solano-Agama, Carmen; Mendoza-Garrido, M Eugenia

2012-12-15

The adaptation of GH(3) cells to different microenvironments is a consequence of a partial compromise with the tumor phenotype. A collagen type IV enriched microenvironment favors an invasive phenotype and increases the substrate adhesion capacity, whereas it decreases the phosphorylation of the regulatory myosin light chain and the aggregation capacity. In contrast, the higher internal tension and increased aggregation capacity induced by collagen type I/III are factors that reduce the invasion rate. Our results show, for the first time, the importance of collagen subtypes in determining the migratory strategy: collagen I/III favors mesenchymal-like motility, whereas collagen type IV induces an ameboid-type displacement. The reciprocal modulation of the myosin light chain kinase and the Rho-kinase determines the invasive capacity through changes in tissue cohesion, extracellular matrix affinity, regulatory myosin light chain phosphorylation and spatial distribution. The collagen subtype determines which of the mechano-transduction signaling pathways will regulate the tensional homeostasis and affect the invasion ability as well as the preferred migration strategy of the cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Fiscal year 1980-81 implementation plan in support of technical development and integration of sampling and aggregation procedures. [crop acreage estimation

NASA Technical Reports Server (NTRS)

1981-01-01

The specific objectives of the FY 1980-81 tasks are: (1) further refinements to the weighted aggregation procedure; (2) improved approaches for estimating within-stratum variance; (3) more intensive investigation of alternative sampling strategies such as full-frame sampling strategy, and (4) further developments in regard to a simulated approach for assessing the performance of the overall designed sampling and aggregation system.

Sediment composition for the assessment of water erosion and nonpoint source pollution in natural and fire-affected landscapes.

PubMed

Carkovic, Athena B; Pastén, Pablo A; Bonilla, Carlos A

2015-04-15

Water erosion is a leading cause of soil degradation and a major nonpoint source pollution problem. Many efforts have been undertaken to estimate the amount and size distribution of the sediment leaving the field. Multi-size class water erosion models subdivide eroded soil into different sizes and estimate the aggregate's composition based on empirical equations derived from agricultural soils. The objective of this study was to evaluate these equations on soil samples collected from natural landscapes (uncultivated) and fire-affected soils. Chemical, physical, and soil fractions and aggregate composition analyses were performed on samples collected in the Chilean Patagonia and later compared with the equations' estimates. The results showed that the empirical equations were not suitable for predicting the sediment fractions. Fine particles, including primary clay, primary silt, and small aggregates (<53 μm) were over-estimated, and large aggregates (>53 μm) and primary sand were under-estimated. The uncultivated and fire-affected soils showed a reduced fraction of fine particles in the sediment, as clay and silt were mostly in the form of large aggregates. Thus, a new set of equations was developed for these soils, where small aggregates were defined as particles with sizes between 53 μm and 250 μm and large aggregates as particles>250 μm. With r(2) values between 0.47 and 0.98, the new equations provided better estimates for primary sand and large aggregates. The aggregate's composition was also well predicted, especially the silt and clay fractions in the large aggregates from uncultivated soils (r(2)=0.63 and 0.83, respectively) and the fractions of silt in the small aggregates (r(2)=0.84) and clay in the large aggregates (r(2)=0.78) from fire-affected soils. Overall, these new equations proved to be better predictors for the sediment and aggregate's composition in uncultivated and fire-affected soils, and they reduce the error when estimating soil loss in natural landscapes. Copyright © 2015 Elsevier B.V. All rights reserved.

Alzheimer’s disease: biological aspects, therapeutic perspectives and diagnostic tools

NASA Astrophysics Data System (ADS)

Di Carlo, M.; Giacomazza, D.; San Biagio, P. L.

2012-06-01

Alzheimer’s disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person’s ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (Aβ) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of Aβ misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.

New developments in sampling and aggregation for remotely sensed surveys

NASA Technical Reports Server (NTRS)

Feiveson, A. H. (Principal Investigator)

1979-01-01

Sampling techniques used to construct large area crop estimates are briefly reviewed. Problem areas in sampling and aggregation are covered. The natural sampling strategy, two phase sampling, weighted aggregation, and multiyear estimation are among the topics discussed.

Robustness of the Process of Nucleoid Exclusion of Protein Aggregates in Escherichia coli

PubMed Central

Neeli-Venkata, Ramakanth; Martikainen, Antti; Gupta, Abhishekh; Gonçalves, Nadia; Fonseca, Jose

2016-01-01

ABSTRACT Escherichia coli segregates protein aggregates to the poles by nucleoid exclusion. Combined with cell divisions, this generates heterogeneous aggregate distributions in subsequent cell generations. We studied the robustness of this process with differing medium richness and antibiotics stress, which affect nucleoid size, using multimodal, time-lapse microscopy of live cells expressing both a fluorescently tagged chaperone (IbpA), which identifies in vivo the location of aggregates, and HupA-mCherry, a fluorescent variant of a nucleoid-associated protein. We find that the relative sizes of the nucleoid's major and minor axes change widely, in a positively correlated fashion, with medium richness and antibiotic stress. The aggregate's distribution along the major cell axis also changes between conditions and in agreement with the nucleoid exclusion phenomenon. Consequently, the fraction of aggregates at the midcell region prior to cell division differs between conditions, which will affect the degree of asymmetries in the partitioning of aggregates between cells of future generations. Finally, from the location of the peak of anisotropy in the aggregate displacement distribution, the nucleoid relative size, and the spatiotemporal aggregate distribution, we find that the exclusion of detectable aggregates from midcell is most pronounced in cells with mid-sized nucleoids, which are most common under optimal conditions. We conclude that the aggregate management mechanisms of E. coli are significantly robust but are not immune to stresses due to the tangible effect that these have on nucleoid size. IMPORTANCE Escherichia coli segregates protein aggregates to the poles by nucleoid exclusion. From live single-cell microscopy studies of the robustness of this process to various stresses known to affect nucleoid size, we find that nucleoid size and aggregate preferential locations change concordantly between conditions. Also, the degree of influence of the nucleoid on aggregate positioning differs between conditions, causing aggregate numbers at midcell to differ in cell division events, which will affect the degree of asymmetries in the partitioning of aggregates between cells of future generations. Finally, we find that aggregate segregation to the cell poles is most pronounced in cells with mid-sized nucleoids. We conclude that the energy-free process of the midcell exclusion of aggregates partially loses effectiveness under stressful conditions. PMID:26728194

Characterization of Depression in Children with Autism Spectrum Disorders

PubMed Central

Magnuson, Katherine M.; Constantino, John N.

2011-01-01

Depressive syndromes represent a disabling comorbidity for many children with autism spectrum disorders (ASD), however the ascertainment of depression can be complicated by phenotypic overlap between the two conditions, by ways in which autistic symptomatology can mask cardinal features of depression, and by atypical manifestations of depression in children with ASD. These issues have contributed to wide variation in the estimation of prevalence rates of depression in individuals with ASD, and invoke the need for new approaches to the specific detection of depression and other neuropsychiatric comorbidities that aggregate in children affected by ASD. We review the scientific literature relevant to the occurrence of depression in ASD, and consider important parameters of risk, including psychosocial factors such as insight into affectation status, as well as biological factors such as the aggregation of depressive syndromes in certain families affected by autism, which has suggested possible overlap in genetic influences underlying the two conditions. Variability in the manifestations of depression across environmental contexts provides important clues to intervention, and underscores the potential importance of involving multiple informants in ascertaining depression in children and adolescents with ASD. A practical strategy for evaluating the presence of depression in youth with ASD is synthesized from the available data and discussed. PMID:21502871

Conformational stability as a design target to control protein aggregation.

PubMed

Costanzo, Joseph A; O'Brien, Christopher J; Tiller, Kathryn; Tamargo, Erin; Robinson, Anne Skaja; Roberts, Christopher J; Fernandez, Erik J

2014-05-01

Non-native protein aggregation is a prevalent problem occurring in many biotechnological manufacturing processes and can compromise the biological activity of the target molecule or induce an undesired immune response. Additionally, some non-native aggregation mechanisms lead to amyloid fibril formation, which can be associated with debilitating diseases. For natively folded proteins, partial or complete unfolding is often required to populate aggregation-prone conformational states, and therefore one proposed strategy to mitigate aggregation is to increase the free energy for unfolding (ΔGunf) prior to aggregation. A computational design approach was tested using human γD crystallin (γD-crys) as a model multi-domain protein. Two mutational strategies were tested for their ability to reduce/increase aggregation rates by increasing/decreasing ΔGunf: stabilizing the less stable domain and stabilizing the domain-domain interface. The computational protein design algorithm, RosettaDesign, was implemented to identify point variants. The results showed that although the predicted free energies were only weakly correlated with the experimental ΔGunf values, increased/decreased aggregation rates for γD-crys correlated reasonably well with decreases/increases in experimental ΔGunf, illustrating improved conformational stability as a possible design target to mitigate aggregation. However, the results also illustrate that conformational stability is not the sole design factor controlling aggregation rates of natively folded proteins.

Characterizing the Role of Nanoparticle Design on Tumor Transport and Stability in the Extracellular Environment

NASA Astrophysics Data System (ADS)

Albanese, Alexandre

Nanotechnology has emerged as an exciting strategy for the delivery of diagnostic and therapeutic agents into established tumors. Advancements in nanomaterial synthesis have generated an extensive number of nanoparticle designs made from different materials. Unfortunately, it remains impossible to predict a design's effectiveness for in vivo tumor accumulation. Little is known about how a nanoparticle's morphology and surface chemistry affect its interactions with cells and proteins inside the tumor tissue. This thesis focuses on the development of in vitro experimental tools to evaluate how nanoparticle design affects transport in a three-dimensional tumor tissue and stability in the tumor microenvironment. Nanoparticle transport was evaluated using a novel 'tumor-on-a-chip' system where multicellular tumor spheroids were immobilized in a microfluidic channel. This setup created a three-dimensional tumor environment displaying physiological cell density, extracellular matrix organization, and interstitial flow rates. The tumor-on-a-chip demonstrated that accumulation of nanoparticles was limited to diameters below 110 nm and was improved by receptor targeting. Nanoparticle stability in the tumor microenvironment was evaluated using media isolated from different tumor cell lines. Nanoparticle diameter and surface chemistry were important determinants of stability in cancer cell-conditioned media. Small nanoparticles with unstable surface chemistries adsorbed cellular proteins on their surface and were prone to aggregation. Nanoparticle aggregation altered cellular interactions leading to changes in cell uptake. Using a novel technique to generate different aggregate sizes possessing a uniform surface composition, it was determined that aggregation can change receptor affinity, cell internalization mechanisms and sub-cellular sequestration patterns. Data from this thesis characterize the behavior of nanoparticles within modeled tumor environments and provide some preliminary design guidelines for maximizing nanoparticle tumor accumulation. This work highlights the importance of characterizing nano-bio interactions for engineering successful nanomaterial-based delivery systems.

Structural hot spots for the solubility of globular proteins

PubMed Central

Ganesan, Ashok; Siekierska, Aleksandra; Beerten, Jacinte; Brams, Marijke; Van Durme, Joost; De Baets, Greet; Van der Kant, Rob; Gallardo, Rodrigo; Ramakers, Meine; Langenberg, Tobias; Wilkinson, Hannah; De Smet, Frederik; Ulens, Chris; Rousseau, Frederic; Schymkowitz, Joost

2016-01-01

Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human α-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function. PMID:26905391

The sum of all fears: conceptual challenges with measuring fear of cancer recurrence.

PubMed

Costa, Daniel S J; Smith, Allan Ben; Fardell, Joanna E

2016-01-01

Fear of cancer recurrence (FCR) is increasingly recognised as a major concern for people with cancer once active treatment is completed. Several instruments have been designed to assess FCR; however, no gold standard has emerged. Many instruments conceptualise FCR as a multidimensional construct. However, this potentially conflates FCR as an outcome with its antecedents and consequences. This is problematic when an aggregate of distinct dimensions is calculated, as is commonly recommended. For example, the total score on the Fear of Cancer Recurrence Inventory is an aggregate of items from seven sub-scales: triggers, severity, psychological distress, coping strategies, functioning impairments, insight and reassurance. Similarly, the total score on the Fear of Progression Questionnaire is an aggregate of affective reaction, partnership/family, work and loss of autonomy. Arguably, the severity and affective reaction domains represent fear, and the other sub-scales represent related concepts, rather than "dimensions" of FCR. The total score represents a combination of concepts whose meaning is unclear. The same total score could be produced by patients with very different experiences, and patients with the same level of fear could have very different total scores. Therefore, we argue that although the level of FCR may be determined by a complex network of antecedents and modifiers and have variable consequences, FCR itself may be a simple concept, which can be assessed using a smaller number of items. Conceptual clarity in its research infancy should prevent FCR becoming a construct that is vaguely operationalised and interpreted.

Formation, Fate, and Impacts of Microscopic and Macroscopic Oil-Sediment Residues in Nearshore Marine Environments: A Critical Review

NASA Astrophysics Data System (ADS)

Gustitus, Sarah A.; Clement, T. Prabhakar

2017-12-01

Crude oil that is spilled in marine environments often interacts with suspended sediments to form residues that can impact the recovery of the affected nearshore ecosystems. When spilled oil and sediment interact, they can form either small microscopic aggregates, commonly referred to as oil-particle aggregates, or large macroscopic agglomerates, referred to as sediment-oil agglomerates or sediment-oil mats. Although these different sized oil-sediment residues have similar compositions, they are formed under different conditions and have different fates in nearshore environments; the goal of this review is to synthesize our current understanding of these two types of residues. We believe that researchers who focus solely on studying either microscopic aggregates or macroscopic agglomerates could benefit from understanding the research findings available in the other field. In this study, we compare and contrast various processes that control the formation, fate, and impacts of these two types of residues in nearshore environments and point out some of the knowledge gaps in this field. Additionally, these residues have been referred to by many names in the past, leading to confusion and misconceptions at times. In this effort, we recommend a uniform nomenclature to distinguish them based on their physical size. Our overall aim is to bridge the gap between microscopic and macroscopic oil-sediment residue literature to foster a robust exchange of ideas, which we believe can lead to the development of efficient strategies for managing oil spills that affect nearshore environments.

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease.

PubMed

Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R; Challa, Pavan Kumar; Cohen, Samuel I A; Linse, Sara; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

2017-01-10

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.

Heat shock proteins as potential targets for protective strategies in neurodegeneration.

PubMed

Kampinga, Harm H; Bergink, Steven

2016-06-01

Protein aggregates are hallmarks of nearly all age-related neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and several polyglutamine diseases such as Huntington's disease and different forms of spinocerebellar ataxias (SCA; SCA1-3, SCA6, and SCA7). The collapse of cellular protein homoeostasis can be both a cause and a consequence of this protein aggregation. Boosting components of the cellular protein quality control system has been widely investigated as a strategy to counteract protein aggregates or their toxic consequences. Heat shock proteins (HSPs) play a central part in regulating protein quality control and contribute to protein aggregation and disaggregation. Therefore, HSPs are viable targets for the development of drugs aimed at reducing pathogenic protein aggregates that are thought to contribute to the development of so many neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Aggregate IRT Procedure for Exploratory Factor Analysis

ERIC Educational Resources Information Center

Camilli, Gregory; Fox, Jean-Paul

2015-01-01

An aggregation strategy is proposed to potentially address practical limitation related to computing resources for two-level multidimensional item response theory (MIRT) models with large data sets. The aggregate model is derived by integration of the normal ogive model, and an adaptation of the stochastic approximation expectation maximization…

Study on Effects of Different Replacement Rate on Bending Behavior of Big Recycled Aggregate Self Compacting Concrete

NASA Astrophysics Data System (ADS)

Li, Jing; Guo, Tiantian; Gao, Shuai; Jiang, Lin; Zhao, Zhijun; Wang, Yalin

2018-03-01

Big recycled aggregate self compacting concrete is a new type of recycled concrete, which has the advantages of low hydration heat and green environmental protection, but its bending behavior can be affected by different replacement rate. Therefor, in this paper, the research status of big Recycled aggregate self compacting concrete was systematically introduced, and the effect of different replacement rate of big recycled aggregate on failure mode, crack distribution and bending strength of the beam were studied through the bending behavior test of 4 big recycled aggregate self compacting concrete beams. The results show that: The crack distribution of the beam can be affected by the replacement rate; The failure modes of big recycled aggregate beams are the same as those of ordinary concrete; The plane section assumption is applicable to the big recycled aggregate self compacting concrete beam; The higher the replacement rate, the lower the bending strength of big recycled aggregate self compacting concrete beams.

Generalized Aggregation and Coordination of Residential Loads in a Smart Community

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, He; Somani, Abhishek; Lian, Jianming

2015-11-02

Flexibility from residential loads presents an enormous potential to provide various services to the smart grid. In this paper, we propose a unified hierarchical framework for aggregation and coordination of various residential loads in a smart community, such as Thermostatically Controlled Loads (TCLs), Distributed Energy Storages (DESs), residential Pool Pumps (PPs), and Electric Vehicles (EVs). A central idea of this framework is a virtual battery model, which provides a simple and intuitive tool to aggregate the flexibility of distributed loads. Moreover, a multi-stage Nash-bargainingbased coordination strategy is proposed to coordinate different aggregations of residential loads for demand response. Case studiesmore » are provided to demonstrate the efficacy of our proposed framework and coordination strategy in managing peak power demand in a smart residential community.« less

A formulation to analyze system-of-systems problems: A case study of airport metroplex operations

NASA Astrophysics Data System (ADS)

Ayyalasomayajula, Sricharan Kishore

A system-of-systems (SoS) can be described as a collection of multiple, heterogeneous, distributed, independent components interacting to achieve a range of objectives. A generic formulation was developed to model component interactions in an SoS to understand their influence on overall SoS performance. The formulation employs a lexicon to aggregate components into hierarchical interaction networks and understand how their topological properties affect the performance of the aggregations. Overall SoS performance is evaluated by monitoring the changes in stakeholder profitability due to changes in component interactions. The formulation was applied to a case study in air transportation focusing on operations at airport metroplexes. Metroplexes are geographical regions with two or more airports in close proximity to one another. The case study explored how metroplex airports interact with one another, what dependencies drive these interactions, and how these dependencies affect metroplex throughput and capacity. Metrics were developed to quantify runway dependencies at a metroplex and were correlated with its throughput and capacity. Operations at the New York/New Jersey metroplex (NYNJ) airports were simulated to explore the feasibility of operating very large aircraft (VLA), such as the Airbus A380, as a delay-mitigation strategy at these airports. The proposed formulation was employed to analyze the impact of this strategy on different stakeholders in the national air transportation system (ATS), such as airlines and airports. The analysis results and their implications were used to compare the pros and cons of operating VLAs at NYNJ from the perspectives of airline profitability, and flight delays at NYNJ and across the ATS.

7 CFR 51.1564 - External defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the potato or when green color affects more than 50 percent of the surface in the aggregate. Growth Cracks When the growth crack(s) affects more than 1/2 the length of the potato in the aggregate on round... that as outlined in Table V. (See Table V.) When the growth crack(s) affects more than 3/4 the length...

Organizational Productivity Measurement: The Development and Evaluation of an Integrated Approach.

DTIC Science & Technology

1987-07-01

measurement and aggregation strategy also has applications in management r information systems, performance appraisal , and other situations where multiple...larger organizational units. The basic measurement and aggregation strategy also has applications in manage- "".". ment information systems, criterion...much has been written on the subject of organizational productiv- ity, there is little consensus concerning its definition ( Tuttle , 1983). Such a lack

Aggregation, impaired degradation and immunization targeting of amyloid-beta dimers in Alzheimer’s disease: a stochastic modelling approach

PubMed Central

2012-01-01

Background Alzheimer’s disease (AD) is the most frequently diagnosed neurodegenerative disorder affecting humans, with advanced age being the most prominent risk factor for developing AD. Despite intense research efforts aimed at elucidating the precise molecular underpinnings of AD, a definitive answer is still lacking. In recent years, consensus has grown that dimerisation of the polypeptide amyloid-beta (Aß), particularly Aß42, plays a crucial role in the neuropathology that characterise AD-affected post-mortem brains, including the large-scale accumulation of fibrils, also referred to as senile plaques. This has led to the realistic hope that targeting Aß42 immunotherapeutically could drastically reduce plaque burden in the ageing brain, thus delaying AD onset or symptom progression. Stochastic modelling is a useful tool for increasing understanding of the processes underlying complex systems-affecting disorders such as AD, providing a rapid and inexpensive strategy for testing putative new therapies. In light of the tool’s utility, we developed computer simulation models to examine Aß42 turnover and its aggregation in detail and to test the effect of immunization against Aß dimers. Results Our model demonstrates for the first time that even a slight decrease in the clearance rate of Aß42 monomers is sufficient to increase the chance of dimers forming, which could act as instigators of protofibril and fibril formation, resulting in increased plaque levels. As the process is slow and levels of Aβ are normally low, stochastic effects are important. Our model predicts that reducing the rate of dimerisation leads to a significant reduction in plaque levels and delays onset of plaque formation. The model was used to test the effect of an antibody mediated immunological response. Our results showed that plaque levels were reduced compared to conditions where antibodies are not present. Conclusion Our model supports the current thinking that levels of dimers are important in initiating the aggregation process. Although substantial knowledge exists regarding the process, no therapeutic intervention is on offer that reliably decreases disease burden in AD patients. Computer modelling could serve as one of a number of tools to examine both the validity of reliable biomarkers and aid the discovery of successful intervention strategies. PMID:22748062

Aggregation protects flexible-shelled reptile eggs from severe hydric stress.

PubMed

Marco, Adolfo; Díaz-Paniagua, Carmen

2008-03-01

Many reptiles lay eggs with flexible shells that can progressively lose water until lethal dehydration under dry soil conditions. The number of eggs that develop together may influence the water exchange in the nest. We hypothesise that egg aggregation could reduce water lost under dry conditions. We exposed aggregated and isolated eggs to severe hydric stress followed by a period of rehydration. Hydric stress caused a general loss of water in common chameleon eggs. Initial egg mass did not affect survival but eggs that had lost more water had higher mortality and produced smaller hatchlings. Mass loss was higher and even lethal for isolated Chamaeleo chameleon eggs. However, aggregated eggs lost less water and most survived this period. After hydric stress, all surviving eggs gained mass via water absorption, and aggregation negatively affected water uptake. Isolated eggs hatched at smaller sizes than aggregated eggs. Aggregation also favoured hatching synchrony. Large clutches may favour hatching success of terrestrial flexible-shelled eggs incubated under severe drought conditions.

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease

PubMed Central

Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R.; Challa, Pavan Kumar; Cohen, Samuel I. A.; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2017-01-01

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer’s disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery. PMID:28011763

Programmed coherent coupling in a synthetic DNA-based excitonic circuit

NASA Astrophysics Data System (ADS)

Boulais, Étienne; Sawaya, Nicolas P. D.; Veneziano, Rémi; Andreoni, Alessio; Banal, James L.; Kondo, Toru; Mandal, Sarthak; Lin, Su; Schlau-Cohen, Gabriela S.; Woodbury, Neal W.; Yan, Hao; Aspuru-Guzik, Alán; Bathe, Mark

2018-02-01

Natural light-harvesting systems spatially organize densely packed chromophore aggregates using rigid protein scaffolds to achieve highly efficient, directed energy transfer. Here, we report a synthetic strategy using rigid DNA scaffolds to similarly program the spatial organization of densely packed, discrete clusters of cyanine dye aggregates with tunable absorption spectra and strongly coupled exciton dynamics present in natural light-harvesting systems. We first characterize the range of dye-aggregate sizes that can be templated spatially by A-tracts of B-form DNA while retaining coherent energy transfer. We then use structure-based modelling and quantum dynamics to guide the rational design of higher-order synthetic circuits consisting of multiple discrete dye aggregates within a DX-tile. These programmed circuits exhibit excitonic transport properties with prominent circular dichroism, superradiance, and fast delocalized exciton transfer, consistent with our quantum dynamics predictions. This bottom-up strategy offers a versatile approach to the rational design of strongly coupled excitonic circuits using spatially organized dye aggregates for use in coherent nanoscale energy transport, artificial light-harvesting, and nanophotonics.

Aggregate stability and water retention near saturation characteristics as affected by soil texture, aggregate size and polyacrylamide application

USDA-ARS?s Scientific Manuscript database

Understanding the effects of soil intrinsic properties and extrinsic conditions on aggregate stability is essential for the development of effective soil and water conservation practices. Our objective was to evaluate the combined role of soil texture, aggregate size and application of a stabilizing...

Thermal aggregation of glycated bovine serum albumin.

PubMed

Rondeau, Philippe; Navarra, Giovanna; Cacciabaudo, Francesco; Leone, Maurizio; Bourdon, Emmanuel; Militello, Valeria

2010-04-01

Aggregation and glycation processes in proteins have a particular interest in medicine fields and in food technology. Serum albumins are model proteins which are able to self-assembly in aggregates and also sensitive to a non-enzymatic glycation in cases of diabetes. In this work, we firstly reported a study on the glycation and oxidation effects on the structure of bovine serum albumin (BSA). The experimental approach is based on the study of conformational changes of BSA at secondary and tertiary structures by FTIR absorption and fluorescence spectroscopy, respectively. Secondly, we analysed the thermal aggregation process on BSA glycated with different glucose concentrations. Additional information on the aggregation kinetics are obtained by light scattering measurements. The results show that glycation process affects the native structure of BSA. Then, the partial unfolding of the tertiary structure which accompanies the aggregation process is similar both in native and glycated BSA. In particular, the formation of aggregates is progressively inhibited with growing concentration of glucose incubated with BSA. These results bring new insights on how aggregation process is affected by modification of BSA induced by glycation. Copyright 2009 Elsevier B.V. All rights reserved.

Injury Profile SIMulator, a Qualitative Aggregative Modelling Framework to Predict Crop Injury Profile as a Function of Cropping Practices, and the Abiotic and Biotic Environment. I. Conceptual Bases

PubMed Central

Aubertot, Jean-Noël; Robin, Marie-Hélène

2013-01-01

The limitation of damage caused by pests (plant pathogens, weeds, and animal pests) in any agricultural crop requires integrated management strategies. Although significant efforts have been made to i) develop, and to a lesser extent ii) combine genetic, biological, cultural, physical and chemical control methods in Integrated Pest Management (IPM) strategies (vertical integration), there is a need for tools to help manage Injury Profiles (horizontal integration). Farmers design cropping systems according to their goals, knowledge, cognition and perception of socio-economic and technological drivers as well as their physical, biological, and chemical environment. In return, a given cropping system, in a given production situation will exhibit a unique injury profile, defined as a dynamic vector of the main injuries affecting the crop. This simple description of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator), a modelling framework to predict injury profiles as a function of cropping practices, abiotic and biotic environment. Due to the tremendous complexity of agroecosystems, a simple holistic aggregative approach was chosen instead of attempting to couple detailed models. This paper describes the conceptual bases of IPSIM, an aggregative hierarchical framework and a method to help specify IPSIM for a given crop. A companion paper presents a proof of concept of the proposed approach for a single disease of a major crop (eyespot on wheat). In the future, IPSIM could be used as a tool to help design ex-ante IPM strategies at the field scale if coupled with a damage sub-model, and a multicriteria sub-model that assesses the social, environmental, and economic performances of simulated agroecosystems. In addition, IPSIM could also be used to help make diagnoses on commercial fields. It is important to point out that the presented concepts are not crop- or pest-specific and that IPSIM can be used on any crop. PMID:24019908

Injury Profile SIMulator, a qualitative aggregative modelling framework to predict crop injury profile as a function of cropping practices, and the abiotic and biotic environment. I. Conceptual bases.

PubMed

Aubertot, Jean-Noël; Robin, Marie-Hélène

2013-01-01

The limitation of damage caused by pests (plant pathogens, weeds, and animal pests) in any agricultural crop requires integrated management strategies. Although significant efforts have been made to i) develop, and to a lesser extent ii) combine genetic, biological, cultural, physical and chemical control methods in Integrated Pest Management (IPM) strategies (vertical integration), there is a need for tools to help manage Injury Profiles (horizontal integration). Farmers design cropping systems according to their goals, knowledge, cognition and perception of socio-economic and technological drivers as well as their physical, biological, and chemical environment. In return, a given cropping system, in a given production situation will exhibit a unique injury profile, defined as a dynamic vector of the main injuries affecting the crop. This simple description of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator), a modelling framework to predict injury profiles as a function of cropping practices, abiotic and biotic environment. Due to the tremendous complexity of agroecosystems, a simple holistic aggregative approach was chosen instead of attempting to couple detailed models. This paper describes the conceptual bases of IPSIM, an aggregative hierarchical framework and a method to help specify IPSIM for a given crop. A companion paper presents a proof of concept of the proposed approach for a single disease of a major crop (eyespot on wheat). In the future, IPSIM could be used as a tool to help design ex-ante IPM strategies at the field scale if coupled with a damage sub-model, and a multicriteria sub-model that assesses the social, environmental, and economic performances of simulated agroecosystems. In addition, IPSIM could also be used to help make diagnoses on commercial fields. It is important to point out that the presented concepts are not crop- or pest-specific and that IPSIM can be used on any crop.

A Protein Aggregation Based Test for Screening of the Agents Affecting Thermostability of Proteins

PubMed Central

Eronina, Tatyana; Borzova, Vera; Maloletkina, Olga; Kleymenov, Sergey; Asryants, Regina; Markossian, Kira; Kurganov, Boris

2011-01-01

To search for agents affecting thermal stability of proteins, a test based on the registration of protein aggregation in the regime of heating with a constant rate was used. The initial parts of the dependences of the light scattering intensity (I) on temperature (T) were analyzed using the following empiric equation: I = K agg(T−T 0)2, where K agg is the parameter characterizing the initial rate of aggregation and T 0 is a temperature at which the initial increase in the light scattering intensity is registered. The aggregation data are interpreted in the frame of the model assuming the formation of the start aggregates at the initial stages of the aggregation process. Parameter T 0 corresponds to the moment of the origination of the start aggregates. The applicability of the proposed approach was demonstrated on the examples of thermal aggregation of glycogen phosphorylase b from rabbit skeletal muscles and bovine liver glutamate dehydrogenase studied in the presence of agents of different chemical nature. The elaborated approach to the study of protein aggregation may be used for rapid identification of small molecules that interact with protein targets. PMID:21760963

Intracellular Biosynthesis of Fluorescent CdSe Quantum Dots in Bacillus subtilis: A Strategy to Construct Signaling Bacterial Probes for Visually Detecting Interaction Between Bacillus subtilis and Staphylococcus aureus.

PubMed

Yan, Zheng-Yu; Ai, Xiao-Xia; Su, Yi-Long; Liu, Xin-Ying; Shan, Xiao-Hui; Wu, Sheng-Mei

2016-02-01

In this work, fluorescent Bacillus subtilis (B. subtilis) cells were developed as probes for imaging applications and to explore behaviorial interaction between B. subtilis and Staphylococcus aureus (S. aureus). A novel biological strategy of coupling intracellular biochemical reactions for controllable biosynthesis of CdSe quantum dots by living B. subtilis cells was demonstrated, through which highly luminant and photostable fluorescent B. subtilis cells were achieved with good uniformity. With the help of the obtained fluorescent B. subtilis cells probes, S. aureus cells responded to co-cultured B. subtilis and to aggregate. The degree of aggregation was calculated and nonlinearly fitted to a polynomial model. Systematic investigations of their interactions implied that B. subtilis cells inhibit the growth of neighboring S. aureus cells, and this inhibition was affected by both the growth stage and the amount of surrounding B. subtilis cells. Compared to traditional methods of studying bacterial interaction between two species, such as solid culture medium colony observation and imaging mass spectrometry detection, the procedures were more simple, vivid, and photostable due to the efficient fluorescence intralabeling with less influence on the cells' surface, which might provide a new paradigm for future visualization of microbial behavior.

Using partial site aggregation to reduce bias in random utility travel cost models

NASA Astrophysics Data System (ADS)

Lupi, Frank; Feather, Peter M.

1998-12-01

We propose a "partial aggregation" strategy for defining the recreation sites that enter choice sets in random utility models. Under the proposal, the most popular sites and sites that will be the subject of policy analysis enter choice sets as individual sites while remaining sites are aggregated into groups of similar sites. The scheme balances the desire to include all potential substitute sites in the choice sets with practical data and modeling constraints. Unlike fully aggregate models, our analysis and empirical applications suggest that the partial aggregation approach reasonably approximates the results of a disaggregate model. The partial aggregation approach offers all of the data and computational advantages of models with aggregate sites but does not suffer from the same degree of bias as fully aggregate models.

AGGREGATION PATHWAYS OF THE AMYLOID β(1–42) PEPTIDE DEPEND ON ITS COLLOIDAL STABILITY AND ORDERED β-SHEET STACKING

PubMed Central

Jiang, Dianlu; Rauda, Iris; Han, Shubo; Chen, Shu; Zhou, Feimeng

2012-01-01

Amyloid β (Aβ) fibrils are present as a major component in senile plaques, the hallmark of Alzheimer’s disease (AD). Diffuse plaques (non-fibrous, loosely packed Aβ aggregates) containing amorphous Aβ aggregates are also formed in brain. This work examines the influence of Cu2+ complexation by Aβ on the aggregation process in the context of charge and structural variations. Changes in the surface charges of Aβ molecules due to Cu2+ binding, measured with a zeta potential measurement device, were correlated with the aggregate morphologies examined by atomic force microscopy. As a result of the charge variation, the “colloid-like” stability of the aggregation intermediates, which is essential to the fibrillation process, is affected. Consequently Cu2+ enhances the amorphous aggregate formation. By monitoring variations in the secondary structures with circular dichroism spectroscopy, a direct transformation from the unstructured conformation to the β-sheet structure was observed for all types of aggregates observed (oligomers, fibrils, and/or amorphous aggregates). Compared to the Aβ aggregation pathway in the absence of Cu2+ and taking other factors affecting Aβ aggregation (i.e., pH and temperature) into account, our investigation indicates that formations of amorphous and fibrous aggregates diverge from the same β-sheet-containing partially folded intermediate. This study suggests that the hydrophilic domain of Aβ also plays a role in the Aβ aggregation process. A kinetic model was proposed to account for the effects of the Cu2+ binding on these two aggregation pathways in terms of charge and structural variations. PMID:22870885

Stripping in hot mix asphalt produced by aggregates from construction and demolition waste.

PubMed

Pérez, I; Pasandín, A R; Gallego, J

2012-01-01

This paper analyses the effect of water on the durability of hot asphalt mixtures made with recycled aggregates from construction and demolition debris. Indirect tensile stress tests were carried out to evaluate stripping behaviour. The mixtures tested were fabricated with 0, 20, 40 and 60% recycled aggregates. Two types of natural aggregates were used: schist and calcite dolomite. An increase in the percentage of recycled aggregates was found to produce a decrease in the tensile stress ratio of the hot asphalt mixtures. To study this phenomenon, two and three factor analyses of variance (ANOVA) were performed with indirect tensile stress being used as the dependent variable. The factors studied were the percentage of recycled aggregates (0, 20, 40 and 60%), the moisture state (dry, wet) and the type of natural aggregate (schist, calcite). On the basis of the ANOVA results, it was found that the most important factor affecting resistance was the moisture state (dry, wet) of the specimens. The percentage of recycled aggregate also affected indirect tensile stress, especially in the dry state. The type of natural aggregate did not have a significant effect on indirect tensile stress. The hot asphalt mixture specimens made with different percentages of recycled aggregates from construction and demolition debris and of natural quarry aggregates showed poor stripping behaviour. This stripping behaviour can be related to both the poor adhesion of the recycled aggregates and the high absorption of the mortar of cement adhered to them.

Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

PubMed

Estrada, L D; Soto, C

2007-01-01

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

The evolution of the competition-dispersal trade-off affects α- and β-diversity in a heterogeneous metacommunity.

PubMed

Laroche, Fabien; Jarne, Philippe; Perrot, Thomas; Massol, Francois

2016-04-27

Difference in dispersal ability is a key driver of species coexistence in metacommunities. However, the available frameworks for interpreting species diversity patterns in natura often overlook trade-offs and evolutionary constraints associated with dispersal. Here, we build a metacommunity model accounting for dispersal evolution and a competition-dispersal trade-off. Depending on the distribution of carrying capacities among communities, species dispersal values are distributed either around a single strategy (evolutionarily stable strategy, ESS), or around distinct strategies (evolutionary branching, EB). We show that limited dispersal generates spatial aggregation of dispersal traits in ESS and EB scenarios, and that the competition-dispersal trade-off strengthens the pattern in the EB scenario. Importantly, individuals in larger (respectively (resp.) smaller) communities tend to harbour lower (resp. higher) dispersal, especially under the EB scenario. We explore how dispersal evolution affects species diversity patterns by comparing those from our model to the predictions of a neutral metacommunity model. The most marked difference is detected under EB, with distinctive values of both α- and β-diversity (e.g. the dissimilarity in species composition between small and large communities was significantly larger than neutral predictions). We conclude that, from an empirical perspective, jointly assessing community carrying capacity with species dispersal strategies should improve our understanding of diversity patterns in metacommunities. © 2016 The Author(s).

Characterization of Aggregation Propensity of a Human Fc-Fusion Protein Therapeutic by Hydrogen/Deuterium Exchange Mass Spectrometry

NASA Astrophysics Data System (ADS)

Huang, Richard Y.-C.; Iacob, Roxana E.; Krystek, Stanley R.; Jin, Mi; Wei, Hui; Tao, Li; Das, Tapan K.; Tymiak, Adrienne A.; Engen, John R.; Chen, Guodong

2017-05-01

Aggregation of protein therapeutics has long been a concern across different stages of manufacturing processes in the biopharmaceutical industry. It is often indicative of aberrant protein therapeutic higher-order structure. In this study, the aggregation propensity of a human Fc-fusion protein therapeutic was characterized. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was applied to examine the conformational dynamics of dimers collected from a bioreactor. HDX-MS data combined with spatial aggregation propensity calculations revealed a potential aggregation interface in the Fc domain. This study provides a general strategy for the characterization of the aggregation propensity of Fc-fusion proteins at the molecular level.

Phosphorylated α-Synuclein Accumulations and Lewy Body-like Pathology Distributed in Parkinson's Disease-Related Brain Areas of Aged Rhesus Monkeys Treated with MPTP.

PubMed

Huang, Baihui; Wu, Shihao; Wang, Zhengbo; Ge, Longjiao; Rizak, Joshua D; Wu, Jing; Li, Jiali; Xu, Lin; Lv, Longbao; Yin, Yong; Hu, Xintian; Li, Hao

2018-05-21

Phosphorylation of α-synuclein at serine 129 (P-Ser 129 α-syn) is involved in the pathogenesis of Parkinson's disease (PD) and Lewy body (LB) formation. However, there is no clear evidence indicates the quantitative relation of P-Ser 129 α-syn accumulation and dopaminergic cell loss, LBs pathology and the affected brain areas in PD monkeys. Here, pathological changes in the substantia nigra (SN) and PD-related brain areas were measured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) utilizing a modeling-recovery-remodeling strategy. Compared to age-matched controls, the MPTP-treated monkeys showed significantly reduced tyrosine hydroxylase (TH)-positive neurons and increased P-Ser 129 α-syn-positive aggregations in the SN. Double-labeling Immunofluorescence found some TH-positive neurons to be co-localized with P-Ser129 α-syn in the SN, suggesting the inverse correlation between P-Ser 129 α-syn aggregations and dopaminergic cell loss in the SN may represent an interactive association related to the progression of the PD symptoms in the model. P-Ser 129 α-syn aggregations or LB-like pathology was also found in the midbrain and the neocortex, specifically in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC) and in cells surrounding the third ventricle. Notably, the occipital cortex (OC) was P-Ser 129 α-syn negative. The findings of LB-like pathologies, dopaminergic cell loss and the stability of the PD symptoms in this model suggest that the modeling-recovery-remodeling strategy in aged monkeys may provide a new platform for biomedical investigations into the pathogenesis of PD and potential therapeutic development. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Regulating Molecular Aggregations of Polymers via Ternary Copolymerization Strategy for Efficient Solar Cells.

PubMed

Wang, Qian; Wang, Yingying; Zheng, Wei; Shahid, Bilal; Qiu, Meng; Wang, Di; Zhu, Dangqiang; Yang, Renqiang

2017-09-20

For many high-performance photovoltaic materials in polymer solar cells (PSCs), the active layers usually need to be spin-coated at high temperature due to the strong intermolecular aggregation of donor polymers, which is unfavorable in device repeatability and large-scale PSC printing. In this work, we adopted a ternary copolymerization strategy to regulate polymer solubility and molecular aggregation. A series of D-A 1 -D-A 2 random polymers based on different acceptors, strong electron-withdrawing unit ester substituted thieno[3,4-b]thiophene (TT-E), and highly planar dithiazole linked TT-E (DTzTT) were constructed to realize the regulation of molecular aggregation and simplification of device fabrication. The results showed that as the relative proportion of TT-E segment in the backbone increased, the absorption evidently red-shifted with a gradually decreased aggregation in solution, eventually leading to the active layers that can be fabricated at low temperature. Furthermore, due to the excellent phase separation and low recombination, the optimized solar cells based on the terpolymer P1 containing 30% of TT-E segment exhibit high power conversion efficiency (PCE) of 9.09% with a significantly enhanced fill factor up to 72.86%. Encouragingly, the photovoltaic performance is insensitive to the fabrication temperature of the active layer, and it still could maintain high PCE of 8.82%, even at room temperature. This work not only develops the highly efficient photovoltaic materials for low temperature processed PSCs through ternary copolymerization strategy but also preliminarily constructs the relationship between aggregation and photovoltaic performance.

Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling

PubMed Central

Chapman, Lloyd A. C.; Shipley, Rebecca J.; Whiteley, Jonathan P.; Ellis, Marianne J.; Byrne, Helen M.; Waters, Sarah L.

2014-01-01

The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges to (equivalent to to ) and to (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells. PMID:25157635

Microscopic analysis of protein oxidative damage: effect of carbonylation on structure, dynamics, and aggregability of villin headpiece.

PubMed

Petrov, Drazen; Zagrovic, Bojan

2011-05-11

One of the most important irreversible oxidative modifications of proteins is carbonylation, the process of introducing a carbonyl group in reaction with reactive oxygen species. Notably, carbonylation increases with the age of cells and is associated with the formation of intracellular protein aggregates and the pathogenesis of age-related disorders such as neurodegenerative diseases and cancer. However, it is still largely unclear how carbonylation affects protein structure, dynamics, and aggregability at the atomic level. Here, we use classical molecular dynamics simulations to study structure and dynamics of the carbonylated headpiece domain of villin, a key actin-organizing protein. We perform an exhaustive set of molecular dynamics simulations of a native villin headpiece together with every possible combination of carbonylated versions of its seven lysine, arginine, and proline residues, quantitatively the most important carbonylable amino acids. Surprisingly, our results suggest that high levels of carbonylation, far above those associated with cell death in vivo, may be required to destabilize and unfold protein structure through the disruption of specific stabilizing elements, such as salt bridges or proline kinks, or tampering with the hydrophobic effect. On the other hand, by using thermodynamic integration and molecular hydrophobicity potential approaches, we quantitatively show that carbonylation of hydrophilic lysine and arginine residues is equivalent to introducing hydrophobic, charge-neutral mutations in their place, and, by comparison with experimental results, we demonstrate that this by itself significantly increases the intrinsic aggregation propensity of both structured, native proteins and their unfolded states. Finally, our results provide a foundation for a novel experimental strategy to study the effects of carbonylation on protein structure, dynamics, and aggregability using site-directed mutagenesis. © 2011 American Chemical Society

Effect of cocoa products and flavanols on platelet aggregation in humans: a systematic review.

PubMed

Peluso, Ilaria; Palmery, Maura; Serafini, Mauro

2015-07-01

Previous evidence suggested an active role of cocoa products and flavanols in modulating platelet aggregation. However, cocoa flavanols are characterized by a low bioavailability that can deeply affect their presence in biological fluids and raise questions on their biological effect in humans. We performed a systematic search on Medline, Embase, Cochrane and ProQuest databases, until April 2015, on the effect of cocoa products on platelet aggregation in human intervention studies. We identified 13 interventions, of which only five involved repeated administration. Different effects were observed on the basis of the platelet aggregation test used, whereas neither a longer duration of treatment nor a higher dose was associated with a higher inhibition of platelet aggregation. In conclusion, the reviewed results suggest that consumption of cocoa products in bolus administration positively affects platelet aggregation in both healthy subjects and diseased patients. On the other hand, more evidence is required in order to assess the effect of long-term cocoa product ingestion and to identify the bioactive components involved.

Effect of antimicrobial preservatives on partial protein unfolding and aggregation†

PubMed Central

Hutchings, Regina L.; Singh, Surinder M.; Cabello-Villegas, Javier; Mallela, Krishna M. G.

2014-01-01

One-third of protein formulations are multi-dose. These require antimicrobial preservatives (APs); however, some APs have been shown to cause protein aggregation. Our previous work on a model protein cytochrome c indicated that partial protein unfolding, rather than complete unfolding, triggers aggregation. Here, we examined the relative strength of five commonly used APs on such unfolding and aggregation, and explored whether stabilizing the aggregation “hot-spot” reduces such aggregation. All APs induced protein aggregation in the order m-cresol > phenol > benzyl alcohol > phenoxyethanol > chlorobutanol. All these enhanced the partial protein unfolding that includes a local region which was predicted to be the aggregation “hot-spot”. The extent of destabilization correlated with the extent of aggregation. Further, we show that stabilizing the “hot-spot” reduces aggregation induced by all five APs. These results indicate that m-cresol causes the most protein aggregation, whereas chlorobutanol causes the least protein aggregation. The same protein region acts as the “hot-spot” for aggregation induced by different APs, implying that developing strategies to prevent protein aggregation induced by one AP will also work for others. PMID:23169345

7 CFR 51.1564 - External defects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... than 50 percent of the surface in the aggregate. Growth Cracks When the growth crack(s) affects more... Table V.) When the growth crack(s) affects more than 3/4 the length of the potato in the aggregate or.... Second Growth When materially detracting from the appearance of the potato When seriously detracting from...

7 CFR 51.1564 - External defects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... than 50 percent of the surface in the aggregate. Growth Cracks When the growth crack(s) affects more... Table V.) When the growth crack(s) affects more than 3/4 the length of the potato in the aggregate or.... Second Growth When materially detracting from the appearance of the potato When seriously detracting from...

7 CFR 51.1414 - Serious damage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... as serious damage: (a) Adhering hull material or dark stains affecting an aggregate of more than 20...) Decay affecting any portion of the kernel; (g) Insect injury when the insect, web or frass is present... than three dark spots on either half of the kernel, or when any spot or the aggregate of two or more...

7 CFR 51.1414 - Serious damage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... as serious damage: (a) Adhering hull material or dark stains affecting an aggregate of more than 20...) Decay affecting any portion of the kernel; (g) Insect injury when the insect, web or frass is present... than three dark spots on either half of the kernel, or when any spot or the aggregate of two or more...

7 CFR 51.1414 - Serious damage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... as serious damage: (a) Adhering hull material or dark stains affecting an aggregate of more than 20...) Decay affecting any portion of the kernel; (g) Insect injury when the insect, web or frass is present... than three dark spots on either half of the kernel, or when any spot or the aggregate of two or more...

How insurance affects altruistic provision in threshold public goods games.

PubMed

Zhang, Jianlei; Zhang, Chunyan; Cao, Ming

2015-03-13

The occurrence and maintenance of cooperative behaviors in public goods systems have attracted great research attention across multiple disciplines. A threshold public goods game requires a minimum amount of contributions to be collected from a group of individuals for provision to occur. Here we extend the common binary-strategy combination of cooperation and defection by adding a third strategy, called insured cooperation, which corresponds to buying an insurance covering the potential loss resulted from the unsuccessful public goods game. Particularly, only the contributing agents can opt to be insured, which is an effort decreasing the amount of the potential loss occurring. Theoretical computations suggest that when agents face the potential aggregate risk in threshold public goods games, more contributions occur with increasing compensation from insurance. Moreover, permitting the adoption of insurance significantly enhances individual contributions and facilitates provision, especially when the required threshold is high. This work also relates the strategy competition outcomes to different allocation rules once the resulted contributions exceed the threshold point in populations nested within a dilemma.

Erythrocyte deformability and aggregation responses to intermittent and continuous artificial gravity exposure

NASA Astrophysics Data System (ADS)

Marijke, Grau; Vera, Abeln; Tobias, Vogt; Wilhelm, Bloch; Stefan, Schneider

2017-02-01

Artificial gravity protocols are used to improve g-tolerance of aviators and discussed as countermeasure during prolonged space flight. Little is known about the impact of artificial gravity on the red blood cells (RBC). The purpose of the study was to test how artificial gravity affects RBC deformability and aggregation, which are important determinants of microcirculation. Nine male subjects were exposed to two hypergravity protocols using a short arm human centrifuge: a continuous (CONT) protocol with constant +2 Gz for 30 min and an intermittent (INTER) protocol with repeated intervals of +2 Gz and rest. Blood was sampled pre and post interventions to measure basal blood parameters, RBC nitrite, RBC deformability, aggregation, and to determine the shear rate balancing aggregation and disaggregation (γ at dIsc min). To test for orthostasis effects, five male subjects were asked to stay for 46 min, corresponding to the length of the centrifuge protocols, with blood sampling pre and post intervention. Artificial gravity programs did not affect basal blood parameters or RBC nitrite levels; a marker for RBC deformability influencing nitric oxide. The INTER program did not affect any of the tested parameters. The CONT program did not remarkably affect RBC deformability or γ at dIsc min but significantly aggravated aggregation. Orthostasis effects were thus excluded. The results indicate that continuous artificial gravity, especially with higher g-forces applied, may negatively affect the RBC system and that for a prolonged space flight intermittent but not continuous artificial gravity might represent an appropriate countermeasure.

Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans

PubMed Central

Bendesky, Andres; Pitts, Jason; Rockman, Matthew V.; Chen, William C.; Tan, Man-Wah; Kruglyak, Leonid; Bargmann, Cornelia I.

2012-01-01

Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%–8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation. PMID:23284308

Inhalation of Whole Diesel Exhaust but not Gas-Phase Components Affects In Vitro Platelet Aggregation in Hypertensive Rats

EPA Science Inventory

Rationale: Intravascular thrombosis and platelet aggregation are enhanced following exposure to diesel exhaust (DE) and other respirable particulate matter; however, the roles of endothelial and circulating mediators on platelet aggregation remain unclear. We hypothesized that ad...

Aggregate Stability of Tropical Soils Under Long-Term Eucalyptus Cultivation

USDA-ARS?s Scientific Manuscript database

Eucalyptus cultivation has increased in all Brazilian regions. Despite the large amount of cultivated area, little is known about how this kind of management system affects soil properties, mainly the aggregate stability. Aggregate stability analyses have proved to be a sensitive tool to measure soi...

Ralstonia insidiosa induces cell aggregation by Listeria monocytogenes

USDA-ARS?s Scientific Manuscript database

Biofilm formation is an important strategy for foodborne bacterial pathogens to survive in stressful environments such as fresh produce processing facilities. Bacterial cell aggregation strongly promotes the initiation of microcolonies and the formation of biofilms on abiological surfaces. We previ...

Aggregates from natural and recycled sources; economic assessments for construction applications; a materials flow study

USGS Publications Warehouse

Wilburn, David R.; Goonan, Thomas G.

1998-01-01

Increased amounts of recycled materials are being used to supplement natural aggregates (derived from crushed stone, sand and gravel) in road construction. An understanding of the economics and factors affecting the level of aggregates recycling is useful in estimating the potential for recycling and in assessing the total supply picture of aggregates. This investigation includes a descriptive analysis of the supply sources, technology, costs, incentives, deterrents, and market relationships associated with the production of aggregates.

Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability

NASA Astrophysics Data System (ADS)

Camilloni, Carlo; Sala, Benedetta Maria; Sormanni, Pietro; Porcari, Riccardo; Corazza, Alessandra; De Rosa, Matteo; Zanini, Stefano; Barbiroli, Alberto; Esposito, Gennaro; Bolognesi, Martino; Bellotti, Vittorio; Vendruscolo, Michele; Ricagno, Stefano

2016-05-01

A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed β2m variants that alter the aggregation-prone exposed surface of wild-type and W60G β2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in β2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.

Liquid crystals from mesogens containing gold nanoparticles

NASA Astrophysics Data System (ADS)

Lewandowski, Wiktor; Gorecka, Ewa

Long-range ordered structures made of nanoparticles are perspective materials for future optical, electronic and sensing technologies. Conspicuous physicochemical features of nanoparticle aggregates originate from distant-dependent collective interactions, therefore lately a lot of attention was put to the development of assembly strategies allowing control over nanoparticle spatial distribution. In this chapter we will focus on the assembly process based on using thermotropic liquid-crystalline molecules as surface nanoparticle ligands. First, we discuss architectural parameters that inuence structure and thermal properties of the aggregates. Then, we show that this approach enables formation of assemblies with metamaterial characteristic, gives access to dynamic materials with light-, magneto- and thermo-responsive behavior and allows formation of aggregates with unique structures, which all make this strategy an attractive object of research.

Soils are sensitive reactors - do we need a paradigm change towards a more sustainable soil use?

NASA Astrophysics Data System (ADS)

Horn, Rainer; Holthusen, Dörthe

2015-04-01

The aim of the lecture is to clarify the effect of soil management and the consequences of physical degradation on processes like soil aggregation and changes in the accessibility and functionality of structured soils. If due to soil management strategies the internal soil strength will be exceeded by external stresses applied not only the available pore space is reduced while the solid mass is increased but especially the pore continuity and the accessibility of exchange places for nutrients or heavy metals are altered. In addition, the root distribution in soils becomes not only reduced but also unevenly distributed which again hinders the possibility to evenly uptake plant available water and nutrient out of the pores. The applied stresses also create an anisotropic arrangement of the pores and their functions and also result in a more pronounced lateral mass transport by surface runoff including soil erosion by water and wind. Thus, also the water balance on all scales (from the pedon to the catchment) shows an increased water loss by evaporation and surface water while the groundwater recharge and the transpiration rates are reduced. If we analyze the scale dependency of nutrient adsorption and desorption phenomena it has to be stated, that the accessibility of exchange places within soil aggregates are the better the more structured and the more rigid these aggregates are, while with increasing mechanical stress applied aggregates are deformed and as a consequences they become less porous with a severe differentiation between the outer and the inner part of the aggregate volume. On the bulk soil scale, we can analyze the platy structure as a visible hint for anthropogenic soil degradation which affects amongst others also the ion exchange processes. Furthermore an uneven aeration within such degraded soils results in a very pronounced anoxia on all scales (from the aggregate to the hectare scale) which can be quantified not only by corresponding measurements of the spatial distribution of redox potential values. In recent studies under "normal" wheeling conditions in arable fields and also in harvested forest sites it was proofed that Eh values close to 0 mV or even a methane emission have to be expected (with consequences for the global warming). Finally anoxic conditions also affect the redox induced mobilization of Fe and Mn which even results in a more rapid soil development with consequences also for yield and further soil functions. Consequently a shift to a more sustainable landuse or soil management strategy is urgently requested in order to prevent a further soil degradation. The scenario of peak soil must and can be prevented by a more site specific soil management. In the lecture, these effects will be discussed as well as a soil protection guide line (based on the German soil protection law) will be presented in order to prevent further irreversible soil degradation phenomena. Keywords: mechanical strength, mechanical stress and strain effects soil degradation, pore functions, ad-/desorption processes, redox potential, anoxia;, global change

Entrapment of Aβ1-40 peptide in unstructured aggregates

NASA Astrophysics Data System (ADS)

Corsale, C.; Carrotta, R.; Mangione, M. R.; Vilasi, S.; Provenzano, A.; Cavallaro, G.; Bulone, D.; San Biagio, P. L.

2012-06-01

Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggregates. They appear stable or at least metastable with respect to fiber growth, therefore appearing as an incidental product in the pathway of fibrillogenesis.

Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane

PubMed Central

Zhang, Liang; Trushin, Sergey; Christensen, Trace A.; Tripathi, Utkarsh; Hong, Courtney; Geroux, Rachel E.; Howell, Kyle G.; Poduslo, Joseph F.; Trushina, Eugenia

2018-01-01

Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer’s Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a valid therapeutic target. Moreover, while some investigations identify Aβ oligomers as the culprit of trafficking inhibition, others propose that fibrils play the detrimental role. We have examined the effect of a panel of Aβ peptides with different mutations found in familial AD on mitochondrial motility in primary cortical mouse neurons. Peptides with higher propensity to aggregate inhibit mitochondrial trafficking to a greater extent with fibrils inducing the strongest inhibition. Binding of Aβ peptides to the plasma membrane was sufficient to induce trafficking inhibition where peptides with reduced plasma membrane binding and internalization had lesser effect on mitochondrial motility. We also found that Aβ peptide with Icelandic mutation A673T affects axonal trafficking of mitochondria but has very low rates of plasma membrane binding and internalization in neurons, which could explain its relatively low toxicity. Inhibition of mitochondrial dynamics caused by Aβ peptides or fibrils did not instantly affect mitochondrial bioenergetic and function. Our results support a mechanism where inhibition of axonal trafficking is initiated at the plasma membrane by soluble low molecular weight Aβ species and is exacerbated by fibrils. Since trafficking inhibition does not coincide with the loss of mitochondrial function, restoration of axonal transport could be beneficial at early stages of AD progression. However, strategies designed to block Aβ aggregation or fibril formation alone without ensuring the efficient clearance of soluble Aβ may not be sufficient to alleviate the trafficking phenotype. PMID:29477640

Plasmonic colorimetric sensors based on etching and growth of noble metal nanoparticles: Strategies and applications.

PubMed

Zhang, Zhiyang; Wang, Han; Chen, Zhaopeng; Wang, Xiaoyan; Choo, Jaebum; Chen, Lingxin

2018-08-30

Plasmonic colorimetric sensors have emerged as a powerful tool in chemical and biological sensing applications due to the localized surface plasmon resonance (LSPR) extinction in the visible range. Among the plasmonic sensors, the most famous sensing mode is the "aggregation" plasmonic colorimetric sensor which is based on plasmon coupling due to nanoparticle aggregation. Herein, this review focuses on the newly-developing plasmonic colorimetric sensing mode - the etching or the growth of metal nanoparticles induces plasmon changes, namely, "non-aggregation" plasmonic colorimetric sensor. This type of sensors has attracted increasing interest because of their exciting properties of high sensitivity, multi-color changes, and applicability to make a test strip. Of particular interest, the test strip by immobilization of nanoparticles on the substrate can avoid the influence of nanoparticle auto-aggregation and increase the simplicity in storage and use. Although there are many excellent reviews available that describe the advance of plasmonic sensors, limited attention has been paid to the plasmonic colorimetric sensors based on etching or growth of metal nanoparticles. This review highlights recent progress on strategies and application of "non-aggregation" plasmonic colorimetric sensors. We also provide some personal insights into current challenges associated with "non-aggregation" plasmonic colorimetric sensors and propose future research directions. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost-Aware Design of a Discrimination Strategy for Unexploded Ordnance Cleanup

DTIC Science & Technology

2011-02-25

Acronyms ANN: Artificial Neural Network AUC: Area Under the Curve BRAC: Base Realignment And Closure DLRT: Distance Likelihood Ratio Test EER...Discriminative Aggregate Nonparametric [25] Artificial Neural Network ANN Discriminative Aggregate Parametric [33] 11 Results and Discussion Task #1

Multi-criteria, personalized route planning using quantifier-guided ordered weighted averaging operators

NASA Astrophysics Data System (ADS)

Nadi, S.; Delavar, M. R.

2011-06-01

This paper presents a generic model for using different decision strategies in multi-criteria, personalized route planning. Some researchers have considered user preferences in navigation systems. However, these prior studies typically employed a high tradeoff decision strategy, which used a weighted linear aggregation rule, and neglected other decision strategies. The proposed model integrates a pairwise comparison method and quantifier-guided ordered weighted averaging (OWA) aggregation operators to form a personalized route planning method that incorporates different decision strategies. The model can be used to calculate the impedance of each link regarding user preferences in terms of the route criteria, criteria importance and the selected decision strategy. Regarding the decision strategy, the calculated impedance lies between aggregations that use a logical "and" (which requires all the criteria to be satisfied) and a logical "or" (which requires at least one criterion to be satisfied). The calculated impedance also includes taking the average of the criteria scores. The model results in multiple alternative routes, which apply different decision strategies and provide users with the flexibility to select one of them en-route based on the real world situation. The model also defines the robust personalized route under different decision strategies. The influence of different decision strategies on the results are investigated in an illustrative example. This model is implemented in a web-based geographical information system (GIS) for Isfahan in Iran and verified in a tourist routing scenario. The results demonstrated, in real world situations, the validity of the route planning carried out in the model.

Implication of alcohol consumption on aggregate wellbeing.

PubMed

Parackal, Mathew; Parackal, Sherly

2017-07-01

The effects of drinking alcohol extend beyond the individuals concerned to the wider community. While there is recognition of such a global implication, currently no study has quantified the impact of alcohol consumption on aggregate wellbeing. This study aims to address this gap and attempts to investigate the impact of various levels of alcohol consumption on aggregate happiness. The study was carried out on a random selection of participants ( n = 1,817) drawn from the 3Di consumer panel, comprising over 170,000 New Zealanders aged 18 and above. Using a subjective happiness scale (SHS) in conjunction with the Alcohol Use Disorders Identification Test (AUDIT), investigation was carried out to find whether drinking behaviour affected aggregate happiness. SHS and AUDIT scores were negatively correlated and the strength of the correlation increased with the intensity of problematic drinking. Regression analysis showed that the beta coefficient was positive for the low-risk (.074) and negative for the high-risk (-.081) category, suggesting approaches to intervene with the growing problem of alcohol consumption in modern societies. Measurements of happiness can explain the global implication of alcohol in wellbeing terms. The findings of this study indicated that low-risk drinkers affected aggregate happiness positively, whereas high-risk drinkers affected aggregate happiness negatively. While the latter observation is not new, the former raises the need to promote moderation in drinking alcohol for the common good of everyone.

The Properties of Mortar Mixtures Blended with Natural, Crushed, and Recycled Fine Aggregates for Building Construction Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Myoung-Youl; Lee, Jae-Yong; Chung, Chul-Woo

2012-01-12

In this research, the possible applicability of fine aggregates blended with natural, crushed, and recycled fine aggregate are discussed. The fresh and hardened properties of mortar using blended fine aggregates are monitored depending on various blending ratio of fine aggregates. Newly developed ternary diagram was also utilized for better interpretation of the data. It was found that air content increased and unit weight decreased as recycled fine aggregate content increased. With moisture type processing of recycled fine aggregate, the mortar flow was not negatively affected by increase in the recycled fine aggregate content. The ternary diagram is found to bemore » an effective graphical presentation tool that can be used for the quality evaluation of mortar using blended fine aggregate.« less

Heating of Porous Icy Dust Aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirono, Sin-iti

At the beginning of planetary formation, highly porous dust aggregates are formed through coagulation of dust grains. Outside the snowline, the main component of an aggregate is H{sub 2}O ice. Because H{sub 2}O ice is formed in amorphous form, its thermal conductivity is extremely small. Therefore, the thermal conductivity of an icy dust aggregate is low. There is a possibility of heating inside an aggregate owing to the decay of radionuclides. It is shown that the temperature increases substantially inside an aggregate, leading to crystallization of amorphous ice. During the crystallization, the temperature further increases sufficiently to continue sintering. Themore » mechanical properties of icy dust aggregates change, and the collisional evolution of dust aggregates is affected by the sintering.« less

Structure-activity relationships of β-hairpin mimics as modulators of amyloid β-peptide aggregation.

PubMed

Tonali, Nicolo; Kaffy, Julia; Soulier, Jean-Louis; Gelmi, Maria Luisa; Erba, Emanuela; Taverna, Myriam; van Heijenoort, Carine; Ha-Duong, Tap; Ongeri, Sandrine

2018-05-18

Aggregation of amyloid proteins is currently involved in more than 20 serious human diseases that are actually untreated, such as Alzheimer's disease (AD). Despite many efforts made to target the amyloid cascade in AD, finding an aggregation inhibiting compound and especially modulating early oligomerization remains a relevant and challenging strategy. We report herein the first examples of small and non-peptide mimics of acyclic beta-hairpins, showing an ability to delay the fibrillization of amyloid-β (Aβ 1-42 ) peptide and deeply modify its early oligomerization process. Modifications providing better druggability properties such as increased hydrophilicity and reduced peptidic character were performed. We also demonstrate that an appropriate balance between flexibility and stability of the β-hairpin must be reached to adapt to the different shape of the various aggregated forms of the amyloid peptide. This strategy can be investigated to target other challenging amyloid proteins. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Surface tension driven aggregation of organic nanowires via lab in a droplet.

PubMed

Gu, Jianmin; Yin, Baipeng; Fu, Shaoyan; Feng, Man; Zhang, Ziming; Dong, Haiyun; Gao, Faming; Zhao, Yong Sheng

2018-06-05

Directing the architecture of complex organic nanostructures is desirable and still remains a challenge in areas of materials science due to their structure-dependent collective optoelectronic properties. Herein, we demonstrate a simple and versatile solution strategy that allows surface tension to drive low-dimensional nanostructures to aggregate into complex structures via a lab in a droplet technique. By selecting a suitable combination of a solvent and an anti-solvent with controllable surface tension difference, the droplets can be automatically cracked into micro-droplets, which provides an aggregation force directed toward the centre of the droplet to drive the low-dimensional building blocks to form the special aggregations during the self-assembly process. This synthetic strategy has been shown to be universal for organic materials, which is beneficial for further optimizing the optoelectronic properties. These results contribute to gaining an insightful understanding on the detailed growth mechanism of complex organic nanostructures and greatly promoting the development of organic nanophotonics.

Effect of aggregate graining compositions on skid resistance of Exposed Aggregate Concrete pavement

NASA Astrophysics Data System (ADS)

Wasilewska, Marta; Gardziejczyk, Wladysław; Gierasimiuk, Pawel

2018-05-01

The paper presents the evaluation of skid resistance of EAC (Exposed Aggregate Concrete) pavements which differ in aggregate graining compositions. The tests were carried out on concrete mixes with a maximum aggregate size of 8 mm. Three types of coarse aggregates were selected depending on their resistance to polishing which was determined on the basis of the PSV (Polished Stone Value). Basalt (PSV 48), gabbro (PSV 50) and trachybasalt (PSV 52) aggregates were chosen. For each type of aggregate three graining compositions were designed, which differed in the content of coarse aggregate > 4mm. Their content for each series was as follows: A - 38%, B - 50% and C - 68%. Evaluation of the skid resistance has been performed using the FAP (Friction After Polishing) test equipment also known as the Wehner/Schulze machine. Laboratory method enables to compare the skid resistance of different types of wearing course under specified conditions simulating polishing processes. In addition, macrotexture measurements were made on the surface of each specimen using the Elatexure laser profile. Analysis of variance showed that at significance level α = 0.05, aggregate graining compositions as well as the PSV have a significant influence on the obtained values of the friction coefficient μm of the tested EAC pavements. The highest values of the μm have been obtained for EAC with the lowest amount of coarse aggregates (compositions A). In these cases the resistance to polishing of the aggregate does not significantly affect the friction coefficients. This is related to the large areas of cement mortar between the exposed coarse grains. Based on the analysis of microscope images, it was observed that the coarse aggregates were not sufficiently exposed. It has been proved that PSV significantly affected the coefficient of friction in the case of compositions B and C. This is caused by large areas of exposed coarse aggregate. The best parameters were achieved for the EAC pavements with graining composition B and C and trachybasalt aggregate.

A Two-Dimensional Numerical Investigation of Transport of Malaria-Infected Red Blood Cells in Stenotic Microchannels

PubMed Central

Tao, Yong; Rongin, Uwitije; Xing, Zhongwen

2016-01-01

The malaria-infected red blood cells experience a significant decrease in cell deformability and increase in cell membrane adhesion. Blood hemodynamics in microvessels is significantly affected by the alteration of the mechanical property as well as the aggregation of parasitized red blood cells. In this study, we aim to numerically study the connection between cell-level mechanobiological properties of human red blood cells and related malaria disease state by investigating the transport of multiple red blood cell aggregates passing through microchannels with symmetric stenosis. Effects of stenosis magnitude, aggregation strength, and cell deformability on cell rheology and flow characteristics were studied by a two-dimensional model using the fictitious domain-immersed boundary method. The results indicated that the motion and dissociation of red blood cell aggregates were influenced by these factors and the flow resistance increases with the increase of aggregating strength and cell stiffness. Further, the roughness of the velocity profile was enhanced by cell aggregation, which considerably affected the blood flow characteristics. The study may assist us in understanding cellular-level mechanisms in disease development. PMID:28105411

On Market-Based Coordination of Thermostatically Controlled Loads With User Preference

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Sen; Zhang, Wei; Lian, Jianming

2014-12-15

This paper presents a market-based control framework to coordinate a group of autonomous Thermostatically Controlled Loads (TCL) to achieve the system-level objectives with pricing incentives. The problem is formulated as maximizing the social welfare subject to feeder power constraint. It allows the coordinator to affect the aggregated power of a group of dynamical systems, and creates an interactive market where the users and the coordinator cooperatively determine the optimal energy allocation and energy price. The optimal pricing strategy is derived, which maximizes social welfare while respecting the feeder power constraint. The bidding strategy is also designed to compute the optimalmore » price in real time (e.g., every 5 minutes) based on local device information. The coordination framework is validated with realistic simulations in GridLab-D. Extensive simulation results demonstrate that the proposed approach effectively maximizes the social welfare and decreases power congestion at key times.« less

Protein aggregation and misfolding: good or evil?

NASA Astrophysics Data System (ADS)

Pastore, Annalisa; Temussi, Pierandrea

2012-06-01

Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open.

Protein aggregation and misfolding: good or evil?

PubMed

Pastore, Annalisa; Temussi, Pierandrea

2012-06-20

Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open.

Game Design and Analysis for Price-Based Demand Response: An Aggregate Game Approach.

PubMed

Ye, Maojiao; Hu, Guoqiang

2016-02-18

In this paper, an aggregate game is adopted for the modeling and analysis of energy consumption control in smart grid. Since the electricity users' cost functions depend on the aggregate energy consumption, which is unknown to the end users, an average consensus protocol is employed to estimate it. By neighboring communication among the users about their estimations on the aggregate energy consumption, Nash seeking strategies are developed. Convergence properties are explored for the proposed Nash seeking strategies. For energy consumption game that may have multiple isolated Nash equilibria, a local convergence result is derived. The convergence is established by utilizing singular perturbation analysis and Lyapunov stability analysis. Energy consumption control for a network of heating, ventilation, and air conditioning systems is investigated. Based on the uniqueness of the Nash equilibrium, it is shown that the players' actions converge to a neighborhood of the unique Nash equilibrium nonlocally. More specially, if the unique Nash equilibrium is an inner Nash equilibrium, an exponential convergence result is obtained. Energy consumption game with stubborn players is studied. In this case, the actions of the rational players can be driven to a neighborhood of their best response strategies by using the proposed method. Numerical examples are presented to verify the effectiveness of the proposed methods.

Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity.

PubMed

Oliveri, Valentina; Zimbone, Stefania; Giuffrida, Maria Laura; Bellia, Francesco; Tomasello, Marianna Flora; Vecchio, Graziella

2018-04-25

Although fibrillar amyloid beta peptide (Aβ) aggregates are one of the major hallmarks of Alzheimer's disease, increasing evidence suggests that soluble Aβ oligomers are the primary toxic species. Targeting the oligomeric species could represent an effective strategy to interfere with Aβ toxicity. In this work, the biological properties of 5[4-(6-O-β-cyclodextrin)-phenyl],10,15,20-tri(4-hydroxyphenyl)-porphyrin and its zinc complex were tested, as new molecules that interact with Aβ and effectively prevent its cytotoxicity. We found that these systems can cross the cell membrane to deliver Aβ intracellularly and promote its clearance. Our results provide evidence for the use of cyclodextrin-porphyrin derivatives as a promising strategy to target amyloid aggregation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of field variables on infield biomass bales aggregation strategies

USDA-ARS?s Scientific Manuscript database

Infield aggregation of bales, an essential logistics operation of clearing the field for subsequent cropping, is influenced by several field variables, such as field shape, area, randomness on bale layout, biomass yield per unit area, bale row spacing, number of bales handled simultaneously, collect...

Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab.

PubMed

Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

2016-01-01

The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions.

Activity-driven changes in the mechanical properties of fire ant aggregations

NASA Astrophysics Data System (ADS)

Tennenbaum, Michael; Fernandez-Nieves, Alberto

2017-11-01

Fire ant aggregations are active materials composed of individual constituents that are able to transform internal energy into work. We find using rheology and direct visualization that the aggregation undergoes activity cycles that affect the mechanical properties of the system. When the activity is high, the aggregation approximately equally stores and dissipates energy, it is more homogeneous, and exerts a high outward force. When the activity is low, the aggregation is predominantly elastic, it is more heterogeneous, and it exerts a small outward force. We rationalize our results using a simple kinetic model where the number of active ants within the aggregation is the essential quantity.

Privacy-Enhanced and Multifunctional Health Data Aggregation under Differential Privacy Guarantees

PubMed Central

Ren, Hao; Li, Hongwei; Liang, Xiaohui; He, Shibo; Dai, Yuanshun; Zhao, Lian

2016-01-01

With the rapid growth of the health data scale, the limited storage and computation resources of wireless body area sensor networks (WBANs) is becoming a barrier to their development. Therefore, outsourcing the encrypted health data to the cloud has been an appealing strategy. However, date aggregation will become difficult. Some recently-proposed schemes try to address this problem. However, there are still some functions and privacy issues that are not discussed. In this paper, we propose a privacy-enhanced and multifunctional health data aggregation scheme (PMHA-DP) under differential privacy. Specifically, we achieve a new aggregation function, weighted average (WAAS), and design a privacy-enhanced aggregation scheme (PAAS) to protect the aggregated data from cloud servers. Besides, a histogram aggregation scheme with high accuracy is proposed. PMHA-DP supports fault tolerance while preserving data privacy. The performance evaluation shows that the proposal leads to less communication overhead than the existing one. PMID:27626417

Privacy-Enhanced and Multifunctional Health Data Aggregation under Differential Privacy Guarantees.

PubMed

Ren, Hao; Li, Hongwei; Liang, Xiaohui; He, Shibo; Dai, Yuanshun; Zhao, Lian

2016-09-10

With the rapid growth of the health data scale, the limited storage and computation resources of wireless body area sensor networks (WBANs) is becoming a barrier to their development. Therefore, outsourcing the encrypted health data to the cloud has been an appealing strategy. However, date aggregation will become difficult. Some recently-proposed schemes try to address this problem. However, there are still some functions and privacy issues that are not discussed. In this paper, we propose a privacy-enhanced and multifunctional health data aggregation scheme (PMHA-DP) under differential privacy. Specifically, we achieve a new aggregation function, weighted average (WAAS), and design a privacy-enhanced aggregation scheme (PAAS) to protect the aggregated data from cloud servers. Besides, a histogram aggregation scheme with high accuracy is proposed. PMHA-DP supports fault tolerance while preserving data privacy. The performance evaluation shows that the proposal leads to less communication overhead than the existing one.

Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

PubMed Central

2012-01-01

Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine. Result Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA), weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4- and pdiA-) and colony size (smlA- and ctnA-) and restore their parental aggregate size. Conclusion Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size. Our data strongly suggests that cytosolic glucose and extracellular cAMP levels are the other major determinants regulating aggregate size and pattern. Importantly, the aggregation process is conserved among different lineages of cellular slime molds despite using unrelated signalling molecules for aggregation. PMID:22269093

Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds.

PubMed

Jaiswal, Pundrik; Soldati, Thierry; Thewes, Sascha; Baskar, Ramamurthy

2012-01-23

Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine. Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA), weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4- and pdiA-) and colony size (smlA- and ctnA-) and restore their parental aggregate size. Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size. Our data strongly suggests that cytosolic glucose and extracellular cAMP levels are the other major determinants regulating aggregate size and pattern. Importantly, the aggregation process is conserved among different lineages of cellular slime molds despite using unrelated signalling molecules for aggregation.

Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core

PubMed Central

Lin, Hsiang-Kai; Boatz, Jennifer C.; Krabbendam, Inge E.; Kodali, Ravindra; Hou, Zhipeng; Wetzel, Ronald; Dolga, Amalia M.; Poirier, Michelle A.; van der Wel, Patrick C. A.

2017-01-01

Polyglutamine expansion in the huntingtin protein is the primary genetic cause of Huntington's disease (HD). Fragments coinciding with mutant huntingtin exon1 aggregate in vivo and induce HD-like pathology in mouse models. The resulting aggregates can have different structures that affect their biochemical behaviour and cytotoxic activity. Here we report our studies of the structure and functional characteristics of multiple mutant htt exon1 fibrils by complementary techniques, including infrared and solid-state NMR spectroscopies. Magic-angle-spinning NMR reveals that fibrillar exon1 has a partly mobile α-helix in its aggregation-accelerating N terminus, and semi-rigid polyproline II helices in the proline-rich flanking domain (PRD). The polyglutamine-proximal portions of these domains are immobilized and clustered, limiting access to aggregation-modulating antibodies. The polymorphic fibrils differ in their flanking domains rather than the polyglutamine amyloid structure. They are effective at seeding polyglutamine aggregation and exhibit cytotoxic effects when applied to neuronal cells. PMID:28537272

Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core

NASA Astrophysics Data System (ADS)

Lin, Hsiang-Kai; Boatz, Jennifer C.; Krabbendam, Inge E.; Kodali, Ravindra; Hou, Zhipeng; Wetzel, Ronald; Dolga, Amalia M.; Poirier, Michelle A.; van der Wel, Patrick C. A.

2017-05-01

Polyglutamine expansion in the huntingtin protein is the primary genetic cause of Huntington's disease (HD). Fragments coinciding with mutant huntingtin exon1 aggregate in vivo and induce HD-like pathology in mouse models. The resulting aggregates can have different structures that affect their biochemical behaviour and cytotoxic activity. Here we report our studies of the structure and functional characteristics of multiple mutant htt exon1 fibrils by complementary techniques, including infrared and solid-state NMR spectroscopies. Magic-angle-spinning NMR reveals that fibrillar exon1 has a partly mobile α-helix in its aggregation-accelerating N terminus, and semi-rigid polyproline II helices in the proline-rich flanking domain (PRD). The polyglutamine-proximal portions of these domains are immobilized and clustered, limiting access to aggregation-modulating antibodies. The polymorphic fibrils differ in their flanking domains rather than the polyglutamine amyloid structure. They are effective at seeding polyglutamine aggregation and exhibit cytotoxic effects when applied to neuronal cells.

Monetary Policy Rules, Supply Shocks, and the Price-Level Elasticity of Aggregate Demand: A Graphical Examination.

ERIC Educational Resources Information Center

Kyer, Ben L.; Maggs, Gary E.

1995-01-01

Utilizes two-dimensional price and output graphs to demonstrate the way that the price-level elasticity of aggregate demand affects alternative monetary policy rules designed to cope with random aggregate supply shocks. Includes graphs illustrating price-level, real Gross Domestic Product (GDP), nominal GDP, and nominal money supply targeting.…

Platelet aggregation caused by Carybdea rastonii toxins (CrTX-I, II and III) obtained from a jellyfish, Carybdea rastonii.

PubMed

Azuma, H; Sekizaki, S; Satoh, A; Nakajima, T

1986-05-01

The pharmacological mechanisms of platelet aggregation induced by highly toxic proteins (CrTX-I, CrTX-II, and CrTX-III) obtained from tentacles of a jellyfish, Carybdea rastonii, were investigated. When the partially purified toxin (pCrTX) and CrTXs were added to the citrated platelet-rich plasma (PRP), aggregation was produced in a concentration-dependent manner. The activity of CrTXs was approximately 100 times more potent than pCrTX. The CrTXs-induced aggregation was little affected by indomethacin and quinacrine at concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. The CrTXs-induced aggregation in washed platelets was significantly augmented in the presence of Ca2+. The pretreatment with verapamil failed to modify this augmentation of aggregation. The concentration of cytoplasmic-free calcium ([Ca2+]i) of platelets was increased by CrTXs at the same concentrations that produced aggregation. This effect of CrTXs was again little affected by verapamil. CrTXs at the same concentrations as those that produced aggregation and increased [Ca2+]i caused depolarization of platelets, which was unchanged after pretreatment with sodium or potassium transport inhibitors. CrTX-I significantly increased the 22Na flux into platelets and this effect of CrTX-I was unaffected by tetrodotoxin. The CrTX-I-induced aggregation, depolarization, and increase in [Ca2+]i were all significantly attenuated in the low Na+ medium. These results suggest that CrTXs cause a massive depolarization by increasing cation permeability and this generalized depolarization permits an inward movement of Ca2+ down its electrochemical gradient which, in turn, triggers platelet aggregation.

1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside delays amyloid-β42 aggregation and reduces amyloid cytotoxicity.

PubMed

Dhouafli, Zohra; Leri, Manuela; Bucciantini, Monica; Stefani, Massimo; Gadhoumi, Hamza; Mahjoub, Borhane; Ben Jannet, Hichem; Guillard, Jérôme; Ksouri, Riadh; Saidani Tounsi, Moufida; Soto, Claudio; Hayouni, El Akrem

2018-03-26

Presently, misfolding and aggregation of amyloid-β 42 (Aβ 42 ) are considered early events in Alzheimer's disease (AD) pathogenesis. The use of natural products to inhibit the aggregation process and to protect cells from cytotoxicity of early aggregate grown at the onset of the aggregation path is one of the promising strategies against AD. Recently, we have purified a new powerful antioxidant and inhibitor of Aβ 42 aggregation from the leaves of Lawsonia inermis. The new compound was identified as a new Lawsoniaside; 1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside (THNG). Herein, we show that THNG interferes with Aβ 42 aggregation, inhibits its conformational change to a β-sheet-rich structure, decreases its polymerization into large fibrillar species, reduces oxidative stress, and aggregate cytotoxicity. These results indicate that THNG has great potential as a neuroprotective and therapeutic agent against AD. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies.

PubMed

Vicente Miranda, Hugo; Szego, Éva M; Oliveira, Luís M A; Breda, Carlo; Darendelioglu, Ekrem; de Oliveira, Rita M; Ferreira, Diana G; Gomes, Marcos A; Rott, Ruth; Oliveira, Márcia; Munari, Francesca; Enguita, Francisco J; Simões, Tânia; Rodrigues, Eva F; Heinrich, Michael; Martins, Ivo C; Zamolo, Irina; Riess, Olaf; Cordeiro, Carlos; Ponces-Freire, Ana; Lashuel, Hilal A; Santos, Nuno C; Lopes, Luisa V; Xiang, Wei; Jovin, Thomas M; Penque, Deborah; Engelender, Simone; Zweckstetter, Markus; Klucken, Jochen; Giorgini, Flaviano; Quintas, Alexandre; Outeiro, Tiago F

2017-05-01

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PIGN prevents protein aggregation in the endoplasmic reticulum independently of its function in the GPI synthesis.

PubMed

Ihara, Shinji; Nakayama, Sohei; Murakami, Yoshiko; Suzuki, Emiko; Asakawa, Masayo; Kinoshita, Taroh; Sawa, Hitoshi

2017-02-01

Quality control of proteins in the endoplasmic reticulum (ER) is essential for ensuring the integrity of secretory proteins before their release into the extracellular space. Secretory proteins that fail to pass quality control form aggregates. Here we show the PIGN-1/PIGN is required for quality control in Caenorhabditis elegans and in mammalian cells. In C. elegans pign-1 mutants, several proteins fail to be secreted and instead form abnormal aggregation. PIGN-knockout HEK293 cells also showed similar protein aggregation. Although PIGN-1/PIGN is responsible for glycosylphosphatidylinositol (GPI)-anchor biosynthesis in the ER, certain mutations in C. elegans pign-1 caused protein aggregation in the ER without affecting GPI-anchor biosynthesis. These results show that PIGN-1/PIGN has a conserved and non-canonical function to prevent deleterious protein aggregation in the ER independently of the GPI-anchor biosynthesis. PIGN is a causative gene for some human diseases including multiple congenital seizure-related syndrome (MCAHS1). Two pign-1 mutations created by CRISPR/Cas9 that correspond to MCAHS1 also cause protein aggregation in the ER, implying that the dysfunction of the PIGN non-canonical function might affect symptoms of MCAHS1 and potentially those of other diseases. © 2017. Published by The Company of Biologists Ltd.

Dabigatran affects thrombin-dependent platelet aggregation after a week-long therapy.

PubMed

Sokol, Juraj; Nehaj, Frantisek; Ivankova, Jela; Mokan, Michal; Mokan, Marian; Stasko, Jan

2018-05-29

Dabigatran is a direct thrombin inhibitor. As the main adverse event is bleeding, it is relevant whether dabigatran has additional effects on platelet function. If so, it could affect the bleeding risk. We aimed to assess in vitro aggregation in patients with atrial fibrillation (AF) receiving dabigatran. We evaluated 32 AF patients treated with dabigatran (study group) and 18 non-anticoagulated non-AF blood donors (control group). We assessed light transmittance platelet aggregation (LTA) with 100 nmol/L γ-thrombin in both groups. The LTA was performed at two time-points in our dabigatran group of patients. The thrombin-induced platelet aggregation was significantly lower two hours after dabigatran was taken compared to baseline measurement (9% ± 6% vs. 29% ± 21%) in our study group. Moreover, we observed that the baseline value of platelet aggregation in patients on dabigatran treatment was significantly lower compared to healthy volunteers (29% ± 21% vs. 89 ± 8). However, one subanalysis showed that this significant reduction in platelet aggregation at baseline was only observed in patients who received dabigatran for over a week. The thrombin-induced platelet aggregation is reduced in non-valvular AF patients receiving dabigatran after a week-long therapy.

The Effects of Different Fine Recycled Concrete Aggregates on the Properties of Mortar

PubMed Central

Fan, Cheng-Chih; Huang, Ran; Hwang, Howard; Chao, Sao-Jeng

2015-01-01

The practical use of recycled concrete aggregate produced by crushing concrete waste reduces the consumption of natural aggregate and the amount of concrete waste that ends up in landfills. This study investigated two methods used in the production of fine recycled concrete aggregate: (1) a method that produces fine as well as coarse aggregate, and (2) a method that produces only fine aggregate. Mortar specimens were tested using a variety of mix proportions to determine how the characteristics of fine recycled concrete aggregate affect the physical and mechanical properties of the resulting mortars. Our results demonstrate the superiority of mortar produced using aggregate produced using the second of the two methods. Nonetheless, far more energy is required to render concrete into fine aggregate than is required to produce coarse as well as fine aggregate simultaneously. Thus, the performance benefits of using only fine recycled concrete aggregate must be balanced against the increased impact on the environment.

Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.

PubMed

Pradhan, Mohan R; Pal, Arumay; Hu, Zhongqiao; Kannan, Srinivasaraghavan; Chee Keong, Kwoh; Lane, David P; Verma, Chandra S

2016-02-01

Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using "Dehydrons." "Dehydrons" are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non-conserved dehydron-residues) from other interaction interfaces (conserved dehydron-residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. © 2015 Wiley Periodicals, Inc.

Impact of Amendments on the Physical Properties of Soil under Tropical Long-Term No Till Conditions

PubMed Central

Mooney, Sacha J.

2016-01-01

Tropical regions have been considered the world’s primary agricultural frontier; however, some physico-chemical deficiencies, such as low soil organic matter content, poor soil structure, high erodibility, soil acidity, and aluminum toxicity, have affected their productive capacity. Lime and gypsum are commonly used to improve soil chemical fertility, but no information exists about the long-term effects of these products on the physical attributes and C protection mechanisms of highly weathered Oxisols. A field trial was conducted in a sandy clay loam (kaolinitic, thermic Typic Haplorthox) under a no-tillage system for 12 years. The trial consisted of four treatments: a control with no soil amendment application, the application of 2.1 Mg ha-1 phosphogypsum, the application of 2.0 Mg ha-1 lime, and the application of lime + phosphogypsum (2.0 + 2.1 Mg ha-1, respectively). Since the experiment was established in 2002, the rates have been applied three times (2002, 2004, and 2010). Surface liming effectively increased water-stable aggregates > 2.0 mm at a depth of up to 0.2 m; however, the association with phosphogypsum was considered a good strategy to improve the macroaggregate stability in subsoil layers (0.20 to 0.40 m). Consequently, both soil amendments applied together increased the mean weight diameter (MWD) and geometric mean diameter (GMD) in all soil layers, with increases of up to 118 and 89%, respectively, according to the soil layer. The formation and stabilization of larger aggregates contributed to a higher accumulation of total organic carbon (TOC) on these structures. In addition to TOC, the MWD and aggregate stability index were positively correlated with Ca2+ and Mg2+ levels and base saturation. Consequently, the increase observed in the aggregate size class resulted in a better organization of soil particles, increasing the macroporosity and reducing the soil bulk density and penetration resistance. Therefore, adequate soil chemical management plays a fundamental role in improving the soil’s physical attributes in tropical areas under conservative management and highly affected by compaction caused by intensive farming. PMID:27959897

Impact of Amendments on the Physical Properties of Soil under Tropical Long-Term No Till Conditions.

PubMed

Carmeis Filho, Antonio C A; Crusciol, Carlos A C; Guimarães, Tiara M; Calonego, Juliano C; Mooney, Sacha J

2016-01-01

Tropical regions have been considered the world's primary agricultural frontier; however, some physico-chemical deficiencies, such as low soil organic matter content, poor soil structure, high erodibility, soil acidity, and aluminum toxicity, have affected their productive capacity. Lime and gypsum are commonly used to improve soil chemical fertility, but no information exists about the long-term effects of these products on the physical attributes and C protection mechanisms of highly weathered Oxisols. A field trial was conducted in a sandy clay loam (kaolinitic, thermic Typic Haplorthox) under a no-tillage system for 12 years. The trial consisted of four treatments: a control with no soil amendment application, the application of 2.1 Mg ha-1 phosphogypsum, the application of 2.0 Mg ha-1 lime, and the application of lime + phosphogypsum (2.0 + 2.1 Mg ha-1, respectively). Since the experiment was established in 2002, the rates have been applied three times (2002, 2004, and 2010). Surface liming effectively increased water-stable aggregates > 2.0 mm at a depth of up to 0.2 m; however, the association with phosphogypsum was considered a good strategy to improve the macroaggregate stability in subsoil layers (0.20 to 0.40 m). Consequently, both soil amendments applied together increased the mean weight diameter (MWD) and geometric mean diameter (GMD) in all soil layers, with increases of up to 118 and 89%, respectively, according to the soil layer. The formation and stabilization of larger aggregates contributed to a higher accumulation of total organic carbon (TOC) on these structures. In addition to TOC, the MWD and aggregate stability index were positively correlated with Ca2+ and Mg2+ levels and base saturation. Consequently, the increase observed in the aggregate size class resulted in a better organization of soil particles, increasing the macroporosity and reducing the soil bulk density and penetration resistance. Therefore, adequate soil chemical management plays a fundamental role in improving the soil's physical attributes in tropical areas under conservative management and highly affected by compaction caused by intensive farming.

Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

NASA Astrophysics Data System (ADS)

Araya, Eyleen; Olmedo, Ivonne; Bastus, Neus G.; Guerrero, Simón; Puntes, Víctor F.; Giralt, Ernest; Kogan, Marcelo J.

2008-11-01

Peptide-Gold nanoparticles selectively attached to β-amyloid protein (Aβ) amyloidogenic aggregates were irradiated with microwave. This treatment produces dramatic effects on the Aβ aggregates, inhibiting both the amyloidogenesis and the restoration of the amyloidogenic potential. This novel approach offers a new strategy to inhibit, locally and remotely, the amyloidogenic process, which could have application in Alzheimer’s disease therapy. We have studied the irradiation effect on the amyloidogenic process in the presence of conjugates peptide-nanoparticle by transmission electronic microscopy observations and by Thioflavine T assays to quantify the amount of fibrils in suspension. The amyloidogenic aggregates rather than the amyloid fibrils seem to be better targets for the treatment of the disease. Our results could contribute to the development of a new therapeutic strategy to inhibit the amyloidogenic process in Alzheimer’s disease.

H-aggregate analysis of P3HT thin films-Capability and limitation of photoluminescence and UV/Vis spectroscopy.

PubMed

Ehrenreich, Philipp; Birkhold, Susanne T; Zimmermann, Eugen; Hu, Hao; Kim, Kwang-Dae; Weickert, Jonas; Pfadler, Thomas; Schmidt-Mende, Lukas

2016-09-01

Polymer morphology and aggregation play an essential role for efficient charge carrier transport and charge separation in polymer-based electronic devices. It is a common method to apply the H-aggregate model to UV/Vis or photoluminescence spectra in order to analyze polymer aggregation. In this work we present strategies to obtain reliable and conclusive information on polymer aggregation and morphology based on the application of an H-aggregate analysis on UV/Vis and photoluminescence spectra. We demonstrate, with P3HT as model system, that thickness dependent reflection behavior can lead to misinterpretation of UV/Vis spectra within the H-aggregate model. Values for the exciton bandwidth can deviate by a factor of two for polymer thicknesses below 150 nm. In contrast, photoluminescence spectra are found to be a reliable basis for characterization of polymer aggregation due to their weaker dependence on the wavelength dependent refractive index of the polymer. We demonstrate this by studying the influence of surface characteristics on polymer aggregation for spin-coated thin-films that are commonly used in organic and hybrid solar cells.

Performance Testing of Hot-Mix Asphalt Aggregates

DOT National Transportation Integrated Search

1999-12-01

Hot mix asphalt (HMA) pavements are subject to thermal cracking, fatigue cracking, rutting, stripping, raveling, and freeze-thaw damage. Some of these distresses are directly affected by the choice of aggregates. Particle shape, surface texture, part...

Soil aggregate stratification of nematodes and ammonia oxidizers affects nitrification in an acid soil.

PubMed

Jiang, Yuji; Jin, Chen; Sun, Bo

2014-10-01

Nitrification plays a central role in global nitrogen cycle, which is affected by interaction between soil microfauna and microorganisms. The impact of synchronized changes in nematodes and ammonia oxidizers within aggregate fractions on nitrification was investigated in an acid soil under 10-year manure application. Nematodes, ammonia oxidizers and potential nitrification activity (PNA) were examined in three soil aggregate fractions under four fertilization regimes. Pyrosequencing data revealed that the dominant bacterial amoA operational taxonomic units (OTUs) were related to Nitrosospira species, while archaeal OTUs were affiliated with Nitrososphaera and Nitrosotalea species. PNA was more strongly correlated with ammonia-oxidizing bacteria (AOB) abundance than ammonia-oxidizing archaea (AOA) abundance, although AOA were dominant in the acid soil. Plant parasites had a negative effect on AOB abundance; however, bacterivores stimulated AOB abundance and contributed more to PNA than plant parasites. Aggregate fractions exerted significant impacts on AOA abundance and AOB community composition. Total carbon content strongly affected the abundance and composition of AOA community, while soil pH primarily affected that of AOB community. Soil variables explained 62.7% and 58.1% variations, and nematode variables explained 11.7% and 19.5% variations in the AOA and AOB community composition respectively. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.

PubMed

Menzies, Fiona M; Fleming, Angeleen; Caricasole, Andrea; Bento, Carla F; Andrews, Stephen P; Ashkenazi, Avraham; Füllgrabe, Jens; Jackson, Anne; Jimenez Sanchez, Maria; Karabiyik, Cansu; Licitra, Floriana; Lopez Ramirez, Ana; Pavel, Mariana; Puri, Claudia; Renna, Maurizio; Ricketts, Thomas; Schlotawa, Lars; Vicinanza, Mariella; Won, Hyeran; Zhu, Ye; Skidmore, John; Rubinsztein, David C

2017-03-08

Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective. Copyright © 2017 Elsevier Inc. All rights reserved.

PM10 emissions from aggregate fractions of an Entic Haplustoll under two contrasting tillage systems

NASA Astrophysics Data System (ADS)

Mendez, Mariano J.; Aimar, Silvia B.; Buschiazzo, Daniel E.

2015-12-01

Tillage systems affect physical and chemical properties of soils modifying its aggregation. How changes of the aggregate size distribution affect the capacity of the soil to emit fine particulate matter (PM10) to the atmosphere during wind erosion processes, is a less investigated issue. In order to answer this question, PM10 emissions from an Entic Haplustoll submitted to 25 years of continuous conventional tillage (LC) and no-till (NT) were analyzed. Soil samples were sieved with a rotary sieve in order to determine the aggregate size distribution (fractions : <0.42 mm, 0.42-0.84 mm, 0.84-2 mm, 2-6.4 mm, 6.4-19.2 mm, and >19.2 mm), the dry aggregate stability (DAS) and the erodible fraction (EF). The organic matter contents (OM), the particle size composition and the PM10 emission of each aggregate fraction were also measured. Results showed that NT promoted OM accumulations in all aggregate fractions which favored DAS and soil aggregation. The <0.42 mm sized aggregates (27%) predominated in CT and the >19.2 mm (41.7%) in NT, while the proportion of the other aggregate fractions was similar in both tillage systems. As a consequence of the smaller proportion of the <0.42 mm aggregates, the erodible fraction was lower in NT (EF: 17.3%) than in CT (30.8%). PM10 emissions of each aggregate fraction (AE) decreased exponentially with increasing size of the fractions in both tillage systems, mainly as a consequence of the smaller size and higher specific surface. AE was higher in CT than in NT for all aggregate fractions, but the higher differences were found in the <0.42 mm aggregates (18 μg g-1 in CT vs 8 μg g-1 in NT). The PM10 emission of the whole soil was three times higher in CT than in NT, while the emission of the erodible fraction (EFE) was in CT four times higher than in NT. PM10 emissions of the <0.42 mm aggregates represented over 50% of SE and 90% of EFE. We concluded that NT reduced the capacity of soils of the semiarid Pampas to emit PM10 because it produced a better aggregation that reduced the proportion and emission of the <0.42 mm aggregates. These aggregates had, by far, the highest emission potential.

Spatial pattern affects diversity-productivity relationships in experimental meadow communities

NASA Astrophysics Data System (ADS)

Lamošová, Tereza; Doležal, Jiří; Lanta, Vojtěch; Lepš, Jan

2010-05-01

Plant species create aggregations of conspecifics as a consequence of limited seed dispersal, clonal growth and heterogeneous environment. Such intraspecific aggregation increases the importance of intraspecific competition relative to interspecific competition which may slow down competitive exclusion and promote species coexistence. To examine how spatial aggregation impacts the functioning of experimental assemblages of varying species richness, eight perennial grassland species of different growth form were grown in random and aggregated patterns in monocultures, two-, four-, and eight-species mixtures. In mixtures with an aggregated pattern, monospecific clumps were interspecifically segregated. Mixed model ANOVA was used to test (i) how the total productivity and productivity of individual species is affected by the number of species in a mixture, and (ii) how these relationships are affected by spatial pattern of sown plants. The main patterns of productivity response to species richness conform to other studies: non-transgressive overyielding is omnipresent (the productivity of mixtures is higher than the average of its constituent species so that the net diversity, selection and complementarity effects are positive), whereas transgressive overyielding is found only in a minority of cases (average of log(overyielding) being close to zero or negative). The theoretical prediction that plants in a random pattern should produce more than in an aggregated pattern (the distances to neighbours are smaller and consequently the competition among neighbours stronger) was confirmed in monocultures of all the eight species. The situation is more complicated in mixtures, probably as a consequence of complicated interplay between interspecific and intraspecific competition. The most productive species ( Achillea, Holcus, Plantago) were competitively superior and increased their relative productivity with mixture richness. The intraspecific competition of these species is stronger than that of most other species. The aggregated pattern in the full mixture increased the survival of subordinate species, and consequently, we conclude that an aggregated pattern can promote species coexistence (or at least postpone competitive exclusion), particularly in comparison with homogeneously sown mixtures.

What Drives University Applications? An Attempt to Explain Aggregate Demand for Higher Education

ERIC Educational Resources Information Center

Vieira, Carlos; Vieira, Isabel

2014-01-01

Low educational attainment is frequently pointed out as a barrier to social and economic development and most governments aim at increasing participation in higher education. However, effective strategies to increase aggregate demand require information on its most relevant determinants, which is difficult to obtain because applications to higher…

The Aggregation of Single-Case Results Using Hierarchical Linear Models

ERIC Educational Resources Information Center

Van den Noortgate, Wim; Onghena, Patrick

2007-01-01

To investigate the generalizability of the results of single-case experimental studies, evaluating the effect of one or more treatments, in applied research various simultaneous and sequential replication strategies are used. We discuss one approach for aggregating the results for single-cases: the use of hierarchical linear models. This approach…

Ionization and Anion-π+ Interaction: A New Strategy for Structural Design of Aggregation-Induced Emission Luminogens.

PubMed

Wang, Jianguo; Gu, Xinggui; Zhang, Pengfei; Huang, Xiaobo; Zheng, Xiaoyan; Chen, Ming; Feng, Haitao; Kwok, Ryan T K; Lam, Jacky W Y; Tang, Ben Zhong

2017-11-22

Recent years have witnessed the significant role of anion-π + interactions in many areas, which potentially brings the opportunity for the development of aggregation-induced emission (AIE) systems. Here, a new strategy that utilized anion-π + interactions to block detrimental π-π stacking was first proposed to develop inherent-charged AIE systems. Two AIE-active luminogens, namely, 1,2,3,4-tetraphenyloxazolium (TPO-P) and 2,3,5-triphenyloxazolium (TriPO-PN), were successfully synthesized. Comprehensive techniques such as single-crystal analysis, theoretical calculation, and conductivity measurement were used to illustrate the effects of anion-π + interactions on the AIE feature. Their analogues tetraphenylfuran (TPF) and 2,4,5-triphenyloxazole (TriPO-C) without anion-π + interactions suffered from the aggregation-caused emission quenching in the aggregate state, demonstrating the important role of anion-π + interactions in suppressing π-π stacking. TriPO-PN was biocompatible and could specifically target lysosome in fluorescence turn-on and wash-free manners. This suggested that it was a promising contrast agent for bioimaging.

Sensitive colorimetric visualization of dihydronicotinamide adenine dinucleotide based on anti-aggregation of gold nanoparticles via boronic acid-diol binding.

PubMed

Liu, Shufeng; Du, Zongfeng; Li, Peng; Li, Feng

2012-05-15

A facile, highly sensitive colorimetric strategy for dihydronicotinamide adenine dinucleotide (NADH) detection is proposed based on anti-aggregation of gold nanoparticles (AuNPs) via boronic acid-diol binding chemistry. The aggregation agent, 4-mercaptophenylboronic acid (MPBA), has specific affinity for AuNPs through Au-S interaction, leading to the aggregation of AuNPs by self-dehydration condensation at a certain concentration, which is responsible for a visible color change of AuNPs from wine red to blue. With the addition of NADH, MPBA would prefer reacting with NADH to form stable borate ester via boronic acid-diol binding dependent on the pH and solvent, revealing an obvious color change from blue to red with increasing the concentration of NADH. The anti-aggregation effect of NADH on AuNPs was seen by the naked eye and monitored by UV-vis extinction spectra. The linear range of the colorimetric sensor for NADH is from 8.0 × 10(-9)M to 8.0 × 10(-6)M, with a low detection limit of 2.0 nM. The as-established colorimetric strategy opened a new avenue for NADH determination. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of surfaces and leachables on the stability of biopharmaceuticals.

PubMed

Bee, Jared S; Randolph, Theodore W; Carpenter, John F; Bishop, Steven M; Dimitrova, Mariana N

2011-10-01

Therapeutic proteins are exposed to various potential contact surfaces, particles, and leachables during manufacturing, shipping, storage, and delivery. In this review, we present published examples of interfacial- or leachable-induced aggregation or particle formation, and discuss the mitigation strategies that were successfully utilized. Adsorption to interfaces or interactions with leachables and/or particles in some cases has been reported to cause protein aggregation or particle formation. Identification of the cause(s) of particle formation involving minute amounts of protein over extended periods of time can be challenging. Various formulation strategies such as addition of a nonionic surfactant (e.g., polysorbate) have been demonstrated to effectively mitigate adsorption-induced protein aggregation. However, not all stability problems associated with interfaces or leachables are best resolved by formulation optimization. Detectable leachables do not necessarily have any adverse impact on the protein but control of the leachable source is preferred when there is a concern. In other cases, preventing protein aggregation and particle formation may require manufacturing process and/or equipment changes, use of compatible materials at contact interfaces, and so on. This review summarizes approaches that have been used to minimize protein aggregation and particle formation during manufacturing and fill-finish operations, product storage and transportation, and delivery of protein therapeutics. Copyright © 2011 Wiley-Liss, Inc.

The 'Direct Attack' Strategy for Poverty Removal: Implementation Methodology.

ERIC Educational Resources Information Center

Sinha, Sanjay

1981-01-01

Discusses elements of an implementation methodology for the removal of poverty in India. Includes background, methodology, aggregation of demands, economics of the strategy, complementary activities and infrastructure, mechanics of implementation, and monitoring. (CT)

Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab

PubMed Central

Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

2016-01-01

The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions. PMID:26514585

7 CFR 51.2933 - Serious damage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... seriously affects the appearance. (e) Scab spots when cracked or when well healed and aggregating more than... aggregating more than one-half inch (12.7 mm) in diameter. (g) Hail when the skin has been broken or when more...

7 CFR 51.2933 - Serious damage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... seriously affects the appearance. (e) Scab spots when cracked or when well healed and aggregating more than... aggregating more than one-half inch (12.7 mm) in diameter. (g) Hail when the skin has been broken or when more...

7 CFR 51.2933 - Serious damage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... seriously affects the appearance. (e) Scab spots when cracked or when well healed and aggregating more than... aggregating more than one-half inch (12.7 mm) in diameter. (g) Hail when the skin has been broken or when more...

Evaluating the road safety effects of a fuel cost increase measure by means of zonal crash prediction modeling.

PubMed

Pirdavani, Ali; Brijs, Tom; Bellemans, Tom; Kochan, Bruno; Wets, Geert

2013-01-01

Travel demand management (TDM) consists of a variety of policy measures that affect the transportation system's effectiveness by changing travel behavior. The primary objective to implement such TDM strategies is not to improve traffic safety, although their impact on traffic safety should not be neglected. The main purpose of this study is to evaluate the traffic safety impact of conducting a fuel-cost increase scenario (i.e. increasing the fuel price by 20%) in Flanders, Belgium. Since TDM strategies are usually conducted at an aggregate level, crash prediction models (CPMs) should also be developed at a geographically aggregated level. Therefore zonal crash prediction models (ZCPMs) are considered to present the association between observed crashes in each zone and a set of predictor variables. To this end, an activity-based transportation model framework is applied to produce exposure metrics which will be used in prediction models. This allows us to conduct a more detailed and reliable assessment while TDM strategies are inherently modeled in the activity-based models unlike traditional models in which the impact of TDM strategies are assumed. The crash data used in this study consist of fatal and injury crashes observed between 2004 and 2007. The network and socio-demographic variables are also collected from other sources. In this study, different ZCPMs are developed to predict the number of injury crashes (NOCs) (disaggregated by different severity levels and crash types) for both the null and the fuel-cost increase scenario. The results show a considerable traffic safety benefit of conducting the fuel-cost increase scenario apart from its impact on the reduction of the total vehicle kilometers traveled (VKT). A 20% increase in fuel price is predicted to reduce the annual VKT by 5.02 billion (11.57% of the total annual VKT in Flanders), which causes the total NOCs to decline by 2.83%. Copyright © 2012 Elsevier Ltd. All rights reserved.

Computational design and biophysical characterization of aggregation-resistant point mutations for γD crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity.

PubMed

Sahin, Erinc; Jordan, Jacob L; Spatara, Michelle L; Naranjo, Andrea; Costanzo, Joseph A; Weiss, William F; Robinson, Anne Skaja; Fernandez, Erik J; Roberts, Christopher J

2011-02-08

γD crystallin is a natively monomeric eye-lens protein that is associated with hereditary juvenile cataract formation. It is an attractive model system as a multidomain Greek-key protein that aggregates through partially folded intermediates. Point mutations M69Q and S130P were used to test (1) whether the protein-design algorithm RosettaDesign would successfully predict mutants that are resistant to aggregation when combined with informatic sequence-based predictors of peptide aggregation propensity and (2) how the mutations affected relative unfolding free energies (ΔΔG(un)) and intrinsic aggregation propensity (IAP). M69Q was predicted to have ΔΔG(un) ≫ 0, without significantly affecting IAP. S130P was predicted to have ΔΔG(un) ∼ 0 but with reduced IAP. The stability, conformation, and aggregation kinetics in acidic solution were experimentally characterized and compared for the variants and wild-type (WT) protein using circular dichroism and intrinsic fluorescence spectroscopy, calorimetric and chemical unfolding, thioflavin-T binding, chromatography, static laser light scattering, and kinetic modeling. Monomer secondary and tertiary structures of both variants were indistinguishable from WT, while ΔΔG(un) > 0 for M69Q and ΔΔG(un) < 0 for S130P. Surprisingly, despite being the least conformationally stable, S130P was the most resistant to aggregation, indicating a significant decrease of its IAP compared to WT and M69Q.

Optimization and influence of parameter affecting the compressive strength of geopolymer concrete containing recycled concrete aggregate: using full factorial design approach

NASA Astrophysics Data System (ADS)

Krishnan, Thulasirajan; Purushothaman, Revathi

2017-07-01

There are several parameters that influence the properties of geopolymer concrete, which contains recycled concrete aggregate as the coarse aggregate. In the present study, the vital parameters affecting the compressive strength of geopolymer concrete containing recycled concrete aggregate are analyzedby varying four parameters with two levels using full factorial design in statistical software Minitab® 17. The objective of the present work is to gain an idea on the optimization, main parameter effects, their interactions and the predicted response of the model generated using factorial design. The parameters such as molarity of sodium hydroxide (8M and 12M), curing time (6hrs and 24 hrs), curing temperature (60°C and 90°C) and percentage of recycled concrete aggregate (0% and 100%) are considered. The results show that the curing time, molarity of sodium hydroxide and curing temperature were the orderly significant parameters and the percentage of Recycled concrete aggregate (RCA) was statistically insignificant in the production of geopolymer concrete. Thus, it may be noticeable that the RCA content had negligible effect on the compressive strength of geopolymer concrete. The expected responses from the generated model showed a satisfactory and rational agreement to the experimental data with the R2 value of 97.70%. Thus, geopolymer concrete comprising recycled concrete aggregate can solve the major social and environmental concerns such as the depletion of the naturally available aggregate sources and disposal of construction and demolition waste into the landfill.

Engineering cell aggregates through incorporated polymeric microparticles.

PubMed

Ahrens, Caroline C; Dong, Ziye; Li, Wei

2017-10-15

Ex vivo cell aggregates must overcome significant limitations in the transport of nutrients, drugs, and signaling proteins compared to vascularized native tissue. Further, engineered extracellular environments often fail to sufficiently replicate tethered signaling cues and the complex architecture of native tissue. Co-cultures of cells with microparticles (MPs) is a growing field directed towards overcoming many of these challenges by providing local and controlled presentation of both soluble and tethered proteins and small molecules. Further, co-cultured MPs offer a mechanism to better control aggregate architecture and even to report key characteristics of the local microenvironment such as pH or oxygen levels. Herein, we provide a brief introduction to established and developing strategies for MP production including the choice of MP materials, fabrication techniques, and techniques for incorporating additional functionality. In all cases, we emphasize the specific utility of each approach to form MPs useful for applications in cell aggregate co-culture. We review established techniques to integrate cells and MPs. We highlight those strategies that promote targeted heterogeneity or homogeneity, and we describe approaches to engineer cell-particle and particle-particle interactions that enhance aggregate stability and biological response. Finally, we review advances in key application areas of MP aggregates and future areas of development. Cell-scaled polymer microparticles (MPs) integrated into cellular aggregates have been shown to be a powerful tool to direct cell response. MPs have supported the development of healthy cartilage, islets, nerves, and vasculature by the maintenance of soluble gradients as well as by the local presentation of tethered cues and diffusing proteins and small molecules. MPs integrated with pluripotent stem cells have directed in vivo expansion and differentiation. Looking forward, MPs are expected to support both the characterization and development of in vitro tissue systems for applications such as drug testing platforms. However, useful co-cultures must be designed keeping in mind the limitations and attributes of each material strategy within the context of the overall tissue biology. The present review integrates prospectives from materials development, drug delivery, and tissue engineering to provide a toolbox for the development and application of MPs useful for long-term co-culture within cell aggregates. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Non-Arrhenius protein aggregation.

PubMed

Wang, Wei; Roberts, Christopher J

2013-07-01

Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be linked with cytotoxicity and patient immunogenicity. Therefore, investigations of protein aggregation remain a major focus in pharmaceutical companies and academic institutions. Due to the complexity of the aggregation process and temperature-dependent conformational stability, temperature-induced protein aggregation is often non-Arrhenius over even relatively small temperature windows relevant for product development, and this makes low-temperature extrapolation difficult based simply on accelerated stability studies at high temperatures. This review discusses the non-Arrhenius nature of the temperature dependence of protein aggregation, explores possible causes, and considers inherent hurdles for accurately extrapolating aggregation rates from conventional industrial approaches for selecting accelerated conditions and from conventional or more advanced methods of analyzing the resulting rate data.

Stable J-aggregation enabled dual photoacoustic and fluorescence nanoparticles for intraoperative cancer imaging

NASA Astrophysics Data System (ADS)

Shakiba, Mojdeh; Ng, Kenneth K.; Huynh, Elizabeth; Chan, Harley; Charron, Danielle M.; Chen, Juan; Muhanna, Nidal; Foster, F. Stuart; Wilson, Brian C.; Zheng, Gang

2016-06-01

J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications.J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/C5NR08165C

Influence of Relative Humidity on AC Corona Discharge from Algae Attached on the Silicone Rubber

NASA Astrophysics Data System (ADS)

Sato, Daisuke; Hara, Yoshiaki; Kokufu, Morihide; Higashiyama, Yoshio

To make clear the influence of algae growth at the surface of a polymer insulator in a practical transmission line, the characteristics of ac corona discharge from an aggregate algae particle were investigated. The aggregate algae particle was made of Protococcus viridis. Corona onset voltage from an aggregate algae particle was decreased as relative humidity increased. Under the condition of relatively higher relative humidity, luminous channel of corona discharge became more strongly and the number of corona pulses in the current waveform was increased. For an aggregate algae particle contaminated with sea salt including MgCl2, corona onset voltage decreased drastically at relative humidity above 40%. This property would result from deliquescence of MgCl2. Corona discharge was strongly affected by existence of MgCl2 in an aggregate algae particle. Surface resistance of algae attached to the surface of the silicone rubber sheet decreased in fourth figures for relative humidity from 20 to 90%. Therefore, the existence of algae on the polymer insulator inevitably affects the electric property and the surface property of the polymer insulator.

O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease

NASA Astrophysics Data System (ADS)

Marotta, Nicholas P.; Lin, Yu Hsuan; Lewis, Yuka E.; Ambroso, Mark R.; Zaro, Balyn W.; Roth, Maxwell T.; Arnold, Don B.; Langen, Ralf; Pratt, Matthew R.

2015-11-01

Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation.

Inhibition of the aggregation of lactoferrin and (-)-epigallocatechin gallate in the presence of polyphenols, oligosaccharides, and collagen peptide.

PubMed

Yang, Wei; Liu, Fuguo; Xu, Chenqi; Sun, Cuixia; Yuan, Fang; Gao, Yanxiang

2015-05-27

The aggregation of lactoferrin and (-)-epigallocatechin gallate (EGCG) was inhibited by polyphenols, oligosaccharides, and collagen peptide in this study. Polyphenols, oligosaccharides, or collagen peptide can effectively prevent the formation of lactoferrin-EGCG aggregates, respectively. The addition sequence of lactoferrin, polyphenols (oligosaccharides or collagen peptide) and EGCG can affect the turbidity and particle size of the ternary complexes in the buffer solution; however, it hardly affected the ζ-potential and fluorescence characteristics. With either positive or negative charge, polyphenols and collagen peptide disrupted the formation of lactoferrin-EGCG aggregate mainly through the mechanism of its competition with EGCG molecules which surrounded the lactoferrin molecule surface with weaker binding affinities, forming polyphenols or a collagen peptide-lactoferrin-EGCG ternary complex; for neutral oligosaccharides, the ternary complex was generated mainly through steric effects, accompanied by a change in the lactoferrin secondary structure induced by gallic acid, chlorogenic acid, and xylo-oligosaccharide. Polyphenols, oligosaccharides, or collagen peptide restraining the formation of lactoferrin-EGCG aggregate could be applied in the design of clear products in the food, pharmaceutical, and cosmetic industries.

Real-time monitoring of quorum sensing in 3D-printed bacterial aggregates using scanning electrochemical microscopy.

PubMed

Connell, Jodi L; Kim, Jiyeon; Shear, Jason B; Bard, Allen J; Whiteley, Marvin

2014-12-23

Microbes frequently live in nature as small, densely packed aggregates containing ∼10(1)-10(5) cells. These aggregates not only display distinct phenotypes, including resistance to antibiotics, but also, serve as building blocks for larger biofilm communities. Aggregates within these larger communities display nonrandom spatial organization, and recent evidence indicates that this spatial organization is critical for fitness. Studying single aggregates as well as spatially organized aggregates remains challenging because of the technical difficulties associated with manipulating small populations. Micro-3D printing is a lithographic technique capable of creating aggregates in situ by printing protein-based walls around individual cells or small populations. This 3D-printing strategy can organize bacteria in complex arrangements to investigate how spatial and environmental parameters influence social behaviors. Here, we combined micro-3D printing and scanning electrochemical microscopy (SECM) to probe quorum sensing (QS)-mediated communication in the bacterium Pseudomonas aeruginosa. Our results reveal that QS-dependent behaviors are observed within aggregates as small as 500 cells; however, aggregates larger than 2,000 bacteria are required to stimulate QS in neighboring aggregates positioned 8 μm away. These studies provide a powerful system to analyze the impact of spatial organization and aggregate size on microbial behaviors.

Aggregation behavior of sodium lauryl ether sulfate with a positively bicharged organic salt and effects of the mixture on fluorescent properties of conjugated polyelectrolytes.

PubMed

Tang, Yongqiang; Liu, Zhang; Zhu, Linyi; Han, Yuchun; Wang, Yilin

2015-02-24

The aggregation behavior of anionic single-chain surfactant sodium lauryl ether sulfate containing three ether groups (SLE3S) with positively bicharged organic salt 1,2-bis(2-benzylammoniumethoxy)ethane dichloride (BEO) has been investigated in aqueous solution, and the effects of the BEO/SLE3S aggregate transitions on the fluorescent properties of anionic conjugated polyelectrolyte MPS-PPV with a larger molecular weight and cationic conjugated oligoelectrolyte DAB have been evaluated. Without BEO, SLE3S does not affect the fluorescent properties of MPS-PPV and only affects the fluorescent properties of DAB at a higher SLE3S concentration. With the addition of BEO, SLE3S and BEO form gemini-like surfactant (SLE3S)2-BEO. When the BEO/SLE3S molar ratio is fixed at 0.25, with increasing the BEO/SLE3S concentration, the BEO/SLE3S mixture forms large, loosely arranged aggregates and then transforms to closely packed spherical aggregates and finally to long thread-like micelles. The photoluminescence (PL) intensity of MPS-PPV varies with the morphologies of the BEO/SLE3S aggregates, while the PL intensity of DAB is almost independent of the aggregate morphologies. The results demonstrate that gemini-like surfactants formed through intermolecular interactions can effectively adjust the fluorescent properties of conjugated polyelectrolytes.

Effects of recombinant protein misfolding and aggregation on bacterial membranes.

PubMed

Ami, D; Natalello, A; Schultz, T; Gatti-Lafranconi, P; Lotti, M; Doglia, S M; de Marco, A

2009-02-01

The expression of recombinant proteins is known to induce a metabolic rearrangement in the host cell. We used aggregation-sensitive model systems to study the effects elicited in Escherichia coli cells by the aggregation of recombinant glutathione-S-transferase and its fusion with the green fluorescent protein that, according to the expression conditions, accumulate intracellularly as soluble protein, or soluble and insoluble aggregates. We show that the folding state of the recombinant protein and the complexity of the intracellular aggregates critically affect the cell response. Specifically, protein misfolding and aggregation induce changes in specific host proteins involved in lipid metabolism and oxidative stress, a reduction in the membrane permeability, as well as a rearrangement of its lipid composition. The temporal evolution of the host cell response and that of the aggregation process pointed out that the misfolded protein and soluble aggregates are responsible for the membrane modifications and the changes in the host protein levels. Interestingly, native recombinant protein and large insoluble aggregates do not seem to activate stress markers and membrane rearrangements.

Using Human iPSC-Derived Neurons to Model TAU Aggregation

PubMed Central

Verheyen, An; Diels, Annick; Dijkmans, Joyce; Oyelami, Tutu; Meneghello, Giulia; Mertens, Liesbeth; Versweyveld, Sofie; Borgers, Marianne; Buist, Arjan; Peeters, Pieter; Cik, Miroslav

2015-01-01

Alzheimer’s disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation. PMID:26720731

Graphene quantum dots for the inhibition of β amyloid aggregation

NASA Astrophysics Data System (ADS)

Liu, Yibiao; Xu, Li-Ping; Dai, Wenhao; Dong, Haifeng; Wen, Yongqiang; Zhang, Xueji

2015-11-01

The aggregation of Aβ peptides is a crucial factor leading to Alzheimer's disease (AD). Inhibiting the Aβ peptide aggregation has become one of the most essential strategies to treat AD. In this work, efficient and low-cytotoxicity inhibitors, graphene quantum dots (GQDs) are reported for their application in inhibiting the aggregation of Aβ peptides. Compared to other carbon materials, the low cytotoxicity and great biocompatibility of GQDs give an advantage to the clinical research for AD. In addition, the GQDs may cross the blood-brain barrier (BBB) because of the small size. It is believed that GQDs may be therapeutic agents against AD. This work provides a novel insight into the development of Alzheimer's drugs.The aggregation of Aβ peptides is a crucial factor leading to Alzheimer's disease (AD). Inhibiting the Aβ peptide aggregation has become one of the most essential strategies to treat AD. In this work, efficient and low-cytotoxicity inhibitors, graphene quantum dots (GQDs) are reported for their application in inhibiting the aggregation of Aβ peptides. Compared to other carbon materials, the low cytotoxicity and great biocompatibility of GQDs give an advantage to the clinical research for AD. In addition, the GQDs may cross the blood-brain barrier (BBB) because of the small size. It is believed that GQDs may be therapeutic agents against AD. This work provides a novel insight into the development of Alzheimer's drugs. Electronic supplementary information (ESI) available: Dose-dependent inhibition of Aβ1-42 fibrillization by GQDs; the photoluminescence spectra of all five GQDs with different charges in water/ethanol; TEM images of other four GQDs with different charges. See DOI: 10.1039/c5nr06282a

Aggregation increases prey survival time in group chase and escape

NASA Astrophysics Data System (ADS)

Yang, Sicong; Jiang, Shijie; Jiang, Li; Li, Geng; Han, Zhangang

2014-08-01

Recently developed chase-and-escape models have addressed a fascinating pursuit-and-evasion problem that may have both theoretical significance and potential applications. We introduce three aggregation strategies for the prey in a group chase model on a lattice. Simulation results show that aggregation dramatically increases the group survival time, even allowing immortal prey. The average survival time τ and the aggregation probability P have a power-law dependence of \\tau \\sim {{(1-P)}^{-1}} for P\\in [0.9,0.997]. With increasing numbers of predators, there is still a phase transition. When the number of predators is less than the critical point value, the prey group survival time increases significantly.

Radiocesium distribution in aggregate-size fractions of cropland and forest soils affected by the Fukushima nuclear accident.

PubMed

Koarashi, Jun; Nishimura, Syusaku; Atarashi-Andoh, Mariko; Matsunaga, Takeshi; Sato, Tsutomu; Nagao, Seiya

2018-08-01

The Fukushima Daiichi nuclear power plant accident caused serious radiocesium ( 137 Cs) contamination in soils in a range of terrestrial ecosystems. It is well documented that the interaction of 137 Cs with soil constituents, particularly clay minerals, in surface soil layers exerts strong control on the behavior of this radionuclide in the environment; however, there is little understanding of how soil aggregation-the binding of soil particles together into aggregates-can affect the mobility and bioavailability of 137 Cs in soils. To explore this, soil samples were collected at seven sites under different land-use conditions in Fukushima and were separated into four aggregate-size fractions: clay-sized (<2 μm); silt-sized (2-20 μm); sand-sized (20-212 μm); and macroaggregates (212-2000 μm). The fractions were then analyzed for 137 Cs content and extractability and mineral composition. In forest soils, aggregate formation was significant, and 69%-83% of 137 Cs was associated with macroaggregates and sand-sized aggregates. In contrast, there was less aggregation in agricultural field soils, and approximately 80% of 137 Cs was in the clay- and silt-sized fractions. Across all sites, the 137 Cs extractability was higher in the sand-sized aggregate fractions than in the clay-sized fractions. Mineralogical analysis showed that, in most soils, clay minerals (vermiculite and kaolinite) were present even in the larger-sized aggregate fractions. These results demonstrate that larger-sized aggregates are a significant reservoir of potentially mobile and bioavailable 137 Cs in organic-rich (forest and orchard) soils. Our study suggests that soil aggregation reduces the mobility of particle-associated 137 Cs through erosion and resuspension and also enhances the bioavailability of 137 Cs in soils. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sunlight affects aggregation and deposition of graphene oxide in the aquatic environment.

EPA Science Inventory

In this study, we investigate the role of simulated sunlight on the physicochemical properties, aggregation, and deposition of graphene oxide (GO) in aquatic environments. Results show that light exposure under varied environmental conditions significantly impacts the physicochem...

Reflections on Teaching Referencing: What Four Case Studies Can Tell Us about Developing Effective Teaching Strategies

ERIC Educational Resources Information Center

Hyland, Theresa

2010-01-01

Two contradictions are inherent in our research into referencing practices and the subsequent development of teaching strategies to remedy inappropriate practices. First, aggregate studies and teaching strategies that tend toward a one-size-fits-all formula for researching and teaching referencing do not consider individual differences in…

Dynamics of soil biogeochemical gas emissions shaped by remolded aggregate sizes and carbon configurations under hydration cycles.

PubMed

Ebrahimi, Ali; Or, Dani

2018-01-01

Changes in soil hydration status affect microbial community dynamics and shape key biogeochemical processes. Evidence suggests that local anoxic conditions may persist and support anaerobic microbial activity in soil aggregates (or in similar hot spots) long after the bulk soil becomes aerated. To facilitate systematic studies of interactions among environmental factors with biogeochemical emissions of CO 2 , N 2 O and CH 4 from soil aggregates, we remolded silt soil aggregates to different sizes and incorporated carbon at different configurations (core, mixed, no addition). Assemblies of remolded soil aggregates of three sizes (18, 12, and 6 mm) and equal volumetric proportions were embedded in sand columns at four distinct layers. The water table level in each column varied periodically while obtaining measurements of soil GHG emissions for the different aggregate carbon configurations. Experimental results illustrate that methane production required prolonged inundation and highly anoxic conditions for inducing measurable fluxes. The onset of unsaturated conditions (lowering water table) resulted in a decrease in CH 4 emissions while temporarily increasing N 2 O fluxes. Interestingly, N 2 O fluxes were about 80% higher form aggregates with carbon placement in center (anoxic) core compared to mixed carbon within aggregates. The fluxes of CO 2 were comparable for both scenarios of carbon sources. These experimental results highlight the importance of hydration dynamics in activating different GHG production and affecting various transport mechanisms about 80% of total methane emissions during lowering water table level are attributed to physical storage (rather than production), whereas CO 2 emissions (~80%) are attributed to biological activity. A biophysical model for microbial activity within soil aggregates and profiles provides a means for results interpretation and prediction of trends within natural soils under a wide range of conditions. © 2017 John Wiley & Sons Ltd.

Effect of cobalt ions on the interaction between macrophages and titanium.

PubMed

Pettersson, Mattias; Pettersson, Jean; Thorén, Margareta Molin; Johansson, Anders

2018-04-30

Inflammation and bone reduction around dental implants are described as peri-implantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL-1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro-inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP-1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL-1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy (ICP-AES) and electron microscopy. Co at a concentration of 100 µM neutralized the IL-1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti-induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti-induced activation and release of active IL-1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal-protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localisation after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri-implant tissue. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Effects of life-history traits on parasitism in a monogamous mammal, the eastern rock sengi ( Elephantulus myurus)

NASA Astrophysics Data System (ADS)

Lutermann, Heike; Medger, Katarina; Horak, Ivan G.

2012-02-01

The distribution of parasites is often characterised by substantial aggregation with a small proportion of hosts harbouring the majority of parasites. This pattern can be generated by abiotic and biotic factors that affect hosts and determine host exposure and susceptibility to parasites. Climate factors can change a host's investment in life-history traits (e.g. growth, reproduction) generating temporal patterns of parasite aggregation. Similarly, host age may affect such investment. Furthermore, sex-biased parasitism is common among vertebrates and has been linked to sexual dimorphism in morphology, behaviour and physiology. Studies exploring sex-biased parasitism have been almost exclusively conducted on polygynous species where dimorphic traits are often correlated. We investigated the effects of season and life-history traits on tick loads of the monogamous eastern rock sengi ( Elephantulus myurus). We found larger tick burdens during the non-breeding season possibly as a result of energetic constraints and/or climate effects on the tick. Reproductive investment resulted in increased larval abundance for females but not males and may be linked to sex-specific life-history strategies. The costs of reproduction could also explain the observed age effect with yearling individuals harbouring lower larval burdens than adults. Although adult males had the greatest larval tick loads, host sex appears to play a minor role in generating the observed parasite heterogeneities. Our study suggests that reproductive investment plays a major role for parasite patterns in the study species.

Neuroforecasting Aggregate Choice

PubMed Central

Knutson, Brian; Genevsky, Alexander

2018-01-01

Advances in brain-imaging design and analysis have allowed investigators to use neural activity to predict individual choice, while emerging Internet markets have opened up new opportunities for forecasting aggregate choice. Here, we review emerging research that bridges these levels of analysis by attempting to use group neural activity to forecast aggregate choice. A survey of initial findings suggests that components of group neural activity might forecast aggregate choice, in some cases even beyond traditional behavioral measures. In addition to demonstrating the plausibility of neuroforecasting, these findings raise the possibility that not all neural processes that predict individual choice forecast aggregate choice to the same degree. We propose that although integrative choice components may confer more consistency within individuals, affective choice components may generalize more broadly across individuals to forecast aggregate choice. PMID:29706726

Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane.

PubMed

Zhang, Liang; Trushin, Sergey; Christensen, Trace A; Tripathi, Utkarsh; Hong, Courtney; Geroux, Rachel E; Howell, Kyle G; Poduslo, Joseph F; Trushina, Eugenia

2018-06-01

Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer's Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a valid therapeutic target. Moreover, while some investigations identify Aβ oligomers as the culprit of trafficking inhibition, others propose that fibrils play the detrimental role. We have examined the effect of a panel of Aβ peptides with different mutations found in familial AD on mitochondrial motility in primary cortical mouse neurons. Peptides with higher propensity to aggregate inhibit mitochondrial trafficking to a greater extent with fibrils inducing the strongest inhibition. Binding of Aβ peptides to the plasma membrane was sufficient to induce trafficking inhibition where peptides with reduced plasma membrane binding and internalization had lesser effect on mitochondrial motility. We also found that Aβ peptide with Icelandic mutation A673T affects axonal trafficking of mitochondria but has very low rates of plasma membrane binding and internalization in neurons, which could explain its relatively low toxicity. Inhibition of mitochondrial dynamics caused by Aβ peptides or fibrils did not instantly affect mitochondrial bioenergetic and function. Our results support a mechanism where inhibition of axonal trafficking is initiated at the plasma membrane by soluble low molecular weight Aβ species and is exacerbated by fibrils. Since trafficking inhibition does not coincide with the loss of mitochondrial function, restoration of axonal transport could be beneficial at early stages of AD progression. However, strategies designed to block Aβ aggregation or fibril formation alone without ensuring the efficient clearance of soluble Aβ may not be sufficient to alleviate the trafficking phenotype. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Disease spread across multiple scales in a spatial hierarchy: effect of host spatial structure and of inoculum quantity and distribution.

PubMed

Gosme, Marie; Lucas, Philippe

2009-07-01

Spatial patterns of both the host and the disease influence disease spread and crop losses. Therefore, the manipulation of these patterns might help improve control strategies. Considering disease spread across multiple scales in a spatial hierarchy allows one to capture important features of epidemics developing in space without using explicitly spatialized variables. Thus, if the system under study is composed of roots, plants, and planting hills, the effect of host spatial pattern can be studied by varying the number of plants per planting hill. A simulation model based on hierarchy theory was used to simulate the effects of large versus small planting hills, low versus high level of initial infections, and aggregated versus uniform distribution of initial infections. The results showed that aggregating the initially infected plants always resulted in slower epidemics than spreading out the initial infections uniformly. Simulation results also showed that, in most cases, disease epidemics were slower in the case of large host aggregates (100 plants/hill) than with smaller aggregates (25 plants/hill), except when the initially infected plants were both numerous and spread out uniformly. The optimal strategy for disease control depends on several factors, including initial conditions. More importantly, the model offers a framework to account for the interplay between the spatial characteristics of the system, rates of infection, and aggregation of the disease.

A generalized ligand-exchange strategy enabling sequential surface functionalization of colloidal nanocrystals.

PubMed

Dong, Angang; Ye, Xingchen; Chen, Jun; Kang, Yijin; Gordon, Thomas; Kikkawa, James M; Murray, Christopher B

2011-02-02

The ability to engineer surface properties of nanocrystals (NCs) is important for various applications, as many of the physical and chemical properties of nanoscale materials are strongly affected by the surface chemistry. Here, we report a facile ligand-exchange approach, which enables sequential surface functionalization and phase transfer of colloidal NCs while preserving the NC size and shape. Nitrosonium tetrafluoroborate (NOBF4) is used to replace the original organic ligands attached to the NC surface, stabilizing the NCs in various polar, hydrophilic media such as N,N-dimethylformamide for years, with no observed aggregation or precipitation. This approach is applicable to various NCs (metal oxides, metals, semiconductors, and dielectrics) of different sizes and shapes. The hydrophilic NCs obtained can subsequently be further functionalized using a variety of capping molecules, imparting different surface functionalization to NCs depending on the molecules employed. Our work provides a versatile ligand-exchange strategy for NC surface functionalization and represents an important step toward controllably engineering the surface properties of NCs.

Real-Time Charging Strategies for an Electric Vehicle Aggregator to Provide Ancillary Services

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wenzel, George; Negrete-Pincetic, Matias; Olivares, Daniel E.

Real-time charging strategies, in the context of vehicle to grid (V2G) technology, are needed to enable the use of electric vehicle (EV) fleets batteries to provide ancillary services (AS). Here, we develop tools to manage charging and discharging in a fleet to track an Automatic Generation Control (AGC) signal when aggregated. We also propose a real-time controller that considers bidirectional charging efficiency and extend it to study the effect of looking ahead when implementing Model Predictive Control (MPC). Simulations show that the controller improves tracking error as compared with benchmark scheduling algorithms, as well as regulation capacity and battery cycling.

Real-Time Charging Strategies for an Electric Vehicle Aggregator to Provide Ancillary Services

DOE PAGES

Wenzel, George; Negrete-Pincetic, Matias; Olivares, Daniel E.; ...

2017-03-13

Real-time charging strategies, in the context of vehicle to grid (V2G) technology, are needed to enable the use of electric vehicle (EV) fleets batteries to provide ancillary services (AS). Here, we develop tools to manage charging and discharging in a fleet to track an Automatic Generation Control (AGC) signal when aggregated. We also propose a real-time controller that considers bidirectional charging efficiency and extend it to study the effect of looking ahead when implementing Model Predictive Control (MPC). Simulations show that the controller improves tracking error as compared with benchmark scheduling algorithms, as well as regulation capacity and battery cycling.

Across species-pool aggregation alters grassland productivity and diversity.

PubMed

McKenna, Thomas P; Yurkonis, Kathryn A

2016-08-01

Plant performance is determined by the balance of intra- and interspecific neighbors within an individual's zone of influence. If individuals interact over smaller scales than the scales at which communities are measured, then altering neighborhood interactions may fundamentally affect community responses. These interactions can be altered by changing the number (species richness), abundances (species evenness), and positions (species pattern) of the resident plant species, and we aimed to test whether aggregating species at planting would alter effects of species richness and evenness on biomass production at a common scale of observation in grasslands. We varied plant species richness (2, 4, or 8 species and monocultures), evenness (0.64, 0.8, or 1.0), and pattern (planted randomly or aggregated in groups of four individuals) within 1 × 1 m plots established with transplants from a pool of 16 tallgrass prairie species and assessed plot-scale biomass production and diversity over the first three growing seasons. As expected, more species-rich plots produced more biomass by the end of the third growing season, an effect associated with a shift from selection to complementarity effects over time. Aggregating conspecifics at a 0.25-m scale marginally reduced biomass production across all treatments and increased diversity in the most even plots, but did not alter biodiversity effects or richness-productivity relationships. Results support the hypothesis that fine-scale species aggregation affects diversity by promoting species coexistence in this system. However, results indicate that inherent changes in species neighborhood relationships along grassland diversity gradients may only minimally affect community (meter) - scale responses among similarly designed biodiversity-ecosystem function studies. Given that species varied in their responses to local aggregation, it may be possible to use such species-specific results to spatially design larger-scale grassland communities to achieve desired diversity and productivity responses.

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

PubMed Central

Reeg, Sandra

2015-01-01

Abstract Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239–255. PMID:25178482

Particularism in health care: challenging the authority of the aggregate.

PubMed

Tanenbaum, Sandra J

2014-12-01

In health care, particularism asserts the primacy of the individual case. Moral particularists, such as Jonsen and Toulmin, reject deduction from universal moral principles and instead seek warrants for action from the multiple sources unique to a given patient. Another kind of health care particularism, here referred to as the knowledge of particulars, is offered as a corrective to evidence-based medicine (EBM), its influence on health care practice and policy, and specifically to EBM's reliance on the aggregate. This paper describes the knowledge of particulars and identifies strategies for its legitimation in health care policy and practice. First, the paper documents the ascendancy of the aggregate through EBM's definition of 'what works' in health care. Second, it delineates the limits of health care knowledge based on the analysis of aggregates, not only for the care of individual patients but for the formulation of policies about patient care. Third, the paper analyses prominent rejections of the particular in contemporary health policy discourse and relates them to larger political purposes. Finally, it depicts the knowledge of particulars as the basis for clinical prudence and offers three potential strategies for promoting particularism as essential to high-quality care. © 2014 John Wiley & Sons, Ltd.

Reliable Adaptive Data Aggregation Route Strategy for a Trade-off between Energy and Lifetime in WSNs

PubMed Central

Guo, Wenzhong; Hong, Wei; Zhang, Bin; Chen, Yuzhong; Xiong, Naixue

2014-01-01

Mobile security is one of the most fundamental problems in Wireless Sensor Networks (WSNs). The data transmission path will be compromised for some disabled nodes. To construct a secure and reliable network, designing an adaptive route strategy which optimizes energy consumption and network lifetime of the aggregation cost is of great importance. In this paper, we address the reliable data aggregation route problem for WSNs. Firstly, to ensure nodes work properly, we propose a data aggregation route algorithm which improves the energy efficiency in the WSN. The construction process achieved through discrete particle swarm optimization (DPSO) saves node energy costs. Then, to balance the network load and establish a reliable network, an adaptive route algorithm with the minimal energy and the maximum lifetime is proposed. Since it is a non-linear constrained multi-objective optimization problem, in this paper we propose a DPSO with the multi-objective fitness function combined with the phenotype sharing function and penalty function to find available routes. Experimental results show that compared with other tree routing algorithms our algorithm can effectively reduce energy consumption and trade off energy consumption and network lifetime. PMID:25215944

Informed herbivore movement and interplant communication determine the effects of induced resistance in an individual-based model.

PubMed

Rubin, Ilan N; Ellner, Stephen P; Kessler, André; Morrell, Kimberly A

2015-09-01

1. Plant induced resistance to herbivory affects the spatial distribution of herbivores, as well as their performance. In recent years, theories regarding the benefit to plants of induced resistance have shifted from ideas of optimal resource allocation towards a more eclectic set of theories that consider spatial and temporal plant variability and the spatial distribution of herbivores among plants. However, consensus is lacking on whether induced resistance causes increased herbivore aggregation or increased evenness, as both trends have been experimentally documented. 2. We created a spatial individual-based model that can describe many plant-herbivore systems with induced resistance, in order to analyse how different aspects of induced resistance might affect herbivore distribution, and the total damage to a plant population, during a growing season. 3. We analyse the specific effects on herbivore aggregation of informed herbivore movement (preferential movement to less-damaged plants) and of information transfer between plants about herbivore attacks, in order to identify mechanisms driving both aggregation and evenness. We also investigate how the resulting herbivore distributions affect the total damage to plants and aggregation of damage. 4. Even, random and aggregated herbivore distributions can all occur in our model with induced resistance. Highest levels of aggregation occurred in the models with informed herbivore movement, and the most even distributions occurred when the average number of herbivores per plant was low. With constitutive resistance, only random distributions occur. Damage to plants was spatially correlated, unless plants recover very quickly from damage; herbivore spatial autocorrelation was always weak. 5. Our model and results provide a simple explanation for the apparent conflict between experimental results, indicating that both increased aggregation and increased evenness of herbivores can result from induced resistance. We demonstrate that information transfer from plants to herbivores, and from plants to neighbouring plants, can both be major factors in determining non-random herbivore distributions. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

The role of synaptotagmin I C2A calcium-binding domain in synaptic vesicle clustering during synapse formation

PubMed Central

Gardzinski, Peter; Lee, David W K; Fei, Guang-He; Hui, Kwokyin; Huang, Guan J; Sun, Hong-Shuo; Feng, Zhong-Ping

2007-01-01

Synaptic vesicles aggregate at the presynaptic terminal during synapse formation via mechanisms that are poorly understood. Here we have investigated the role of the putative calcium sensor synaptotagmin I in vesicle aggregation during the formation of soma–soma synapses between identified partner cells using a simple in vitro synapse model in the mollusc Lymnaea stagnalis. Immunocytochemistry, optical imaging and electrophysiological recording techniques were used to monitor synapse formation and vesicle localization. Within 6 h, contact between appropriate synaptic partner cells up-regulated global synaptotagmin I expression, and induced a localized aggregation of synaptotagmin I at the contact site. Cell contacts between non-synaptic partner cells did not affect synaptotagmin I expression. Application of an human immunodeficiency virus type-1 transactivator (HIV-1 TAT)-tagged peptide corresponding to loop 3 of the synaptotagmin I C2A domain prevented synaptic vesicle aggregation and synapse formation. By contrast, a TAT-tagged peptide containing the calcium-binding motif of the C2B domain did not affect synaptic vesicle aggregation or synapse formation. Calcium imaging with Fura-2 demonstrated that TAT–C2 peptides did not alter either basal or evoked intracellular calcium levels. These results demonstrate that contact with an appropriate target cell is necessary to initiate synaptic vesicle aggregation during nascent synapse formation and that the initial aggregation of synaptic vesicles is dependent on loop 3 of the C2A domain of synaptotagmin I. PMID:17317745

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity.

PubMed

Cerchiari, Alec E; Garbe, James C; Jee, Noel Y; Todhunter, Michael E; Broaders, Kyle E; Peehl, Donna M; Desai, Tejal A; LaBarge, Mark A; Thomson, Matthew; Gartner, Zev J

2015-02-17

Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo- and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.

Role of prion protein aggregation in neurotoxicity.

PubMed

Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Nizzari, Mario; Florio, Tullio

2012-01-01

In several neurodegenerative diseases, such as Parkinson, Alzheimer's, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP), the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126) and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.

Role of Prion Protein Aggregation in Neurotoxicity

PubMed Central

Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Nizzari, Mario; Florio, Tullio

2012-01-01

In several neurodegenerative diseases, such as Parkinson, Alzheimer’s, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP), the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126) and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death. PMID:22942726

Familial aggregation of age-related macular degeneration in the Utah population.

PubMed

Luo, Ling; Harmon, Jennifer; Yang, Xian; Chen, Haoyu; Patel, Shrena; Mineau, Geraldine; Yang, Zhenglin; Constantine, Ryan; Buehler, Jeanette; Kaminoh, Yuuki; Ma, Xiang; Wong, Tien Y; Zhang, Maonian; Zhang, Kang

2008-02-01

We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.

Pulsed electric field (PEF)-induced aggregation between lysozyme, ovalbumin and ovotransferrin in multi-protein system.

PubMed

Wu, Li; Zhao, Wei; Yang, Ruijin; Yan, Wenxu

2015-05-15

The aggregation of multi-proteins is of great interest in food processing and a good understanding of the formation of aggregates during PEF processing is needed for the application of the process to pasteurize protein-based foods. The aggregates formation of a multi-protein system (containing ovalbumin, ovotransferrin and lysozyme) was studied through turbidity, size exclusion chromatography and SDS-PAGE patterns for interaction studies and binding forces. Results from size exclusion chromatography indicated that there was no soluble aggregates formed during PEF processing. The existence of lysozyme was important to form insoluble aggregates in the chosen ovalbumin solution. The results of SDS-PAGE patterns indicated that lysozyme was prone to precipitate, and was relatively the higher component of aggregates. Citric acid could be effective in inhibiting lysozyme from interacting with other proteins during PEF processing. Blocking the free sulphydryl by N-ethylmaleimide (NEM) did not affect aggregation inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Downstream processing of biopharmaceutical proteins produced in plants: the pros and cons of flocculants.

PubMed

Buyel, Johannes Felix; Fischer, Rainer

2014-01-01

All biological platforms for the manufacture of biopharmaceutical proteins produce an initially turbid extract that must be clarified to avoid fouling sensitive media such as chromatography resins. Clarification is more challenging if the feed stream contains large amounts of dispersed particles, because these rapidly clog the filter media typically used to remove suspended solids. Charged polymers (flocculants) can increase the apparent size of the dispersed particles by aggregation, facilitating the separation of solids and liquids, and thus reducing process costs. However, many different factors can affect the behavior of flocculants, including the pH and conductivity of the medium, the size and charge distribution of the particulates, and the charge density and molecular mass of the polymer. Importantly, these properties can also affect the recovery of the target protein and the overall safety profile of the process. We therefore used a design of experiments approach to establish reliable predictive models that characterize the impact of flocculants during the downstream processing of biopharmaceutical proteins. We highlight strategies for the selection of flocculants during process optimization. These strategies will contribute to the quality by design aspects of process development and facilitate the development of safe and efficient downstream processes for plant-derived pharmaceutical proteins.

';Best' Practices for Aggregating Subset Results from Archived Datasets

NASA Astrophysics Data System (ADS)

Baskin, W. E.; Perez, J.

2013-12-01

In response to the exponential growth in science data analysis and visualization capabilities Data Centers have been developing new delivery mechanisms to package and deliver large volumes of aggregated subsets of archived data. New standards are evolving to help data providers and application programmers deal with growing needs of the science community. These standards evolve from the best practices gleaned from new products and capabilities. The NASA Atmospheric Sciences Data Center (ASDC) has developed and deployed production provider-specific search and subset web applications for the CALIPSO, CERES, TES, and MOPITT missions. This presentation explores several use cases that leverage aggregated subset results and examines the standards and formats ASDC developers applied to the delivered files as well as the implementation strategies for subsetting and processing the aggregated products. The following topics will be addressed: - Applications of NetCDF CF conventions to aggregated level 2 satellite subsets - Data-Provider-Specific format requirements vs. generalized standards - Organization of the file structure of aggregated NetCDF subset output - Global Attributes of individual subsetted files vs. aggregated results - Specific applications and framework used for subsetting and delivering derivative data files

Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection.

PubMed

Cohen, Ehud; Du, Deguo; Joyce, Derek; Kapernick, Erik A; Volovik, Yuli; Kelly, Jeffery W; Dillin, Andrew

2010-04-01

Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late-onset human neurodegenerative disorders. Reduction of insulin/IGF-1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer's disease-linked Abeta peptide. We utilized transgenic nematodes that express human Abeta and found that late life IIS reduction efficiently protects from Abeta toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)-1 to modulate a protein disaggregase, while DAF-16 regulates a presumptive active aggregase, raising the question of how these opposing activities could be co-regulated. One possibility is that HSF-1 and DAF-16 have distinct temporal requirements for protection from proteotoxicity. Using a conditional RNAi approach, we found an early requirement for HSF-1 that is distinct from the adult functions of DAF-16 for protection from proteotoxicity. Our data also indicate that late life IIS reduction can protect from proteotoxicity when it can no longer promote longevity, strengthening the prospect that IIS reduction might be a promising strategy for the treatment of neurodegenerative disorders caused by proteotoxicity.

Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration.

PubMed

Busch, Albert; Hoffjan, Sabine; Bergmann, Frauke; Hartung, Birgit; Jung, Helena; Hanel, Daniela; Tzschach, Andeas; Kadar, Janos; von Kodolitsch, Yskert; Germer, Christoph-Thomas; Trobisch, Heiner; Strasser, Erwin; Wildenauer, René

2016-08-03

The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.

Modulation of protein stability and aggregation properties by surface charge engineering.

PubMed

Raghunathan, Govindan; Sokalingam, Sriram; Soundrarajan, Nagasundarapandian; Madan, Bharat; Munussami, Ganapathiraman; Lee, Sun-Gu

2013-09-01

An attempt to alter protein surface charges through traditional protein engineering approaches often affects the native protein structure significantly and induces misfolding. This limitation is a major hindrance in modulating protein properties through surface charge variations. In this study, as a strategy to overcome such a limitation, we attempted to co-introduce stabilizing mutations that can neutralize the destabilizing effect of protein surface charge variation. Two sets of rational mutations were designed; one to increase the number of surface charged amino acids and the other to decrease the number of surface charged amino acids by mutating surface polar uncharged amino acids and charged amino acids, respectively. These two sets of mutations were introduced into Green Fluorescent Protein (GFP) together with or without stabilizing mutations. The co-introduction of stabilizing mutations along with mutations for surface charge modification allowed us to obtain functionally active protein variants (s-GFP(+15-17) and s-GFP(+5-6)). When the protein properties such as fluorescent activity, folding rate and kinetic stability were assessed, we found the possibility that the protein stability can be modulated independently of activity and folding by engineering protein surface charges. The aggregation properties of GFP could also be altered through the surface charge engineering.

A truncated apoptin protein variant selectively kills cancer cells.

PubMed

Ruiz-Martínez, Santiago; Castro, Jessica; Vilanova, Maria; Bruix, Marta; Laurents, Douglas V; Ribó, Marc; Benito, Antoni

2017-06-01

Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However, the use of Apoptin as an anticancer drug is restricted by its strong tendency to aggregate. A number of methods to overcome this problem have been proposed, including transduction techniques to deliver the Apoptin gene into tumor cells, but all such methods have certain drawbacks. Here we describe that a truncated variant of Apoptin, lacking residues 1 to 43, is a soluble, non-aggregating protein that maintains most of the biological properties of wild-type Apoptin when transfected into cells. We show that the cytotoxic effect of this variant is also present when it is added exogenously to cancer cells, but not to normal cells. In addition to the interest this protein has attracted as a promising therapeutic strategy, it is also an excellent model to study the structural properties of Apoptin and how they relate to its mechanism of action.

An Interdomain Interaction of the Androgen Receptor Is Required for Its Aggregation and Toxicity in Spinal and Bulbar Muscular Atrophy*

PubMed Central

Orr, Christopher R.; Montie, Heather L.; Liu, Yuhong; Bolzoni, Elena; Jenkins, Shannon C.; Wilson, Elizabeth M.; Joseph, James D.; McDonnell, Donald P.; Merry, Diane E.

2010-01-01

Polyglutamine expansion within the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA) and is associated with misfolded and aggregated species of the mutant AR. We showed previously that nuclear localization of the mutant AR was necessary but not sufficient for SBMA. Here we show that an interdomain interaction of the AR that is central to its function within the nucleus is required for AR aggregation and toxicity. Ligands that prevent the interaction between the amino-terminal FXXLF motif and carboxyl-terminal AF-2 domain (N/C interaction) prevented toxicity and AR aggregation in an SBMA cell model and rescued primary SBMA motor neurons from 5α-dihydrotestosterone-induced toxicity. Moreover, genetic mutation of the FXXLF motif prevented AR aggregation and 5α-dihydrotestosterone toxicity. Finally, selective androgen receptor modulators, which prevent the N/C interaction, ameliorated AR aggregation and toxicity while maintaining AR function, highlighting a novel therapeutic strategy to prevent the SBMA phenotype while retaining AR transcriptional function. PMID:20826791

The ongoing search for small molecules to study metal-associated amyloid-β species in Alzheimer's disease.

PubMed

Savelieff, Masha G; DeToma, Alaina S; Derrick, Jeffrey S; Lim, Mi Hee

2014-08-19

The development of a cure for Alzheimer's disease (AD) has been impeded by an inability to pinpoint the root cause of this disorder. Although numerous potential pathological factors have been indicated, acting either individually or mutually, the molecular mechanisms leading to disease onset and progression have not been clear. Amyloid-β (Aβ), generated from proteolytic processing of the amyloid precursor protein (APP), and its aggregated forms, particularly oligomers, are suggested as key pathological features in AD-affected brains. Historically, highly concentrated metals are found colocalized within Aβ plaques. Metal binding to Aβ (metal-Aβ) generates/stabilizes potentially toxic Aβ oligomers, and produces reactive oxygen species (ROS) in vitro (redox active metal ions; plausible contribution to oxidative stress). Consequently, clarification of the relationship between Aβ, metal ions, and toxicity, including oxidative stress via metal-Aβ, can lead to a deeper understanding of AD development. To probe the involvement of metal-Aβ in AD pathogenesis, rationally designed and naturally occurring molecules have been examined as chemical tools to target metal-Aβ species, modulate the interaction between the metal and Aβ, and subsequently redirect their aggregation into nontoxic, off-pathway unstructured aggregates. These ligands are also capable of attenuating the generation of redox active metal-Aβ-induced ROS to mitigate oxidative stress. One rational design concept, the incorporation approach, installs a metal binding site into a framework known to interact with Aβ. This approach affords compounds with the simultaneous ability to chelate metal ions and interact with Aβ. Natural products capable of Aβ interaction have been investigated for their influence on metal-induced Aβ aggregation and have inspired the construction of synthetic analogues. Systematic studies of these synthetic or natural molecules could uncover relationships between chemical structures, metal/Aβ/metal-Aβ interactions, and inhibition of Aβ/metal-Aβ reactivity (i.e., aggregation modes of Aβ/metal-Aβ; associated ROS production), suggesting mechanisms to refine the design strategy. Interdisciplinary investigations have demonstrated that the designed molecules and natural products control the aggregation pathways of metal-Aβ species transforming their size/conformation distribution. The aptitude of these molecules to impact metal-Aβ aggregation pathways, either via inhibition of Aβ aggregate formation, most importantly of oligomers, or disaggregation of preformed fibrils, could originate from their formation of complexes with metal-Aβ. Potentially, these molecules could direct metal-Aβ size/conformational states into alternative nontoxic unstructured oligomers, and control the geometry at the Aβ-ligated metal center for limited ROS formation to lessen the overall toxicity induced by metal-Aβ. Complexation between small molecules and Aβ/metal-Aβ has been observed by nuclear magnetic resonance spectroscopy (NMR) and ion mobility-mass spectrometry (IM-MS) pointing to molecular level interactions, validating the design strategy. In addition, these molecules exhibit other attractive properties, such as antioxidant capacity, prevention of ROS production, potential blood-brain barrier (BBB) permeability, and reduction of Aβ-/metal-Aβ-induced cytotoxicity, making them desirable tools for unraveling AD complexity. In this Account, we summarize the recent development of small molecules, via both rational design and the selection and modification of natural products, as tools for investigating metal-Aβ complexes, to advance our understanding of their relation to AD pathology.

Traffic Flow Management Using Aggregate Flow Models and the Development of Disaggregation Methods

NASA Technical Reports Server (NTRS)

Sun, Dengfeng; Sridhar, Banavar; Grabbe, Shon

2010-01-01

A linear time-varying aggregate traffic flow model can be used to develop Traffic Flow Management (tfm) strategies based on optimization algorithms. However, there are no methods available in the literature to translate these aggregate solutions into actions involving individual aircraft. This paper describes and implements a computationally efficient disaggregation algorithm, which converts an aggregate (flow-based) solution to a flight-specific control action. Numerical results generated by the optimization method and the disaggregation algorithm are presented and illustrated by applying them to generate TFM schedules for a typical day in the U.S. National Airspace System. The results show that the disaggregation algorithm generates control actions for individual flights while keeping the air traffic behavior very close to the optimal solution.

Silicone Oil- and Agitation-Induced Aggregation of a Monoclonal Antibody in Aqueous Solution

PubMed Central

Thirumangalathu, Renuka; Krishnan, Sampathkumar; Ricci, Margaret Speed; Brems, David N.; Randolph, Theodore W.; Carpenter, John F.

2009-01-01

Silicone oil, which is used as a lubricant or coating in devices such as syringes, needles and pharmaceutical containers, has been implicated in aggregation and particulation of proteins and antibodies. Aggregation of therapeutic protein products induced by silicone oil can pose a challenge to their development and commercialization. To systematically characterize the role of silicone oil on protein aggregation, the effects of agitation, temperature, pH and ionic strength on silicone oil-induced loss of monomeric anti-streptavidin IgG 1 antibody were examined. Additionally, the influences of excipients polysorbate20 and sucrose on protein aggregation were investigated. In the absence of agitation, protein absorbed to silicone oil with approximately monolayer coverage, however silicone oil did not stimulate aggregation during isothermal incubation unless samples were also agitated. A synergistic stimulation of aggregation by a combination of agitation and silicone oil was observed. Solution conditions which reduced colloidal stability of the antibody, as assessed by determination of osmotic second virial coefficients, accelerated aggregation during agitation with silicone oil. Polysorbate20 completely inhibited silicone oil-induced monomer loss during agitation. A formulation strategy optimizing colloidal stability of the antibody as well as incorporation of surfactants such as polysorbate20 is proposed to reduce silicone oil-induced aggregation of therapeutic protein products. PMID:19360857

Proteins with Intrinsically Disordered Domains Are Preferentially Recruited to Polyglutamine Aggregates

PubMed Central

O’Meally, Robert; Sonnenberg, Jason L.; Cole, Robert N.; Shewmaker, Frank P.

2015-01-01

Intracellular protein aggregation is the hallmark of several neurodegenerative diseases. Aggregates formed by polyglutamine (polyQ)-expanded proteins, such as Huntingtin, adopt amyloid-like structures that are resistant to denaturation. We used a novel purification strategy to isolate aggregates formed by human Huntingtin N-terminal fragments with expanded polyQ tracts from both yeast and mammalian (PC-12) cells. Using mass spectrometry we identified the protein species that are trapped within these polyQ aggregates. We found that proteins with very long intrinsically-disordered (ID) domains (≥100 amino acids) and RNA-binding proteins were disproportionately recruited into aggregates. The removal of the ID domains from selected proteins was sufficient to eliminate their recruitment into polyQ aggregates. We also observed that several neurodegenerative disease-linked proteins were reproducibly trapped within the polyQ aggregates purified from mammalian cells. Many of these proteins have large ID domains and are found in neuronal inclusions in their respective diseases. Our study indicates that neurodegenerative disease-associated proteins are particularly vulnerable to recruitment into polyQ aggregates via their ID domains. Also, the high frequency of ID domains in RNA-binding proteins may explain why RNA-binding proteins are frequently found in pathological inclusions in various neurodegenerative diseases. PMID:26317359

UV Irradiation and Humic Acid Mediate Aggregation of Aqueous Fullerene (nC60) Nanoparticles

EPA Science Inventory

The transport and fate of engineered nanomaterials is affected by multiple environmental factors, including sunlight and natural organic matter. In this study, the initial aggregation kinetics of aqueous fullerene (nC60) nanoparticles before and after UVA irradiation was investig...

Aggregate Unemployment Decreases Individual Returns to Education

ERIC Educational Resources Information Center

Ammermueller, Andreas; Kuckulenz, Anja; Zwick, Thomas

2009-01-01

Aggregate unemployment may affect individual returns to education through qualification-specific responses in participation and wage bargaining. This paper shows that an increase in regional unemployment by 1% decreases returns to education by 0.005 percentage points. This implies that higher skilled employees are better sheltered from labour…

A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila

NASA Astrophysics Data System (ADS)

Apostol, Barbara L.; Kazantsev, Alexsey; Raffioni, Simona; Illes, Katalin; Pallos, Judit; Bodai, Laszlo; Slepko, Natalia; Bear, James E.; Gertler, Frank B.; Hersch, Steven; Housman, David E.; Marsh, J. Lawrence; Michels Thompson, Leslie

2003-05-01

The formation of polyglutamine-containing aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation and may provide therapeutic benefit. We have developed inducible PC12 cell-culture models to screen for loss of visible aggregates. To test the validity of this approach, compounds that inhibit aggregation in the PC12 cell-based screen were tested in a Drosophila model of polyglutamine-repeat disease. The disruption of aggregation in PC12 cells strongly correlates with suppression of neuronal degeneration in Drosophila. Thus, the engineered PC12 cells coupled with the Drosophila model provide a rapid and effective method to screen and validate compounds.

Protein Misfolding Diseases.

PubMed

Hartl, F Ulrich

2017-06-20

The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies. To prevent or regulate protein aggregation, all cells contain an extensive protein homeostasis (or proteostasis) network comprising molecular chaperones and other factors. These defense systems tend to decline during aging, facilitating the manifestation of aggregate deposition diseases. This volume of the Annual Review of Biochemistry contains a set of three articles addressing our current understanding of the structures of pathological protein aggregates and their associated disease mechanisms. These articles also discuss recent insights into the strategies cells have evolved to neutralize toxic aggregates by sequestering them in specific cellular locations.

Sound absorption and morphology characteristic of porous concrete paving blocks

NASA Astrophysics Data System (ADS)

Halim, N. H. Abd; Nor, H. Md; Ramadhansyah, P. J.; Mohamed, A.; Hassan, N. Abdul; Ibrahim, M. H. Wan; Ramli, N. I.; Nazri, F. Mohamed

2017-11-01

In this study, sound absorption and morphology characteristic of Porous Concrete Paving Blocks (PCPB) at different sizes of coarse aggregate were presented. Three different sizes of coarse aggregate were used; passing 10 mm retained 5 mm (as Control), passing 8 mm retained 5 mm (8 - 5) and passing 10 mm retained 8 mm (10 - 8). The sound absorption test was conducted through the impedance tube at different frequency. It was found that the size of coarse aggregate affects the level of absorption of the specimens. It also shows that PCPB 10 - 8 resulted in high sound absorption compared to the other blocks. On the other hand, microstructure morphology of PCPB shows a clearer version of existing micro-cracks and voids inside the specimens which affecting the results of sound absorption.

Effects of Combined Application of Biogas Slurry and Chemical Fertilizer on Soil Aggregation and C/N Distribution in an Ultisol.

PubMed

Zheng, Xuebo; Fan, Jianbo; Xu, Lei; Zhou, Jing

2017-01-01

Unreasonable use of chemical fertilizer (CF) on agricultural soil leads to massive losses of soil organic carbon (SOC) and total nitrogen (TN) in tropical and subtropical areas, where soil conditions are unfavorable for aggregate formation. This study evaluated the effects of combined application of biogas slurry (BS) plus CF on soil aggregation and aggregate-associated C/N concentration and storage in an Ultisol. Six treatments included: no fertilizer (T1), CF only (T2), partial (15% (T3), 30% (T4) and 45% (T5)) substitution of TN with BS and BS only (T6). Soil mechanical-stable aggregates (MSAs) formation and stability as well as MSAs-associated C/N concentration and storage were observed in different aggregate sizes (>5, 5-2, 2-1, 1.0-0.5, 0.50-0.25 and <0.25 mm). The proportion of MSAs >5 mm significantly increased with BS substitution (T5), while the proportions of MSAs 1.0-0.5 mm, MSAs 0.50-0.25 mm and MSAs <0.25 mm significantly decreased. Both mean weight diameter and geometric mean diameter were highest in T5, which improved soil aggregation stability as well as resulted in significantly higher SOC and TN concentrations and storage in MSAs >0.5 mm that constituted 72-82% of MSAs. Stepwise regression analysis showed that MSAs >5 mm, SOC in MSAs >5 mm and TN in MSAs >5 mm were the dominant variables affecting aggregate stability. Meanwhile SOC in MSAs <0.25 mm and TN in MSAs 2-1 mm were independent variables affecting SOC and TN concentrations in bulk soils. Therefore, certain rate of combined application of BS plus CF is an effective, eco-friendly way to improve soil quality in an Ultisol.

Aggregate Stability and Erodibility of Purple Soil on Sloping Farmland as affected by different Soil Thickness

NASA Astrophysics Data System (ADS)

Huang, Xinjun; Zhang, Qingwen; Chen, Shanghong; Dong, Yuequn; Xiao, Meijia; Hamed, Lamy Mamdoh Mohamed

2017-04-01

Soil thickness is basic limiting condition for purple soil, not only due to its effect on crop production, but also its effect on soil structure. Steady-state of soil thickness will be achieved over time, as result the soil aggregate which the key factor of soil erodibility can be enhanced as well. However, the effect of soil thickness on aggregates stability and the characteristics of soil erodibility in sloping land have not yet fully understood.A field survey was conducted in hilly area of Sichuan region located in southeast China to study the relationship between soil aggregate stability and soil erodibility on sloping farmland under different four thickness (100cm, 80cm, 60cm, 30cm) of purple soil. Based on two different sieving methods (Dry and Wet sieving), we analyzed soil aggregate stability and its effect on soil erodibility within depth of 0-30cm soil layers. The results indicated that: Water stable aggregate on sloping farmland was ranged between 37.9% to 58.6%, where it increased with increasing the soil thickness. Moreover, fractal dimension calculated from dry-sieving and wet-sieving was 2.06-2.49 and 2.70-2.85 respectively, where it decreased with decreasing the soil thickness. The overall soil erodibility was 0.05-1.00 and a negative significant correlation was found between soil aggregate stability and erodibility(P<0.01). Moreover, farmland with thick soil profile tended to be high in soil erodibility within the top soil layer (0-30cm). The results reveal that soil thickness can affect soil aggregate stability as well as erodibility. As soil thickness increased, the top soil became more stable and less erodible. Keywords：purple soil; soil thickness; soil aggregate；soil erodibility

Increases in soil aggregation following phosphorus additions in a tropical premontane forest are not driven by root and arbuscular mycorrhizal fungal abundances

NASA Astrophysics Data System (ADS)

Camenzind, Tessa; Papathanasiou, Helena; Foerster, Antje; Dietrich, Karla; Hertel, Dietrich; Homeier, Juergen; Oelmann, Yvonne; Olsson, Pål Axel; Suárez, Juan; Rillig, Matthias

2015-12-01

Tropical ecosystems have an important role in global change scenarios, in part because they serve as a large terrestrial carbon pool. Carbon protection is mediated by soil aggregation processes, whereby biotic and abiotic factors influence the formation and stability of aggregates. Nutrient additions may affect soil structure indirectly by simultaneous shifts in biotic factors, mainly roots and fungal hyphae, but also via impacts on abiotic soil properties. Here, we tested the hypothesis that soil aggregation will be affected by nutrient additions primarily via changes in arbuscular mycorrhizal fungal (AMF) hyphae and root length in a pristine tropical forest system. Therefore, the percentage of water-stable macroaggregates (> 250µm) (WSA) and the soil mean weight diameter (MWD) was analyzed, as well as nutrient contents, pH, root length and AMF abundance. Phosphorus additions significantly increased the amount of WSA, which was consistent across two different sampling times. Despite a positive effect of phosphorus additions on extraradical AMF biomass, no relationship between WSA and extra-radical AMF nor roots was revealed by regression analyses, contrary to the proposed hypothesis. These findings emphasize the importance of analyzing soil structure in understudied tropical systems, since it might be affected by increasing nutrient deposition expected in the future.

A Robust Damage Reporting Strategy for Polymeric Materials Enabled by Aggregation Induced Emission

DTIC Science & Technology

2016-08-17

and Technology, ‡Department of Chemistry, ∥Department of Materials Science and Engineering, ⊥Department of Mechanical Science and Engineering, and...enabled by aggregation-induced emission (AIE). This simple, yet powerful system relies on a single active component, and the general mechanism ...delivers outstanding performance in a wide variety of materials with diverse chemical and mechanical properties. Small (micrometer) scale damage in

Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors.

PubMed

Olivier, Christoph B; Weik, Patrick; Meyer, Melanie; Weber, Susanne; Diehl, Philipp; Bode, Christoph; Moser, Martin; Zhou, Qian

2016-08-01

Dabigatran and rivaroxaban are novel, vitamin K-independent oral anticoagulants (NOACs) and act via antagonism of the coagulation factor (F) IIa (dabigatran) or FXa (rivaroxaban), respectively. Compared to vitamin-K-antagonists, NOACs have shown non-inferiority of risk and benefit in patients with non valvular atrial fibrillation (AF). In clinical practice there is increasing use of NOACs combined with platelet inhibitors in patients with AF and coronary artery disease. However, whether NOACs affect the function of platelet inhibitors remains incompletely known. This observational study aimed to assess the platelet function in patients receiving dabigatran or rivaroxaban and concomitant platelet inhibitors. A single centre observational study was performed analysing the platelet aggregation of patients treated with dabigatran or rivaroxaban with or without concomitant platelet inhibitors. Measurements before the initiation of NOAC therapy served as the respective control group. Platelet aggregation was measured by multiple electrode aggregometry and was induced with adenosine diphosphate (ADP, 6.5 µM) and arachidonic acid (AA, 0.5 mM), respectively. In order to evaluate whether NOACs interact with platelet inhibition by ASA or the P2Y12-antagonist clopidogrel, 87 patients were grouped according to their concomitant antiplatelet medication. Comparing the ADP- and AA-induced platelet aggregation in patients without concomitant platelet inhibitors (n = 45) no significant differences under therapy with dabigatran (d) or rivaroxaban (r) compared to the control group (c) were observed. In patients taking clopidogrel as a concomitant platelet inhibitor (n = 21), neither dabigatran nor rivaroxaban affected the ADP-induced platelet aggregation (c 20 ± 11, d 21 ± 14, r 18 ± 8 AU*min, p = 0.200). Patients receiving dabigatran or rivaroxaban in combination with ASA (n = 42; 21 ASA only, 21 ASA + clopidogrel) showed no significant differences of the AA-induced aggregation compared to the control group (c 10 ± 8, d 9 ± 7, r 10 ± 8 AU*min, p = 0.810). The antiplatelet effects of ASA and clopidogrel monitored by AA- or ADP-induced platelet aggregation were not affected by NOAC therapy.

Multi-load Groups Coordinated Load Control Strategy Considering Power Network Constraints

NASA Astrophysics Data System (ADS)

Liu, Meng; Zhao, Binchao; Wang, Jun; Zhang, Guohui; Wang, Xin

2017-05-01

Loads with energy storage property can actively participate in power balance for power systems, this paper takes air conditioner as a controllable load example, proposing a multi-load groups coordinated load control strategy considering power network constraints. Firstly, two load control modes considering recovery of load diversity are designed, blocking power oscillation of aggregated air conditioners. As the same time, air conditioner temperature setpoint recovery control strategy is presented to avoid power recovery peak. Considering inherent characteristics of two load control modes, an coordinated load control mode is designed by combining the both. Basing on this, a multi-load groups coordinated load control strategy is proposed. During the implementing of load control, power network constraints should be satisfied. An indice which can reflect the security of power system operating is defined. By minimizing its value through optimization, the change of air conditioning loads’ aggregated power on each load bus can be calculated. Simulations are conducted on an air conditioners group and New England 10-generator 39-bus system, verifying the effectiveness of the proposed multi-load groups coordinated load control strategy considering power network constraints.

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.

PubMed

Paranjape, Smita R; Riley, Andrew P; Somoza, Amber D; Oakley, C Elizabeth; Wang, Clay C C; Prisinzano, Thomas E; Oakley, Berl R; Gamblin, T Chris

2015-05-20

The aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including Alzheimer's disease. The inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. Fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. We have previously screened Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis. We therefore tested 11 azaphilone derivatives to determine their tau assembly inhibition properties in vitro. All compounds tested inhibited tau filament assembly to some extent, and four of the 11 compounds had the advantageous property of disassembling preformed tau aggregates in a dose-dependent fashion. The addition of these compounds to the tau aggregates reduced both the total length and number of tau polymers. The most potent compounds were tested in in vitro reactions to determine whether they interfere with tau's normal function of stabilizing microtubules (MTs). We found that they did not completely inhibit MT assembly in the presence of tau. These derivatives are very promising lead compounds for tau aggregation inhibitors and, more excitingly, for compounds that can disassemble pre-existing tau filaments. They also represent a new class of anti-tau aggregation compounds with a novel structural scaffold.

Value of travel-time reliability, part II : a study of tradeoffs between travel reliability, congestion-mitigation strategies and emissions.

DOT National Transportation Integrated Search

2012-09-01

Capacity, demand, and vehicle based emissions reduction strategies are compared for several pollutants employing aggregate US : congestion and vehicle fleet condition data. We find that congestion mitigation does not inevitably lead to reduced emissi...

Long-term costs of introducing HPV-DNA post-treatment surveillance to national cervical cancer screening in Ireland.

PubMed

Agapova, Maria; Duignan, Andrea; Smith, Alan; O'Neill, Ciaran; Basu, Anirban

2015-01-01

Co-testing (cytology plus human papillomavirus DNA testing) as part of cervical cancer surveillance in Ireland increases one-time testing costs. Of interest to policy makers was the long-term impact of these costs accompanied by decreases in intensity of recalls for women with no detected abnormalities. A cost analysis of cytology-only and co-testing strategy was implemented using decision analytic modeling, aggregating testing utilization and costs for each of the two strategies over 12 years. Aggregated incremental costs of the co-testing strategy were positive for the first 3 years but became negative thereafter, generating a cost savings of roughly €20 million in favor of the cytology-only strategy over a 12-year period. Results were robust over a range of sensitivity analyses with respect to discount and attrition rates. This analysis provided valuable information to policy makers contributing to the introduction of co-testing for post-treatment surveillance (PTS) in Ireland.

SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic Heating

NASA Astrophysics Data System (ADS)

Fazio, Barbara; D'Andrea, Cristiano; Foti, Antonino; Messina, Elena; Irrera, Alessia; Donato, Maria Grazia; Villari, Valentina; Micali, Norberto; Maragò, Onofrio M.; Gucciardi, Pietro G.

2016-06-01

Strategies for in-liquid molecular detection via Surface Enhanced Raman Scattering (SERS) are currently based on chemically-driven aggregation or optical trapping of metal nanoparticles in presence of the target molecules. Such strategies allow the formation of SERS-active clusters that efficiently embed the molecule at the “hot spots” of the nanoparticles and enhance its Raman scattering by orders of magnitude. Here we report on a novel scheme that exploits the radiation pressure to locally push gold nanorods and induce their aggregation in buffered solutions of biomolecules, achieving biomolecular SERS detection at almost neutral pH. The sensor is applied to detect non-resonant amino acids and proteins, namely Phenylalanine (Phe), Bovine Serum Albumin (BSA) and Lysozyme (Lys), reaching detection limits in the μg/mL range. Being a chemical free and contactless technique, our methodology is easy to implement, fast to operate, needs small sample volumes and has potential for integration in microfluidic circuits for biomarkers detection.

Aggregation, Validation, and Generalization of Qualitative Data - Methodological and Practical Research Strategies Illustrated by the Research Process of an empirically Based Typology.

PubMed

Weis, Daniel; Willems, Helmut

2017-06-01

The article deals with the question of how aggregated data which allow for generalizable insights can be generated from single-case based qualitative investigations. Thereby, two central challenges of qualitative social research are outlined: First, researchers must ensure that the single-case data can be aggregated and condensed so that new collective structures can be detected. Second, they must apply methods and practices to allow for the generalization of the results beyond the specific study. In the following, we demonstrate how and under what conditions these challenges can be addressed in research practice. To this end, the research process of the construction of an empirically based typology is described. A qualitative study, conducted within the framework of the Luxembourg Youth Report, is used to illustrate this process. Specifically, strategies are presented which increase the likelihood of generalizability or transferability of the results, while also highlighting their limitations.

SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic Heating

PubMed Central

Fazio, Barbara; D’Andrea, Cristiano; Foti, Antonino; Messina, Elena; Irrera, Alessia; Donato, Maria Grazia; Villari, Valentina; Micali, Norberto; Maragò, Onofrio M.; Gucciardi, Pietro G.

2016-01-01

Strategies for in-liquid molecular detection via Surface Enhanced Raman Scattering (SERS) are currently based on chemically-driven aggregation or optical trapping of metal nanoparticles in presence of the target molecules. Such strategies allow the formation of SERS-active clusters that efficiently embed the molecule at the “hot spots” of the nanoparticles and enhance its Raman scattering by orders of magnitude. Here we report on a novel scheme that exploits the radiation pressure to locally push gold nanorods and induce their aggregation in buffered solutions of biomolecules, achieving biomolecular SERS detection at almost neutral pH. The sensor is applied to detect non-resonant amino acids and proteins, namely Phenylalanine (Phe), Bovine Serum Albumin (BSA) and Lysozyme (Lys), reaching detection limits in the μg/mL range. Being a chemical free and contactless technique, our methodology is easy to implement, fast to operate, needs small sample volumes and has potential for integration in microfluidic circuits for biomarkers detection. PMID:27246267

Reconstructing Economics in Light of the 2007-? Financial Crisis

ERIC Educational Resources Information Center

Friedman, Benjamin M.

2010-01-01

The lessons learned from the recent financial crisis should significantly reshape the economics profession's thinking, including, importantly, what we teach our students. Five such lessons are that we live in a monetary economy and therefore aggregate demand and policies that affect aggregate demand are determinants of real economic outcomes; that…

Lumpy Demand and the Diagrammatics of Aggregation.

ERIC Educational Resources Information Center

Shmanske, Stephen; Packey, Daniel

1999-01-01

Illustrates how a simple discontinuity in an individual's demand curve, or inverse-demand curve, affects the shape of market aggregate curves. Shows, for private goods, that an infinitesimal change in quantity can lead to large changes in consumption patterns; for collective goods, the analysis suggests a theory of coalition building. (DSK)

Abrupt Strategy Change Underlies Gradual Performance Change: Bayesian Hierarchical Models of Component and Aggregate Strategy Use

ERIC Educational Resources Information Center

Wynton, Sarah K. A.; Anglim, Jeromy

2017-01-01

While researchers have often sought to understand the learning curve in terms of multiple component processes, few studies have measured and mathematically modeled these processes on a complex task. In particular, there remains a need to reconcile how abrupt changes in strategy use can co-occur with gradual changes in task completion time. Thus,…

Shear-induced aggregation dynamics in a polymer microrod suspension

NASA Astrophysics Data System (ADS)

Kumar, Pramukta S.

A non-Brownian suspension of micron scale rods is found to exhibit reversible shear-driven formation of disordered aggregates resulting in dramatic viscosity enhancement at low shear rates. Aggregate formation is imaged at low magnification using a combined rheometer and fluorescence microscope system. The size and structure of these aggregates are found to depend on shear rate and concentration, with larger aggregates present at lower shear rates and higher concentrations. Quantitative measurements of the early-stage aggregation process are modeled by a collision driven growth of porous structures which show that the aggregate density increases with a shear rate. A Krieger-Dougherty type constitutive relation and steady-state viscosity measurements are used to estimate the intrinsic viscosity of complex structures developed under shear. Higher magnification images are collected and used to validate the aggregate size versus density relationship, as well as to obtain particle flow fields via PIV. The flow fields provide a tantalizing view of fluctuations involved in the aggregation process. Interaction strength is estimated via contact force measurements and JKR theory and found to be extremely strong in comparison to shear forces present in the system, estimated using hydrodynamic arguments. All of the results are then combined to produce a consistent conceptual model of aggregation in the system that features testable consequences. These results represent a direct, quantitative, experimental study of aggregation and viscosity enhancement in rod suspension, and demonstrate a strategy for inferring inaccessible microscopic geometric properties of a dynamic system through the combination of quantitative imaging and rheology.

Aggregate complexes of HIV-1 induced by multimeric antibodies.

PubMed

Stieh, Daniel J; King, Deborah F; Klein, Katja; Liu, Pinghuang; Shen, Xiaoying; Hwang, Kwan Ki; Ferrari, Guido; Montefiori, David C; Haynes, Barton; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Michael, Nelson L; Robb, Merlin L; Kim, Jerome H; Denny, Thomas N; Tomaras, Georgia D; Shattock, Robin J

2014-10-02

Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry. The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA. These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

Retrospective determination of 137Cs specific activity distribution in spruce bark and bark aggregated transfer factor in forests on the scale of the Czech Republic ten years after the Chernobyl accident.

PubMed

Suchara, I; Rulík, P; Hůlka, J; Pilátová, H

2011-04-15

The (137)Cs specific activities (mean 32Bq kg(-1)) were determined in spruce bark samples that had been collected at 192 sampling plots throughout the Czech Republic in 1995, and were related to the sampling year. The (137)Cs specific activities in spruce bark correlated significantly with the (137)Cs depositions in areas affected by different precipitation sums operating at the time of the Chernobyl fallout in 1986. The ratio of the (137)Cs specific activities in bark and of the (137)Cs deposition levels yielded bark aggregated transfer factor T(ag) about 10.5×10(-3)m(-2)kg(-1). Taking into account the residual specific activities of (137)Cs in bark 20Bq kg(-1) and the available pre-Chernobyl data on the (137)Cs deposition loads on the soil surface in the Czech Republic, the real aggregated transfer factor after and before the Chernobyl fallout proved to be T*(ag)=3.3×10(-3)m(-2)kg(-1) and T**(ag)=4.0×10(-3)m(-2)kg(-1), respectively. The aggregated transfer factors T*(ag) for (137)Cs and spruce bark did not differ significantly in areas unequally affected by the (137)Cs fallout in the Czech Republic in 1986, and the figures for these aggregated transfer factors were very similar to the mean bark T(ag) values published from the extensively affected areas near Chernobyl. The magnitude of the (137)Cs aggregated transfer factors for spruce bark for the pre-Chernobyl and post-Chernobyl period in the Czech Republic was also very similar. The variability in spruce bark acidity caused by the operation of local anthropogenic air pollution sources did not significantly influence the accumulation and retention of (137)Cs in spruce bark. Increasing elevation of the bark sampling plots had a significant effect on raising the remaining (137)Cs specific activities in bark in areas affected by precipitation at the time when the plumes crossed, because the sums of this precipitation increased with elevation (covariable). Copyright © 2011 Elsevier B.V. All rights reserved.

A Theoretical Study of some Rheological Properties of the Aggregation of the Molecules Deoxy- Hemoglobin S

NASA Astrophysics Data System (ADS)

Mensah, Francis; Grant, Julius; Thorpe, Arthur

2010-02-01

Sickle cell disease is a serious public health problem that affects many people worldwide. In this paper, the Langevin equation is used for hemoglobin's aggregation in sickle cell anemia. Several parameters are explored such as the time-dependent deformation of the aggregates whose plot gives a sigmoid, the time-dependent expressions obtained for the coefficient of viscosity and the elastic modulus which characterize the aggregation of the sickle hemoglobin. Other properties such as the viscoelastic and the elasto-thixotropic properties of the sickle hemoglobin polymer are also described. An attempt is made to approach the polymerization process in terms of a dynamical system. )

Modelling strategies to break transmission of lymphatic filariasis--aggregation, adherence and vector competence greatly alter elimination.

PubMed

Irvine, M A; Reimer, L J; Njenga, S M; Gunawardena, S; Kelly-Hope, L; Bockarie, M; Hollingsworth, T D

2015-10-22

With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be analysed to effectively tailor programmes in the drive for elimination.

β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces

NASA Astrophysics Data System (ADS)

Brown, James W. P.; Buell, Alexander K.; Michaels, Thomas C. T.; Meisl, Georg; Carozza, Jacqueline; Flagmeier, Patrick; Vendruscolo, Michele; Knowles, Tuomas P. J.; Dobson, Christopher M.; Galvagnion, Céline

2016-11-01

α-Synuclein is an intrinsically disordered protein that is associated with the pathogenesis of Parkinson’s disease through the processes involved in the formation of amyloid fibrils. α and β-synuclein are homologous proteins found at comparable levels in presynaptic terminals but β-synuclein has a greatly reduced propensity to aggregate and indeed has been found to inhibit α-synuclein aggregation. In this paper, we describe how sequence differences between α- and β-synuclein affect individual microscopic processes in amyloid formation. In particular, we show that β-synuclein strongly suppresses both lipid-induced aggregation and secondary nucleation of α-synuclein by competing for binding sites at the surfaces of lipid vesicles and fibrils, respectively. These results suggest that β-synuclein can act as a natural inhibitor of α-synuclein aggregation by reducing both the initiation of its self-assembly and the proliferation of its aggregates.

Cholesterol impairment contributes to neuroserpin aggregation

NASA Astrophysics Data System (ADS)

Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

2017-03-01

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

Memantine inhibits β-amyloid aggregation and disassembles preformed β-amyloid aggregates.

PubMed

Takahashi-Ito, Kaori; Makino, Mitsuhiro; Okado, Keiko; Tomita, Taisuke

2017-11-04

Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy. Memantine inhibited the formation of Aβ(1-42) aggregates in a concentration-dependent manner, whereas amantadine, a structurally similar compound, did not affect Aβ aggregation at the same concentrations. Furthermore, memantine inhibited the formation of different types of Aβ aggregates, including Aβs carrying familial AD mutations, and disaggregated preformed Aβ(1-42) fibrils. These results suggest that the inhibition of Aβ aggregation and induction of Aβ disaggregation may be involved in the mechanisms by which memantine reduces Aβ deposition in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Atomistic Structure of Mineral Nano-aggregates from Simulated Compaction and Dewatering.

PubMed

Ho, Tuan Anh; Greathouse, Jeffery A; Wang, Yifeng; Criscenti, Louise J

2017-11-10

The porosity of clay aggregates is an important property governing chemical reactions and fluid flow in low-permeability geologic formations and clay-based engineered barrier systems. Pore spaces in clays include interlayer and interparticle pores. Under compaction and dewatering, the size and geometry of such pore spaces may vary significantly (sub-nanometer to microns) depending on ambient physical and chemical conditions. Here we report a molecular dynamics simulation method to construct a complex and realistic clay-like nanoparticle aggregate with interparticle pores and grain boundaries. The model structure is then used to investigate the effect of dewatering and water content on micro-porosity of the aggregates. The results suggest that slow dewatering would create more compact aggregates compared to fast dewatering. Furthermore, the amount of water present in the aggregates strongly affects the particle-particle interactions and hence the aggregate structure. Detailed analyses of particle-particle and water-particle interactions provide a molecular-scale view of porosity and texture development of the aggregates. The simulation method developed here may also aid in modeling the synthesis of nanostructured materials through self-assembly of nanoparticles.

Effect of lightweight aggregates prepared from fly ash on lightweight concrete performances

NASA Astrophysics Data System (ADS)

Punlert, S.; Laoratanakul, P.; Kongdee, R.; Suntako, R.

2017-09-01

Lightweight aggregates were prepared from fly ash of by-products from the paper industry. The influence of the ratio of clay to fly ash and processing conditions on lightweight aggregates properties were investigated. It was found that the amount of fly ash directly affected to porosity of lightweight aggregates. Lightweight aggregates with the ratio of clay to fly ash at 80:20 wt% using the sintering temperature at 1210°C exhibits bulk density of 1.66 g cm-3, compressive strength of 25 MPa and water absorption of 0.55%. The replacement of coarse aggregates with lightweight aggregates at 100 wt% for concrete production showed the ultimate properties of concrete with density of 1780 g cm-3, water absorption of 3.55%, compressive strength of 40.94 MPa and thermal conductivity of 0.77 W m-1K-1. The concrete had more than 25% weight reduction while keeping a similar compressive strength to an ordinary concrete. This is revealed that lightweight aggregates could be applied into structural concrete because it was able to reduce work load and increase safety factor of construction.

Atomistic Structure of Mineral Nano-aggregates from Simulated Compaction and Dewatering

DOE PAGES

Ho, Tuan Anh; Greathouse, Jeffery A.; Wang, Yifeng; ...

2017-11-10

The porosity of clay aggregates is an important property governing chemical reactions and fluid flow in low-permeability geologic formations and clay-based engineered barrier systems. Pore spaces in clays include interlayer and interparticle pores. Under compaction and dewatering, the size and geometry of such pore spaces may vary significantly (sub-nanometer to microns) depending on ambient physical and chemical conditions. Here we report a molecular dynamics simulation method to construct a complex and realistic clay-like nanoparticle aggregate with interparticle pores and grain boundaries. The model structure is then used to investigate the effect of dewatering and water content on micro-porosity of themore » aggregates. The results suggest that slow dewatering would create more compact aggregates compared to fast dewatering. Furthermore, the amount of water present in the aggregates strongly affects the particle-particle interactions and hence the aggregate structure. Detailed analyses of particle-particle and water-particle interactions provide a molecular-scale view of porosity and texture development of the aggregates. The simulation method developed here may also aid in modeling the synthesis of nanostructured materials through self-assembly of nanoparticles.« less

Modelling foraging movements of diving predators: a theoretical study exploring the effect of heterogeneous landscapes on foraging efficiency

PubMed Central

Bartoń, Kamil A.; Scott, Beth E.; Travis, Justin M.J.

2014-01-01

Foraging in the marine environment presents particular challenges for air-breathing predators. Information about prey capture rates, the strategies that diving predators use to maximise prey encounter rates and foraging success are still largely unknown and difficult to observe. As well, with the growing awareness of potential climate change impacts and the increasing interest in the development of renewable sources it is unknown how the foraging activity of diving predators such as seabirds will respond to both the presence of underwater structures and the potential corresponding changes in prey distributions. Motivated by this issue we developed a theoretical model to gain general understanding of how the foraging efficiency of diving predators may vary according to landscape structure and foraging strategy. Our theoretical model highlights that animal movements, intervals between prey capture and foraging efficiency are likely to critically depend on the distribution of the prey resource and the size and distribution of introduced underwater structures. For multiple prey loaders, changes in prey distribution affected the searching time necessary to catch a set amount of prey which in turn affected the foraging efficiency. The spatial aggregation of prey around small devices (∼ 9 × 9 m) created a valuable habitat for a successful foraging activity resulting in shorter intervals between prey captures and higher foraging efficiency. The presence of large devices (∼ 24 × 24 m) however represented an obstacle for predator movement, thus increasing the intervals between prey captures. In contrast, for single prey loaders the introduction of spatial aggregation of the resources did not represent an advantage suggesting that their foraging efficiency is more strongly affected by other factors such as the timing to find the first prey item which was found to occur faster in the presence of large devices. The development of this theoretical model represents a useful starting point to understand the energetic reasons for a range of potential predator responses to spatial heterogeneity and environmental uncertainties in terms of search behaviour and predator–prey interactions. We highlight future directions that integrated empirical and modelling studies should take to improve our ability to predict how diving predators will be impacted by the deployment of manmade structures in the marine environment. PMID:25250211

An energy landscape approach to protein aggregation

NASA Astrophysics Data System (ADS)

Buell, Alexander; Knowles, Tuomas

2012-02-01

Protein aggregation into ordered fibrillar structures is the hallmark of a class of diseases, the most prominent examples of which are Alzheimer's and Parkinson's disease. Recent results (e.g. Baldwin et al. J. Am. Chem. Soc. 2011) suggest that the aggregated state of a protein is in many cases thermodynamically more stable than the soluble state. Therefore the solubility of proteins in a cellular context appears to be to a large extent under kinetic control. Here, we first present a conceptual framework for the description of protein aggregation ( see AK Buell et al., Phys. Rev. Lett. 2010) that is an extension to the generally accepted energy landscape model for protein folding. Then we apply this model to analyse and interpret a large set of experimental data on the kinetics of protein aggregation, acquired mainly with a novel biosensing approach (see TPJK Knowles et al, Proc. Nat. Acad. Sc. 2007). We show how for example the effect of sequence modifications on the kinetics and thermodynamics of human lysozyme aggregation can be understood and quantified (see AK Buell et al., J. Am. Chem. Soc. 2011). These results have important implications for therapeutic strategies against protein aggregation disorders, in this case lysozyme systemic amyloidosis.

Seasonal distribution, aggregation, and habitat selection of common carp in Clear Lake, Iowa

USGS Publications Warehouse

Penne, C.R.; Pierce, C.L.

2008-01-01

The common carp Cyprinus carpio is widely distributed and frequently considered a nuisance species outside its native range. Common carp are abundant in Clear Lake, Iowa, where their presence is both a symptom of degradation and an impediment to improving water quality and the sport fishery. We used radiotelemetry to quantify seasonal distribution, aggregation, and habitat selection of adult and subadult common carp in Clear Lake during 2005-2006 in an effort to guide future control strategies. Over a 22-month period, we recorded 1,951 locations of 54 adults and 60 subadults implanted with radio transmitters. Adults demonstrated a clear tendency to aggregate in an offshore area during the late fall and winter and in shallow, vegetated areas before and during spring spawning. Late-fall and winter aggregations were estimated to include a larger percentage of the tracked adults than spring aggregations. Subadults aggregated in shallow, vegetated areas during the spring and early summer. Our study, when considered in combination with previous research, suggests repeatable patterns of distribution, aggregation, and habitat selection that should facilitate common carp reduction programs in Clear Lake and similar systems. ?? Copyright by the American Fisheries Society 2008.

Timescales alter the inferred strength and temporal consistency of intraspecific diet specialization

USGS Publications Warehouse

Novak, Mark; Tinker, M. Tim

2015-01-01

Many populations consist of individuals that differ substantially in their diets. Quantification of the magnitude and temporal consistency of such intraspecific diet variation is needed to understand its importance, but the extent to which different approaches for doing so reflect instantaneous vs. time-aggregated measures of individual diets may bias inferences. We used direct observations of sea otter individuals (Enhydra lutris nereis) to assess how: (1) the timescale of sampling, (2) under-sampling, and (3) the incidence- vs. frequency-based consideration of prey species affect the inferred strength and consistency of intraspecific diet variation. Analyses of feeding observations aggregated over hourly to annual intervals revealed a substantial bias associated with time aggregation that decreases the inferred magnitude of specialization and increases the inferred consistency of individuals’ diets. Time aggregation also made estimates of specialization more sensitive to the consideration of prey frequency, which decreased estimates relative to the use of prey incidence; time aggregation did not affect the extent to which under-sampling contributed to its overestimation. Our analyses demonstrate the importance of studying intraspecific diet variation with an explicit consideration of time and thereby suggest guidelines for future empirical efforts. Failure to consider time will likely produce inconsistent predictions regarding the effects of intraspecific variation on predator–prey interactions.

Curcumin and kaempferol prevent lysozyme fibril formation by modulating aggregation kinetic parameters.

PubMed

Borana, Mohanish S; Mishra, Pushpa; Pissurlenkar, Raghuvir R S; Hosur, Ramakrishna V; Ahmad, Basir

2014-03-01

Interaction of small molecule inhibitors with protein aggregates has been studied extensively, but how these inhibitors modulate aggregation kinetic parameters is little understood. In this work, we investigated the ability of two potential aggregation inhibiting drugs, curcumin and kaempferol, to control the kinetic parameters of aggregation reaction. Using thioflavin T fluorescence and static light scattering, the kinetic parameters such as amplitude, elongation rate constant and lag time of guanidine hydrochloride-induced aggregation reactions of hen egg white lysozyme were studied. We observed a contrasting effect of inhibitors on the kinetic parameters when aggregation reactions were measured by these two probes. The interactions of these inhibitors with hen egg white lysozyme were investigated using fluorescence quench titration method and molecular dynamics simulations coupled with binding free energy calculations. We conclude that both the inhibitors prolong nucleation of amyloid aggregation through binding to region of the protein which is known to form the core of the protein fibril, but once the nucleus is formed the rate of elongation is not affected by the inhibitors. This work would provide insight into the mechanism of aggregation inhibition by these potential drug molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity

PubMed Central

Weisberg, Sarah J.; Lyakhovetsky, Roman; Werdiger, Ayelet-chen; Gitler, Aaron D.; Soen, Yoav; Kaganovich, Daniel

2012-01-01

Neurodegenerative diseases constitute a class of illnesses marked by pathological protein aggregation in the brains of affected individuals. Although these disorders are invariably characterized by the degeneration of highly specific subpopulations of neurons, protein aggregation occurs in all cells, which indicates that toxicity arises only in particular cell biological contexts. Aggregation-associated disorders are unified by a common cell biological feature: the deposition of the culprit proteins in inclusion bodies. The precise function of these inclusions remains unclear. The starting point for uncovering the origins of disease pathology must therefore be a thorough understanding of the general cell biological function of inclusions and their potential role in modulating the consequences of aggregation. Here, we show that in human cells certain aggregate inclusions are active compartments. We find that toxic aggregates localize to one of these compartments, the juxtanuclear quality control compartment (JUNQ), and interfere with its quality control function. The accumulation of SOD1G93A aggregates sequesters Hsp70, preventing the delivery of misfolded proteins to the proteasome. Preventing the accumulation of SOD1G93A in the JUNQ by enhancing its sequestration in an insoluble inclusion reduces the harmful effects of aggregation on cell viability. PMID:22967507

Does the Level of Occupational Aggregation Affect Estimates of the Gender Wage Gap?

ERIC Educational Resources Information Center

Kidd, Michael P.; Shannon, Michael

1996-01-01

Using data from the 1989 Canadian Labour-Market Activity Survey, when occupation is treated as a productivity-related characteristic, gender wage gap estimates are distorted. Using a larger number of occupations, the occupational aggregation by gender reflects barriers women face in attempting to enter male-dominated occupations. (SK)

Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy for decreasing neuronal proteotoxicity and aging.

PubMed

Loos, Ben; Klionsky, Daniel J; Wong, Esther

2017-09-01

Accumulation of toxic protein aggregates in the nerve cells is a hallmark of neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to improve neuronal proteostasis have a direct impact on promoting neuronal health and forestalling age-related decline in brain function. Autophagy is a lysosomal degradative pathway pivotal for neuronal protein quality control. Different types of autophagic mechanisms participate in protein handling in neurons. Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles to the lysosomes for destruction, while chaperone-mediated autophagy (CMA) degrades specific soluble cytosolic proteins delivered to the lysosomes by chaperones. Dysfunctions in macroautophagy and CMA contribute to proteo- and neuro-toxicity associated with neurodegeneration and aging. Thus, augmenting or preserving both autophagic mechanisms pose significant benefits in delaying physiological and pathological neuronal demises. Recently, life-style interventions that modulate metabolite ketone bodies, energy intake by caloric restriction and energy expenditure by exercise have shown to enhance both autophagy and brain health. However, to what extent these interventions affect neuronal autophagy to promote brain fitness remains largely unclear. Here, we review the functional connections of how macroautophagy and CMA are affected by ketone bodies, caloric restriction and exercise in the context of neurodegeneration. A concomitant assessment of yeast Saccharomyces cerevisiae is performed to reveal the conserved nature of such autophagic responses to substrate perturbations. In doing so, we provide novel insights and integrated evidence for a potential adjuvant therapeutic strategy to intervene in the neuronal decline in neurodegenerative diseases by controlling both macroautophagy and CMA fluxes favorably. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Mechanisms of Aberrant Protein Aggregation

NASA Astrophysics Data System (ADS)

Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

2012-02-01

We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00215g Click here for additional data file.

PubMed Central

Meisl, Georg; Yang, Xiaoting

2017-01-01

The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network that unifies the experimental kinetics under a wide range of different conditions. More generally, this universal reaction network connects previously separate systems, such as charge mutants of the Aβ42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of Aβ42. PMID:28979758

Electrochemical imaging of cells and tissues

PubMed Central

Lin, Tzu-En; Rapino, Stefania; Girault, Hubert H.

2018-01-01

The technological and experimental progress in electrochemical imaging of biological specimens is discussed with a view on potential applications for skin cancer diagnostics, reproductive medicine and microbial testing. The electrochemical analysis of single cell activity inside cell cultures, 3D cellular aggregates and microtissues is based on the selective detection of electroactive species involved in biological functions. Electrochemical imaging strategies, based on nano/micrometric probes scanning over the sample and sensor array chips, respectively, can be made sensitive and selective without being affected by optical interference as many other microscopy techniques. The recent developments in microfabrication, electronics and cell culturing/tissue engineering have evolved in affordable and fast-sampling electrochemical imaging platforms. We believe that the topics discussed herein demonstrate the applicability of electrochemical imaging devices in many areas related to cellular functions. PMID:29899947

Protein aggregation in bacteria: the thin boundary between functionality and toxicity.

PubMed

Bednarska, Natalia G; Schymkowitz, Joost; Rousseau, Frederic; Van Eldere, Johan

2013-09-01

Misfolding and aggregation of proteins have a negative impact on all living organisms. In recent years, aggregation has been studied in detail due to its involvement in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, and type II diabetes--all associated with accumulation of amyloid fibrils. This research highlighted the central importance of protein homeostasis, or proteostasis for short, defined as the cellular state in which the proteome is both stable and functional. It implicates an equilibrium between synthesis, folding, trafficking, aggregation, disaggregation and degradation. In accordance with the eukaryotic systems, it has been documented that protein aggregation also reduces fitness of bacterial cells, but although our understanding of the cellular protein quality control systems is perhaps most detailed in bacteria, the use of bacterial proteostasis as a drug target remains little explored. Here we describe protein aggregation as a normal physiological process and its role in bacterial virulence and we shed light on how bacteria defend themselves against the toxic threat of aggregates. We review the impact of aggregates on bacterial viability and look at the ways that bacteria use to maintain a balance between aggregation and functionality. The proteostasis in bacteria can be interrupted via overexpression of proteins, certain antibiotics such as aminoglycosides, as well as antimicrobial peptides--all leading to loss of cell viability. Therefore intracellular protein aggregation and disruption of proteostatic balance in bacteria open up another strategy that should be explored towards the discovery of new antimicrobials.

MMP-2, MMP-9, and TIMP-4 and Response to Aspirin in Diabetic and Nondiabetic Patients with Stable Coronary Artery Disease: A Pilot Study

PubMed Central

Kuliczkowski, Wiktor; Radomski, Marek; Gąsior, Mariusz; Urbaniak, Joanna; Kaczmarski, Jacek; Mysiak, Andrzej; Negrusz-Kawecka, Marta

2017-01-01

Background High on-aspirin treatment platelets reactivity (HPR) is a significant problem in long-term secondary prevention of cardiovascular events. We hypothesize that imbalance between platelets MMPs/TIMPs results in cardiovascular disorders. We also explored whether chronically elevated blood glucose affects MMP-2/TIMP-4 release from platelets. Materials and Methods Seventy patients with stable coronary artery disease, supplemented with aspirin, participated in this pilot study. The presence of HPR and/or diabetes mellitus was considered as the differentiating factor. Light aggregometry, impedance aggregometry, and ELISA tests for TXB2, MMP-2, MMP-9, and TIMP-4 were performed in serum, plasma, platelet-rich plasma, and platelets-poor plasma, as appropriate. Results Aspirin-HPR did not affect plasma MMP-2, MMP-9, and TIMP-4. Arachidonic acid-induced aggregation of platelets from aspirin-HPR patients did not lead to increased release of MMP-2, MMP-9, and TIMP-4. Studying patients at the lowest TXB2 serum concentration quartile revealed that high concentration of plasma TIMP-4 and TIMP-4 negatively correlated with TXB2 and platelet aggregation. Diabetics showed an increased plasma MMP-2 as well as an increased MMP-2 in supernatants after platelet aggregation. However, diabetes mellitus did not affect MMP-9 and TIMP-4. Conclusion Aspirin-HPR did not affect the translocation and release of MMPs and TIMP-4 from platelets. TIMP-4 may serve as a marker of TXA2-mediated platelet aggregation. Chronically elevated plasma glucose increases plasma MMP-2, and HPR potentiates this phenomenon. PMID:28770228

Soil aggregation and aggregating agents as affected by long term contrasting management of an Anthrosol

NASA Astrophysics Data System (ADS)

Zhang, Shulan; Wang, Renjie; Yang, Xueyun; Sun, Benhua; Li, Qinghui

2016-12-01

Soil aggregation was studied in a 21-year experiment conducted on an Anthrosol. The soil management regimes consisted of cropland abandonment, bare fallow without vegetation and cropping system. The cropping system was combined with the following nutrient management treatments: control (CONTROL, no nutrient input); nitrogen, phosphorus and potassium (NPK); straw plus NPK (SNPK); and manure (M) plus NPK (MNPK). Compared with the CONTROL treatment, the abandonment treatment significantly increased the formation of large soil macroaggregates (>2 mm) and consequently improved the stability of aggregates in the surface soil layer due to enhancement of hyphal length and of soil organic matter content. However, in response to long-term bare fallow treatment aggregate stability was low, as were the levels of aggregating agents. Long term fertilization significantly redistributed macroaggregates; this could be mainly ascribed to soil organic matter contributing to the formation of 0.5-2 mm classes of aggregates and a decrease in the formation of the >2 mm class of aggregates, especially in the MNPK treatment. Overall, hyphae represented a major aggregating agent in both of the systems tested, while soil organic compounds played significantly different roles in stabilizing aggregates in Anthrosol when the cropping system and the soil management regimes were compared.

Mechanical Performance Evaluation of Self-Compacting Concrete with Fine and Coarse Recycled Aggregates from the Precast Industry.

PubMed

Santos, Sara A; da Silva, Pedro R; de Brito, Jorge

2017-08-04

This paper intends to evaluate the feasibility of reintroducing recycled concrete aggregates in the precast industry. The mechanical properties of self-compacting concrete (SCC) with incorporation of recycled aggregates (RA) (coarse recycled aggregates (CRA) and fine recycled aggregates (FRA)) from crushed precast elements were evaluated. The goal was to evaluate the ability of producing SCC with a minimum pre-established performance in terms of mechanical strength, incorporating variable ratios of RA (FRA/CRA%: 0/0%, 25/25%, 50/50%, 0/100% and 100/0%) produced from precast source concretes with similar target performances. This replication in SCC was made for two strength classes (45 MPa and 65 MPa), with the intention of obtaining as final result concrete with recycled aggregates whose characteristics are compatible with those of a SCC with natural aggregates in terms of workability and mechanical strength. The results enabled conclusions to be established regarding the SCC's produced with fine and coarse recycled aggregates from the precast industry, based on its mechanical properties. The properties studied are strongly affected by the type and content of recycled aggregates. The potential demonstrated, mainly in the hardened state, by the joint use of fine and coarse recycled aggregate is emphasized.

Mechanical Performance Evaluation of Self-Compacting Concrete with Fine and Coarse Recycled Aggregates from the Precast Industry

PubMed Central

Santos, Sara A.; da Silva, Pedro R.; de Brito, Jorge

2017-01-01

This paper intends to evaluate the feasibility of reintroducing recycled concrete aggregates in the precast industry. The mechanical properties of self-compacting concrete (SCC) with incorporation of recycled aggregates (RA) (coarse recycled aggregates (CRA) and fine recycled aggregates (FRA)) from crushed precast elements were evaluated. The goal was to evaluate the ability of producing SCC with a minimum pre-established performance in terms of mechanical strength, incorporating variable ratios of RA (FRA/CRA%: 0/0%, 25/25%, 50/50%, 0/100% and 100/0%) produced from precast source concretes with similar target performances. This replication in SCC was made for two strength classes (45 MPa and 65 MPa), with the intention of obtaining as final result concrete with recycled aggregates whose characteristics are compatible with those of a SCC with natural aggregates in terms of workability and mechanical strength. The results enabled conclusions to be established regarding the SCC’s produced with fine and coarse recycled aggregates from the precast industry, based on its mechanical properties. The properties studied are strongly affected by the type and content of recycled aggregates. The potential demonstrated, mainly in the hardened state, by the joint use of fine and coarse recycled aggregate is emphasized. PMID:28777316

Effect of saliva viscosity on the co-aggregation between oral streptococci and Actinomyces naeslundii.

PubMed

Kitada, Katsuhiro; Oho, Takahiko

2012-06-01

The co-aggregation of oral bacteria leads to their clearance from the oral cavity. Poor oral hygiene and high saliva viscosity are common amongst the elderly; thus, they frequently suffer from pneumonia caused by the aspiration of oral microorganisms. To examine the direct effect of saliva viscosity on the co-aggregation of oral streptococci with actinomyces. Fifteen oral streptococcal and a single actinomyces strain were used. Co-aggregation was assessed by a visual assay in phosphate buffer and a spectrophotometric assay in the same buffer containing 0-60% glycerol or whole saliva. Nine oral streptococci co-aggregated with Actinomyces naeslundii ATCC12104 in the visual assay and were subsequently used for the spectrophotometric analysis. All tested strains displayed a decrease in co-aggregation with increasing amounts of glycerol in the buffer. The co-aggregation of Streptococcus oralis with A. naeslundii recovered to baseline level following the removal of glycerol. The per cent co-aggregation of S. oralis with A. naeslundii was significantly correlated with the viscosity in unstimulated and stimulated whole saliva samples (correlation coefficients: -0.52 and -0.48, respectively). This study suggests that saliva viscosity affects the co-aggregation of oral streptococci with actinomyces and that bacterial co-aggregation decreases with increasing saliva viscosity. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

Soil aggregation and aggregating agents as affected by long term contrasting management of an Anthrosol

PubMed Central

Zhang, Shulan; Wang, Renjie; Yang, Xueyun; Sun, Benhua; Li, Qinghui

2016-01-01

Soil aggregation was studied in a 21-year experiment conducted on an Anthrosol. The soil management regimes consisted of cropland abandonment, bare fallow without vegetation and cropping system. The cropping system was combined with the following nutrient management treatments: control (CONTROL, no nutrient input); nitrogen, phosphorus and potassium (NPK); straw plus NPK (SNPK); and manure (M) plus NPK (MNPK). Compared with the CONTROL treatment, the abandonment treatment significantly increased the formation of large soil macroaggregates (>2 mm) and consequently improved the stability of aggregates in the surface soil layer due to enhancement of hyphal length and of soil organic matter content. However, in response to long-term bare fallow treatment aggregate stability was low, as were the levels of aggregating agents. Long term fertilization significantly redistributed macroaggregates; this could be mainly ascribed to soil organic matter contributing to the formation of 0.5–2 mm classes of aggregates and a decrease in the formation of the >2 mm class of aggregates, especially in the MNPK treatment. Overall, hyphae represented a major aggregating agent in both of the systems tested, while soil organic compounds played significantly different roles in stabilizing aggregates in Anthrosol when the cropping system and the soil management regimes were compared. PMID:27958366

Inhibition of Human Amylin Aggregation and Cellular Toxicity by Lipoic Acid and Ascorbic Acid.

PubMed

Azzam, Sarah Kassem; Jang, Hyunwoo; Choi, Myung Chul; Alsafar, Habiba; Lukman, Suryani; Lee, Sungmun

2018-04-30

More than 30 human degenerative diseases result from protein aggregation such as Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Islet amyloid deposits, a hallmark in T2DM, are found in pancreatic islets of more than 90 % of T2DM patients. An association between amylin aggregation and reduction in β-cell mass was also established by post-mortem studies. A strategy in preventing protein aggregation-related disorders is to inhibit the protein aggregation and associated toxicity. In this study we demonstrated that two inhibitors, lipoic acid and ascorbic acid, significantly inhibited amylin aggregation. Compared to amylin (15 μM) as 100 %, lipoic acid and ascorbic acid reduced amylin fibril formation to 42.1 ± 17.2 % and 42.9 ± 12.8 % respectively, which is confirmed by fluorescence and TEM images. In cell viability tests, both inhibitors protected RIN-m5f β-cells from the toxicity of amylin aggregates. At 10:1 molar ratio of lipoic acid to amylin, lipoic acid with amylin increased the cell viability to 70.3 %, whereas only 42.8 % RIN-m5f β-cells survived in amylin aggregates. For ascorbic acid, an equimolar ratio achieved the highest cell viability of 63.3 % as compared to 42.8 % with amylin aggregates only. Docking results showed that lipoic acid and ascorbic acid physically interact with amylin amyloidogenic region (residues Ser20-Ser29) via hydrophobic interactions; hence reducing aggregation levels. Therefore, lipoic acid and ascorbic acid prevented amylin aggregation via hydrophobic interactions, which resulted in the prevention of cell toxicity in vitro.

A study in cost analysis of aggregate production as depending on drilling and blasting design

NASA Astrophysics Data System (ADS)

Bilim, Niyazi; Çelik, Arif; Kekeç, Bilgehan

2017-10-01

Since aggregate production has vital importance for many engineering projects-such as construction, highway and plant-mixed concrete production-this study was undertaken to determine how the costs for such production are affected by the design of drilling and blasting processes used. Aggregates are used in the production of concrete and asphalt, which are critical resources for the construction sector. The ongoing population increase and the growth of living standards around the world drive the increasing demand for these products. As demand grows, competition has naturally arisen among producers in the industry. Competition in the market has directly affected prices, which leads to the need for new measures and cost analysis on production costs. The cost calculation is one of the most important parameters in mining activities. Aggregate production operations include drilling, blasting, secondary crushing (if necessary), loading, hauling and crushing-screening, and each of these factors affects cost. In this study, drilling and blasting design parameters (such as hole diameter, hole depth, hole distance and burden) were investigated and evaluated for their effect on the total cost of quarrying these products, based on a particular quarry selected for this research. As the result of evaluation, the parameters actually driving costs have been identified, and their effects on the cost have been determined. In addition, some suggestions are presented regarding production design which may lead to avoiding increased production costs.

Explaining Differences in Subjective Well-Being Across 33 Nations Using Multilevel Models: Universal Personality, Cultural Relativity, and National Income.

PubMed

Cheng, Cecilia; Cheung, Mike W-L; Montasem, Alex

2016-02-01

This multinational study simultaneously tested three prominent hypotheses--universal disposition, cultural relativity, and livability--that explained differences in subjective well-being across nations. We performed multilevel structural equation modeling to examine the hypothesized relationships at both individual and cultural levels in 33 nations. Participants were 6,753 university students (2,215 men; 4,403 women; 135 did not specify), and the average age of the entire sample was 20.97 years (SD = 2.39). Both individual- and cultural-level analyses supported the universal disposition and cultural relativity hypotheses by revealing significant associations of subjective well-being with Extraversion, Neuroticism, and independent self-construal. In addition, interdependent self-construal was positively related to life satisfaction at the individual level only, whereas aggregated negative affect was positively linked with aggregate levels of Extraversion and interdependent self-construal at the cultural level only. Consistent with the livability hypothesis, gross national income (GNI) was related to aggregate levels of negative affect and life satisfaction. There was also a quadratic relationship between GNI and aggregated positive affect. Our findings reveal that universal disposition, cultural self-construal, and national income can elucidate differences in subjective well-being, but the multilevel analyses advance the literature by yielding new findings that cannot be identified in studies using individual-level analyses alone. © 2014 Wiley Periodicals, Inc.

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

PubMed Central

Cerchiari, Alec E.; Garbe, James C.; Jee, Noel Y.; Todhunter, Michael E.; Broaders, Kyle E.; Peehl, Donna M.; Desai, Tejal A.; LaBarge, Mark A.; Thomson, Matthew; Gartner, Zev J.

2015-01-01

Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer. PMID:25633040

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing

PubMed Central

Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A.; Alves, Paula M.

2016-01-01

To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. Significance The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. PMID:27025693

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing.

PubMed

Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A; Serra, Margarida; Alves, Paula M

2016-05-01

To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. ©AlphaMed Press.

Effect of degassing on the aggregation of carbon nanotubes dispersed in water

NASA Astrophysics Data System (ADS)

Chen, C.-J.; Huang, J.-R.; Hwang, I.-S.; Choi, H. J.; Lai, P.-Y.; Chan, C. K.

2017-10-01

Dynamic light scattering (DLS) along with centrifugation and shaking tests reveal that dissolved gases can significantly affect the aggregation behavior of carbon nanotubes (CNTs) dispersed in water. The CNTs in non-degassed samples form loose, stable networks having the DLS result reminiscent of semidilute polymer solutions, whereas the CNTs in degassed samples aggregate to form Brownian colloids that sediment quickly. Interestingly, the CNTs dispersed in acetone, with or without degassing, also behave like semidilute polymers in DLS experiments. We propose a surface nanobubble-assisted mechanism to explain the observed aggregation behaviors. Our work signifies that dissolved gases may play an important role in determining hydrophobicity and biomolecular functions in aqueous environments.

On the radiative properties of soot aggregates part 1: Necking and overlapping

NASA Astrophysics Data System (ADS)

Yon, J.; Bescond, A.; Liu, F.

2015-09-01

There is a strong interest in accurately modelling the radiative properties of soot aggregates (also known as black carbon particles) emitted from combustion systems and fires to gain improved understanding of the role of black carbon to global warming. This study conducted a systematic investigation of the effects of overlapping and necking between neighbouring primary particles on the radiative properties of soot aggregates using the discrete dipole approximation. The degrees of overlapping and necking are quantified by the overlapping and necking parameters. Realistic soot aggregates were generated numerically by constructing overlapping and necking to fractal aggregates formed by point-touch primary particles simulated using a diffusion-limited cluster aggregation algorithm. Radiative properties (differential scattering, absorption, total scattering, specific extinction, asymmetry factor and single scattering albedo) were calculated using the experimentally measured soot refractive index over the spectral range of 266-1064 nm for 9 combinations of the overlapping and necking parameters. Overlapping and necking affect significantly the absorption and scattering properties of soot aggregates, especially in the near UV spectrum due to the enhanced multiple scattering effects within an aggregate. By using correctly modified aggregate properties (fractal dimension, prefactor, primary particle radius, and the number of primary particle) and by accounting for the effects of multiple scattering, the simple Rayleigh-Debye-Gans theory for fractal aggregates can reproduce reasonably accurate radiative properties of realistic soot aggregates.

Integrating Ecosystem Engineering and Food Web Ecology: Testing the Effect of Biogenic Reefs on the Food Web of a Soft-Bottom Intertidal Area

PubMed Central

De Smet, Bart; Fournier, Jérôme; De Troch, Marleen; Vincx, Magda; Vanaverbeke, Jan

2015-01-01

The potential of ecosystem engineers to modify the structure and dynamics of food webs has recently been hypothesised from a conceptual point of view. Empirical data on the integration of ecosystem engineers and food webs is however largely lacking. This paper investigates the hypothesised link based on a field sampling approach of intertidal biogenic aggregations created by the ecosystem engineer Lanice conchilega (Polychaeta, Terebellidae). The aggregations are known to have a considerable impact on the physical and biogeochemical characteristics of their environment and subsequently on the abundance and biomass of primary food sources and the macrofaunal (i.e. the macro-, hyper- and epibenthos) community. Therefore, we hypothesise that L. conchilega aggregations affect the structure, stability and isotopic niche of the consumer assemblage of a soft-bottom intertidal food web. Primary food sources and the bentho-pelagic consumer assemblage of a L. conchilega aggregation and a control area were sampled on two soft-bottom intertidal areas along the French coast and analysed for their stable isotopes. Despite the structural impacts of the ecosystem engineer on the associated macrofaunal community, the presence of L. conchilega aggregations only has a minor effect on the food web structure of soft-bottom intertidal areas. The isotopic niche width of the consumer communities of the L. conchilega aggregations and control areas are highly similar, implying that consumer taxa do not shift their diet when feeding in a L. conchilega aggregation. Besides, species packing and hence trophic redundancy were not affected, pointing to an unaltered stability of the food web in the presence of L. conchilega. PMID:26496349

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes

NASA Astrophysics Data System (ADS)

Habchi, Johnny; Chia, Sean; Galvagnion, Céline; Michaels, Thomas C. T.; Bellaiche, Mathias M. J.; Ruggeri, Francesco Simone; Sanguanini, Michele; Idini, Ilaria; Kumita, Janet R.; Sparr, Emma; Linse, Sara; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele

2018-06-01

Alzheimer's disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer's disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer's disease and the impairment of cholesterol homeostasis.

Guidance to Achieve Accurate Aggregate Quantitation in Biopharmaceuticals by SV-AUC.

PubMed

Arthur, Kelly K; Kendrick, Brent S; Gabrielson, John P

2015-01-01

The levels and types of aggregates present in protein biopharmaceuticals must be assessed during all stages of product development, manufacturing, and storage of the finished product. Routine monitoring of aggregate levels in biopharmaceuticals is typically achieved by size exclusion chromatography (SEC) due to its high precision, speed, robustness, and simplicity to operate. However, SEC is error prone and requires careful method development to ensure accuracy of reported aggregate levels. Sedimentation velocity analytical ultracentrifugation (SV-AUC) is an orthogonal technique that can be used to measure protein aggregation without many of the potential inaccuracies of SEC. In this chapter, we discuss applications of SV-AUC during biopharmaceutical development and how characteristics of the technique make it better suited for some applications than others. We then discuss the elements of a comprehensive analytical control strategy for SV-AUC. Successful implementation of these analytical control elements ensures that SV-AUC provides continued value over the long time frames necessary to bring biopharmaceuticals to market. © 2015 Elsevier Inc. All rights reserved.

Aggregation Trade Offs in Family Based Recommendations

NASA Astrophysics Data System (ADS)

Berkovsky, Shlomo; Freyne, Jill; Coombe, Mac

Personalized information access tools are frequently based on collaborative filtering recommendation algorithms. Collaborative filtering recommender systems typically suffer from a data sparsity problem, where systems do not have sufficient user data to generate accurate and reliable predictions. Prior research suggested using group-based user data in the collaborative filtering recommendation process to generate group-based predictions and partially resolve the sparsity problem. Although group recommendations are less accurate than personalized recommendations, they are more accurate than general non-personalized recommendations, which are the natural fall back when personalized recommendations cannot be generated. In this work we present initial results of a study that exploits the browsing logs of real families of users gathered in an eHealth portal. The browsing logs allowed us to experimentally compare the accuracy of two group-based recommendation strategies: aggregated group models and aggregated predictions. Our results showed that aggregating individual models into group models resulted in more accurate predictions than aggregating individual predictions into group predictions.

Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

PubMed

Li, Meng; Guan, Yijia; Zhao, Andong; Ren, Jinsong; Qu, Xiaogang

2017-01-01

Development of sensitive detectors of Aβ aggregates and effective inhibitors of Aβ aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional Aβ fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known Aβ inhibitors, Aβ15-20 and polyoxometalates (POMs). The synthesized AuP can effectively inhibit Aβ aggregation and dissociate amyloid deposits with NIR irradiation both in buffer and in mice cerebrospinal fluid (CSF), and protect cells from Aβ-related toxicity upon NIR irradiation. In addition, with the shape and size-dependent optical properties, the nanorods can also act as effective diagnostic probes to sensitively detect the Aβ aggregates. This is the first report to integrate 3 segments, an Aβ-targeting element, a reporter and inhibitors, in one drug delivery system for AD treatment.

Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease

PubMed Central

Li, Meng; Guan, Yijia; Zhao, Andong; Ren, Jinsong; Qu, Xiaogang

2017-01-01

Development of sensitive detectors of Aβ aggregates and effective inhibitors of Aβ aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional Aβ fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known Aβ inhibitors, Aβ15-20 and polyoxometalates (POMs). The synthesized AuP can effectively inhibit Aβ aggregation and dissociate amyloid deposits with NIR irradiation both in buffer and in mice cerebrospinal fluid (CSF), and protect cells from Aβ-related toxicity upon NIR irradiation. In addition, with the shape and size-dependent optical properties, the nanorods can also act as effective diagnostic probes to sensitively detect the Aβ aggregates. This is the first report to integrate 3 segments, an Aβ-targeting element, a reporter and inhibitors, in one drug delivery system for AD treatment. PMID:28839459

Role of data aggregation in biosurveillance detection strategies with applications from ESSENCE.

PubMed

Burkom, Howard S; Elbert, Y; Feldman, A; Lin, J

2004-09-24

Syndromic surveillance systems are used to monitor daily electronic data streams for anomalous counts of features of varying specificity. The monitored quantities might be counts of clinical diagnoses, sales of over-the-counter influenza remedies, school absenteeism among a given age group, and so forth. Basic data-aggregation decisions for these systems include determining which records to count and how to group them in space and time. This paper discusses the application of spatial and temporal data-aggregation strategies for multiple data streams to alerting algorithms appropriate to the surveillance region and public health threat of interest. Such a strategy was applied and evaluated for a complex, authentic, multisource, multiregion environment, including >2 years of data records from a system-evaluation exercise for the Defense Advanced Research Project Agency (DARPA). Multivariate and multiple univariate statistical process control methods were adapted and applied to the DARPA data collection. Comparative parametric analyses based on temporal aggregation were used to optimize the performance of these algorithms for timely detection of a set of outbreaks identified in the data by a team of epidemiologists. The sensitivity and timeliness of the most promising detection methods were tested at empirically calculated thresholds corresponding to multiple practical false-alert rates. Even at the strictest false-alert rate, all but one of the outbreaks were detected by the best method, and the best methods achieved a 1-day median time before alert over the set of test outbreaks. These results indicate that a biosurveillance system can provide a substantial alerting-timeliness advantage over traditional public health monitoring for certain outbreaks. Comparative analyses of individual algorithm results indicate further achievable improvement in sensitivity and specificity.

Compressive Strength and Water Absorption of Pervious Concrete that Using the Fragments of Ceramics and Roof Tiles

NASA Astrophysics Data System (ADS)

Prahara, E.; Meilani

2014-03-01

Pervious concrete was introduced in America in 2003, popularized by Dan Brown and used as a rigid pavement in the open parking lot. Rigid pavement using pervious concrete can absorb water in the surface to go straight through the concrete to the ground below.This water flow is one of the benefit of using the pervious concrete. Using of wastes such as broken roof and ceramics tiles are not commonly used in Indonesia. Utilization these kind of wastes is predicted lower the compressive strength of pervious concrete as they are used as a substitute for coarse aggregate.In this research, pervious concrete is made using a mixture of the fragment of ceramics and roof tiles.This research using broken ceramics and roof tiles with a grain size that loose from 38 mm sieve, retained on 19 mm sieve and the coarse aggregate from crushed stone that loose 12.5 mm sieve, retained on 9.5 mm sieve. The water cement ratio is 0.3 and to assist the mixing process, the addition of addictive in pervious concrete is used.The size of coarse aggregate used in the mixture affects the strength of pervious concrete. The larger the size of aggregate, the obtained compressive strength becomes smaller. It also affects the density of pervious concrete. The using of mixture of ceramics and roof tiles only reduce 2 MPa of pervious concrete compressive strength so this mixture can be used as a substitute for coarse aggregate with a maximum portion of 30 %. The high porosity of the specimens causes the reduction of pervious concrete density that affect the compressive strength. This high level of porosity can be seen from the high level of water absorption that exceed the required limit of water infiltration.

Does Aggregated Returns Disclosure Increase Portfolio Risk Taking?

PubMed

Beshears, John; Choi, James J; Laibson, David; Madrian, Brigitte C

2017-06-01

Many experiments have found that participants take more investment risk if they see returns less frequently, see portfolio-level returns (rather than each individual asset's returns), or see long-horizon (rather than one-year) historical return distributions. In contrast, we find that such information aggregation treatments do not affect total equity investment when we make the investment environment more realistic than in prior experiments. Previously documented aggregation effects are not robust to changes in the risky asset's return distribution or the introduction of a multi-day delay between portfolio choice and return realizations.

COSMIC DUST AGGREGATION WITH STOCHASTIC CHARGING

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, Lorin S.; Hyde, Truell W.; Shotorban, Babak, E-mail: Lorin_Matthews@baylor.edu

2013-10-20

The coagulation of cosmic dust grains is a fundamental process which takes place in astrophysical environments, such as presolar nebulae and circumstellar and protoplanetary disks. Cosmic dust grains can become charged through interaction with their plasma environment or other processes, and the resultant electrostatic force between dust grains can strongly affect their coagulation rate. Since ions and electrons are collected on the surface of the dust grain at random time intervals, the electrical charge of a dust grain experiences stochastic fluctuations. In this study, a set of stochastic differential equations is developed to model these fluctuations over the surface ofmore » an irregularly shaped aggregate. Then, employing the data produced, the influence of the charge fluctuations on the coagulation process and the physical characteristics of the aggregates formed is examined. It is shown that dust with small charges (due to the small size of the dust grains or a tenuous plasma environment) is affected most strongly.« less

Controlling Photoconductivity in PBI Films by Supramolecular Assembly.

PubMed

Draper, Emily R; Archibald, Lewis J; Nolan, Michael C; Schweins, Ralf; Zwijnenburg, Martijn A; Sproules, Stephen; Adams, Dave J

2018-03-15

Perylene bisimides (PBIs) self-assemble in solution. The solubility of the PBIs is commonly changed through the choice of substituents at the imide positions. It is generally assumed this substitution does not affect the electronic properties of the PBI, and that the properties of the self-assembled aggregate are essentially that of the isolated molecule. However, substituents do affect the self-assembly, resulting in potentially different packing in the formed aggregates. Here, we show that the photoconductivity of films formed from a library of substituted PBIs varies strongly with the substituent and demonstrate that this is due to the different ways in which they pack. Our results open the possibility for tuning the optoelectronic properties of self-assembled PBIs by controlling the aggregate structure through careful choice of substituent, as demonstrated by us here optimising the photoconductivity of PBI films in this way. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Controlling Photoconductivity in PBI Films by Supramolecular Assembly

PubMed Central

Archibald, Lewis J.; Nolan, Michael C.; Schweins, Ralf; Zwijnenburg, Martijn A.; Sproules, Stephen

2018-01-01

Abstract Perylene bisimides (PBIs) self‐assemble in solution. The solubility of the PBIs is commonly changed through the choice of substituents at the imide positions. It is generally assumed this substitution does not affect the electronic properties of the PBI, and that the properties of the self‐assembled aggregate are essentially that of the isolated molecule. However, substituents do affect the self‐assembly, resulting in potentially different packing in the formed aggregates. Here, we show that the photoconductivity of films formed from a library of substituted PBIs varies strongly with the substituent and demonstrate that this is due to the different ways in which they pack. Our results open the possibility for tuning the optoelectronic properties of self‐assembled PBIs by controlling the aggregate structure through careful choice of substituent, as demonstrated by us here optimising the photoconductivity of PBI films in this way. PMID:29405458

Effects of Grape Xylem Sap and Cell-Wall Constituents on In Vitro Growth, Biofilm Formation and Cellular Aggregation of Xylella fastidiosa

USDA-ARS?s Scientific Manuscript database

Purified cell-wall constituents or grape xylem sap added to media affected in vitro growth, biofilm formation, cell aggregation and gene expression of Xylella fastidiosa. Media containing xylem sap from Pierce’s disease (PD)-susceptible plants provided better support for bacterial growth and biofil...

12 CFR 723.17 - Are there any exceptions to the aggregate loan limit?

Code of Federal Regulations, 2010 CFR

2010-01-01

... AFFECTING CREDIT UNIONS MEMBER BUSINESS LOANS § 723.17 Are there any exceptions to the aggregate loan limit.... Loans that are excepted from the definition of member business loans are not counted for the purpose of... for the purpose of making member business loans and can provide documentary evidence (such evidence...

Effects of Phytoplankton Growth Phase on Delayed Settling Behavior of Marine Snow Aggregates at Sharp Density Transitions

NASA Astrophysics Data System (ADS)

Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.

2016-02-01

Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.

Aggregation of recombinant human botulinum protein antigen serotype C in varying solution conditions: implications of conformational stability for aggregation kinetics.

PubMed

Bai, Shujun; Manning, Mark Cornell; Randolph, Theodore W; Carpenter, John F

2011-03-01

Solution conditions greatly affect the aggregation rate of a protein. Elucidating these influences provides insight into the critical factors governing aggregation. In this study, recombinant human botulinum protein antigen serotype C [rBoNTC (H(c))] was employed as a model protein. rBoNTC (H(c)) aggregated irreversibly during incubation at 42°C. The aggregation rate was studied as a function of solution conditions, including varying the pH from 3.5 to 8.0 and with or without 150 mM NaCl, 7.5% (w/v) trehalose, and 0.5 M urea. Some solution conditions retarded rBoNTC (H(c)) aggregation, whereas others accelerated aggregation, particularly acidic pH and addition of NaCl or urea. To better understand the mechanism by which these solution conditions influenced aggregation rates, the structure of rBoNTC (H(c)) was characterized using circular dichroism, fluorescence, and ultraviolet absorbance spectroscopies. Conformational stability was assessed from equilibrium urea-induced unfolding studies and by using differential scanning calorimetry (DSC). The activation energy of the aggregation reaction (E(a)) was estimated from an analysis of the heating-rate dependence of the thermal transition observed during DSC heating scans. Overall, for rBoNTC (H(c)), an inverse correlation was found between conformational stability and aggregation rate, as well as between the kinetic barrier to unfolding (i.e., E(a)) and aggregation rate. Copyright © 2010 Wiley-Liss, Inc.

Survivors of School Bullying: A Collective Case Study

ERIC Educational Resources Information Center

Ramirez, Octavio

2013-01-01

This article explores the coping strategies of five junior-high school students with a history of peer victimization and how those strategies help them manage the effects of bullying. The data were collected using observations, interviews, and a review of school records. The data were analyzed using categorical aggregation, direct interpretation,…

Effect of spatial averaging on multifractal properties of meteorological time series

NASA Astrophysics Data System (ADS)

Hoffmann, Holger; Baranowski, Piotr; Krzyszczak, Jaromir; Zubik, Monika

2016-04-01

Introduction The process-based models for large-scale simulations require input of agro-meteorological quantities that are often in the form of time series of coarse spatial resolution. Therefore, the knowledge about their scaling properties is fundamental for transferring locally measured fluctuations to larger scales and vice-versa. However, the scaling analysis of these quantities is complicated due to the presence of localized trends and non-stationarities. Here we assess how spatially aggregating meteorological data to coarser resolutions affects the data's temporal scaling properties. While it is known that spatial aggregation may affect spatial data properties (Hoffmann et al., 2015), it is unknown how it affects temporal data properties. Therefore, the objective of this study was to characterize the aggregation effect (AE) with regard to both temporal and spatial input data properties considering scaling properties (i.e. statistical self-similarity) of the chosen agro-meteorological time series through multifractal detrended fluctuation analysis (MFDFA). Materials and Methods Time series coming from years 1982-2011 were spatially averaged from 1 to 10, 25, 50 and 100 km resolution to assess the impact of spatial aggregation. Daily minimum, mean and maximum air temperature (2 m), precipitation, global radiation, wind speed and relative humidity (Zhao et al., 2015) were used. To reveal the multifractal structure of the time series, we used the procedure described in Baranowski et al. (2015). The diversity of the studied multifractals was evaluated by the parameters of time series spectra. In order to analyse differences in multifractal properties to 1 km resolution grids, data of coarser resolutions was disaggregated to 1 km. Results and Conclusions Analysing the spatial averaging on multifractal properties we observed that spatial patterns of the multifractal spectrum (MS) of all meteorological variables differed from 1 km grids and MS-parameters were biased by -29.1 % (precipitation; width of MS) up to >4 % (min. Temperature, Radiation; asymmetry of MS). Also, the spatial variability of MS parameters was strongly affected at the highest aggregation (100 km). Obtained results confirm that spatial data aggregation may strongly affect temporal scaling properties. This should be taken into account when upscaling for large-scale studies. Acknowledgements The study was conducted within FACCE MACSUR. Please see Baranowski et al. (2015) for details on funding. References Baranowski, P., Krzyszczak, J., Sławiński, C. et al. (2015). Climate Research 65, 39-52. Hoffman, H., G. Zhao, L.G.J. Van Bussel et al. (2015). Climate Research 65, 53-69. Zhao, G., Siebert, S., Rezaei E. et al. (2015). Agricultural and Forest Meteorology 200, 156-171.

Protein quality control system in neurodegeneration: a healing company hard to beat but failure is fatal.

PubMed

Chhangani, Deepak; Mishra, Amit

2013-08-01

A common feature in most neurodegenerative diseases and aging is the progressive accumulation of damaged proteins. Proteins are essential for all crucial biological functions. Under some notorious conditions, proteins loss their three dimensional native conformations and are converted into disordered aggregated structures. Such changes rise into pathological conditions and eventually cause serious protein conformation disorders. Protein aggregation and inclusion bodies formation mediated multifactorial proteotoxic stress has been reported in the progression of Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Prion disease. Ongoing studies have been remarkably informative in providing a systematic outlook for better understanding the concept and fundamentals of protein misfolding and aggregations. However, the precise role of protein quality control system and precursors of this mechanism remains elusive. In this review, we highlight recent insights and discuss emerging cytoprotective strategies of cellular protein quality control system implicated in protein deposition diseases. Our current review provides a clear, understandable framework of protein quality control system that may offer the more suitable therapeutic strategies for protein-associated diseases.

Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

PubMed Central

Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

2014-01-01

Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

Stoichiometric modelling of assimilatory and dissimilatory biomass utilisation in a microbial community

PubMed Central

Hunt, Kristopher A.; Jennings, Ryan deM.; Inskeep, William P.; Carlson, Ross P.

2017-01-01

Summary Assimilatory and dissimilatory utilisation of autotroph biomass by heterotrophs is a fundamental mechanism for the transfer of nutrients and energy across trophic levels. Metagenome data from a tractable, thermoacidophilic microbial community in Yellowstone National Park was used to build an in silico model to study heterotrophic utilisation of autotroph biomass using elementary flux mode analysis and flux balance analysis. Assimilatory and dissimilatory biomass utilisation was investigated using 29 forms of biomass-derived dissolved organic carbon (DOC) including individual monomer pools, individual macromolecular pools and aggregate biomass. The simulations identified ecologically competitive strategies for utilizing DOC under conditions of varying electron donor, electron acceptor or enzyme limitation. The simulated growth environment affected which form of DOC was the most competitive use of nutrients; for instance, oxygen limitation favoured utilisation of less reduced and fermentable DOC while carbon-limited environments favoured more reduced DOC. Additionally, metabolism was studied considering two encompassing metabolic strategies: simultaneous versus sequential use of DOC. Results of this study bound the transfer of nutrients and energy through microbial food webs, providing a quantitative foundation relevant to most microbial ecosystems. PMID:27387069

Embryo Aggregation in Pig Improves Cloning Efficiency and Embryo Quality.

PubMed

Buemo, Carla Paola; Gambini, Andrés; Moro, Lucia Natalia; Hiriart, María Inés; Fernández-Martín, Rafael; Collas, Philippe; Salamone, Daniel Felipe

2016-01-01

In this study, we analyzed the effects of the cloned embryo aggregation on in vitro embryo development and embryo quality by measuring blastocyst diameter and cell number, DNA fragmentation levels and the expression of genes associated with pluripotency, apoptosis, trophoblast and DNA methylation in the porcine. Zona-free reconstructed cloned embryos were cultured in the well of the well system, placing one (1x non aggregated group) or three (3x group) embryos per microwell. Our results showed that aggregation of three embryos increased blastocyst formation rate and blastocyst diameter of cloned pig embryos. DNA fragmentation levels in 3x aggregated cloned blastocysts were significantly decreased compared to 1x blastocysts. Levels of Oct4, Klf4, Igf2, Bax and Dnmt 1 transcripts were significantly higher in aggregated embryos, whereas Nanog levels were not affected. Transcripts of Cdx2 and Bcl-xl were essentially non-detectable. Our study suggests that embryo aggregation in the porcine may be beneficial for cloned embryo development and embryo quality, through a reduction in apoptotic levels and an improvement in cell reprogramming.

Light-scattering changes caused by RBC aggregation: physical basis for new approach to noninvasive blood count

NASA Astrophysics Data System (ADS)

Shvartsman, Leonid D.; Fine, Ilya

2001-06-01

We develop theoretical models of light transmission through whole blood considering RBC aggregation. RBC aggregates are considered to be the main centers of scattering in red/near- infrared spectral region. In pulsatile blood flow the periodic changes of aggregate geometry cause oscillations of light scattering. Thus scattering-assisted mechanism has to be taken into account in pulse oximeter calibration. In case of over-systolic vessel occlusion the size of aggregates grows, and the light transmission rises. Light diffraction on a single scatterer makes the transmission growth non- monotonic for certain spectral range. For the most typical set of aggregate parameters this range corresponds to wavelengths below 760 nm, and this prediction fits well both in vivo and in vitro experimental results. This spectral range depends on the refraction index mismatch and the geometry of aggregates. Both of them may be affected by the chemistry of blood. For instance, changes of glucose and hemoglobin have different effect on light transmission time response. Consequently, their content may be determined from time evolution of optical transmission.

Computational study of aggregation mechanism in human lysozyme[D67H

PubMed Central

Patel, Dharmeshkumar

2017-01-01

Aggregation of proteins is an undesired phenomena that affects both human health and bioengineered products such as therapeutic proteins. Finding preventative measures could be facilitated by a molecular-level understanding of dimer formation, which is the first step in aggregation. Here we present a molecular dynamics (MD) study of dimer formation propensity in human lysozyme and its D67H variant. Because the latter protein aggregates while the former does not, they offer an ideal system for testing the feasibility of the proposed MD approach which comprises three stages: i) partially unfolded conformers involved in dimer formation are generated via high-temperature MD simulations, ii) potential dimer structures are searched using docking and refined with MD, iii) free energy calculations are performed to find the most stable dimer structure. Our results provide a detailed explanation for how a single mutation (D67H) turns human lysozyme from non-aggregating to an aggregating protein. Conversely, the proposed method can be used to identify the residues causing aggregation in a protein, which can be mutated to prevent it. PMID:28467454

Cryptic Amyloidogenic Elements in the 3′ UTRs of Neurofilament Genes Trigger Axonal Neuropathy

PubMed Central

Rebelo, Adriana P.; Abrams, Alexander J.; Cottenie, Ellen; Horga, Alejandro; Gonzalez, Michael; Bis, Dana M.; Sanchez-Mejias, Avencia; Pinto, Milena; Buglo, Elena; Markel, Kasey; Prince, Jeffrey; Laura, Matilde; Houlden, Henry; Blake, Julian; Woodward, Cathy; Sweeney, Mary G.; Holton, Janice L.; Hanna, Michael; Dallman, Julia E.; Auer-Grumbach, Michaela; Reilly, Mary M.; Zuchner, Stephan

2016-01-01

Abnormal protein aggregation is observed in an expanding number of neurodegenerative diseases. Here, we describe a mechanism for intracellular toxic protein aggregation induced by an unusual mutation event in families affected by axonal neuropathy. These families carry distinct frameshift variants in NEFH (neurofilament heavy), leading to a loss of the terminating codon and translation of the 3′ UTR into an extra 40 amino acids. In silico aggregation prediction suggested the terminal 20 residues of the altered NEFH to be amyloidogenic, which we confirmed experimentally by serial deletion analysis. The presence of this amyloidogenic motif fused to NEFH caused prominent and toxic protein aggregates in transfected cells and disrupted motor neurons in zebrafish. We identified a similar aggregation-inducing mechanism in NEFL (neurofilament light) and FUS (fused in sarcoma), in which mutations are known to cause aggregation in Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis, respectively. In summary, we present a protein-aggregation-triggering mechanism that should be taken into consideration during the evaluation of stop-loss variants. PMID:27040688

Fractal-like Tar Ball Aggregates from Wildfire Smoke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Girotto, Giulia; China, Swarup; Bhandari, Janarjan

Tar balls are atmospheric particles abundant in slightly aged biomass burning smoke and have a significant, but highly uncertain, role on Earth's radiative balance. Tar balls are typically detected using electron microscopy; they are resistant to the electron beam, and generally, they are observed as individual spheres. Here, we report new observations of a significant fraction of tar ball aggregates (~27% by number) from samples collected in a plume of the Whitewater-Baldy Complex fire in New Mexico. The structure of these aggregates is fractal-like and follows a scale invariant power law similar to that of soot particles, despite the considerablymore » larger size and smaller number of monomers. We also present observations of tar ball aggregates from four other geographical locations, including from a remote high elevation site in the North Atlantic Ocean. Aggregation affects the particle optical properties and therefore, their climatic impact. We performed numerical simulations based on the observed morphology and estimated the effects of aggregation on the tar balls optical properties. We find that aggregation can enhance single scattering albedo by up to 41%.« less

Robustness and percolation of holes in complex networks

NASA Astrophysics Data System (ADS)

Zhou, Andu; Maletić, Slobodan; Zhao, Yi

2018-07-01

Efficient robustness and fault tolerance of complex network is significantly influenced by its connectivity, commonly modeled by the structure of pairwise relations between network elements, i.e., nodes. Nevertheless, aggregations of nodes build higher-order structures embedded in complex network, which may be more vulnerable when the fraction of nodes is removed. The structure of higher-order aggregations of nodes can be naturally modeled by simplicial complexes, whereas the removal of nodes affects the values of topological invariants, like the number of higher-dimensional holes quantified with Betti numbers. Following the methodology of percolation theory, as the fraction of nodes is removed, new holes appear, which have the role of merger between already present holes. In the present article, relationship between the robustness and homological properties of complex network is studied, through relating the graph-theoretical signatures of robustness and the quantities derived from topological invariants. The simulation results of random failures and intentional attacks on networks suggest that the changes of graph-theoretical signatures of robustness are followed by differences in the distribution of number of holes per cluster under different attack strategies. In the broader sense, the results indicate the importance of topological invariants research for obtaining further insights in understanding dynamics taking place over complex networks.

Filamentous bacteriophage as a novel therapeutic tool for Alzheimer's disease treatment.

PubMed

Solomon, Beka

2008-10-01

Antibodies towards the N-terminal region of the amyloid-beta peptide (AbetaP) bind to Abeta fibrils, leading to their disaggregation. We developed an immunization procedure using filamentous phages displaying the only four amino acids EFRH encompassing amino acids 3-6 of the 42 residues of AbetaP, found to be the main regulatory site for Abeta formation. Phages displaying EFRH epitope are effective in eliciting humoral response against AbetaP which, in turn, relieves amyloid burden in brains of amyloid-beta protein precursor transgenic mice, improving their ability to perform cognitive tasks. In order to overcome the low permeability of the blood brain barrier for targeting 'anti-aggregating' monoclonal antibodies (mAbs) to Abeta plaques in the brain, we applied antibody engineering methods to minimize the size of mAbs while maintaining their biological activity. Single-chain antibodies displayed on the surface of filamentous phage showed the ability to enter the central nervous system (CNS). The genetically engineered filamentous bacteriophage proved to be an efficient, nontoxic viral delivery vector to the brain, offering an obvious advantage over other mammalian vectors. The feasibility of these novel strategies for production and targeting of anti-aggregating antibodies against Abeta plaques to disease affected regions in the CNS may have clinical potential for treatment of Alzheimer's disease.

Sequestration of synaptic proteins by alpha-synuclein aggregates leading to neurotoxicity is inhibited by small peptide

PubMed Central

Choi, Mal-Gi; Kim, Mi Jin; Kim, Do-Geun; Yu, Ri; Jang, You-Na

2018-01-01

α-Synuclein (α-syn) is a major component of Lewy bodies found in synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Under the pathological conditions, α-syn tends to generate a diverse form of aggregates showing toxicity to neuronal cells and able to transmit across cells. However, mechanisms by which α-syn aggregates affect cytotoxicity in neurons have not been fully elucidated. Here we report that α-syn aggregates preferentially sequester specific synaptic proteins such as vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 (SNAP25) through direct binding which is resistant to SDS. The sequestration effect of α-syn aggregates was shown in a cell-free system, cultured primary neurons, and PD mouse model. Furthermore, we identified a specific blocking peptide derived from VAMP2 which partially inhibited the sequestration by α-syn aggregates and contributed to reduced neurotoxicity. These results provide a mechanism of neurotoxicity mediated by α-syn aggregates and suggest that the blocking peptide interfering with the pathological role of α-syn aggregates could be useful for designing a potential therapeutic drug for the treatment of PD. PMID:29608598

Evaluation of Aggregated Ag85B Antigen for Its Biophysical Properties, Immunogenicity, and Vaccination Potential in a Murine Model of Tuberculosis Infection

PubMed Central

Ahmad, Faraz; Zubair, Swaleha; Gupta, Pushpa; Gupta, Umesh Datta; Patel, Rakesh; Owais, Mohammad

2017-01-01

Protein aggregates have been reported to act as a reservoir that can release biologically active, native form of precursor protein. Keeping this fact into consideration, it is tempting to exploit protein aggregate-based antigen delivery system as a functional vaccine to expand desirable immunological response in the host. Herein, we explored the capacity of aggregated Ag85B of Mycobacterium tuberculosis (Mtb) to act as a prophylactic vaccine system that releases the precursor antigen in slow and sustained manner. Being particulate system with exposed hydrophobic residues, aggregated Ag85B is likely to be avidly taken up by both phagocytosis as well as fusion with plasma membrane of antigen presenting cells, leading to its direct delivery to their cytosol. Its unique ability to access cytosol of target cells is further evident from the fact that immunization with aggregated Ag85B led to the induction of Th1-dominant immune response along with upregulated expression of qualitatively superior polyfunctional T cells in the mice. Antibodies generated following immunization with aggregated antigen recognized both native and monomeric Ag85B released from protein aggregate. The implicated immunization strategy offers protection at par to that of established BCG vaccine with desirable central and effector memory responses against subsequent Mtb aerosol challenge. The study highlights the potential of aggregated Ag85B as promising antigen delivery system and paves the way to design better prophylactic regimes against various intracellular pathogens including Mtb. PMID:29230211

Active aggregation among sexes in bean flower thrips (Megalurothrips sjostedti) on cowpea (Vigna unguiculata)

PubMed Central

Niassy, Saliou; Ekesi, Sunday; Maniania, Nguya K; Orindi, Benedict; Moritz, Gerald B; de Kogel, Willem J; Subramanian, Sevgan

2016-01-01

Male sexual aggregations are a common territorial, mating-related or resource-based, behaviour observed in diverse organisms, including insects such as thrips. The influence of factors such as plant substrate, time of day, and geographic location on aggregation of thrips is uncertain, therefore we monitored the dispersion of male and female bean flower thrips (BFT), Megalurothrips sjostedti (Trybom) (Thysanoptera: Thripidae), on cowpea, Vigna unguiculata (L.) Walp. (Fabaceae), over three cowpea growth stages and across three cowpea-growing areas of Kenya. Our results indicated that for all the crop growth stages, the density of BFTs varied over the time of day, with higher densities at 10:00, 13:00, and 16:00 hours than at 07:00 hours. Thrips densities did not differ among blocks at the budding stage, but they did at peak flowering and podding stages. Dispersion indices suggested that both male and female BFTs were aggregated. Active male aggregation occurred only on green plant parts and it varied across blocks, crop stages, and locations. Similarly, active female aggregation was observed in peak flowering and podding stages. Such active aggregation indicates a semiochemical or behaviour-mediated aggregation. Identification of such a semiochemical may offer new opportunities for refining monitoring and management strategies for BFT on cowpea, the most important grain legume in sub-Saharan Africa. PMID:26726262

Active aggregation among sexes in bean flower thrips (Megalurothrips sjostedti) on cowpea (Vigna unguiculata).

PubMed

Niassy, Saliou; Ekesi, Sunday; Maniania, Nguya K; Orindi, Benedict; Moritz, Gerald B; de Kogel, Willem J; Subramanian, Sevgan

2016-01-01

Male sexual aggregations are a common territorial, mating-related or resource-based, behaviour observed in diverse organisms, including insects such as thrips. The influence of factors such as plant substrate, time of day, and geographic location on aggregation of thrips is uncertain, therefore we monitored the dispersion of male and female bean flower thrips (BFT), Megalurothrips sjostedti (Trybom) (Thysanoptera: Thripidae), on cowpea, Vigna unguiculata (L.) Walp. (Fabaceae), over three cowpea growth stages and across three cowpea-growing areas of Kenya. Our results indicated that for all the crop growth stages, the density of BFTs varied over the time of day, with higher densities at 10:00, 13:00, and 16:00 hours than at 07:00 hours. Thrips densities did not differ among blocks at the budding stage, but they did at peak flowering and podding stages. Dispersion indices suggested that both male and female BFTs were aggregated. Active male aggregation occurred only on green plant parts and it varied across blocks, crop stages, and locations. Similarly, active female aggregation was observed in peak flowering and podding stages. Such active aggregation indicates a semiochemical or behaviour-mediated aggregation. Identification of such a semiochemical may offer new opportunities for refining monitoring and management strategies for BFT on cowpea, the most important grain legume in sub-Saharan Africa.

Aggregate-based sub-CMC Solubilization of Hexadecane by Surfactants.

PubMed

Zhong, Hua; Yang, Lei; Zeng, Guangming; Brusseau, Mark L; Wang, Yake; Li, Yang; Liu, Zhifeng; Yuan, Xingzhong; Tan, Fei

Solubilization of hexadecane by two surfactants, SDBS and Triton X-100, at concentrations near the critical micelle concentration (CMC) and the related aggregation behavior was investigated in this study. Solubilization was observed at surfactant concentrations lower than CMC, and the apparent solubility of hexadecane increased linearly with surfactant concentration for both surfactants. The capacity of SDBS to solubilize hexadecane is stronger at concentrations below CMC than above CMC. In contrast, Triton X-100 shows no difference. The results of dynamic light scattering (DLS) and cryogenic TEM analysis show aggregate formation at surfactant concentrations lower than CMC. DLS-based size of the aggregates ( d ) decreases with increasing surfactant concentration. Zeta potential of the SDBS aggregates decreases with increasing SDBS concentration, whereas it increases for Triton X-100. The surface excess (Γ) of SDBS calculated based on hexadecane solubility and aggregate size data increases rapidly with increasing bulk concentration, and then asymptotically approaches the maximum surface excess (Γ max ). Conversely, there is only a minor increase in Γ for Triton X-100. Comparison of Γ and d indicates that excess of surfactant molecules at aggregate surface has great impact on surface curvature. The results of this study demonstrate formation of aggregates at surfactant concentrations below CMC for hexadecane solubilization, and indicate the potential of employing low-concentration strategy for surfactant application such as remediation of HOC contaminated sites.

In vitro study of α-synuclein protofibrils by cryo-EM suggests a Cu(2+)-dependent aggregation pathway.

PubMed

Zhang, Hangyu; Griggs, Amy; Rochet, Jean-Christophe; Stanciu, Lia A

2013-06-18

The aggregation of α-synuclein is thought to play a role in the death of dopamine neurons in Parkinson's disease (PD). Alpha-synuclein transitions itself through an aggregation pathway consisting of pathogenic species referred to as protofibrils (or oligomer), which ultimately convert to mature fibrils. The structural heterogeneity and instability of protofibrils has significantly impeded advance related to the understanding of their structural characteristics and the amyloid aggregation mystery. Here, we report, to our knowledge for the first time, on α-synuclein protofibril structural characteristics with cryo-electron microscopy. Statistical analysis of annular protofibrils revealed a constant wall thickness as a common feature. The visualization of the assembly steps enabled us to propose a novel, to our knowledge, mechanisms for α-synuclein aggregation involving ring-opening and protofibril-protofibril interaction events. The ion channel-like protofibrils and their membrane permeability have also been found in other amyloid diseases, suggesting a common molecular mechanism of pathological aggregation. Our direct visualization of the aggregation pathway of α-synuclein opens up fresh opportunities to advance the understanding of protein aggregation mechanisms relevant to many amyloid diseases. In turn, this information would enable the development of additional therapeutic strategies aimed at suppressing toxic protofibrils of amyloid proteins involved in neurological disorders. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Modeling Multivalent Ligand-Receptor Interactions with Steric Constraints on Configurations of Cell-Surface Receptor Aggregates

PubMed Central

Monine, Michael I.; Posner, Richard G.; Savage, Paul B.; Faeder, James R.; Hlavacek, William S.

2010-01-01

Abstract We use flow cytometry to characterize equilibrium binding of a fluorophore-labeled trivalent model antigen to bivalent IgE-FcεRI complexes on RBL cells. We find that flow cytometric measurements are consistent with an equilibrium model for ligand-receptor binding in which binding sites are assumed to be equivalent and ligand-induced receptor aggregates are assumed to be acyclic. However, this model predicts extensive receptor aggregation at antigen concentrations that yield strong cellular secretory responses, which is inconsistent with the expectation that large receptor aggregates should inhibit such responses. To investigate possible explanations for this discrepancy, we evaluate four rule-based models for interaction of a trivalent ligand with a bivalent cell-surface receptor that relax simplifying assumptions of the equilibrium model. These models are simulated using a rule-based kinetic Monte Carlo approach to investigate the kinetics of ligand-induced receptor aggregation and to study how the kinetics and equilibria of ligand-receptor interaction are affected by steric constraints on receptor aggregate configurations and by the formation of cyclic receptor aggregates. The results suggest that formation of linear chains of cyclic receptor dimers may be important for generating secretory signals. Steric effects that limit receptor aggregation and transient formation of small receptor aggregates may also be important. PMID:20085718

Pre-Saturation Technique of the Recycled Aggregates: Solution to the Water Absorption Drawback in the Recycled Concrete Manufacture †

PubMed Central

García-González, Julia; Rodríguez-Robles, Desirée; Juan-Valdés, Andrés; Morán-del Pozo, Julia Mª; Guerra-Romero, M. Ignacio

2014-01-01

The replacement of natural aggregates by recycled aggregates in the concrete manufacturing has been spreading worldwide as a recycling method to counteract the large amount of construction and demolition waste. Although legislation in this field is still not well developed, many investigations demonstrate the possibilities of success of this trend given that concrete with satisfactory mechanical and durability properties could be achieved. However, recycled aggregates present a low quality compared to natural aggregates, the water absorption being their main drawback. When used untreated in concrete mix, the recycled aggregate absorb part of the water initially calculated for the cement hydration, which will adversely affect some characteristics of the recycled concrete. This article seeks to demonstrate that the technique of pre-saturation is able to solve the aforementioned problem. In order to do so, the water absorption of the aggregates was tested to determine the necessary period of soaking to bring the recycled aggregates into a state of suitable humidity for their incorporation into the mixture. Moreover, several concrete mixes were made with different replacement percentages of natural aggregate and various periods of pre-saturation. The consistency and compressive strength of the concrete mixes were tested to verify the feasibility of the proposed technique. PMID:28788188

Template mediated protein self-assembly as a valuable tool in regenerative therapy.

PubMed

Kundu, B; Eltohamy, M; Yadavalli, V K; Reis, R L; Kim, H W

2018-04-11

The assembly of natural proteinaceous biopolymers into macro-scale architectures is of great importance in synthetic biology, soft-material science and regenerative therapy. The self-assembly of protein tends to be limited due to anisotropic interactions among protein molecules, poor solubility and stability. Here, we introduce a unique platform to self-immobilize diverse proteins (fibrous and globular, positively and negatively charged, low and high molecular weight) using silicon surfaces with pendant -NH 2 groups via a facile one step diffusion limited aggregation (DLA) method. All the experimental proteins (type I collagen, bovine serum albumin and cytochrome C) self-assemble into seaweed-like branched dendritic architectures via classical DLA in the absence of any electrolytes. The notable differences in branching architectures are due to dissimilarities in protein colloidal sub-units, which is typical for each protein type, along with the heterogeneous distribution of surface -NH 2 groups. Fractal analysis of assembled structures is used to explain the underlying route of fractal deposition; which concludes how proteins with different functionality can yield similar assembly. Further, the nano-micro-structured surfaces can be used to provide functional topographical cues to study cellular responses, as demonstrated using rat bone marrow stem cells. The results indicate that the immobilization of proteins via DLA does not affect functionality, instead serving as topographical cues to guide cell morphology. This indicates a promising design strategy at the tissue-material interface and is anticipated to guide future surface modifications. A cost-effective standard templating strategy is therefore proposed for fundamental and applied particle aggregation studies, which can be used at multiple length scales for biomaterial design and surface reformation.

The effect of reduced street lighting on road casualties and crime in England and Wales: controlled interrupted time series analysis

PubMed Central

Steinbach, Rebecca; Perkins, Chloe; Tompson, Lisa; Johnson, Shane; Armstrong, Ben; Green, Judith; Grundy, Chris; Wilkinson, Paul

2015-01-01

Background Many local authorities in England and Wales have reduced street lighting at night to save money and reduce carbon emissions. There is no evidence to date on whether these reductions impact on public health. We quantified the effect of 4 street lighting adaptation strategies (switch off, part-night lighting, dimming and white light) on casualties and crime in England and Wales. Methods Observational study based on analysis of geographically coded police data on road traffic collisions and crime in 62 local authorities. Conditional Poisson models were used to analyse longitudinal changes in the counts of night-time collisions occurring on affected roads during 2000–2013, and crime within census Middle Super Output Areas during 2010–2013. Effect estimates were adjusted for regional temporal trends in casualties and crime. Results There was no evidence that any street lighting adaptation strategy was associated with a change in collisions at night. There was significant statistical heterogeneity in the effects on crime estimated at police force level. Overall, there was no evidence for an association between the aggregate count of crime and switch off (RR 0.11; 95% CI 0.01 to 2.75) or part-night lighting (RR 0.96; 95% CI 0.86 to 1.06). There was weak evidence for a reduction in the aggregate count of crime and dimming (RR 0.84; 95% CI 0.70 to 1.02) and white light (RR 0.89; 95% CI 0.77 to 1.03). Conclusions This study found little evidence of harmful effects of switch off, part-night lighting, dimming, or changes to white light/LEDs on road collisions or crime in England and Wales. PMID:26219885

NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation

PubMed Central

Nivon, Mathieu; Fort, Loïc; Muller, Pascale; Richet, Emma; Simon, Stéphanie; Guey, Baptiste; Fournier, Maëlenn; Arrigo, André-Patrick; Hetz, Claudio; Atkin, Julie D.; Kretz-Remy, Carole

2016-01-01

During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopathy and familial amyotrophic lateral sclerosis. To fight against aggregates, cells are equipped with protein quality control mechanisms. Here we report that NFκB transcription factor is activated by misincorporation of amino acid analogues into proteins, inhibition of proteasomal activity, expression of the R120G mutated form of HspB5 (associated with myofibrillar myopathy), or expression of the G985R and G93A mutated forms of superoxide dismutase 1 (linked to familial amyotrophic lateral sclerosis). This noncanonical stimulation of NFκB triggers the up-regulation of BAG3 and HspB8 expression, two activators of selective autophagy, which relocalize to protein aggregates. Then NFκB-dependent autophagy allows the clearance of protein aggregates. Thus NFκB appears as a central and major regulator of protein aggregate clearance by modulating autophagic activity. In this context, the pharmacological stimulation of this quality control pathway might represent a valuable strategy for therapies against protein conformational diseases. PMID:27075172

Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats.

PubMed

Gadi, Dounia; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Legrand, Chantal; Lafeve, Françoise Fauvel; Mekhfi, Hassane

2009-08-17

Many cardiovascular diseases are associated with an increase in blood platelet activity. In Morocco, parsley (Petroselinum crispum, Apiaceae) is one of the medicinal herbs used to treat cardiovascular diseases such as arterial hypertension. In this study, crude aqueous extract (CAE) of parsley was evaluated for its anti-platelet activity in experimental animals on platelet aggregation in vitro and ex vivo; and on bleeding time in vivo. The in vitro aggregation was monitored after pre-incubation of platelets with CAE. The bleeding time and ex vivo aggregation were performed after oral treatment. CAE inhibited dose dependently platelet aggregation in vitro induced by thrombin, ADP, collagen and epinephrine. The oral administration of CAE (3g/kg) inhibited significantly (p<0.001) platelet aggregation ex vivo and prolonged bleeding time (p<0.001) without changes in the platelet amount. The prolongation of bleeding time by CAE may be attributed to the observed inhibition of platelet aggregation. These effects could be related in part to the polyphenolic compounds present in the extract. These results support the hypothesis that the dietary intake of parsley may be benefit in the normalization of platelet hyperactivation, in the nutritional prevention of cardiovascular diseases and are potentially interesting in the development of new prevention strategies.

Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid Aggregation.

PubMed

Pilkington, Emily H; Lai, May; Ge, Xinwei; Stanley, William J; Wang, Bo; Wang, Miaoyi; Kakinen, Aleksandr; Sani, Marc-Antonie; Whittaker, Michael R; Gurzov, Esteban N; Ding, Feng; Quinn, John F; Davis, Thomas P; Ke, Pu Chun

2017-12-11

Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis is to minimize the populations of toxic oligomers and protofibrils by inhibiting protein aggregation with small molecules or nanoparticles. However, melanin synthesis in nature is realized by accelerated protein fibrillation to circumvent accumulation of toxic intermediates. Accordingly, we designed and demonstrated the use of star-shaped poly(2-hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide involved in glycemic control and the pathology of type 2 diabetes. The binding of PHEA elevated the β-sheet content in IAPP aggregates while rendering a new morphology of "stelliform" amyloids originating from the polymers. Atomistic molecular dynamics simulations revealed that the PHEA arms served as rodlike scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by increased local peptide concentration. The tertiary structure of the star nanoparticles was found to be essential for driving the specific interactions required to impel the accelerated IAPP aggregation. This study sheds new light on the structure-toxicity relationship of IAPP and points to the potential of exploiting star polymers as a new class of therapeutic agents against amyloidogenesis.

Preserving privacy whilst maintaining robust epidemiological predictions.

PubMed

Werkman, Marleen; Tildesley, Michael J; Brooks-Pollock, Ellen; Keeling, Matt J

2016-12-01

Mathematical models are invaluable tools for quantifying potential epidemics and devising optimal control strategies in case of an outbreak. State-of-the-art models increasingly require detailed individual farm-based and sensitive data, which may not be available due to either lack of capacity for data collection or privacy concerns. However, in many situations, aggregated data are available for use. In this study, we systematically investigate the accuracy of predictions made by mathematical models initialised with varying data aggregations, using the UK 2001 Foot-and-Mouth Disease Epidemic as a case study. We consider the scenario when the only data available are aggregated into spatial grid cells, and develop a metapopulation model where individual farms in a single subpopulation are assumed to behave uniformly and transmit randomly. We also adapt this standard metapopulation model to capture heterogeneity in farm size and composition, using farm census data. Our results show that homogeneous models based on aggregated data overestimate final epidemic size but can perform well for predicting spatial spread. Recognising heterogeneity in farm sizes improves predictions of the final epidemic size, identifying risk areas, determining the likelihood of epidemic take-off and identifying the optimal control strategy. In conclusion, in cases where individual farm-based data are not available, models can still generate meaningful predictions, although care must be taken in their interpretation and use. Copyright © 2016. Published by Elsevier B.V.

Effects of ocean acidification on the ballast of surface aggregates sinking through the twilight zone.

PubMed

de Jesus Mendes, Pedro A; Thomsen, Laurenz

2012-01-01

The dissolution of CaCO(3) is one of the ways ocean acidification can, potentially, greatly affect the ballast of aggregates. A diminution of the ballast could reduce the settling speed of aggregates, resulting in a change in the carbon flux to the deep sea. This would mean lower amounts of more refractory organic matter reaching the ocean floor. This work aimed to determine the effect of ocean acidification on the ballast of sinking surface aggregates. Our hypothesis was that the decrease of pH will increase the dissolution of particulate inorganic carbon ballasting the aggregates, consequently reducing their settling velocity and increasing their residence time in the upper twilight zone. Using a new methodology for simulation of aggregate settling, our results suggest that future pCO(2) conditions can significantly change the ballast composition of sinking aggregates. The change in aggregate composition had an effect on the size distribution of the aggregates, with a shift to smaller aggregates. A change also occurred in the settling velocity of the particles, which would lead to a higher residence time in the water column, where they could be continuously degraded. In the environment, such an effect would result in a reduction of the carbon flux to the deep-sea. This reduction would impact those benthic communities, which rely on the vertical flow of carbon as primary source of energy.

Structural organization of surfactant aggregates in vacuo: a molecular dynamics and well-tempered metadynamics study.

PubMed

Longhi, Giovanna; Fornili, Sandro L; Turco Liveri, Vincenzo

2015-07-07

Experimental investigations using mass spectrometry have established that surfactant molecules are able to form aggregates in the gas phase. However, there is no general consensus on the organization of these aggregates and how it depends on the aggregation number and surfactant molecular structure. In the present paper we investigate the structural organization of some surfactants in vacuo by molecular dynamics and well-tempered metadynamics simulations to widely explore the space of their possible conformations in vacuo. To study how the specific molecular features of such compounds affect their organization, we have considered as paradigmatic surfactants, the anionic single-chain sodium dodecyl sulfate (SDS), the anionic double-chain sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and the zwitterionic single-chain dodecyl phosphatidyl choline (DPC) within a wide aggregation number range (from 5 to 100). We observe that for low aggregation numbers the aggregates show in vacuo the typical structure of reverse micelles, while for large aggregation numbers a variety of globular aggregates occur that are characterized by the coexistence of interlaced domains formed by the polar or ionic heads and by the alkyl chains of the surfactants. Well-tempered metadynamics simulations allows us to confirm that the structural organizations obtained after 50 ns of molecular dynamics simulations are practically the equilibrium ones. Similarities and differences of surfactant aggregates in vacuo and in apolar media are also discussed.

Microencapsulation Technology: A Powerful Tool for Integrating Expansion and Cryopreservation of Human Embryonic Stem Cells

PubMed Central

Malpique, Rita; Brito, Catarina; Jensen, Janne; Bjorquist, Petter; Carrondo, Manuel J. T.; Alves, Paula M.

2011-01-01

The successful implementation of human embryonic stem cells (hESCs)-based technologies requires the production of relevant numbers of well-characterized cells and their efficient long-term storage. In this study, cells were microencapsulated in alginate to develop an integrated bioprocess for expansion and cryopreservation of pluripotent hESCs. Different three-dimensional (3D) culture strategies were evaluated and compared, specifically, microencapsulation of hESCs as: i) single cells, ii) aggregates and iii) immobilized on microcarriers. In order to establish a scalable bioprocess, hESC-microcapsules were cultured in stirred tank bioreactors. The combination of microencapsulation and microcarrier technology resulted in a highly efficient protocol for the production and storage of pluripotent hESCs. This strategy ensured high expansion ratios (an approximately twenty-fold increase in cell concentration) and high cell recovery yields (>70%) after cryopreservation. When compared with non-encapsulated cells, cell survival post-thawing demonstrated a three-fold improvement without compromising hESC characteristics. Microencapsulation also improved the culture of hESC aggregates by protecting cells from hydrodynamic shear stress, controlling aggregate size and maintaining cell pluripotency for two weeks. This work establishes that microencapsulation technology may prove a powerful tool for integrating the expansion and cryopreservation of pluripotent hESCs. The 3D culture strategy developed herein represents a significant breakthrough towards the implementation of hESCs in clinical and industrial applications. PMID:21850261

The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.

PubMed

Seidel, K; Vinet, J; Dunnen, W F A den; Brunt, E R; Meister, M; Boncoraglio, A; Zijlstra, M P; Boddeke, H W G M; Rüb, U; Kampinga, H H; Carra, S

2012-02-01

HSPB8 is a small heat shock protein that forms a complex with the co-chaperone BAG3. Overexpression of the HSPB8-BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8-BAG3 could thus play a protective role in protein aggregation diseases and might be specifically upregulated in response to aggregate-prone protein-mediated toxicity. Here we analysed HSPB8-BAG3 expression levels in post-mortem human brain tissue from patients suffering of the following protein conformation disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Western blotting and immunohistochemistry techniques were used to analyse HSPB8 and BAG3 expression levels in fibroblasts from SCA3 patients and post-mortem brain tissues, respectively. In all diseases investigated, we observed a strong upregulation of HSPB8 and a moderate upregulation of BAG3 specifically in astrocytes in the cerebral areas affected by neuronal damage and degeneration. Intriguingly, no significant change in the HSPB8-BAG3 expression levels was observed within neurones, irrespective of their localization or of the presence of proteinaceous aggregates. We propose that the upregulation of HSPB8 and BAG3 may enhance the ability of astrocytes to clear aggregated proteins released from neurones and cellular debris, maintain the local tissue homeostasis and/or participate in the cytoskeletal remodelling that astrocytes undergo during astrogliosis. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

Aggregation in concentrated protein solutions: Insights from rheology, neutron scattering and molecular simulations

NASA Astrophysics Data System (ADS)

Castellanos, Maria Monica

Aggregation of therapeutic proteins is currently one of the major challenges in the bio-pharmaceutical industry, because aggregates could induce immunogenic responses and compromise the quality of the product. Current scientific efforts, both in industry and academia, are focused on developing rational approaches to screen different drug candidates and predict their stability under different conditions. Moreover, aggregation is promoted in highly concentrated protein solutions, which are typically required for subcutaneous injection. In order to gain further understanding about the mechanisms that lead to aggregation, an approach that combined rheology, neutron scattering, and molecular simulations was undertaken. Two model systems were studied in this work: Bovine Serum Albumin in surfactant-free Phosphate Buffered Saline at pH = 7.4 at concentrations from 11 mg/mL up to ˜519 mg/mL, and a monoclonal antibody in 20 mM Histidine/Histidine Hydrochloride at pH = 6.0 with 60 mg/mL trehalose and 0.2 mg/mL polysorbate-80 at concentrations from 53 mg/mL up to ˜220 mg/mL. The antibody used here has three mutations in the CH2 domain, which result in lower stability upon incubation at 40 °C with respect to the wild-type protein, based on size-exclusion chromatography assays. This temperature is below 49 °C, where unfolding of the least stable, CH2 domain occurs, according to differential scanning calorimetry. This dissertation focuses on identifying the role of aggregation on the viscosity of protein solutions. The protein solutions of this work show an increase in the low shear viscosity in the absence of surfactants, because proteins adsorb at the air/water interface forming a viscoelastic film that affects the measured rheology. Stable surfactant-laden protein solutions behave as simple Newtonian fluids. However, the surfactant-laden antibody solution also shows an increase in the low shear viscosity from bulk aggregation, after prolonged incubation at 40 °C. Small-angle neutron scattering experiments were used to characterize the antibody aggregates responsible for this non-Newtonian response. From the neutron scattering data, a weak barrier leading to reversible aggregation is identified. Therefore, proteins aggregate weakly after colliding hydrodynamically, unless they find a favorable contact with high binding energy. Two types of antibody aggregates were identified: oligomers with average radius of gyration of ˜10 nm, and fractal aggregates larger than ˜ 0.1 microm formed by a reaction-limited aggregation process. A characteristic upturn in the scattered intensity at low wavevector and a low shear viscosity increase are observed in aggregated protein solutions. These features are removed by filtering with a 0.2 microm filter, which also eliminates the submicron fractal aggregates. Biophysical characterization supports the conclusions from the rheology and neutron scattering experiments. Finally, molecular dynamics simulations were used to understand the effects of disulfide bonds on the conformational stability of serum albumin. Changes in disulfide bonds in the native structure could lead to partial unfolding, and the formation of aggregates through inter-molecular disulfide bonds. Therefore, it is important to understand the role of each disulfide bond on the structure and dynamics of the protein. After removing disulfide bonds, changes occur in the dynamic correlations between different residues, and the secondary and tertiary structure of albumin. However, not all disulfide bonds affect the conformation of the protein, suggesting that other interactions are more relevant to keep the stability in certain regions. Removal of all disulfide bonds using molecular dynamics is proposed as a practical prescreening tool to identify disulfide bonds that are important for the conformational stability. As a result, some disulfide bonds can be mutated without affecting the conformation of the protein.

Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Aggregation Causes Mitochondrial Dysfunction during Oxidative Stress-induced Cell Death*

PubMed Central

Itakura, Masanori; Kubo, Takeya; Kaneshige, Akihiro; Harada, Naoki; Izawa, Takeshi; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Yamaji, Ryouichi; Takeuchi, Tadayoshi

2017-01-01

Glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional protein that also mediates cell death under oxidative stress. We reported previously that the active-site cysteine (Cys-152) of GAPDH plays an essential role in oxidative stress-induced aggregation of GAPDH associated with cell death, and a C152A-GAPDH mutant rescues nitric oxide (NO)-induced cell death by interfering with the aggregation of wild type (WT)-GAPDH. However, the detailed mechanism underlying GAPDH aggregate-induced cell death remains elusive. Here we report that NO-induced GAPDH aggregation specifically causes mitochondrial dysfunction. First, we observed a correlation between NO-induced GAPDH aggregation and mitochondrial dysfunction, when GAPDH aggregation occurred at mitochondria in SH-SY5Y cells. In isolated mitochondria, aggregates of WT-GAPDH directly induced mitochondrial swelling and depolarization, whereas mixtures containing aggregates of C152A-GAPDH reduced mitochondrial dysfunction. Additionally, treatment with cyclosporin A improved WT-GAPDH aggregate-induced swelling and depolarization. In doxycycline-inducible SH-SY5Y cells, overexpression of WT-GAPDH augmented NO-induced mitochondrial dysfunction and increased mitochondrial GAPDH aggregation, whereas induced overexpression of C152A-GAPDH significantly suppressed mitochondrial impairment. Further, NO-induced cytochrome c release into the cytosol and nuclear translocation of apoptosis-inducing factor from mitochondria were both augmented in cells overexpressing WT-GAPDH but ameliorated in C152A-GAPDH-overexpressing cells. Interestingly, GAPDH aggregates induced necrotic cell death via a permeability transition pore (PTP) opening. The expression of either WT- or C152A-GAPDH did not affect other cell death pathways associated with protein aggregation, such as proteasome inhibition, gene expression induced by endoplasmic reticulum stress, or autophagy. Collectively, these results suggest that NO-induced GAPDH aggregation specifically induces mitochondrial dysfunction via PTP opening, leading to cell death. PMID:28167533

Spatial and seasonal factors are key determinants in the aggregation of helminths in their definitive hosts: Pseudamphistomum truncatum in otters (Lutra lutra).

PubMed

Sherrard-Smith, E; Perkins, S E; Chadwick, E A; Cable, J

2015-01-01

Parasites are typically aggregated within their host populations. The most heavily infected hosts are frequently cited as targets for optimal disease control. Yet a heavily infected individual is not necessarily highly infective and does not automatically contribute a higher proportion of infective parasitic stages than a host with fewer parasites. Here, Pseudamphistomum truncatum (Opisthorchiida) parasitic infection within the definitive otter host (Lutra lutra) is used as a model system. The hypothesis tested is that variation in parasite abundance, aggregation and egg production (fecundity, as a proxy of host infectivity) can be explained by abiotic (season and region) or biotic (host age, sex and body condition) factors. Parasite abundance was affected most strongly by the biotic factors of age and body condition, such that adults and otters with a higher condition index had heavier infections than sub-adults or those with a lower condition index, whilst there were no significant differences in parasite abundance among the seasons, regions (ecological regions defined by river catchment boundaries) or host sexes. Conversely, parasite aggregation was affected most strongly by the abiotic factors of season and region, which were supported by four different measures of parasite aggregation (the corrected moment estimate k, Taylor's Power Law, the Index of Discrepancy D, and Boulinier's J). Pseudamphistomum truncatum was highly aggregated within otters, with aggregation stronger in the Midlands (England) and Wales than in the southwestern region of the United Kingdom. Overall, more parasites were found in fewer hosts during the summer, which coincides with the summer peak in parasite fecundity. Combined, these data suggest that (i) few otters carry the majority of P. truncatum parasites and that there are more infective stages (eggs) produced during summer; and (ii) abiotic factors are most influential when describing parasite aggregation whilst biotic factors have a greater role in defining parasite abundance. Together, parasite abundance, aggregation and fecundity can help predict which hosts make the largest contribution to the spread of infectious diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aggregation of montmorillonite and organic matter in aqueous media containing artificial seawater.

PubMed

Furukawa, Yoko; Watkins, Janet L; Kim, Jinwook; Curry, Kenneth J; Bennett, Richard H

2009-01-23

The dispersion-aggregation behaviors of suspended colloids in rivers and estuaries are affected by the compositions of suspended materials (i.e., clay minerals vs. organic macromolecules) and salinity. Laboratory experiments were conducted to investigate the dispersion and aggregation mechanisms of suspended particles under simulated river and estuarine conditions. The average hydrodynamic diameters of suspended particles (representing degree of aggregation) and zeta potential (representing the electrokinetic properties of suspended colloids and aggregates) were determined for systems containing suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over a range of salinity (0 - 7.2 psu). The montmorillonite-only system increased the degree of aggregation with salinity increase, as would be expected for suspended colloids whose dispersion-aggregation behavior is largely controlled by the surface electrostatic properties and van der Waals forces. When montmorillonite is combined with humic acid or chitin, the aggregation of montmorillonite was effectively inhibited. The surface interaction energy model calculations reveal that the steric repulsion, rather than the increase in electronegativity, is the primary cause for the inhibition of aggregation by the addition of humic acid or chitin. These results help explain the range of dispersion-aggregation behaviors observed in natural river and estuarine systems. It is postulated that the composition of suspended particles, specifically the availability of steric polymers such as those contained in humic acid, determine whether the river suspension is rapidly aggregated and settled or remains dispersed in suspension when it encounters increasingly saline environments of estuaries and oceans.

Aggregation control of quantum dots through ion-mediated hydrogen bonding shielding.

PubMed

Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; He, Xiaoxiao; Wang, Qing; Huang, Jin; Liu, Yan

2012-06-26

Nanoparticle stabilization against detrimental aggregation is a critical parameter that needs to be well controlled. Herein, we present a facile and rapid ion-mediated dispersing technique that leads to hydrophilic aggregate-free quantum dots (QDs). Because of the shielding of the hydrogen bonds between cysteamine-capped QDs, the presence of F(-) ions disassembled the aggregates of QDs and afforded their high colloidal stability. The F(-) ions also greatly eliminated the nonspecific adsorption of the QDs on glass slides and cells. Unlike the conventional colloidal stabilized method that requires the use of any organic ligand and/or polymer for the passivation of the nanoparticle surface, the proposed approach adopts the small size and large diffusion coefficient of inorganic ions as dispersant, which offers the disaggregation a fast reaction dynamics and negligible influence on their intrinsic surface functional properties. Therefore, the ion-mediated dispersing strategy showed great potential in chemosensing and biomedical applications.

Non-cell autonomous cell death caused by transmission of Huntingtin aggregates in Drosophila.

PubMed

Babcock, Daniel T; Ganetzky, Barry

2015-01-01

Recent evidence indicates that protein aggregates can spread between neurons in several neurodegenerative diseases but much remains unknown regarding the underlying mechanisms responsible for this spreading and its role in disease progression. We recently demonstrated that mutant Huntingtin aggregates spread between cells within the Drosophila brain resulting in non-cell autonomous loss of a pair of large neurons in the posterior protocerebrum. However, the full extent of neuronal loss throughout the brain was not determined. Here we examine the effects of driving expression of mutant Huntingtin in Olfactory Receptor Neurons (ORNs) by using a marker for cleaved caspase activity to monitor neuronal apoptosis as a function of age. We find widespread caspase activity in various brain regions over time, demonstrating that non-cell autonomous damage is widespread. Improved understanding of which neurons are most vulnerable and why should be useful in developing treatment strategies for neurodegenerative diseases that involve transcellular spreading of aggregates.

Molecular dynamics analysis of the aggregation propensity of polyglutamine segments

PubMed Central

Wen, Jingran; Scoles, Daniel R.

2017-01-01

Protein misfolding and aggregation is a pathogenic feature shared among at least ten polyglutamine (polyQ) neurodegenerative diseases. While solvent-solution interaction is a key factor driving protein folding and aggregation, the solvation properties of expanded polyQ tracts are not well understood. By using GPU-enabled all-atom molecular dynamics simulations of polyQ monomers in an explicit solvent environment, this study shows that solvent-polyQ interaction propensity decreases as the lengths of polyQ tract increases. This study finds a predominance in long-distance interactions between residues far apart in polyQ sequences with longer polyQ segments, that leads to significant conformational differences. This study also indicates that large loops, comprised of parallel β-structures, appear in long polyQ tracts and present new aggregation building blocks with aggregation driven by long-distance intra-polyQ interactions. Finally, consistent with previous observations using coarse-grain simulations, this study demonstrates that there is a gain in the aggregation propensity with increased polyQ length, and that this gain is correlated with decreasing ability of solvent-polyQ interaction. These results suggest the modulation of solvent-polyQ interactions as a possible therapeutic strategy for treating polyQ diseases. PMID:28542401

17 CFR 230.504 - Exemption for limited offerings and sales of securities not exceeding $1,000,000.

Code of Federal Regulations, 2010 CFR

2010-04-01

... require the public filing and delivery to investors of a substantive disclosure document before sale, and... only to “accredited investors” as defined in § 230.501(a). (2) The aggregate offering price for an... § 230.504 fails to meet the limitation on the aggregate offering price, it does not affect the...

Successful Stabilization of Graphene Oxide in Electrolyte Solutions: Enhancement of Bio-functionalization and Cellular Uptake

PubMed Central

Hong, Bong Jin; Compton, Owen C.; An, Zhi; Eryzazici, Ibrahim; Nguyen, SonBinh T.

2013-01-01

Aqueous dispersions of graphene oxide are inherently unstable in the presence of electrolytes, which screen the electrostatic surface charge on these nanosheets and induce irreversible aggregation. Two complementary strategies, utilizing either electrostatic or steric stabilization, have been developed to enhance the stability of graphene oxide in electrolyte solutions, allowing it to stay dispersed in cell culture media and serum. The electrostatic stabilization approach entails further oxidation of graphene oxide to low C/O ratio (~1.03) and increases ionic tolerance of these nanosheets. The steric stabilization technique employs an amphiphilic block copolymer that serves as a non-covalently bound surfactant to minimize the aggregate-induced nanosheets-nanosheet interactions. Both strategies can stabilize graphene oxide nanosheets with large dimensions (>300 nm) in biological media, allowing for an enhancement of >250% in the bioconjugation efficiency of streptavidin in comparison to untreated nanosheets. Notably, both strategies allow the stabilized nanosheets to be readily uptake by cells, demonstrating their excellent performance as potential drug delivery vehicles. PMID:22017285

Collective input/output under memory constraints

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Yin; Chen, Yong; Zhuang, Yu

2014-12-18

Compared with current high-performance computing (HPC) systems, exascale systems are expected to have much less memory per node, which can significantly reduce necessary collective input/output (I/O) performance. In this study, we introduce a memory-conscious collective I/O strategy that takes into account memory capacity and bandwidth constraints. The new strategy restricts aggregation data traffic within disjointed subgroups, coordinates I/O accesses in intranode and internode layers, and determines I/O aggregators at run time considering memory consumption among processes. We have prototyped the design and evaluated it with commonly used benchmarks to verify its potential. The evaluation results demonstrate that this strategy holdsmore » promise in mitigating the memory pressure, alleviating the contention for memory bandwidth, and improving the I/O performance for projected extreme-scale systems. Given the importance of supporting increasingly data-intensive workloads and projected memory constraints on increasingly larger scale HPC systems, this new memory-conscious collective I/O can have a significant positive impact on scientific discovery productivity.« less

Long-term costs of introducing HPV-DNA post-treatment surveillance to national cervical cancer screening in Ireland

PubMed Central

Agapova, Maria; Duignan, Andrea; Smith, Alan; O'Neill, Ciaran; Basu, Anirban

2018-01-01

Introduction Co-testing (cytology plus human papillomavirus DNA testing) as part of cervical cancer surveillance in Ireland increases one-time testing costs. Of interest to policy makers was the long-term impact of these costs accompanied by decreases in intensity of recalls for women with no detected abnormalities. Methods A cost-analysis of cytology-only and co-testing was implemented using decision analytic modeling, aggregating testing utilization and costs for each of the two strategies over 12 years. Results Aggregated incremental costs of the co-testing strategy were positive for the first 3 years but became negative thereafter, generating a cost savings of roughly €20 million in favor of the cytology-only strategy over a 12-year period. Results were robust over a range of sensitivity analyses with respect to discount and attrition rates. Discussion This analysis provided valuable information to policy makers contributing to the introduction of co-testing for post-treatment surveillance in Ireland. PMID:26377838

Aggregate stability as an indicator of soil erodibility and soil physical quality: review and perspectives

NASA Astrophysics Data System (ADS)

Le Bissonnais, Yves; Chenu, Claire; Darboux, Frédéric; Duval, Odile; Legout, Cédric; Leguédois, Sophie; Gumiere, Silvio

2010-05-01

Aggregate breakdown due to water and rain action may cause surface crusting, slumping, a reduction of infiltration and interrill erosion. Aggregate stability determines the capacity of aggregates to resist the effects of water and rainfall. In this paper, we evaluated and reviewed the relevance of an aggregate stability measurement to characterize soil physical properties as well as to analyse the processes involved in these properties. Stability measurement assesses the sensitivity of soil aggregates to various basic disaggregation mechanisms such as slaking, differential swelling, dispersion and mechanical breakdown. It has been showed that aggregate size distributions of structural stability tests matched the size distributions of eroded aggregates under rainfall simulations and that erosion amount was well predicted using aggregate stability indexes. It means stability tests could be used to estimate both the erodibility and the size fractions that are available for crust formation and erosion processes. Several studies showed that organic matter was one of the main soil properties affecting soil stability. However, it has also been showed that aggregate stability of a given soil could vary within a year or between years. The factors controlling such changes have still to be specified. Aggregate stability appears therefore as a complex property, depending both on permanent soil characteristics and on dynamic factors such as the crusting stage, the climate and the biological activity. Despite, and may be, because of this complexity, aggregate stability seems an integrative and powerful indicator of soil physical quality. Future research efforts should look at the causes of short-term changes of structural stability, in order to fully understand all its aspects.

Microstructure of the regions on a plane copper electrode surface affected by a spark discharge in air in the point-plane gap

NASA Astrophysics Data System (ADS)

Tren'kin, A. A.; Karelin, V. I.; Shibitov, Yu. M.; Blinova, O. M.; Yasnikov, I. S.

2017-09-01

The microstructure of the regions affected by spark discharge on the surface of a plane copper electrode in atmospheric air in the point-plane gap has been studied using a scanning electron microscope for both the positive and negative polarity of the point electrode. It has been found that the affected regions have the shape of round spots or groups of spots with diameters of individual spots varying in the range of 20-200 μm. It has been revealed that the spots have an internal spatial structure in the form of an aggregate of concentric rings. These rings are aggregates of a large number of microscopic craters with diameters of 0.1-1.0 μm.

Multigrid accelerated simulations for Twisted Mass fermions

NASA Astrophysics Data System (ADS)

Bacchio, Simone; Alexandrou, Constantia; Finkerath, Jacob

2018-03-01

Simulations at physical quark masses are affected by the critical slowing down of the solvers. Multigrid preconditioning has proved to deal effectively with this problem. Multigrid accelerated simulations at the physical value of the pion mass are being performed to generate Nf = 2 and Nf = 2 + 1 + 1 gauge ensembles using twisted mass fermions. The adaptive aggregation-based domain decomposition multigrid solver, referred to as DD-αAMG method, is employed for these simulations. Our simulation strategy consists of an hybrid approach of different solvers, involving the Conjugate Gradient (CG), multi-mass-shift CG and DD-αAMG solvers. We present an analysis of the multigrid performance during the simulations discussing the stability of the method. This significant speeds up the Hybrid Monte Carlo simulation by more than a factor 4 at physical pion mass compared to the usage of the CG solver.

Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones.

PubMed

Fosso, Marina Y; LeVine, Harry; Green, Keith D; Tsodikov, Oleg V; Garneau-Tsodikova, Sylvie

2015-09-28

As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu(2+)/Zn(2+), while others were effective at inhibiting the action of AChE.

Semiochemical-mediated flight strategies of two invasive elm bark beetles: a potential factor in competitive displacement.

PubMed

Lee, Jana C; Hamud, Shakeeb M; Negrón, José F; Witcosky, Jeffrey J; Seybold, Steven J

2010-04-01

A seven-state survey showed that the recently detected invasive Asian banded elm bark beetle, Scolytus schevyrewi Semenov, was abundant in areas of Colorado and Wyoming, whereas the long-established European elm bark beetle, S. multistriatus (Marsham), was not as abundant. In one of a series of studies to evaluate whether S. schevyrewi is competitively displacing S. multistriatus in their North American zone of sympatry, we characterized long-range flight responses infested or uninfested to small cut logs of American, Chinese, and Siberian elm, Ulmus americana, U. parvifolia, and U. pumila. Trials were conducted in Colorado and Wyoming to test the flight response of S. schevyrewi; in California to test the response of S. multistriatus; and in Nevada to test the responses of both species simultaneously. Studies with S. schevyrewi showed that males and females aggregated toward Ulmus spp. host volatiles but provided no evidence of a putative aggregation pheromone during the 0- to 48- or 48- to 96-h period of infestation. In contrast, S. multistriatus was attracted to U. pumila over unbaited controls, more to U. pumila infested with conspecific females than without, and more during the 48- to 96- versus 0- to 48-h period of infestation. This confirmed that male and female S. multistriatus aggregated toward host volatiles and that females produced an aggregation pheromone. In a cross-attraction study, S. schevyrewi displayed neither flight preference nor interruption to U. pumila infested with conspecifics, heterospecifics, or a mix of both species. Response of S. multistriatus was too low to draw conclusions. Although S. multistriatus aggregates moderately to host volatiles and strongly to female-derived pheromones emitted after a few days, S. multistriatus may have a relative disadvantage by selecting elm hosts more slowly than S. schevyrewi, which aggregates very strongly to host volatiles. The differential long-range host location strategy may be one factor in a chain of behavioral events that leads to advantageous host colonization and development by S. schevyrewi.

Assessing Effects of Prenatal Alcohol Exposure Using Group-wise Sparse Representation of FMRI Data

PubMed Central

Lv, Jinglei; Jiang, Xi; Li, Xiang; Zhu, Dajiang; Zhao, Shijie; Zhang, Tuo; Hu, Xintao; Han, Junwei; Guo, Lei; Li, Zhihao; Coles, Claire; Hu, Xiaoping; Liu, Tianming

2015-01-01

Task-based fMRI activation mapping has been widely used in clinical neuroscience in order to assess different functional activity patterns in conditions such as prenatal alcohol exposure (PAE) affected brains and healthy controls. In this paper, we propose a novel, alternative approach of group-wise sparse representation of the fMRI data of multiple groups of subjects (healthy control, exposed non-dysmorphic PAE and exposed dysmorphic PAE) and assess the systematic functional activity differences among these three populations. Specifically, a common time series signal dictionary is learned from the aggregated fMRI signals of all three groups of subjects, and then the weight coefficient matrices (named statistical coefficient map (SCM)) associated with each common dictionary were statistically assessed for each group separately. Through inter-group comparisons based on the correspondence established by the common dictionary, our experimental results have demonstrated that the group-wise sparse coding strategy and the SCM can effectively reveal a collection of brain networks/regions that were affected by different levels of severity of PAE. PMID:26195294

Does Aggregated Returns Disclosure Increase Portfolio Risk Taking?

PubMed Central

Beshears, John; Choi, James J.; Laibson, David; Madrian, Brigitte C.

2016-01-01

Many experiments have found that participants take more investment risk if they see returns less frequently, see portfolio-level returns (rather than each individual asset’s returns), or see long-horizon (rather than one-year) historical return distributions. In contrast, we find that such information aggregation treatments do not affect total equity investment when we make the investment environment more realistic than in prior experiments. Previously documented aggregation effects are not robust to changes in the risky asset’s return distribution or the introduction of a multi-day delay between portfolio choice and return realizations. PMID:28553012

Dynamics of aggregate stability and soil organic C distribution as affected by climatic aggressiveness: a mesocosm approach

NASA Astrophysics Data System (ADS)

Pellegrini, Sergio; Elio Agnelli, Alessandro; Costanza Andrenelli, Maria; Barbetti, Roberto; Castelli, Fabio; Costantini, Edoardo A. C.; Lagomarsino, Alessandra; Pasqui, Massimiliano; Tomozeiu, Rodica; Razzaghi, Somayyeh; Vignozzi, Nadia

2014-05-01

In the framework of a research project aimed at evaluating the adaptation scenarios of the Italian agriculture to the current climate change, a mesocosm experiment under controlled conditions was set up for studying the dynamics of soil aggregate stability and organic C in different size fractions. Three alluvial loamy soils (BOV - Typic Haplustalfs coarse-loamy; CAS - Typic Haplustalfs fine-loamy; MED - Typic Hapludalfs fine-loamy) along a climatic gradient (from dryer to moister pedoclimatic conditions) in the river Po valley (northern Italy), under crop rotation for animal husbandry from more than 40 years, were selected. The Ap horizons (0-30cm) were taken and placed in 9 climatic chambers under controlled temperature and rainfall. Each soil was subjected to three different climate scenarios in terms of erosivity index obtained by combining Modified Fournier and Bagnouls-Gaussen indexes: i) typical (TYP), the median year of each site related to the 1961-1990 reference period; ii) maximum aggressive year (MAX) observed in the same period, and iii) the simulated climate (SIM), obtained by projections of climate change precipitation and temperature for the period 2021-2050 as provided by the IPCC-A1B emission scenario. In the climatic chambers the year climate was reduced to six months. The soils were analyzed for particle size distribution, aggregate stability by wet and dry sieving, and organic C content at the beginning and at the end of the trial. The soils showed different behaviour in terms of aggregate stability and dynamics of organic C in the diverse size fractions. The soils significantly differed in terms of initial mean weight diameter (MWD) (CAS>MED>BOV). A general reduction of MWD in all sites was observed at the end of the experiment, with the increase of the smallest aggregate fractions (0.250-0.05 mm). In particular, BOV showed the maximum decrease of the aggregate stability and MED the lowest. C distribution in aggregate fractions significantly changed at the end of the trial, depending of soil types. In CAS and MED a decrease of C content was observed in fractions larger than 0.250 mm, while an accumulation occurred only in CAS microaggregates. BOV showed a singular pattern, with an increase of organic C in all fractions. In this site an improvement of aggregation, involving the coarser fractions, seems to have been favoured during the experiment. Overall, the imposed climate did not affect significantly these trends, except in CAS, where TYP and SIM climates showed an increase of macroaggregates and their C concentration. Soil pedoclimatic characteristics showed to be the main factors affecting C and aggregates dynamics in this mesocosm experiment.

Prevalence and site preferences of heterophyid metacercariae in Tilapia zilli from Ismalia fresh water canal, Egypt.

PubMed

Ibrahim, M M; Soliman, M F M

2010-09-01

Factors affecting prevalence and site preferences of heterophyid metacercariae (MC) were investigated in this study. A total of 173 specimens of a freshwater fish, Tilapia zilli were collected during autumn 2008, winter 2009 and summer 2009, from Ismailia fresh water canal, Egypt. Results showed that the total prevalence of heterophyid MC was 95.37%. The heterophyid MC consisted of Haplorchis yokogawi (47.4%), Pygidiopsis genata (21.4%), and Phagicola ascolonga (93.64%). H. yokogawi MC was detected in striated muscles, P. ascolonga in liver and kidney while, P. genata was detected in muscles, liver and kidney. The aggregation indices showed that all MC were aggregated and the P. genata was the most highly aggregated followed by H. yokogawi and then P. ascolonga. Responses of the heterophyid MC to host sex, weight and season greatly varied according to species of MC. Different responses of interaction for heterophyid MC intensity were found by GLIM analysis and this variation dependant on the type of infection (single or mixed infections). Factors affecting site preference of heterophid MC infection were discussed and further studies in other locations are required to examine the factors affecting site preference.

The missing piece in the puzzle: Prediction of aggregation via the protein-protein interaction parameter A∗2.

PubMed

Koepf, Ellen; Schroeder, Rudolf; Brezesinski, Gerald; Friess, Wolfgang

2018-07-01

The tendency of protein pharmaceuticals to form aggregates is a major challenge during formulation development, as aggregation affects quality and safety of the product. In particular, the formation of large native-like particles in the context of liquid-air interfacial stress is a well-known but not fully understood problem. Focusing on the two most fundamental criteria of protein formulation affecting protein-protein interaction, the impact of pH and ionic strength on the interaction parameter A ∗ 2 and its link to aggregation upon mechanical stress was investigated. A ∗ 2 of two monoclonal antibodies (mABs) and a polyclonal IgG was determined using dynamic light scattering and was correlated to the number of particles formed upon shaking in vials analyzed by visual inspection, turbidity analysis, light obscuration and micro-flow imaging. A good correlation between aggregation induced by interfacial stress and formulation pH was given. It could be shown that A ∗ 2 was highest for mAB 1 and lowest for IgG, what was in good accordance with the number of particles formed. Shaking of IgG resulted in overall higher numbers of particles compared to the two mABs. A ∗ 2 decreased and particle numbers increased with increasing pH. Different to pH, ionic strength only slightly affected A ∗ 2 . Nevertheless, at high ionic (100 mM) strength the samples exhibited more pronounced particle formation, particularly of large particles >25 µm, which was most pronounced at high pH. Protein solutions were identified to form continuous films with an inhomogeneous protein distribution at the liquid-air interface. These areas of agglomerated, native-like protein material can be transferred into the bulk solution by compression-decompression of the interface. Whether or not those clusters lead to the appearance of large protein aggregates or fall apart depends on the attractive or repulsive forces between protein molecules. Thus, protein aggregation due to interfacial stress is correlated with the protein-protein interactions as determined by A ∗ 2 . This enables to differentiate different antibodies according to their propensity to form particles upon mechanical stress and to identify optimum formulation conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

The combination of simulation and response methodology and its application in an aggregate production plan

NASA Astrophysics Data System (ADS)

Chen, Zhiming; Feng, Yuncheng

1988-08-01

This paper describes an algorithmic structure for combining simulation and optimization techniques both in theory and practice. Response surface methodology is used to optimize the decision variables in the simulation environment. A simulation-optimization software has been developed and successfully implemented, and its application to an aggregate production planning simulation-optimization model is reported. The model's objective is to minimize the production cost and to generate an optimal production plan and inventory control strategy for an aircraft factory.

Creating big data from small: using semantic web technology to facilitate the aggregation of diverse European contaminant data for regulatory assessments

NASA Astrophysics Data System (ADS)

Thomas, R.; Kokkinaki, A.; Lowry, R. K.

2016-12-01

The European Marine Strategy Framework Directive (MSFD) requires evidence-based reporting to assess the quality of European seas by member states to determine whether they are achieving Good Ecological Status by 2020. One descriptor addresses contaminants; fertilizers, pesticides, antifoulants, heavy metals, etc. There are large amounts of contaminant data available to support this process: >600000 data granules identified, ingested and made available from 303 organizations in 38 countries through the EU funded EMODNet Chemistry program, built on the SeaDataNet (SDN) infrastructure. However when marked up consistently with SDN vocabularies the number of unique parameters available is huge (>3000). While many parameters might superficially appear similar the concentrations reported cannot always be considered equivalent, particularly in sediment and biota. The planned regional-scale data products risked being limited to localized patterns. The strategy adopted to make meaningful aggregations for data product development was to capture the knowledge of domain experts about what could be considered equivalent and publish this knowledge as a thesaurus (or SKOS schema) through the NERC Vocabulary Server (NVS). Of the >3000 parameters identified, so far 1095 have been mapped to 222 aggregated terms. This "captured domain knowledge" has been used to harmonize the data granules into aggregated data collections. The publication of this knowledge through NVS allows transparency and reproducibility of the aggregation process. Gridded data products are derived from the data collection with visualizations available as products generated from the gridded data collections: currently 140 products available either as WFS visualization or netCDF file download. This approach shows how small data sets integrated into larger-scale products, some of which can be targeted at non-scientists, have much greater value than envisaged when the data were originally collected.

Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.

PubMed

Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Marette, André; Planel, Emmanuel

2017-10-03

Tau is a microtubule-associated protein that becomes pathological when it undergoes hyperphosphorylation and aggregation as seen in Alzheimer's disease (AD). AD is mostly sporadic, with environmental, biological and/or genetic risks factors, interacting together to promote the disease. In the past decade, reports have suggested that obesity in midlife could be one of these risk factors. On the other hand, caloric restriction and physical exercise have been reported to reduce the incidence and outcome of obesity as well as AD. We evaluated the impact of voluntary physical exercise and caloric restriction on tau pathology during 2months in hTau mice under high caloric diet in order to evaluate if these strategies could prevent AD-like pathology in obese conditions. We found no effects of obesity induced by Western diet on both Tau phosphorylation and aggregation compared to controls. However, exercise reduced tau phosphorylation while caloric restriction exacerbated its aggregation in the brains of obese hTau mice. We then examined the mechanisms underlying changes in tau phosphorylation and aggregation by exploring major tau kinases and phosphatases and key proteins involved in autophagy. However, there were no significant effects of voluntary exercise and caloric restriction on these proteins in hTau mice that could explain our results. In this study, we report differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in our obese mice, namely beneficial effect of exercise on tau phosphorylation and deleterious effect of caloric restriction on tau aggregation. Our results suggest that lifestyle strategies used to reduce metabolic disorders and AD must be selected and studied carefully to avoid exacerbation of pathologies. Copyright © 2017. Published by Elsevier Inc.

Soil physical conditions as livestock treading effect in tropical Agroecosystem of dryland and strategies to mitigate desertification risk

NASA Astrophysics Data System (ADS)

Florentino, A.; Torres, D.; Ospina, A.; Contreras, J.; Palma, Z.; Silvera, J.

2012-04-01

Soil degradation in natural ecosystem of arid and semi-arid zones of Venezuela due to livestock treading (goats) it is an important problem that affect their environment functions; increase soil erodibility, bulk density, water losses and reduce porosity, water infiltration rate and soil structural stability. The presence of biological crust (BSC) in this type of soil it is very common. The objective of this study was to evaluate the soil surface physical quality through the use of selected indicators, mainly some of that related to structural stability, infiltrability and the prediction of soil erosion risk in two zones of Lara state: 1) Quíbor (QUI) and 2) Humocaro Bajo (HB). The study was conducted on two selected plots (30 m x 20 m) in each zone, with natural vegetation and BSC cover, with areas affected by different degree of compaction due to treading in the paths where the goats are moving. Five sites per plot (50 cm x 50 cm) under vegetation cover and five sites over the path with bare soil were sampled (0-7,5 and 7,5-15 cm depth). The results showed that soil macroaggregate stability (equivalent diameter of aggregates >0,25 mm) was significantly higher (p<0,05 %) in soil with vegetation cover and BSC compared with bare soil. Sealing index, as a measure of aggregate stability, determined in laboratory under simulated rain and expressed as hydraulic conductivity of soil surface sealing (Kse), decreased with decreasing soil vegetation cover and the presence of BSC. However, Ksei (i: inicial) and Ksef (f: final) were significantly greater in soil with more than 75 % of BSC in comparison to bare soils. The sealing index it is used to for to estimate changes in soil water losses. As the sealing index increases, the susceptibility of the soil to undergo surface sealing or slaking decrease. These results suggested that soil physical properties are potential indicators of soil quality with regard to soil erodibility and showed that soils under vegetation cover had higher quality level than bare soils. Some predictive regression equation had a high R2 value and was a useful tool for to evaluate the risk of extreme climatic changes and to mitigate their detrimental effects. We conclude that the global climatic change (CCG) will have a negative effect on these agroecosystems functions, mainly in soil and water conservation, carbon sequestration, and productivity. Natural recovery of soil physical properties from treading damage of pastoral soils will be possible in the future with the implementation of soil management strategies, mainly through re-vegetation and recuperation of the BSC. Key word: Soil structure; aggregate stability; soil sealing index; hydraulic conductivity of surface sealing.

Seasonality can induce coexistence of multiple bet-hedging strategies in Dictyostelium discoideum via storage effect.

PubMed

Martínez-García, Ricardo; Tarnita, Corina E

2017-08-07

The social amoeba Dictyostelium discoideum has been recently suggested as an example of bet-hedging in microbes. In the presence of resources, amoebae reproduce as unicellular organisms. Resource depletion, however, leads to a starvation phase in which the population splits between aggregators, which form a fruiting body made of a stalk and resistant spores, and non-aggregators, which remain as vegetative cells. Spores are favored when starvation periods are long, but vegetative cells can exploit resources in environments where food replenishes quickly. The investment in aggregators versus non-aggregators can therefore be understood as a bet-hedging strategy that evolves in response to stochastic starvation times. A genotype (or strategy) is defined by the balance between each type of cells. In this framework, if the ecological conditions on a patch are defined in terms of the mean starvation time (i.e. time between the onset of starvation and the arrival of a new food pulse), a single genotype dominates each environment, which is inconsistent with the huge genetic diversity observed in nature. Here we investigate whether seasonality, represented by a periodic, wet-dry alternation in the mean starvation times, allows the coexistence of several strategies in a single patch. We study this question in a non-spatial (well-mixed) setting in which different strains compete for a common pool of resources over a sequence of growth-starvation cycles. We find that seasonality induces a temporal storage effect that can promote the stable coexistence of multiple genotypes. Two conditions need to be met in our model. First, there has to be a temporal niche partitioning (two well-differentiated habitats within the year), which requires not only different mean starvation times between seasons but also low variance within each season. Second, each season's well-adapted strain has to grow and create a large enough population that permits its survival during the subsequent unfavorable season, which requires the number of growth-starvation cycles within each season to be sufficiently large. These conditions allow the coexistence of two bet-hedging strategies. Additional tradeoffs among life-history traits can expand the range of coexistence and increase the number of coexisting strategies, contributing toward explaining the genetic diversity observed in D. discoideum. Although focused on this cellular slime mold, our results are general and may be easily extended to other microbes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

PubMed Central

Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

2016-01-01

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay

PubMed Central

Heiser, Volker; Engemann, Sabine; Bröcker, Wolfgang; Dunkel, Ilona; Boeddrich, Annett; Waelter, Stephanie; Nordhoff, Eddi; Lurz, Rudi; Schugardt, Nancy; Rautenberg, Susanne; Herhaus, Christian; Barnickel, Gerhard; Böttcher, Henning; Lehrach, Hans; Wanker, Erich E.

2002-01-01

Preventing the formation of insoluble polyglutamine containing protein aggregates in neurons may represent an attractive therapeutic strategy to ameliorate Huntington's disease (HD). Therefore, the ability to screen for small molecules that suppress the self-assembly of huntingtin would have potential clinical and significant research applications. We have developed an automated filter retardation assay for the rapid identification of chemical compounds that prevent HD exon 1 protein aggregation in vitro. Using this method, a total of 25 benzothiazole derivatives that inhibit huntingtin fibrillogenesis in a dose-dependent manner were discovered from a library of ≈184,000 small molecules. The results obtained by the filter assay were confirmed by immunoblotting, electron microscopy, and mass spectrometry. Furthermore, cell culture studies revealed that 2-amino-4,7-dimethyl-benzothiazol-6-ol, a chemical compound similar to riluzole, significantly inhibits HD exon 1 aggregation in vivo. These findings may provide the basis for a new therapeutic approach to prevent the accumulation of insoluble protein aggregates in Huntington's disease and related glutamine repeat disorders. PMID:12200548

Barcoding heat shock proteins to human diseases: looking beyond the heat shock response.

PubMed

Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H

2014-04-01

There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR)--and thus generally restoring the disturbed protein homeostasis associated with such diseases--has often been suggested as a therapeutic strategy. However, most data on activating the HSR or its downstream targets in mouse models of diseases associated with aggregate formation have been rather disappointing. The human chaperonome consists of many more heat shock proteins (HSPs) that are not regulated by the HSR, however, and researchers are now focusing on these as potential therapeutic targets. In this Review, we summarize the existing literature on a set of aggregation diseases and propose that each of them can be characterized or 'barcoded' by a different set of HSPs that can rescue specific types of aggregation. Some of these 'non-canonical' HSPs have demonstrated effectiveness in vivo, in mouse models of protein-aggregation disease. Interestingly, several of these HSPs also cause diseases when mutated--so-called chaperonopathies--which are also discussed in this Review.

Barcoding heat shock proteins to human diseases: looking beyond the heat shock response

PubMed Central

Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H.

2014-01-01

There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR) – and thus generally restoring the disturbed protein homeostasis associated with such diseases – has often been suggested as a therapeutic strategy. However, most data on activating the HSR or its downstream targets in mouse models of diseases associated with aggregate formation have been rather disappointing. The human chaperonome consists of many more heat shock proteins (HSPs) that are not regulated by the HSR, however, and researchers are now focusing on these as potential therapeutic targets. In this Review, we summarize the existing literature on a set of aggregation diseases and propose that each of them can be characterized or ‘barcoded’ by a different set of HSPs that can rescue specific types of aggregation. Some of these ‘non-canonical’ HSPs have demonstrated effectiveness in vivo, in mouse models of protein-aggregation disease. Interestingly, several of these HSPs also cause diseases when mutated – so-called chaperonopathies – which are also discussed in this Review. PMID:24719117

The structure of microbial community in aggregates of a typical chernozem aggregates under contrasting variants of its agricultural use

NASA Astrophysics Data System (ADS)

Ivanova, E. A.; Kutovaya, O. V.; Tkhakakhova, A. K.; Chernov, T. I.; Pershina, E. V.; Markina, L. G.; Andronov, E. E.; Kogut, B. M.

2015-11-01

The taxonomic structure of microbiomes in aggregates of different sizes from typical chernozems was investigated using sequencing of the 16S rRNA gene. The aggregate fractions of <0.25, 2-5, and >7 mm obtained by sieving of the soil samples at natural moisture were used for analysis. The highest prokaryote biomass (bacteria, archaea) was determined in the fractions <0.25 and aggregates 2-5 mm; the bacterial and archaeal biomass decreased in the following series: fallow > permanent black fallow > permanent winter wheat. The greatest number of fungi was recorded in the fraction <0.25 mm from the soils of the permanent black fallow and in all the studied aggregate fractions in the variant with permanent wheat. The system of agricultural use affected more significantly the structure of the prokaryote community in the chernozem than the size of aggregate fractions did. The most diverse microbial community was recorded in the soil samples of the fallow; the statistically significant maximums of the Shannon diversity indices and indices of phylogenetic diversity (PD) were recorded in the fractions <0.25 and 2-5 mm from the fallow soil. On the whole, the fine soil fractions (<0.25 mm) were characterized by higher diversity indices in comparison with those of the coarser aggregate fractions.

Aggregation of Carbocyanine Dyes in Choline Chloride-Based Deep Eutectic Solvents in the Presence of an Aqueous Base.

PubMed

Pal, Mahi; Yadav, Anita; Pandey, Siddharth

2017-09-26

Deep eutectic solvents (DESs) have shown potential as novel media to support molecular aggregation. The self-aggregation behavior of two common and popular carbocyanine dyes, 5,5',6,6'-tetrachloro-1,1'-diethyl-3,3'-di(4-sulfobutyl)-benzimidazole carbocyanine (TDBC) and 5,5'-dichloro-3,3'-di(3-sulfopropyl)-9-methyl-benzothiacarbo cyanine (DMTC), is investigated within DES-based systems under ambient conditions. Although TDBC is known to form J-aggregates in basic aqueous solution, DMTC forms H-aggregates under similar conditions. The DESs used, glyceline and reline, are composed of salt choline chloride and two vastly different H-bond donors, glycerol and urea, respectively, in 1:2 mol ratios. Both DESs in the presence of base are found to support J-aggregates of TDBC. These fluorescent J-aggregates are characterized by small Stokes' shifts and subnanosecond fluorescence lifetimes. Under similar conditions, DMTC forms fluorescent H-aggregates along with J-aggregates within the two DES-based systems. The addition of cationic surfactant cetyltrimethylammonium bromide (CTAB) below its critical micelle concentration (cmc) to a TDBC solution of aqueous base-added glyceline shows the prominent presence of J-aggregates, and increasing the CTAB concentration to above cmc results in the disruption of J-aggregates and the formation of unprecedented H-aggregates. DMTC exclusively forms H-aggregates within a CTAB solution of aqueous base-added glyceline irrespective of the surfactant concentration. Anionic surfactant, sodium dodecylsulfate (SDS), present below its cmc within aqueous base-added DESs supports J-aggregation by TDBC; for similar SDS addition, DMTC forms H-aggregates within the glyceline-based system whereas both H- and J-aggregates exist within the reline-based system. A comparison of the carbocyanine dye behavior in various aqueous base-added DES systems to that in aqueous basic media reveals contrasting aggregation tendencies and/or efficiencies. Surfactants as additives are demonstrated to control and modulate carbocyanine dye self-aggregation within DES-based media. The unique nature of DESs as alternate media toward affecting cyanine dye aggregation is highlighted.

How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer?

NASA Astrophysics Data System (ADS)

Kim, Yuna; Park, Ji-Hyun; Lee, Hyojin; Nam, Jwa-Min

2016-01-01

Here, we studied the effect of the size, shape, and surface charge of Au nanoparticles (AuNPs) on amyloid beta (Aβ) aggregation on a total brain lipid-based supported lipid bilayer (brain SLB), a fluid platform that facilitates Aβ-AuNP aggregation process. We found that larger AuNPs induce large and amorphous aggregates on the brain SLB, whereas smaller AuNPs induce protofibrillar Aβ structures. Positively charged AuNPs were more strongly attracted to Aβ than negatively charged AuNPs, and the stronger interactions between AuNPs and Aβ resulted in fewer β-sheets and more random coil structures. We also compared spherical AuNPs, gold nanorods (AuNRs), and gold nanocubes (AuNCs) to study the effect of nanoparticle shape on Aβ aggregation on the brain SLB. Aβ was preferentially bound to the long axis of AuNRs and fewer fibrils were formed whereas all the facets of AuNCs interacted with Aβ to produce the fibril networks. Finally, it was revealed that different nanostructures induce different cytotoxicity on neuroblastoma cells, and, overall, smaller Aβ aggregates induce higher cytotoxicity. The results offer insight into the roles of NPs and brain SLB in Aβ aggregation on the cell membrane and can facilitate the understanding of Aβ-nanostructure co-aggregation mechanism and tuning Aβ aggregate structures.

Solid-state 13C NMR experiments reveal effects of aggregate size on the chemical composition of particulate organic matter in grazed steppe soils

NASA Astrophysics Data System (ADS)

Steffens, M.; Kölbl, A.; Kögel-Knabner, I.

2009-04-01

Grazing is one of the most important factors that may reduce soil organic matter (SOM) stocks and subsequently deteriorate aggregate stability in grassland topsoils. Land use management and grazing reduction are assumed to increase the input of OM, improve the soil aggregation and change species composition of vegetation (changes depth of OM input). Many studies have evaluated the impact of grazing cessation on SOM quantity. But until today little is known about the impact of grazing cessation on the chemical quality of SOM in density fractions, aggregate size classes and different horizons. The central aim of this study was to analyse the quality of SOM fractions in differently sized aggregates and horizons as affected by increased inputs of organic matter due to grazing exclusion. We applied a combined aggregate size, density and particle size fractionation procedure to sandy steppe topsoils with different organic matter inputs due to different grazing intensities (continuously grazed = Cg, winter grazing = Wg, ungrazed since 1999 = Ug99, ungrazed since 1979 = Ug79). Three different particulate organic matter (POM; free POM, in aggregate occluded POM and small in aggregate occluded POM) and seven mineral-associated organic matter fractions were separated for each of three aggregate size classes (coarse = 2000-6300 m, medium = 630-2000 m and fine =

Understanding the null-to-small association between increased macroeconomic growth and reducing child undernutrition in India: role of development expenditures and poverty alleviation.

PubMed

Joe, William; Rajaram, Ramaprasad; Subramanian, S V

2016-05-01

Empirical evidence suggests that macroeconomic growth in India is not correlated with any substantial reductions in the prevalence of child undernutrition over time. This study investigates the two commonly hypothesized pathways through which macroeconomic growth is expected to reduce child undernutrition: (1) an increase in public developmental expenditure and (2) a reduction in aggregate income-poverty levels. For the anthropometric data on children, we draw on the data from two cross-sectional waves of National Family Health Survey conducted in 1992-1993 and 2005-2006, while the data for per capita net state domestic product and per capita public spending on developmental expenditure and headcount ratio of poverty were obtained from the Reserve Bank of India and the Government of India expert committee reports. We find that between 1992-1993 and 2005-2006, state-level macroeconomic growth was not associated with any substantial increases in public development expenditure or substantial reductions in poverty at the aggregate level. Furthermore, the association between changes in public development expenditure or aggregate poverty and changes in undernutrition was small. In summary, it appears that the inability of macroeconomic growth to translate into reductions in child undernutrition in India is likely a consequence of the macroeconomic growth not translating into substantial investments in development expenditure that could matter for children's nutritional status and neither did it substantially improve incomes of the poor, a group where undernutrition is also the highest. The findings here build a case to advocate a 'support-led' strategy for reducing undernutrition rather than simply relying on a 'growth-mediated' strategy. Key messages Increases in macroeconomic growth have not been accompanied by substantial increases in public developmental spending or reduction in aggregate poverty headcount ratio in India. Association between increases in public development expenditure or poverty headcount ratios and changes in child undernutrition, in particular, child stunting, is small to null. Reducing the burden of undernutrition in India cannot be accomplished solely relying on a growth-mediated strategy, and a concerted support-led strategy is required. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

Understanding the null‐to‐small association between increased macroeconomic growth and reducing child undernutrition in India: role of development expenditures and poverty alleviation

PubMed Central

Joe, William; Rajaram, Ramaprasad

2016-01-01

Abstract Empirical evidence suggests that macroeconomic growth in India is not correlated with any substantial reductions in the prevalence of child undernutrition over time. This study investigates the two commonly hypothesized pathways through which macroeconomic growth is expected to reduce child undernutrition: (1) an increase in public developmental expenditure and (2) a reduction in aggregate income‐poverty levels. For the anthropometric data on children, we draw on the data from two cross‐sectional waves of National Family Health Survey conducted in 1992–1993 and 2005–2006, while the data for per capita net state domestic product and per capita public spending on developmental expenditure and headcount ratio of poverty were obtained from the Reserve Bank of India and the Government of India expert committee reports. We find that between 1992–1993 and 2005–2006, state‐level macroeconomic growth was not associated with any substantial increases in public development expenditure or substantial reductions in poverty at the aggregate level. Furthermore, the association between changes in public development expenditure or aggregate poverty and changes in undernutrition was small. In summary, it appears that the inability of macroeconomic growth to translate into reductions in child undernutrition in India is likely a consequence of the macroeconomic growth not translating into substantial investments in development expenditure that could matter for children's nutritional status and neither did it substantially improve incomes of the poor, a group where undernutrition is also the highest. The findings here build a case to advocate a ‘support‐led’ strategy for reducing undernutrition rather than simply relying on a ‘growth‐mediated’ strategy. Key messages Increases in macroeconomic growth have not been accompanied by substantial increases in public developmental spending or reduction in aggregate poverty headcount ratio in India.Association between increases in public development expenditure or poverty headcount ratios and changes in child undernutrition, in particular, child stunting, is small to null.Reducing the burden of undernutrition in India cannot be accomplished solely relying on a growth‐mediated strategy, and a concerted support‐led strategy is required. PMID:27187916

Are there multiple pathways in the pathogenesis of Huntington's disease?

PubMed Central

Aronin, N; Kim, M; Laforet, G; DiFiglia, M

1999-01-01

Studies of huntingtin localization in human post-mortem brain offer insights and a framework for basic experiments in the pathogenesis of Huntington's disease. In neurons of cortex and striatum, we identified changes in the cytoplasmic localization of huntingtin including a marked perinuclear accumulation of huntingtin and formation of multivesicular bodies, changes conceivably pointing to an altered handling of huntingtin in neurons. In Huntington's disease, huntingtin also accumulates in aberrant subcellular compartments such as nuclear and neuritic aggregates co-localized with ubiquitin. The site of protein aggregation is polyglutamine-dependent, both in juvenile-onset patients having more aggregates in the nucleus and in adult-onset patients presenting more neuritic aggregates. Studies in vitro reveal that the genesis of these aggregates and cell death are tied to cleavage of mutant huntingtin. However, we found that the aggregation of mutant huntingtin can be dissociated from the extent of cell death. Thus properties of mutant huntingtin more subtle than its aggregation, such as its proteolysis and protein interactions that affect vesicle trafficking and nuclear transport, might suffice to cause neurodegeneration in the striatum and cortex. We propose that mutant huntingtin engages multiple pathogenic pathways leading to neuronal death. PMID:10434298

Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation.

PubMed

Betzer, Cristine; Lassen, Louise Berkhoudt; Olsen, Anders; Kofoed, Rikke Hahn; Reimer, Lasse; Gregersen, Emil; Zheng, Jin; Calì, Tito; Gai, Wei-Ping; Chen, Tong; Moeller, Arne; Brini, Marisa; Fu, Yuhong; Halliday, Glenda; Brudek, Tomasz; Aznar, Susana; Pakkenberg, Bente; Andersen, Jens Peter; Jensen, Poul Henning

2018-05-01

Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca 2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca 2+ levels followed by a later Ca 2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro , and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca 2+ CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies. We conclude that α-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA activity is neuroprotective, indicating that SERCA and down-stream processes may be therapeutic targets for treating α-synucleinopathies. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Biosolids increase soil aggregation and protection of soil carbon five years after application on a crested wheatgrass pasture.

PubMed

Wallace, Brian M; Krzic, Maja; Forge, Tom A; Broersma, Klaas; Newman, Reg F

2009-01-01

Biosolids application to rangelands and pastures recycles nutrients and organic matter back to soils. The effects of biosolids (20 and 60 dry Mg ha(-)(1)) and N+P fertilizer on soil aggregate stability, bulk density, aeration porosity, and total C and N of stable aggregates were evaluated 4 and 5 yr after surface application to a crested wheatgrass [Agropyron cristatum (L.) Gaertn.] pasture in the southern interior of British Columbia (BC). The experiment was established in 2001 in a randomized complete block design with four replications. The 60 Mg ha(-1) biosolids treatment (Bio 60) had a greater aggregate mean weight diameter (MWD) and proportion of water-stable soil aggregates > 1 mm relative to the control and fertilizer treatments. Temporal variation in aggregate stability was attributed to seasonal variations in soil water content. Surface application of 60 Mg ha(-1) of biosolids increased C concentrations within water-stable aggregates relative to the control from 29 to 104, 24 to 79, and 12 to 38 g kg(-1) for the 2 to 6, 1 to 2, and 0.25 to 1 mm size fractions, respectively. The concentration of N within aggregates increased in similar proportions to C. Neither soil bulk density, nor aeration porosity were affected by biosolids application. Increased aggregation and the accumulation of soil C within aggregates following biosolids application creates a potential for better soil C storage, soil water retention, nutrient availability, and ultimately the overall health of semiarid perennial pastures.

Selectivity and stoichiometry boosting of beta-cyclodextrin in cationic/anionic surfactant systems: when host-guest equilibrium meets biased aggregation equilibrium.

PubMed

Jiang, Lingxiang; Yu, Caifang; Deng, Manli; Jin, Changwen; Wang, Yilin; Yan, Yun; Huang, Jianbin

2010-02-18

Cationic surfactant/anionic surfactant/beta-CD ternary aqueous systems provide a platform for the coexistence of the host-guest (beta-CD/surfactant) equilibrium and the biased aggregation (monomeric/aggregated surfactants) equilibrium. We report here that the interplay between the two equilibria dominates the systems as follows. (1) The biased aggregation equilibrium imposes an apparent selectivity on the host-guest equilibrium, namely, beta-CD has to always selectively bind the major surfactant (molar fraction > 0.5) even if binding constants of beta-CD to the pair of surfactants are quite similar. (2) In return, the host-guest equilibrium amplifies the bias of the aggregation equilibrium, that is, the selective binding partly removes the major surfactant from the aggregates and leaves the aggregate composition approaching the electroneutral mixing stoichiometry. (3) This composition variation enhances electrostatic attractions between oppositely charged surfactant head groups, thus resulting in less-curved aggregates. In particular, the present apparent host-guest selectivity is of remarkably high values, and the selectivity stems from the bias of the aggregation equilibrium rather than the difference in binding constants. Moreover, beta-CD is defined as a "stoichiometry booster" for the whole class of cationic/anionic surfactant systems, which provides an additional degree of freedom to directly adjust aggregate compositions of the systems. The stoichiometry boosting of the compositions can in turn affect or even determine microstructures and macroproperties of the systems.

Aggregation of montmorillonite and organic matter in aqueous media containing artificial seawater

PubMed Central

2009-01-01

Background The dispersion-aggregation behaviors of suspended colloids in rivers and estuaries are affected by the compositions of suspended materials (i.e., clay minerals vs. organic macromolecules) and salinity. Laboratory experiments were conducted to investigate the dispersion and aggregation mechanisms of suspended particles under simulated river and estuarine conditions. The average hydrodynamic diameters of suspended particles (representing degree of aggregation) and zeta potential (representing the electrokinetic properties of suspended colloids and aggregates) were determined for systems containing suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over a range of salinity (0 – 7.2 psu). Results The montmorillonite-only system increased the degree of aggregation with salinity increase, as would be expected for suspended colloids whose dispersion-aggregation behavior is largely controlled by the surface electrostatic properties and van der Waals forces. When montmorillonite is combined with humic acid or chitin, the aggregation of montmorillonite was effectively inhibited. The surface interaction energy model calculations reveal that the steric repulsion, rather than the increase in electronegativity, is the primary cause for the inhibition of aggregation by the addition of humic acid or chitin. Conclusion These results help explain the range of dispersion-aggregation behaviors observed in natural river and estuarine systems. It is postulated that the composition of suspended particles, specifically the availability of steric polymers such as those contained in humic acid, determine whether the river suspension is rapidly aggregated and settled or remains dispersed in suspension when it encounters increasingly saline environments of estuaries and oceans. PMID:19166595

Functionalization of single-walled carbon nanotubes regulates their effect on hemostasis

NASA Astrophysics Data System (ADS)

Sokolov, A. V.; Aseychev, A. V.; Kostevich, V. A.; Gusev, A. A.; Gusev, S. A.; Vlasova, I. I.

2011-04-01

Applications of single-walled carbon nanotubes (SWNTs) in medical field imply the use of drug-coupled carbon nanotubes as well as carbon nanotubes functionalized with different chemical groups that change nanotube surface properties and interactions between nanotubes and cells. Covalent attachment of polyethylene glycol (PEG) to carboxylated single-walled carbon nanotubes (c-SWNT) is known to prevent the nanotubes from interaction with macrophages. Here we characterized nanotube's ability to stimulate coagulation processes in platelet-poor plasma (PPP), and evaluated the effect of SWNTs on platelet aggregation in platelet-rich plasma (PRP). Our study showed that PEG-SWNT did not affect the rate of clotting in PPP, while c-SWNT shortened the clot formation time five times compared to the control PPP. Since c-SWNT failed to accelerate coagulation in plasma lacking coagulation factor XI, it may be suggested that c-SWNT affects the contact activation pathway. In PRP, platelets responded to both SWNT types with irreversible aggregation, as evidenced by changes in the aggregate mean radius. However, the rate of aggregation induced by c-SWNT was two times higher than it was with PEG-SWNT. Cytological analysis also showed that c-SWNT was two times more efficient when compared to PEG-SWNT in aggregating platelets in PRP. Taken together, our results show that functionalization of nanoparticles can diminish their negative influence on blood cells. As seen from our data, modification of c-SWNT with PEG, when only a one percent of carbon atoms is bound to polymer (70 wt %), decreased the nanotube-induced coagulation in PRP and repelled the accelerating effect on the coagulation in PPP. Thus, when functionalized SWNTs are used for administration into bloodstream of laboratory animals, their possible pro-coagulant and pro-aggregating properties must be taken into account.

Familial aggregation of attention-deficit/hyperactivity disorder.

PubMed

Chen, Qi; Brikell, Isabell; Lichtenstein, Paul; Serlachius, Eva; Kuja-Halkola, Ralf; Sandin, Sven; Larsson, Henrik

2017-03-01

Attention-deficit/hyperactivity disorder (ADHD) aggregates in families. To date, the strength, pattern, and characteristics of the familial aggregation have not been thoroughly assessed in a population-based family sample. In this cohort study, we identified relative pairs of twins, full and half-siblings, and full and half cousins from 1,656,943 unique individuals born in Sweden between 1985 and 2006. The relatives of index persons were followed from their third birthday to 31 December 2009 for ADHD diagnosis. Birth year adjusted hazard ratio (HR), that is, the rate of ADHD in relatives of ADHD-affected index persons compared with the rate of ADHD in relatives of unaffected index persons, was estimated in the different types of relatives using Cox proportional hazards model. During the follow-up, 31,865 individuals were diagnosed with ADHD (male to female ratio was 3.7). The birth year adjusted HRs were as follows: 70.45 for monozygotic twins; 8.44 for dizygotic twins; 8.27 for full siblings; 2.86 for maternal half-siblings; 2.31 for paternal half-siblings; 2.24 for full cousins; 1.47 for half cousins. Maternal half-siblings had significantly higher HR than in paternal half-siblings. The HR did not seem to be affected by index person's sex. Full siblings of index persons with ADHD diagnosis present at age 18 or older had a higher rate of ADHD (HR: 11.49) than full siblings of index persons with ADHD diagnosis only before age 18 (HR: 4.68). Familial aggregation of ADHD increases with increasing genetic relatedness. The familial aggregation is driven by not only genetic factors but also a small amount of shared environmental factors. Persistence of ADHD into adulthood indexes stronger familial aggregation of ADHD. © 2016 Association for Child and Adolescent Mental Health.

Competition between protein folding and aggregation: A three-dimensional lattice-model simulation

NASA Astrophysics Data System (ADS)

Bratko, D.; Blanch, H. W.

2001-01-01

Aggregation of protein molecules resulting in the loss of biological activity and the formation of insoluble deposits represents a serious problem for the biotechnology and pharmaceutical industries and in medicine. Considerable experimental and theoretical efforts are being made in order to improve our understanding of, and ability to control, the process. In the present work, we describe a Monte Carlo study of a multichain system of coarse-grained model proteins akin to lattice models developed for simulations of protein folding. The model is designed to examine the competition between intramolecular interactions leading to the native protein structure, and intermolecular association, resulting in the formation of aggregates of misfolded chains. Interactions between the segments are described by a variation of the Go potential [N. Go and H. Abe, Biopolymers 20, 1013 (1981)] that extends the recognition between attracting types of segments to pairs on distinct chains. For the particular model we adopt, the global free energy minimum of a pair of protein molecules corresponds to a dimer of native proteins. When three or more molecules interact, clusters of misfolded chains can be more stable than aggregates of native folds. A considerable fraction of native structure, however, is preserved in these cases. Rates of conformational changes rapidly decrease with the size of the protein cluster. Within the timescale accessible to computer simulations, the folding-aggregation balance is strongly affected by kinetic considerations. Both the native form and aggregates can persist in metastable states, even if conditions such as temperature or concentration favor a transition to an alternative form. Refolding yield can be affected by the presence of an additional polymer species mimicking the function of a molecular chaperone.

Modeling the impact of soil aggregate size on selenium immobilization

NASA Astrophysics Data System (ADS)

Kausch, M. F.; Pallud, C. E.

2013-03-01

Soil aggregates are mm- to cm-sized microporous structures separated by macropores. Whereas fast advective transport prevails in macropores, advection is inhibited by the low permeability of intra-aggregate micropores. This can lead to mass transfer limitations and the formation of aggregate scale concentration gradients affecting the distribution and transport of redox sensitive elements. Selenium (Se) mobilized through irrigation of seleniferous soils has emerged as a major aquatic contaminant. In the absence of oxygen, the bioavailable oxyanions selenate, Se(VI), and selenite, Se(IV), can be microbially reduced to solid, elemental Se, Se(0), and anoxic microzones within soil aggregates are thought to promote this process in otherwise well-aerated soils. To evaluate the impact of soil aggregate size on selenium retention, we developed a dynamic 2-D reactive transport model of selenium cycling in a single idealized aggregate surrounded by a macropore. The model was developed based on flow-through-reactor experiments involving artificial soil aggregates (diameter: 2.5 cm) made of sand and containing Enterobacter cloacae SLD1a-1 that reduces Se(VI) via Se(IV) to Se(0). Aggregates were surrounded by a constant flow providing Se(VI) and pyruvate under oxic or anoxic conditions. In the model, reactions were implemented with double-Monod rate equations coupled to the transport of pyruvate, O2, and Se species. The spatial and temporal dynamics of the model were validated with data from experiments, and predictive simulations were performed covering aggregate sizes 1-2.5 cm in diameter. Simulations predict that selenium retention scales with aggregate size. Depending on O2, Se(VI), and pyruvate concentrations, selenium retention was 4-23 times higher in 2.5 cm aggregates compared to 1 cm aggregates. Under oxic conditions, aggregate size and pyruvate concentrations were found to have a positive synergistic effect on selenium retention. Promoting soil aggregation on seleniferous agricultural soils, through organic matter amendments and conservation tillage, may thus help decrease the impacts of selenium contaminated drainage water on downstream aquatic ecosystems.

Modeling the impact of soil aggregate size on selenium immobilization

NASA Astrophysics Data System (ADS)

Kausch, M. F.; Pallud, C. E.

2012-09-01

Soil aggregates are mm- to cm-sized microporous structures separated by macropores. Whereas fast advective transport prevails in macropores, advection is inhibited by the low permeability of intra-aggregate micropores. This can lead to mass transfer limitations and the formation of aggregate-scale concentration gradients affecting the distribution and transport of redox sensitive elements. Selenium (Se) mobilized through irrigation of seleniferous soils has emerged as a major aquatic contaminant. In the absence of oxygen, the bioavailable oxyanions selenate, Se(VI), and selenite, Se(IV), can be microbially reduced to solid, elemental Se, Se(0), and anoxic microzones within soil aggregates are thought to promote this process in otherwise well aerated soils. To evaluate the impact of soil aggregate size on selenium retention, we developed a dynamic 2-D reactive transport model of selenium cycling in a single idealized aggregate surrounded by a macropore. The model was developed based on flow-through-reactor experiments involving artificial soil aggregates (diameter: 2.5 cm) made of sand and containing Enterobacter cloacae SLD1a-1 that reduces Se(VI) via Se(IV) to Se(0). Aggregates were surrounded by a constant flow providing Se(VI) and pyruvate under oxic or anoxic conditions. In the model, reactions were implemented with double-Monod rate equations coupled to the transport of pyruvate, O2, and Se-species. The spatial and temporal dynamics of the model were validated with data from experiments and predictive simulations were performed covering aggregate sizes between 1 and 2.5 cm diameter. Simulations predict that selenium retention scales with aggregate size. Depending on O2, Se(VI), and pyruvate concentrations, selenium retention was 4-23 times higher in 2.5-cm-aggregates compared to 1-cm-aggregates. Under oxic conditions, aggregate size and pyruvate-concentrations were found to have a positive synergistic effect on selenium retention. Promoting soil aggregation on seleniferous agricultural soils, through organic matter amendments and conservation tillage, may thus help decrease the impacts of selenium contaminated drainage water on downstream aquatic ecosystems.

Nuclear Enterprise Performance Measurement

DTIC Science & Technology

2011-03-01

xi I. Introduction ...WSA: Weapons Storage Area 1 I. Introduction Overview This paper discusses United States Air Force nuclear enterprise...sustainment systems. Keywords Performance measurement, process measurement, strategy, multicriteria decision- making, aggregation 1. Introduction Nuclear

Structure-activity relationships for a series of compounds that inhibit aggregation of the Alzheimer's peptide, Aβ42.

PubMed

McKoy, Angela F; Chen, Jermont; Schupbach, Trudi; Hecht, Michael H

2014-11-01

Inhibiting aggregation of the amyloid-beta (Aβ) peptide may be an effective strategy for combating Alzheimer's disease. As the high-resolution structure of the toxic Aβ aggregate is unknown, rational design of small molecule inhibitors is not possible, and inhibitors are best isolated by high-throughput screening. We applied high-throughput screening to a collection of 65,000 compounds to identify compound D737 as an inhibitor of Aβ aggregation. D737 diminished the formation of oligomers and fibrils, and reduced Aβ42-induced cytotoxicity. Most importantly, D737 increased the life span and locomotive ability of transgenic flies in a Drosophila melanogaster model of Alzheimer's disease (J Biol Chem, 287, 2012, 38992). To explore the chemical features that make D737 an effective inhibitor of Aβ42 aggregation and toxicity, we tested a small collection of eleven analogues of D737. Overall, the ability of a compound to inhibit Aβ aggregation was a good predictor of its efficacy in prolonging the life span and locomotive ability of transgenic flies expressing human Aβ42 in the central nervous system. Two compounds (D744 and D830) with fluorine substitutions on an aromatic ring were effective inhibitors of Aβ42 aggregation and increased the longevity of transgenic flies beyond that observed for the parent compound, D737. © 2014 John Wiley & Sons A/S.

Effects of Combined Application of Biogas Slurry and Chemical Fertilizer on Soil Aggregation and C/N Distribution in an Ultisol

PubMed Central

Zheng, Xuebo; Fan, Jianbo; Xu, Lei; Zhou, Jing

2017-01-01

Unreasonable use of chemical fertilizer (CF) on agricultural soil leads to massive losses of soil organic carbon (SOC) and total nitrogen (TN) in tropical and subtropical areas, where soil conditions are unfavorable for aggregate formation. This study evaluated the effects of combined application of biogas slurry (BS) plus CF on soil aggregation and aggregate—associated C/N concentration and storage in an Ultisol. Six treatments included: no fertilizer (T1), CF only (T2), partial (15% (T3), 30% (T4) and 45% (T5)) substitution of TN with BS and BS only (T6). Soil mechanical—stable aggregates (MSAs) formation and stability as well as MSAs—associated C/N concentration and storage were observed in different aggregate sizes (>5, 5–2, 2–1, 1.0–0.5, 0.50–0.25 and <0.25 mm). The proportion of MSAs >5 mm significantly increased with BS substitution (T5), while the proportions of MSAs 1.0–0.5 mm, MSAs 0.50–0.25 mm and MSAs <0.25 mm significantly decreased. Both mean weight diameter and geometric mean diameter were highest in T5, which improved soil aggregation stability as well as resulted in significantly higher SOC and TN concentrations and storage in MSAs >0.5 mm that constituted 72–82% of MSAs. Stepwise regression analysis showed that MSAs >5 mm, SOC in MSAs >5 mm and TN in MSAs >5 mm were the dominant variables affecting aggregate stability. Meanwhile SOC in MSAs <0.25 mm and TN in MSAs 2–1 mm were independent variables affecting SOC and TN concentrations in bulk soils. Therefore, certain rate of combined application of BS plus CF is an effective, eco—friendly way to improve soil quality in an Ultisol. PMID:28125647

Effects of Pedogenic Fe Oxides on Soil Aggregate-Associated Carbon

NASA Astrophysics Data System (ADS)

Asefaw Berhe, A.; Jin, L.

2017-12-01

Carbon sequestration is intimately related to the soil structure, mainly soil aggregate dynamics. Carbon storage in soil aggregates has been recognized as an important carbon stabilization mechanism in soils. Organic matter and pedogenic Fe oxides are major binding agents that facilitate soil aggregate formation and stability. However, few studies have investigated how different forms of pedogenic Fe oxides can affect soil carbon distribution in different aggregate-size fractions. We investigated sequentially extracted pedogenic Fe oxides (in the order of organically complexed Fe extracted with sodium pyrophosphate, poorly-crystalline Fe oxides extracted with hydroxylamine hydrochloride, and crystalline Fe oxides extracted with dithionite hydrochloride) and determined the amount and nature of C in macroaggregates (2-0.25mm), microaggregates (0.25-0.053mm), and two silt and clay fractions (0.053-0.02mm, and <0.02mm) in Musick soil from Sierra Nevada mountain in California. We also determined how pedogenic Fe oxides affect soil carbon distribution along soil depth gradients. Findings of our study revealed that the proportion of organic matter complexed Fe decreased, but the proportion of crystalline Fe increased with increasing soil depths. Poorly crystalline Fe oxides (e.g. ferrihydrite) was identified as a major Fe oxide in surface soil, whereas crystalline Fe oxides (e.g. goethite) were found in deeper soil layers. These results suggest that high concentration of organic matter in surface soil suppressed Fe crystallization. Calcium cation was closely related to the pyrophosphate extractable Fe and C, which indicates that calcium may be a major cation that contribute to the organic matter complexed Fe and C pool. Increasing concentrations of extractable Fe and C with decreasing aggregate size fractions also suggests that Fe oxides play an important role in formation and stability of silt and clay fractions, and leading to further stabilization of carbon in soil. Our findings provide mechanistic understanding of how pedogenic Fe oxides play important role in carbon stabilization in different aggregate-size fractions in soil.

Dyadic coping and relationship satisfaction: A meta-analysis.

PubMed

Falconier, Mariana K; Jackson, Jeffrey B; Hilpert, Peter; Bodenmann, Guy

2015-12-01

Meta-analytic methods were used to empirically determine the association between dyadic coping and relationship satisfaction. Dyadic coping is a systemic conceptualization of the processes partners use to cope with stressors, such as stress communication, individual strategies to assist the other partner cope with stress, and partners' strategies to cope together. A total of 72 independent samples from 57 reports with a combined sum of 17,856 participants were included. The aggregated standardized zero-order correlation (r) for total dyadic coping with relationship satisfaction was .45 (p=.000). Total dyadic coping strongly predicted relationship satisfaction regardless of gender, age, relationship length, education level, and nationality. Perceptions of overall dyadic coping by partner and by both partners together were stronger predictors of relationship satisfaction than perceptions of overall dyadic coping by self. Aggregated positive forms of dyadic coping were a stronger predictor of relationship satisfaction than aggregated negative forms of dyadic coping. Comparisons among dyadic coping dimensions indicated that collaborative common coping, supportive coping, and hostile/ambivalent coping were stronger predictors of relationship satisfaction than stress communication, delegated coping, protective buffering coping, and overprotection coping. Clinical implications and recommendations for future research are provided. Copyright © 2015 Elsevier Ltd. All rights reserved.

Super-tough, ultra-stretchable and strongly compressive hydrogels with core-shell latex particles inducing efficient aggregation of hydrophobic chains.

PubMed

Ren, Xiuyan; Huang, Chang; Duan, Lijie; Liu, Baijun; Bu, Lvjun; Guan, Shuang; Hou, Jiliang; Zhang, Huixuan; Gao, Guanghui

2017-05-14

Toughness, strechability and compressibility for hydrogels were ordinarily balanced for their use as mechanically responsive materials. For example, macromolecular microsphere composite hydrogels with chemical crosslinking exhibited excellent compression strength and strechability, but poor tensile stress. Here, a novel strategy for the preparation of a super-tough, ultra-stretchable and strongly compressive hydrogel was proposed by introducing core-shell latex particles (LPs) as crosslinking centers for inducing efficient aggregation of hydrophobic chains. The core-shell LPs always maintained a spherical shape due to the presence of a hard core even by an external force and the soft shell could interact with hydrophobic chains due to hydrophobic interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20 times, but also an excellent compressive performance of 13.5 MPa at a strain of 90%. The Mullins effect was verified for the validity of core-shell LP-reinforced hydrogels by inducing aggregation of hydrophobic chains. The novel strategy strives to provide a better avenue for designing and developing a new generation of hydrophobic association tough hydrogels with excellent mechanical properties.

Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.

PubMed

Ciechanover, Aaron; Kwon, Yong Tae

2015-03-13

Mammalian cells remove misfolded proteins using various proteolytic systems, including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated autophagy (CMA) and macroautophagy. The majority of misfolded proteins are degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated, unfolded and cleaved into small peptides when passing through the narrow chamber of the proteasome. The substrates that expose a specific degradation signal, the KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA. Aggregation-prone substrates resistant to both the UPS and the CMA can be degraded by macroautophagy, in which cargoes are segregated into autophagosomes before degradation by lysosomal hydrolases. Although most misfolded and aggregated proteins in the human proteome can be degraded by cellular protein quality control, some native and mutant proteins prone to aggregation into β-sheet-enriched oligomers are resistant to all known proteolytic pathways and can thus grow into inclusion bodies or extracellular plaques. The accumulation of protease-resistant misfolded and aggregated proteins is a common mechanism underlying protein misfolding disorders, including neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), prion diseases and Amyotrophic Lateral Sclerosis (ALS). In this review, we provide an overview of the proteolytic pathways in neurons, with an emphasis on the UPS, CMA and macroautophagy, and discuss the role of protein quality control in the degradation of pathogenic proteins in neurodegenerative diseases. Additionally, we examine existing putative therapeutic strategies to efficiently remove cytotoxic proteins from degenerating neurons.

Mutant Huntingtin Gene-Dose Impacts on Aggregate Deposition, DARPP32 Expression and Neuroinflammation in HdhQ150 Mice

PubMed Central

Young, Douglas; Mayer, Franziska; Vidotto, Nella; Schweizer, Tatjana; Berth, Ramon; Abramowski, Dorothee; Shimshek, Derya R.; van der Putten, P. Herman; Schmid, Peter

2013-01-01

Huntington's disease (HD) is an autosomal dominant, progressive and fatal neurological disorder caused by an expansion of CAG repeats in exon-1 of the huntingtin gene. The encoded poly-glutamine stretch renders mutant huntingtin prone to aggregation. HdhQ150 mice genocopy a pathogenic repeat (∼150 CAGs) in the endogenous mouse huntingtin gene and model predominantly pre-manifest HD. Treating early is likely important to prevent or delay HD, and HdhQ150 mice may be useful to assess therapeutic strategies targeting pre-manifest HD. This requires appropriate markers and here we demonstrate, that pre-symptomatic HdhQ150 mice show several dramatic mutant huntingtin gene-dose dependent pathological changes including: (i) an increase of neuronal intra-nuclear inclusions (NIIs) in brain, (ii) an increase of extra-nuclear aggregates in dentate gyrus, (iii) a decrease of DARPP32 protein and (iv) an increase in glial markers of neuroinflammation, which curiously did not correlate with local neuronal mutant huntingtin inclusion-burden. HdhQ150 mice developed NIIs also in all retinal neuron cell-types, demonstrating that retinal NIIs are not specific to human exon-1 R6 HD mouse models. Taken together, the striking and robust mutant huntingtin gene-dose related changes in aggregate-load, DARPP32 levels and glial activation markers should greatly facilitate future testing of therapeutic strategies in the HdhQ150 HD mouse model. PMID:24086450

Degradation of misfolded proteins by autophagy: is it a strategy for Huntington's disease treatment?

PubMed

Lin, Fang; Qin, Zheng-Hong

2013-01-01

Autophagy is a degradation pathway for long-lived cytoplasmic proteins, protein complexes, or damaged organelles. The accumulation and aggregation of misfolded proteins are hallmarks of several neurodegenerative diseases. Many researchers have reported that autophagy degrades disease-causing misfolded and aggregated proteins, including mutant huntingtin (Htt) in Huntington's disease, mutant synuclein in familial Parkingson's disease, mutant Cu, Zn-Superoxide dismutase (SOD1) in familial amyotrophic lateral sclerosis. In this review, we will bring up new evidence to elucidate the involvement of autophagy in degradation of mutant Htt, discuss the mechanisms regulating the degradation of mutant Htt by autophagy and the therapeutic effects of drugs that enhance autophagy to improve clearance of mutant Htt. We propose that enhancement of autophagy by drugs may be a strategy to treat or retard progression of Huntington's disease.

Multiwalled Carbon Nanotube Dispersion Methods Affect Their Aggregation, Deposition, and Biomarker Response

EPA Science Inventory

To systematically evaluate how dispersion methods affect the environmental behaviors of multiwalled carbon nanotubes (MWNTs), MWNTs were dispersed in various solutions (e.g., surfactants, natural organic matter (NOM), and etc.) via ultrasonication (SON) and long-term stirring (LT...

Collective behavior in two-dimensional biological systems: Receptor clustering and beta-sheet aggregation

NASA Astrophysics Data System (ADS)

Guo, Chinlin

We studied two particular biomedical systems which exhibit collective molecular behavior. One is clustering of tumor necrosis factor receptor I (TNFR1), and another is β-sheet folding and aggregation. Receptor clustering has been shown to be a crucial step in many signaling events but its biological meaning has not been adequately addressed. Here, via a simple lattice model, we show how cells use this clustering machinery to enhance sensitivity as well as robustness. On the other hand, intracellular deposition of aggregated protein rich in β-sheet is a prominent cytopathological feature of most neurodegenerative diseases. How this aggregation occurs and how it responds to therapy is not completely understood. Here, we started from a reconstruction of the H-bond potential and carry out a full investigation of β-sheet thermodynamics as well as kinetics. We show that β-sheet aggregation is most likely due to molecular stacking and found that the minimal length of an aggregate mutant polymer corresponds well with the number observed in adult Huntington's disease. We have also shown that molecular agents such as dendrimers might fail at high-dose therapy; instead, a potential therapy strategy is to block β-turn formation. Our predictions can be used for future experimental tests and clinical trials.

Real-time protein aggregation monitoring with a Bloch surface wave-based approach

NASA Astrophysics Data System (ADS)

Santi, Sara; Barakat, Elsie; Descrovi, Emiliano; Neier, Reinhard; Herzig, Hans Peter

2014-05-01

The misfolding and aggregation of amyloid proteins has been associated with incurable diseases such as Alzheimer's or Parkinson's disease. In the specific case of Alzheimer's disease, recent studies have shown that cell toxicity is caused by soluble oligomeric forms of aggregates appearing in the early stages of aggregation, rather than by insoluble fibrils. Research on new strategies of diagnosis is imperative to detect the disease prior to the onset of clinical symptoms. Here, we propose the use of an optical method for protein aggregation dynamic studies using a Bloch surface wave based approach. A one dimension photonic crystal made of a periodic stack of silicon oxide and silicon nitride layers is used to excite a Bloch surface wave, which is sensitive to variation of the refractive index of an aqueous solution. The aim is to detect the early dynamic events of protein aggregation and fibrillogenesis of the amyloid-beta peptide Aβ42, which plays a central role in the onset of the Alzheimer's disease. The detection principle relies on the refractive index changes caused by the depletion of the Aβ42 monomer concentration during oligomerization and fibrillization. We demonstrate the efficacy of the Bloch surface wave approach by monitoring in real-time the first crucial steps of Aβ42 oligomerization.

Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant α-Synuclein

PubMed Central

Ahsan, Nuzhat; Mishra, Satyendra; Jain, Manish Kumar; Surolia, Avadhesha; Gupta, Sarika

2015-01-01

Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against α-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies. PMID:25985292

Corrosion Behavior of Steel Reinforcement in Concrete with Recycled Aggregates, Fly Ash and Spent Cracking Catalyst.

PubMed

Gurdián, Hebé; García-Alcocel, Eva; Baeza-Brotons, Francisco; Garcés, Pedro; Zornoza, Emilio

2014-04-21

The main strategy to reduce the environmental impact of the concrete industry is to reuse the waste materials. This research has considered the combination of cement replacement by industrial by-products, and natural coarse aggregate substitution by recycled aggregate. The aim is to evaluate the behavior of concretes with a reduced impact on the environment by replacing a 50% of cement by industrial by-products (15% of spent fluid catalytic cracking catalyst and 35% of fly ash) and a 100% of natural coarse aggregate by recycled aggregate. The concretes prepared according to these considerations have been tested in terms of mechanical strengths and the protection offered against steel reinforcement corrosion under carbonation attack and chloride-contaminated environments. The proposed concrete combinations reduced the mechanical performance of concretes in terms of elastic modulus, compressive strength, and flexural strength. In addition, an increase in open porosity due to the presence of recycled aggregate was observed, which is coherent with the changes observed in mechanical tests. Regarding corrosion tests, no significant differences were observed in the case of the resistance of these types of concretes under a natural chloride attack. In the case of carbonation attack, although all concretes did not stand the highly aggressive conditions, those concretes with cement replacement behaved worse than Portland cement concretes.

Synthetic Proteins and Peptides for the Direct Interrogation of α-Synuclein Posttranslational Modifications

PubMed Central

Pratt, Matthew R.; Abeywardana, Tharindumala; Marotta, Nicholas P.

2015-01-01

α-Synuclein is the aggregation-prone protein associated with Parkinson’s disease (PD) and related neurodegenerative diseases. Complicating both its biological functions and toxic aggregation are a variety of posttranslational modifications. These modifications have the potential to either positively or negatively affect α-synuclein aggregation, raising the possibility that the enzymes that add or remove these modifications could be therapeutic targets in PD. Synthetic protein chemistry is uniquely positioned to generate site-specifically and homogeneously modified proteins for biochemical study. Here, we review the application of synthetic peptides and proteins towards understanding the effects of α-synuclein posttranslational modifications. PMID:26120904

Microplastics and Nanoplastics in Aquatic Environments: Aggregation, Deposition, and Enhanced Contaminant Transport.

PubMed

Alimi, Olubukola S; Farner Budarz, Jeffrey; Hernandez, Laura M; Tufenkji, Nathalie

2018-02-20

Plastic litter is widely acknowledged as a global environmental threat, and poor management and disposal lead to increasing levels in the environment. Of recent concern is the degradation of plastics from macro- to micro- and even to nanosized particles smaller than 100 nm in size. At the nanoscale, plastics are difficult to detect and can be transported in air, soil, and water compartments. While the impact of plastic debris on marine and fresh waters and organisms has been studied, the loads, transformations, transport, and fate of plastics in terrestrial and subsurface environments are largely overlooked. In this Critical Review, we first present estimated loads of plastics in different environmental compartments. We also provide a critical review of the current knowledge vis-à-vis nanoplastic (NP) and microplastic (MP) aggregation, deposition, and contaminant cotransport in the environment. Important factors that affect aggregation and deposition in natural subsurface environments are identified and critically analyzed. Factors affecting contaminant sorption onto plastic debris are discussed, and we show how polyethylene generally exhibits a greater sorption capacity than other plastic types. Finally, we highlight key knowledge gaps that need to be addressed to improve our ability to predict the risks associated with these ubiquitous contaminants in the environment by understanding their mobility, aggregation behavior and their potential to enhance the transport of other pollutants.

Disease Risk Mitigation: The Equivalence of Two Selective Mixing Strategies on Aggregate Contact Patterns & Resulting Epidemic Spread☆

PubMed Central

Morin, Benjamin R; Perrings, Charles; Levin, Simon; Kinzig, Ann

2014-01-01

The personal choices affecting the transmission of infectious diseases include the number of contacts an individual makes, and the risk-characteristics of those contacts. We consider whether these different choices have distinct implications for the course of an epidemic. We also consider whether choosing contact mitigation (how much to mix) and affinity mitigation (with whom to mix) strategies together has different epidemiological effects than choosing each separately. We use a set of differential equation compartmental models of the spread of disease, coupled with a model of selective mixing. We assess the consequences of varying contact or affinity mitigation as a response to disease risk. We do this by comparing disease incidence and dynamics under varying contact volume, contact type, and both combined across several different disease models. Specifically, we construct a change of variables that allows one to transition from contact mitigation to affinity mitigation, and vice versa. In the absence of asymptomatic infection we find no difference in the epidemiological impacts of the two forms of disease risk mitigation. Furthermore, since models that include both mitigation strategies are under-determined, varying both results in no outcome that could not be reached by choosing either separately. Which strategy is actually chosen then depends not on their epidemiological consequences, but on the relative cost of reducing contact volume versus altering contact type. Although there is no fundamental epidemiological difference between the two forms of mitigation, the social cost of alternative strategies can be very different. From a social perspective, therefore, whether one strategy should be promoted over another depends on economic not epidemiological factors. PMID:25150459

Disease risk mitigation: the equivalence of two selective mixing strategies on aggregate contact patterns and resulting epidemic spread.

PubMed

Morin, Benjamin R; Perrings, Charles; Levin, Simon; Kinzig, Ann

2014-12-21

The personal choices affecting the transmission of infectious diseases include the number of contacts an individual makes, and the risk-characteristics of those contacts. We consider whether these different choices have distinct implications for the course of an epidemic. We also consider whether choosing contact mitigation (how much to mix) and affinity mitigation (with whom to mix) strategies together has different epidemiological effects than choosing each separately. We use a set of differential equation compartmental models of the spread of disease, coupled with a model of selective mixing. We assess the consequences of varying contact or affinity mitigation as a response to disease risk. We do this by comparing disease incidence and dynamics under varying contact volume, contact type, and both combined across several different disease models. Specifically, we construct a change of variables that allows one to transition from contact mitigation to affinity mitigation, and vice versa. In the absence of asymptomatic infection we find no difference in the epidemiological impacts of the two forms of disease risk mitigation. Furthermore, since models that include both mitigation strategies are underdetermined, varying both results in no outcome that could not be reached by choosing either separately. Which strategy is actually chosen then depends not on their epidemiological consequences, but on the relative cost of reducing contact volume versus altering contact type. Although there is no fundamental epidemiological difference between the two forms of mitigation, the social cost of alternative strategies can be very different. From a social perspective, therefore, whether one strategy should be promoted over another depends on economic not epidemiological factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Minimizing mixing intensity to improve the performance of rice straw anaerobic digestion via enhanced development of microbe-substrate aggregates.

PubMed

Kim, Moonkyung; Kim, Byung-Chul; Choi, Yongju; Nam, Kyoungphile

2017-12-01

The aim of this work was to study the effect of the differential development of microbe-substrate aggregates at different mixing intensities on the performance of anaerobic digestion of rice straw. Batch and semi-continuous reactors were operated for up to 50 and 300days, respectively, under different mixing intensities. In both batch and semi-continuous reactors, minimal mixing conditions exhibited maximum methane production and lignocellulose biodegradability, which both had strong correlations with the development of microbe-substrate aggregates. The results implied that the aggregated microorganisms on the particulate substrate played a key role in rice straw hydrolysis, determining the performance of anaerobic digestion. Increasing the mixing speed from 50 to 150rpm significantly reduced the methane production rate by disintegrating the microbe-substrate aggregates in the semi-continuous reactor. A temporary stress of high-speed mixing fundamentally affected the microbial communities, increasing the possibility of chronic reactor failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Shaken, but not stirred: how vortical flow drives small-scale aggregations of gyrotactic phytoplankton

NASA Astrophysics Data System (ADS)

Barry, Michael; Durham, William; Climent, Eric; Stocker, Roman

2011-11-01

Coastal ocean observations reveal that motile phytoplankton form aggregations at the Kolmogorov scale (mm-cm), whereas non-motile cells do not. We propose a new mechanism for the formation of this small-scale patchiness based on the interplay of turbulence and gyrotactic motility. Counterintuitively, turbulence does not stir a plankton suspension to homogeneity but drives aggregations instead. Through controlled laboratory experiments we show that the alga Heterosigma akashiwo rapidly forms aggregations in a cavity-driven vortical flow that approximates Kolmogorov eddies. Gyrotactic motility is found to be the key ingredient for aggregation, as non-motile cells remain randomly distributed. Observations are in remarkable agreement with a 3D model, and the validity of this mechanism for generating patchiness has been extended to realistic turbulent flows using Direct Numerical Simulations. Because small-scale patchiness influences rates of predation, sexual reproduction, infection, and nutrient competition, this result indicates that gyrotactic motility can profoundly affect phytoplankton ecology.

Aggregate formation affects ultrasonic disruption of microalgal cells.

PubMed

Wang, Wei; Lee, Duu-Jong; Lai, Juin-Yih

2015-12-01

Ultrasonication is a cell disruption process of low energy efficiency. This study dosed K(+), Ca(2+) and Al(3+) to Chlorella vulgaris cultured in Bold's Basal Medium at 25°C and measured the degree of cell disruption under ultrasonication. Adding these metal ions yielded less negatively charged surfaces of cells, while with the latter two ions large and compact cell aggregates were formed. The degree of cell disruption followed: control=K(+)>Ca(2+)>Al(3+) samples. Surface charges of cells and microbubbles have minimal effects on the microbubble number in the proximity of the microalgal cells. Conversely, cell aggregates with large size and compact interior resist cell disruption under ultrasonication. Staining tests revealed high diffusional resistance of stains over the aggregate interior. Microbubbles may not be effective generated and collapsed inside the compact aggregates, hence leading to low cell disruption efficiencies. Effective coagulation/flocculation in cell harvesting may lead to adverse effect on subsequent cell disruption efficiency. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure evolution of gelatin particles induced by pH and ionic strength.

PubMed

Xu, Jing; Li, Tianduo; Tao, Furong; Cui, Yuezhi; Xia, Yongmei

2013-03-01

Microstructure of gelatin particles played a key role in determining the physicochemical properties of gelatin. Ionic strength and pH as systematic manners were considered to affect gelatin particles structure on the micrometer scale. Scanning electron microscopy was used for depicting the morphologies of gelatin particles. Increasing pH to 10.0 or decreasing pH to 4.0, spherical, spindle, and irregular aggregates of gelatin particles at 2, 6, 10, and 14% solution (w/w) were all transformed to spindle aggregates. When NaCl was added to the system, the molecular chains of gelatin possibly rearranged themselves in a stretched state, and the ribbon aggregates was observed. The structural transitions of gelatin aggregates were strongly depended on the electrostatic repulsion. In the gelatin-sodium dodecyl sulfate (SDS) case, the micrometer scale of aggregates was larger and the different degrees of cross-links were induced through hydrophobic interaction and electrostatic repulsion. Copyright © 2012 Wiley Periodicals, Inc.

Role of organic matter on aggregate stability and related mechanisms through organic amendments

NASA Astrophysics Data System (ADS)

Zaher, Hafida

2010-05-01

To date, only a few studies have tried to simultaneously compare the role of neutral and uronic sugars and lipids on soil structural stability. Moreover, evidence for the mechanisms involved has often been established following wetting of moist aggregates after various pre-treatments thus altering aggregate structure and resulting in manipulations on altered aggregates on which the rapid wetting process may not be involved anymore. To the best of our knowledge, the objective of this work was to study the role of neutral and uronic sugars and lipids in affecting key mechanisms (swelling rate, pressure evolution) involved in the stabilization of soil structure. A long-term incubation study (48-wk) was performed on a clay loam and a silty-clay loam amended with de-inking-secondary sludge mix at three rates (8, 16 and 24 Mg dry matter ha-1), primary-secondary sludge mix at one rate (18 Mg oven-dry ha-1) and composted de-inking sludge at one rate (24 Mg ha-1). Different structural stability indices (stability of moist and dry aggregates, the amount of dispersible clay and loss of soil material following sudden wetting) were measured on a regular basis during the incubation, along with CO2 evolved, neutral and uronic sugar, and lipid contents. During the course of the incubations, significant increases in all stability indices were measured for both soil types. In general, the improvements in stability were proportional to the amount of C added as organic amendments. These improvements were linked to a very intense phase of C mineralization and associated with increases in neutral and uronic sugars as well as lipid contents. The statistical relationships found between the different carbonaceous fractions and stability indices were all highly significant and indicated no clear superiority of one fraction over another. Paper sludge amendments also resulted in significant decreases in maximum internal pressure of aggregate and aggregate swelling following immersion in water, two mechanisms affecting structural stability. Overall, the results suggest that reduction in maximum internal pressure induced by organic amendments most likely resulted from increases in pore surface roughness and pore occlusion rather than by increase in surface wetting angles. This study also supports the view of a non specific action of the lipids, neutral and uronic sugars on aggregate stability to rapid wetting. Key words: soil aggregate stability, polysaccharides, lipids, mechanisms, organic matter

Mesoscale properties of clay aggregates from potential of mean force representation of interactions between nanoplatelets

NASA Astrophysics Data System (ADS)

Ebrahimi, Davoud; Whittle, Andrew J.; Pellenq, Roland J.-M.

2014-04-01

Face-to-face and edge-to-edge free energy interactions of Wyoming Na-montmorillonite platelets were studied by calculating potential of mean force along their center to center reaction coordinate using explicit solvent (i.e., water) molecular dynamics and free energy perturbation methods. Using a series of configurations, the Gay-Berne potential was parametrized and used to examine the meso-scale aggregation and properties of platelets that are initially random oriented under isothermal-isobaric conditions. Aggregates of clay were defined by geometrical analysis of face-to-face proximity of platelets with size distribution described by a log-normal function. The isotropy of the microstructure was assessed by computing a scalar order parameter. The number of platelets per aggregate and anisotropy of the microstructure both increases with platelet plan area. The system becomes more ordered and aggregate size increases with increasing pressure until maximum ordered state at confining pressure of 50 atm. Further increase of pressure slides platelets relative to each other leading to smaller aggregate size. The results show aggregate size of (3-8) platelets for sodium-smectite in agreement with experiments (3-10). The geometrical arrangement of aggregates affects mechanical properties of the system. The elastic properties of the meso-scale aggregate assembly are reported and compared with nanoindentation experiments. It is found that the elastic properties at this scale are close to the cubic systems. The elastic stiffness and anisotropy of the assembly increases with the size of the platelets and the level of external pressure.

Soil Aggregate Stability and Grassland Productivity Associations in a Northern Mixed-Grass Prairie

PubMed Central

Reinhart, Kurt O.; Vermeire, Lance T.

2016-01-01

Soil aggregate stability data are often predicted to be positively associated with measures of plant productivity, rangeland health, and ecosystem functioning. Here we revisit the hypothesis that soil aggregate stability is positively associated with plant productivity. We measured local (plot-to-plot) variation in grassland community composition, plant (aboveground) biomass, root biomass, % water-stable soil aggregates, and topography. After accounting for spatial autocorrelation, we observed a negative association between % water-stable soil aggregates (0.25–1 and 1–2 mm size classes of macroaggregates) and dominant graminoid biomass, and negative associations between the % water-stable aggregates and the root biomass of a dominant sedge (Carex filifolia). However, variation in total root biomass (0–10 or 0–30 cm depths) was either negatively or not appreciably associated with soil aggregate stabilities. Overall, regression slope coefficients were consistently negative thereby indicating the general absence of a positive association between measures of plant productivity and soil aggregate stability for the study area. The predicted positive association between factors was likely confounded by variation in plant species composition. Specifically, sampling spanned a local gradient in plant community composition which was likely driven by niche partitioning along a subtle gradient in elevation. Our results suggest an apparent trade-off between some measures of plant biomass production and soil aggregate stability, both known to affect the land’s capacity to resist erosion. These findings further highlight the uncertainty of plant biomass-soil stability associations. PMID:27467598

HEMORHEOLOGICAL IMPLICATIONS OF PERFLUOROCARBON BASED OXYGEN CARRIER INTERACTION WITH COLLOID PLASMA EXPANDERS AND BLOOD

PubMed Central

Vásquez, Diana M.; Ortiz, Daniel; Alvarez, Oscar A.; Briceño, Juan C.; Cabrales, Pedro

2013-01-01

Perfluorocarbon (PFC) emulsion based oxygen carriers lack colloid osmotic pressure (COP) and must be administered with colloid-based plasma expanders (PEs). Although PFC emulsions have been widely studied, there is limited information about PFC emulsion interaction with PEs and blood. Their interaction forms aggregates due to electrostatic and rheological phenomena, and change blood rheology and blood flow. This study analyzes the effects of the interaction between PFC emulsions with blood in the presence of clinically-used PEs. The rheological behavior of the mixtures was analyzed in parallel with in vivo analysis of blood flow in microvessels using intravital microscopy when administered in a clinically relevant scenario. The interaction between the PFC emulsion and PE with blood produced PFC droplets and red blood cell (RBCs) aggregation, and increased blood viscosity. The PFC droplets formed aggregates when mixed with PEs containing electrolytes, and the aggregation increased with the electrolyte concentration. Mixtures of PFC with PEs that produced PFC aggregates also induced RCBs aggregation when mixed with blood, increasing blood viscosity at low shear rates. The more viscous suspension at low shear rates produced a blunted blood flow velocity profile in vivo relative to non-aggregating mixtures of PFC and PEs. For the PEs evaluated, albumin produced minimal to undetectable aggregation. PFC and PEs interaction with blood can affect sections of the microcirculation with low shear rate (e.g. arterioles, venules, and pulmonary circulation) because aggregates could cause capillary occlusion, decrease perfusion, pulmonary emboli, or focal ischemia. PMID:23606592

Soil Aggregate Stability and Grassland Productivity Associations in a Northern Mixed-Grass Prairie.

PubMed

Reinhart, Kurt O; Vermeire, Lance T

2016-01-01

Soil aggregate stability data are often predicted to be positively associated with measures of plant productivity, rangeland health, and ecosystem functioning. Here we revisit the hypothesis that soil aggregate stability is positively associated with plant productivity. We measured local (plot-to-plot) variation in grassland community composition, plant (aboveground) biomass, root biomass, % water-stable soil aggregates, and topography. After accounting for spatial autocorrelation, we observed a negative association between % water-stable soil aggregates (0.25-1 and 1-2 mm size classes of macroaggregates) and dominant graminoid biomass, and negative associations between the % water-stable aggregates and the root biomass of a dominant sedge (Carex filifolia). However, variation in total root biomass (0-10 or 0-30 cm depths) was either negatively or not appreciably associated with soil aggregate stabilities. Overall, regression slope coefficients were consistently negative thereby indicating the general absence of a positive association between measures of plant productivity and soil aggregate stability for the study area. The predicted positive association between factors was likely confounded by variation in plant species composition. Specifically, sampling spanned a local gradient in plant community composition which was likely driven by niche partitioning along a subtle gradient in elevation. Our results suggest an apparent trade-off between some measures of plant biomass production and soil aggregate stability, both known to affect the land's capacity to resist erosion. These findings further highlight the uncertainty of plant biomass-soil stability associations.

Influence of recycled fine aggregates on the resistance of mortars to magnesium sulfate attack

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Seung-Tae

2009-08-15

The influence of recycled fine aggregates, which had been reclaimed from field-demolished concretes, on the resistance of mortar specimens to magnesium sulfate attack was investigated. Mortar specimens were prepared with recycled fine aggregates at different replacement levels (0%, 25%, 50%, 75% and 100% of natural fine aggregate by mass). The mortar specimens were exposed to 4.24% magnesium sulfate solution for about 1 year at ambient temperature, and regularly monitored for visual appearance, compressive strength loss and expansion. Additionally, in order to identify products of magnesium sulfate attack, mortar samples incorporating 0%, 25% and 100% replacement levels of the recycled finemore » aggregates were examined by X-ray diffraction (XRD) technique. Experimental results confirmed that the use of recycled fine aggregates up to a maximum 50% replacement level is effective under severe magnesium sulfate environment, irrespective of type of recycled fine aggregates. However, the worse performance was observed in mortar specimens incorporating 100% replacement level. It was found that the water absorption of recycled fine aggregates affected deterioration of mortar specimens, especially at a higher replacement level. XRD results indicated that the main cause of deterioration of the mortar specimens was primarily due to the formation of gypsum and thaumasite by magnesium sulfate attack. In addition, it appeared that the conversion of C-S-H into M-S-H by the attack probably influenced mechanical deterioration of mortar specimens with recycled fine aggregates.« less

On the importance of considering heterogeneity in witnesses' competence levels when reconstructing crimes from multiple witness testimonies.

PubMed

Waubert de Puiseau, Berenike; Greving, Sven; Aßfalg, André; Musch, Jochen

2017-09-01

Aggregating information across multiple testimonies may improve crime reconstructions. However, different aggregation methods are available, and research on which method is best suited for aggregating multiple observations is lacking. Furthermore, little is known about how variance in the accuracy of individual testimonies impacts the performance of competing aggregation procedures. We investigated the superiority of aggregation-based crime reconstructions involving multiple individual testimonies and whether this superiority varied as a function of the number of witnesses and the degree of heterogeneity in witnesses' ability to accurately report their observations. Moreover, we examined whether heterogeneity in competence levels differentially affected the relative accuracy of two aggregation procedures: a simple majority rule, which ignores individual differences, and the more complex general Condorcet model (Romney et al., Am Anthropol 88(2):313-338, 1986; Batchelder and Romney, Psychometrika 53(1):71-92, 1988), which takes into account differences in competence between individuals. 121 participants viewed a simulated crime and subsequently answered 128 true/false questions about the crime. We experimentally generated groups of witnesses with homogeneous or heterogeneous competences. Both the majority rule and the general Condorcet model provided more accurate reconstructions of the observed crime than individual testimonies. The superiority of aggregated crime reconstructions involving multiple individual testimonies increased with an increasing number of witnesses. Crime reconstructions were most accurate when competences were heterogeneous and aggregation was based on the general Condorcet model. We argue that a formal aggregation should be considered more often when eyewitness testimonies have to be assessed and that the general Condorcet model provides a good framework for such aggregations.

Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles.

PubMed

Ayyadevara, Srinivas; Mercanti, Federico; Wang, Xianwei; Mackintosh, Samuel G; Tackett, Alan J; Prayaga, Sastry V S; Romeo, Francesco; Shmookler Reis, Robert J; Mehta, Jawahar L

2016-05-01

Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well as proteins thought to be specific for each disease. Aggregation has not previously been reported in the normal, aging heart or the hypertensive heart. Detergent-insoluble protein aggregates were isolated from mouse heart and characterized on 2-dimensional gels. Their levels increased markedly and significantly with aging and after sustained angiotensin II-induced hypertension. Of the aggregate components identified by high-resolution proteomics, half changed in abundance with age (392/787) or with sustained hypertension (459/824), whereas 30% (273/901) changed concordantly in both, each P<0.05. One fifth of these proteins were previously associated with age-progressive neurodegenerative or cardiovascular diseases, or both (eg, ApoE, ApoJ, ApoAIV, clusterin, complement C3, and others involved in stress-response and protein-homeostasis pathways). Because fibrosis is a characteristic of both aged and hypertensive hearts, we posited that aging of fibroblasts may contribute to the aggregates observed in cardiac tissue. Indeed, as cardiac myofibroblasts "senesced" (approached their replicative limit) in vitro, they accrued aggregates with many of the same constituent proteins observed in vivo during natural aging or sustained hypertension. In summary, we have shown for the first time that compact (detergent-insoluble) protein aggregates accumulate during natural aging, chronic hypertension, and in vitro myofibroblast senescence, sharing many common proteins. Thus, aggregates that arise from disparate causes (aging, hypertension, and replicative senescence) may have common underlying mechanisms of accrual. © 2016 American Heart Association, Inc.

Influence of plankton community structure on the sinking velocity of marine aggregates

NASA Astrophysics Data System (ADS)

Bach, L. T.; Boxhammer, T.; Larsen, A.; Hildebrandt, N.; Schulz, K. G.; Riebesell, U.

2016-08-01

About 50 Gt of carbon is fixed photosynthetically by surface ocean phytoplankton communities every year. Part of this organic matter is reprocessed within the plankton community to form aggregates which eventually sink and export carbon into the deep ocean. The fraction of organic matter leaving the surface ocean is partly dependent on aggregate sinking velocity which accelerates with increasing aggregate size and density, where the latter is controlled by ballast load and aggregate porosity. In May 2011, we moored nine 25 m deep mesocosms in a Norwegian fjord to assess on a daily basis how plankton community structure affects material properties and sinking velocities of aggregates (Ø 80-400 µm) collected in the mesocosms' sediment traps. We noted that sinking velocity was not necessarily accelerated by opal ballast during diatom blooms, which could be due to relatively high porosity of these rather fresh aggregates. Furthermore, estimated aggregate porosity (Pestimated) decreased as the picoautotroph (0.2-2 µm) fraction of the phytoplankton biomass increased. Thus, picoautotroph-dominated communities may be indicative for food webs promoting a high degree of aggregate repackaging with potential for accelerated sinking. Blooms of the coccolithophore Emiliania huxleyi revealed that cell concentrations of 1500 cells/mL accelerate sinking by about 35-40%, which we estimate (by one-dimensional modeling) to elevate organic matter transfer efficiency through the mesopelagic from 14 to 24%. Our results indicate that sinking velocities are influenced by the complex interplay between the availability of ballast minerals and aggregate packaging; both of which are controlled by plankton community structure.

Edge strand engineering prevents native-like aggregation in Sulfolobus solfataricus acylphosphatase.

PubMed

de Rosa, Matteo; Bemporad, Francesco; Pellegrino, Sara; Chiti, Fabrizio; Bolognesi, Martino; Ricagno, Stefano

2014-09-01

β-proteins are constantly threatened by the risk of aggregation because β-sheets are inherently structured for edge-to-edge interactions. To avoid native-like aggregation, evolution has resulted in a set of strategies that prevent intermolecular β-interactions. Acylphosphatase from Sulfolobus solfataricus (Sso AcP) represents a suitable model for the study of such a process. Under conditions promoting aggregation, Sso AcP acquires a native-like conformational state whereby an unstructured N-terminal segment interacts with the edge β-strand B4 of an adjacent Sso AcP molecule. Because B4 is poorly protected against aggregation, this interaction triggers the aggregation cascade without the need for unfolding. Recently, three single Sso AcP mutants (V84D, Y86E and V84P) were designed to engineer additional protection against aggregation in B4 and were observed to successfully impair native-like aggregation in all three variants at the expense of a lower stability. To understand the structural basis of the reduced aggregation propensity and lower stability, the crystal structures of the Sso AcP variants were determined in the present study. Structural analysis reveals that the V84D and Y86E mutations exert protection by the insertion of an edge negative charge. A conformationally less regular B4 underlies protection against aggregation in the V84P mutant. The thermodynamic basis of instability is discussed. Moreover, kinetic experiments indicate that aggregation of the three mutants is not native-like and is independent of the interaction between B4 and the unstructured N-terminal segment. The reported data rationalize previous evidence regarding Sso AcP native-like aggregation and provide a basis for the design of aggregation-free proteins. The atomic coordinates and related experimental data for the Sso AcP mutants V84P, V84D, ΔN11 Y86E have been deposited in the Protein Data Bank under accession numbers 4OJ3, 4OJG and 4OJH, respectively. • Sso AcP and Sso AcP bind by fluorescence technology (View interaction). © 2014 FEBS.

Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering.

PubMed

Saldanha, Karl J; Doan, Ryan P; Ainslie, Kristy M; Desai, Tejal A; Majumdar, Sharmila

2011-01-01

To examine mesenchymal stem cell (MSC) labeling with micrometer-sized iron oxide particles (MPIOs) for magnetic resonance imaging (MRI)-based tracking and its application to monitoring articular cartilage regeneration. Rabbit MSCs were labeled using commercial MPIOs. In vitro MRI was performed with gradient echo (GRE) and spin echo (SE) sequences at 3T and quantitatively characterized using line profile and region of interest analysis. Ex vivo MRI of hydrogel-encapsulated labeled MSCs implanted within a bovine knee was performed with spoiled GRE (SPGR) and T(1ρ) sequences. Fluorescence microscopy, labeling efficiency, and chondrogenesis of MPIO-labeled cells were also examined. MPIO labeling results in efficient contrast uptake and signal loss that can be visualized and quantitatively characterized via MRI. SPGR imaging of implanted cells results in ex vivo detection within native tissue, and T(1ρ) imaging is unaffected by the presence of labeled cells immediately following implantation. MPIO labeling does not affect quantitative glycosaminoglycan production during chondrogenesis, but iron aggregation hinders extracellular matrix visualization. This aggregation may result from excess unincorporated particles following labeling and is an issue that necessitates further investigation. This study demonstrates the promise of MPIO labeling for monitoring cartilage regeneration and highlights its potential in the development of cell-based tissue engineering strategies. Published by Elsevier Inc.

A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

PubMed

Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

2016-03-14

The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

Molecular and Clinical Aspects of Protein Aggregation Assays in Neurodegenerative Diseases.

PubMed

Villar-Piqué, Anna; Schmitz, Matthias; Candelise, Niccolò; Ventura, Salvador; Llorens, Franc; Zerr, Inga

2018-02-10

The presence of protein deposits is a common pathological hallmark in patients suffering from neurodegenerative conditions and other proteinopathies. Deciphering the molecular basis of protein misfolding and aggregation is a crucial step towards the full comprehension of the factors that trigger the onset of these diseases and for the development of efficient therapeutical strategies. In this regard, in vitro aggregation assays for misfolded proteins offer an excellent tool to study pathological processes of protein deposition under controlled conditions, where confounders can be easily discriminated. These methods are generally cost-effective and have been proved useful in many fields, including drug discovery and clinical diagnostics. Here, we review the bases of in vitro aggregation and seeding assays, recapitulate their main applications and offer a critical evaluation of their limitations. Comprehending the molecular mechanisms behind these assays and combining them with in vivo or cell-based experiments will maximize their potential and allow the necessary improvement to overcome some of the current drawbacks.

Two compounds in bed bug feces are sufficient to elicit off-host aggregation by bed bugs, Cimex lectularius.

PubMed

Olson, Joelle F; Vers, Leonard M Ver; Moon, Roger D; Kells, Stephen A

2017-01-01

After feeding, bed bugs aggregate in cracks and crevices near a host. Aggregation and arrestment are mediated by tactile and chemical stimuli associated with the bugs' feces and exuviae. Volatiles derived from fecally stained filter papers were analyzed by solid-phase microextraction (SPME) and evaluated using a multichoice behavioral assay to determine their impact on bed bug aggregation. In addition, crude fecal extracts were collected in methanol, analyzed by gas chromatography coupled with electroantennogram detection (GC-EAD) and mass spectrometry (GC-MS) and evaluated in open-air multichoice behavioral assays. The SPME method was used to detect (E)-2-hexenal and (E)-2-octenal in heated bed bug feces. The presence of these two volatile components did not affect aggregation. Analysis of the crude fecal extracts revealed several semi-volatile nitrogenous compounds, a carboxylic acid and a sulfur-based compound. Adult antennae responded to compounds eluted from three regions of the crude extract using GC-EAD. A combination of two compounds, dimethyl trisulfide and methyldiethanolamine, resulted in aggregation responses equivalent to the original crude extract. Bed bug aggregation is mediated by semi-volatile compounds derived from fecal extracts, and two compounds are sufficient to elicit aggregation. The two compounds identified here could be used to enhance the effectiveness of insecticidal applications or improve monitoring techniques. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

The C-Terminal Threonine of Aβ43 Nucleates Toxic Aggregation via Structural and Dynamical Changes in Monomers and Protofibrils

PubMed Central

2015-01-01

Recent studies suggest that deposition of amyloid β (Aβ) into oligomeric aggregates and fibrils, hallmarks of Alzheimer’s disease, may be initiated by the aggregation of Aβ species other than the well-studied 40- and 42-residue forms, Aβ40 and Aβ42, respectively. Here we report on key structural, dynamic, and aggregation kinetic parameters of Aβ43, extended by a single threonine at the C-terminus relative to Aβ42. Using aggregation time course experiments, electron microscopy, and a combination of nuclear magnetic resonance measurements including backbone relaxation, dark-state exchange saturation transfer, and quantification of chemical shift differences and scalar coupling constants, we demonstrate that the C-terminal threonine in Aβ43 increases the rate and extent of protofibril aggregation and confers slow C-terminal motions in the monomeric and protofibril-bound forms of Aβ43. Relative to the neighboring residues, the hydrophilic Thr43 of Aβ43 favors direct contact with the protofibril surface more so than the C-terminus of Aβ40 or Aβ42. Taken together, these results demonstrate the potential of a small chemical modification to affect the properties of Aβ structure and aggregation, providing a mechanism for the potential role of Aβ43 as a primary nucleator of Aβ aggregates in Alzheimer’s disease. PMID:24773532

Impact of reduced tillage and organic inputs on aggregate stability and earthworm community in a Breton context in France

NASA Astrophysics Data System (ADS)

Paillat, Louise; Menasseri, Safya; Busnot, Sylvain; Roucaute, Marc; Benard, Yannick; Morvan, Thierry; Pérès, Guénola

2017-04-01

Soil aggregate stability, which refers to the ability of soil aggregates to resist breakdown when disruptive forces are applied (water, wind), is a good indicator of the sensitivity of soil to crusting and erosion and is a relevant indicator for soil stability. Within soil parameters which affect soil stability, organic matter is one of the main important by functioning as bonding agent between mineral soil particles, but soil organisms such as microorganisms and earthworms are also recognized as efficient agents. However the relationship between earthworms, fungal hyphae and aggregation is still unclear. In order to assess the influence of these biological agents on aggregate dynamics, we have combined a field study and a laboratory experiment. On a long term experiment trial in Brittany, SOERE PRO-EFELE, we have studied the effect of reduced tillage (vs. conventional tillage) combined to organic inputs (vs. mineral inputs) on earthworm community and soil stability. Aggregate stability was measured at different perturbations intensities: fast wetting (FW), slow wetting (SW) and mechanical breakdown (MB). This study showed that after 4 years of experiments, reduced tillage and organic inputs enhanced aggregate stability. Earthworms modulated aggregation process: endogeics reduced FW stability (mechanical binding by hyphae) and anecics increased SW stability (aggregate interparticular cohesion and hydrophobicity). Some precisions were provided by the laboratory experiment, using microcosms, which compared casts of the endogeic Aporectodea c. caliginosa (NCCT) and the anecic Lumbricus terrestris (LT). The presumed hyphae fragmentation by endogeics could not be highlight in NCCT casts. Nevertheless, hyphae were more abundant and C content and aggregate stability were higher in LT casts corroborating the positive contribution of anecics to aggregate stability.

Assessing the dynamics of the upper soil layer relative to soil management practices

NASA Astrophysics Data System (ADS)

Hatfield, J.; Wacha, K.; Dold, C.

2017-12-01

The upper layer of the soil is the critical interface between the soil and the atmosphere and is the most dynamic in response to management practices. One of the soil properties most reflective to changes in management is the stability of the aggregates because this property controls infiltration of water and exchange of gases. An aggregation model has been developed based on the factors that control how aggregates form and the forces which degrade aggregates. One of the major factors for this model is the storage of carbon into the soil and the interaction with the soil biological component. To increase soil biology requires a stable microclimate that provides food, water, shelter, and oxygen which in turn facilitates the incorporation of organic material into forms that can be combined with soil particles to create stable aggregates. The processes that increase aggregate size and stability are directly linked the continual functioning of the biological component which in turn changes the physical and chemical properties of the soil. Soil aggregates begin to degrade as soon as there is no longer a supply of organic material into the soil. These processes can range from removal of organic material and excessive tillage. To increase aggregation of the upper soil layer requires a continual supply of organic material and the biological activity that incorporates organic material into substances that create a stable aggregate. Soils that exhibit stable soil aggregates at the surface have a prolonged infiltration rate with less runoff and a gas exchange that ensures adequate oxygen for maximum biological activity. Quantifying the dynamics of the soil surface layer provides a quantitative understanding of how management practices affect aggregate stability.

[Effects of Tillage on Distribution of Heavy Metals and Organic Matter Within Purple Paddy Soil Aggregates].

PubMed

Shi, Qiong-bin; Zhao, Xiu-lan; Chang, Tong-ju; Lu, Ji-wen

2016-05-15

A long-term experiment was utilized to study the effects of tillage methods on the contents and distribution characteristics of organic matter and heavy metals (Cu, Zn, Pb, Cd, Fe and Mn) in aggregates with different sizes (including 1-2, 0.25-1, 0.05-0.25 mm and < 0.05 mm) in a purple paddy soil under two tillage methods including flooded paddy field (FPF) and paddy-upland rotation (PR). The relationship between heavy metals and organic matter in soil aggregates was also analyzed. The results showed that the aggregates of two tillage methods were dominated by 0.05-0.25 mm and < 0.05 mm particle size, respectively. The contents of organic matter in each aggregate decreased with the decrease of aggregate sizes, however, compared to PR, FPF could significantly increase the contents of organic matter in soils and aggregates. The tillage methods did not significantly affect the contents of heavy metals in soils, but FPF could enhance the accumulation and distribution of aggregate, organic matter and heavy metals in aggregates with diameters of 1-2 mm and 0.25-1 mm. Correlation analysis found that there was a negative correlation between the contents of heavy metals and organic matter in soil aggregates, but a positive correlation between the amounts of heavy metal and organic matter accumulated in soil aggregates. From the slope of the correlation analysis equations, we could found that the sensitivities of heavy metals to the changes of soil organic matters followed the order of Mn > Zn > Pb > Cu > Fe > Cd under the same tillage. When it came to the same heavy metal, it was more sensitive in PR than in FPF.

A Dispersion-Dominated Chromogenic Strategy for Colorimetric Sensing of Glutathione at the Nanomolar Level Using Gold Nanoparticles.

PubMed

Xianyu, Yunlei; Xie, Yangzhouyun; Wang, Nuoxin; Wang, Zhuo; Jiang, Xingyu

2015-11-04

A dispersion-dominated chromogenic strategy for glutathione sensing is developed. Glutathione prevents the aggregation of arginine-modified gold nanoparticles via mercury-thiol interaction, which allows for glutathione sensing at the nanomolar level (10.9 × 10(-9) m) with facile operation and naked-eye readout. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Misfolded rhodopsin mutants display variable aggregation properties.

PubMed

Gragg, Megan; Park, Paul S-H

2018-06-08

The largest class of rhodopsin mutations causing autosomal dominant retinitis pigmentosa (adRP) is mutations that lead to misfolding and aggregation of the receptor. The misfolding mutants have been characterized biochemically, and categorized as either partial or complete misfolding mutants. This classification is incomplete and does not provide sufficient information to fully understand the disease pathogenesis and evaluate therapeutic strategies. A Förster resonance energy transfer (FRET) method was utilized to directly assess the aggregation properties of misfolding rhodopsin mutants within the cell. Partial (P23H and P267L) and complete (G188R, H211P, and P267R) misfolding mutants were characterized to reveal variability in aggregation properties. The complete misfolding mutants all behaved similarly, forming aggregates when expressed alone, minimally interacting with the wild-type receptor when coexpressed, and were unresponsive to treatment with the pharmacological chaperone 9-cis retinal. In contrast, variability was observed between the partial misfolding mutants. In the opsin form, the P23H mutant behaved similarly as the complete misfolding mutants. In contrast, the opsin form of the P267L mutant existed as both aggregates and oligomers when expressed alone and formed mostly oligomers with the wild-type receptor when coexpressed. The partial misfolding mutants both reacted similarly to the pharmacological chaperone 9-cis retinal, displaying improved folding and oligomerization when expressed alone but aggregating with wild-type receptor when coexpressed. The observed differences in aggregation properties and effect of 9-cis retinal predict different outcomes in disease pathophysiology and suggest that retinoid-based chaperones will be ineffective or even detrimental. Copyright © 2018 Elsevier B.V. All rights reserved.

Behavior of crushed rock aggregates used in road construction exposed to cold climate conditions

NASA Astrophysics Data System (ADS)

Kuznetsova, Elena; Pérez Fortes, Ana Patricia; Anastasio, Sara; Willy Danielsen, Svein

2016-04-01

Presently, about 90% of the aggregate production in Europe comes from naturally occurring resources: quarries and pits. Due to the increased demand for sand and gravel for construction purposes, not only in building but also in road construction, the last decade has seen a significant trend towards the use of more crushed rock aggregates. This resource has been more and more preferred to sand and gravel thanks to the significant technological development of its process and use phase. The performance of the aggregates is generally evaluated depending on three main factors: the geological origin (mineral composition, texture, structure, degree of weathering), the aggregate processing (crushing, sieving, washing, storing) and the user technology for a specific area of use (e.g. road construction, asphalt binders). Nevertheless climatic conditions should carefully be taken into account in application such as road construction. Large temperature gradients and high levels of humidity are known to significantly affect the performance of the material. Although the problem is, at least in the asphalt field, considered mostly from the binder point of view, this article aims to investigate the effect of aggregate properties on road performance in cold climatic conditions. Two different climatic areas will be taken into account: Norway and Spain. While both these countries are listed among the main European producers of aggregates, they represent significantly different climatic regions. While Norwegian weather is characterized by humid cold winters and relatively mild summers, Spain has temperate climate with cold regions in mountainous and internal areas. Both countries have been significantly affected by climate change with increasing temperature variations and instability. At the same time, similar winter maintenance measures, including the use of a considerable amount of solid and liquid chemicals to avoid ice formation (e.g. NaCl) and/or to provide better friction, are carried out in both countries. The use of crushed aggregates in both the frost protection layer and asphalt layers is the main topic for our investigations. In existing standards there is large focus on mechanical properties of aggregates and their grain size distribution, but little focus on mineralogy and and its behaviour at low temperatures. With the purpose to study the effect of winter climatic conditions and the use of salts during winter maintenance, different samples of aggregates and asphalt mixtures used in Norwegian and Spanish roads were subjected to freeze-thaw cycles in the laboratory. To evaluate the impact of these cycles to the mechanical properties of the selected materials, Los Angeles test on aggregates and Cantabro test on asphalt have been done and compared with results from the same aggregates and asphalt mixtures but untreated in the laboratory. The results obtained were related to the petrographical analysis of the rocks that compose the aggregates in order to estimate the influence of the rock properties (mineralogy, texture and structure) in road materials behavior, especially when they are exposed to winter conditions.

Sunlight-assisted synthesis of colloidal silver nanoparticles using chitosan as reducing agent

NASA Astrophysics Data System (ADS)

Susilowati, E.; Maryani; Ashadi

2018-04-01

The present study we explore an environmentally friendly colloidal silver nanoparticles preparation using chitosan as reducing agent and stabilizer. It develops a new strategy on preparation of silver nanoparticles through the gel phase using sodium hydroxide (NaOH) as accelerator reagent. Sunlight irradiation was employed to assisted reducing process of silver ions to silver nanoparticles. Localized surface plasmon resonance (LSPR) phenomenon of silver nanoparticles was investigated using UV-Vis spectrophotometer. The shape and size of silver particles were analyzed using TEM. The formation of silver nanoparticles was confirmed by the appearance of LSPR absorption peak at 396.0–412.0 nm. The absorption peak of LSPR were affected by NaOH amount, time of sulight irradiation and concentration of AgNO3. The produced silver nanoparticles were spherical with dominant size range of 5 to 8 nm as shown by TEM images. All colloidals were stable without any aggregation for 30 days after preparation.

Fuzzy-probabilistic model for risk assessment of radioactive material railway transportation.

PubMed

Avramenko, M; Bolyatko, V; Kosterev, V

2005-01-01

Transportation of radioactive materials is obviously accompanied by a certain risk. A model for risk assessment of emergency situations and terrorist attacks may be useful for choosing possible routes and for comparing the various defence strategies. In particular, risk assessment is crucial for safe transportation of excess weapons-grade plutonium arising from the removal of plutonium from military employment. A fuzzy-probabilistic model for risk assessment of railway transportation has been developed taking into account the different natures of risk-affecting parameters (probabilistic and not probabilistic but fuzzy). Fuzzy set theory methods as well as standard methods of probability theory have been used for quantitative risk assessment. Information-preserving transformations are applied to realise the correct aggregation of probabilistic and fuzzy parameters. Estimations have also been made of the inhalation doses resulting from possible accidents during plutonium transportation. The obtained data show the scale of possible consequences that may arise from plutonium transportation accidents.

Metallomics for Alzheimer's disease treatment: Use of new generation of chelators combining metal-cation binding and transport properties.

PubMed

D'Acunto, Cosimo Walter; Kaplánek, Robert; Gbelcová, Helena; Kejík, Zdeněk; Bříza, Tomáš; Vasina, Liudmila; Havlík, Martin; Ruml, Tomáš; Král, Vladimír

2018-04-25

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting tens of million people. Currently marketed drugs have limited therapeutic efficacy and only slowing down the neurodegenerative process. Interestingly, it has been suggested that biometal cations in the amyloid beta (Aβ) aggregate deposits contribute to neurotoxicity and degenerative changes in AD. Thus, chelation therapy could represent novel mode of therapeutic intervention. Here we describe the features of chelators with therapeutically relevant mechanism of action. We have found that the tested compounds effectively reduce the toxicity of exogenous Aβ and suppress its endogenous production as well as decrease oxidative stress. Cholyl hydrazones were found to be the most active compounds. In summary, our data show that cation complexation, together with improving transport efficacy may represent basis for eventual treatment strategy in AD. Copyright © 2018. Published by Elsevier Masson SAS.

Multiple Vibrio fischeri genes are involved in biofilm formation and host colonization

PubMed Central

Chavez-Dozal, Alba; Hogan, David; Gorman, Clayton; Quintanal-Villalonga, Alvaro; Nishiguchi, Michele K.

2012-01-01

Biofilms are increasingly recognized as the predominant form for survival in the environment for most bacteria. The successful colonization of Vibrio fischeri in its squid host Euprymna tasmanica, involves complex microbe-host interactions mediated by specific genes that are essential for biofilm formation and colonization. In the present investigation, structural and regulatory genes were selected to study their role in biofilm formation and host colonization. We have mutated several genes (pilT, pilU, flgF, motY, ibpA and mifB) by an insertional inactivation strategy. Results demonstrate that structural genes responsible for synthesis of type IV pili and flagella are crucial for biofilm formation and host infection. Moreover, regulatory genes affect colony aggregation by various mechanisms including alteration of synthesis of transcriptional factors and regulation of extracellular polysaccharide production. These results reflect the significance of how genetic alterations influence communal behavior, which is important in understanding symbiotic relationships. PMID:22486781

Induction of the Immunoproteasome Subunit Lmp7 Links Proteostasis and Immunity in α-Synuclein Aggregation Disorders.

PubMed

Ugras, Scott; Daniels, Malcolm J; Fazelinia, Hossein; Gould, Neal S; Yocum, Anastasia K; Luk, Kelvin C; Luna, Esteban; Ding, Hua; McKennan, Chris; Seeholzer, Steven; Martinez, Dan; Evans, Perry; Brown, Daniel; Duda, John E; Ischiropoulos, Harry

2018-05-01

Accumulation of aggregated α-synuclein into Lewy bodies is thought to contribute to the onset and progression of dopaminergic neuron degeneration in Parkinson's disease (PD) and related disorders. Although protein aggregation is associated with perturbation of proteostasis, how α-synuclein aggregation affects the brain proteome and signaling remains uncertain. In a mouse model of α-synuclein aggregation, 6% of 6215 proteins and 1.6% of 8183 phosphopeptides changed in abundance, indicating conservation of proteostasis and phosphorylation signaling. The proteomic analysis confirmed changes in abundance of proteins that regulate dopamine synthesis and transport, synaptic activity and integrity, and unearthed changes in mRNA binding, processing and protein translation. Phosphorylation signaling changes centered on axonal and synaptic cytoskeletal organization and structural integrity. Proteostatic responses included a significant increase in the levels of Lmp7, a component of the immunoproteasome. Increased Lmp7 levels and activity were also quantified in postmortem human brains with PD and dementia with Lewy bodies. Functionally, the immunoproteasome degrades α-synuclein aggregates and generates potentially antigenic peptides. Expression and activity of the immunoproteasome may represent testable targets to induce adaptive responses that maintain proteome integrity and modulate immune responses in protein aggregation disorders. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Geologic and societal factors affecting the international oceanic transport of aggregate

USGS Publications Warehouse

Langer, W.H.

1995-01-01

Crushed stone and sand and gravel are the two main sources of natural aggregate, and together comprise approximately half the volume and tonnage of mined material in the United States. Natural aggregate is a bulky, heavy material without special or unique properties, and it is commonly used near its source of production to minimize haulage cost. However, remoteness is no longer an absolute disqualifier for the production of aggregate. Today interstate aggregate routinely is shipped hundreds of kilometers by rail and barge. In addition, during 1992, the United States imported 1,317,000 metric tons of aggregate from Canada and 1,531,000 metric tons from Mexico. A number of ports on the Atlantic Coast and Gulf Coast of the United States receive imports of crushed stone from foreign sources for transport to various parts of the eastern United States. These areas either lack adequate supplies of aggregate or are augmenting their supplies because they have difficulties meeting current demand. These difficulties may include poor stone quality, environmental permitting problems, or transportation. Certain societal and geologic conditions of New York City and Philadelphia along the Atlantic Coast, and Tampa and New Orleans along the Gulf Coast, are discussed to demonstrate the different combinations of issues that contribute to the economic viability of importing crushed stone. ?? 1995 Oxford University Press.

Effects of reclamation years on composition and diversity of soil bacterial communities in Northwest China.

PubMed

Cheng, Zhibo; Zhang, Fenghua; Gale, William Jeffrey; Wang, Weichao; Sang, Wen; Yang, Haichang

2018-01-01

The objective of this study was to evaluate bacterial community structure and diversity in soil aggregate fractions when salinized farmland was reclaimed after >27 years of abandonment and then farmed again for 1, 5, 10, and 15 years. Illumina MiSeq high-throughput sequencing was performed to characterize the soil bacterial communities in 5 aggregate size classes in each treatment. The results indicated that reclamation significantly increased macro-aggregation (>0.25 mm), as well as soil organic C, available N, and available P. The 10-year field had the largest proportion (93.9%) of soil in the macro-aggregate size classes (i.e., >0.25 mm) and the highest soil electrical conductivity. The 5 most dominant phyla in the soil samples were Proteobacteria, Actinobacteria, Gemmatimonadetes, Acidobacteria, and Bacteroidetes. The phylogenetic diversity, Chao1, and Shannon indices increased after the abandoned land was reclaimed for farming, reaching maximums in the 15-year field. Among aggregate size classes, the 1-0.25 mm aggregates generally had the highest phylogenetic diversity, Chao1, and Shannon indices. Soil organic C and soil electrical conductivity were the main environmental factors affecting the soil bacterial communities. The composition and structure of the bacterial communities also varied significantly depending on soil aggregate size and time since reclamation.

Compressive strength and hydration processes of concrete with recycled aggregates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koenders, Eduardus A.B., E-mail: e.a.b.koenders@coc.ufrj.br; Microlab, Delft University of Technology; Pepe, Marco, E-mail: mapepe@unisa.it

2014-02-15

This paper deals with the correlation between the time evolution of the degree of hydration and the compressive strength of Recycled Aggregate Concrete (RAC) for different water to cement ratios and initial moisture conditions of the Recycled Concrete Aggregates (RCAs). Particularly, the influence of such moisture conditions is investigated by monitoring the hydration process and determining the compressive strength development of fully dry or fully saturated recycled aggregates in four RAC mixtures. Hydration processes are monitored via temperature measurements in hardening concrete samples and the time evolution of the degree of hydration is determined through a 1D hydration and heatmore » flow model. The effect of the initial moisture condition of RCAs employed in the considered concrete mixtures clearly emerges from this study. In fact, a novel conceptual method is proposed to predict the compressive strength of RAC-systems, from the initial mixture parameters and the hardening conditions. -- Highlights: •The concrete industry is more and more concerned with sustainability issues. •The use of recycled aggregates is a promising solution to enhance sustainability. •Recycled aggregates affect both hydration processes and compressive strength. •A fundamental approach is proposed to unveil the influence of recycled aggregates. •Some experimental comparisons are presented to validate the proposed approach.« less

Mid-term effects of mine soil reclamation by use of aided phytostabilization

NASA Astrophysics Data System (ADS)

Zornoza, Raúl; Faz, Ángel; Martínez-Martínez, Silvia; Acosta, Jose Alberto; Gómez, María Dolores; Yanardag, Ibrahim

2014-05-01

Abandoned tailing ponds show environmental and human health hazards by the transfer of heavy metals through erosion or leaching. To reduce these hazards, a reclamation strategy has been developed on a tailing pond based on aided phytostabilization. In 2011 marble mud and pig slurry were applied on the tailing pond surface. In spring 2012 thirteen native vegetal species were introduced. During two years (2012-2013) the evolution of different soil properties and the bioavailable fraction of the heavy metals Cd, Pb and Zn has been monitored. Results showed that pH, aggregates stability, organic carbon, nitrogen and cation exchange capacity increased with the application of the amendments and the development of vegetation, while the bioavailable fraction of the heavy metals drastically decreased (90-99%). Thus, the strategy followed resulted positive to reduce the availability of heavy metals, improving soil quality and fertility. These results are promising in areas with extractive activity of carbonated materials, since the generated wastes can be used for reclamation of soils affected with heavy metals, turning a waste into a by-product. Key words: amendments, geochemistry, heavy metals, mining, tailing pond. Acknowledgements: This work has been funded by the European Union LIFE+ project MIPOLARE (LIFE09 ENV/ES/000439).

Familial Aggregation and Heritability of Schizophrenia and Co-aggregation of Psychiatric Illnesses in Affected Families.

PubMed

Chou, I-Jun; Kuo, Chang-Fu; Huang, Yu-Shu; Grainge, Matthew J; Valdes, Ana M; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Huang, Lu-Shuang; Tseng, Wen-Yi; Zhang, Weiya; Doherty, Michael

2017-09-01

Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia made by psychiatrists were ascertained between January 1, 1996 and December 31, 2013. Having an affected co-twin, first-degree relative, second-degree relative, or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55-46.92), 6.30 (6.09-6.53), 2.44 (1.91-3.12), and 1.88 (1.64-2.15), respectively. Compared with the general population, individuals with one affected first-degree relative had a RR (95% CI) of 6.00 (5.79-6.22) and those with 2 or more had a RR (95% CI) of 14.66 (13.00-16.53) for schizophrenia. The accountability for the phenotypic variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared environmental factors, and 37.2% for non-shared environmental factors. The RR (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49 (3.34-3.64) for mood disorders and 3.91 (3.35-4.57) for delusional disorders. A family history of schizophrenia is therefore associated with a higher risk of developing schizophrenia, mood disorders, and delusional disorders. Heritability and environmental factors each account for half of the phenotypic variance of schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Spatiotemporal & Ecological Processes Associated With Goliath Grouper Aggregations in Southeastern Florida

NASA Astrophysics Data System (ADS)

Binder, B. M.; Boswell, K. M.

2016-02-01

The formation of Fish Spawning Aggregations (FSAs) is vital to the life history of many reef fishes, representing the only reproductive opportunity for many species. Unfortunately FSAs present a lucrative target for exploitation which has led to cases of decline and regional extirpation. However, the integration of stakeholders into the design of fisheries management strategies has led to the protection of several species throughout the Greater Caribbean; including the goliath grouper, which has shown evidence of recovery since the moratorium on harvest in 1990. Since the closure, user based and researcher driven initiatives have investigated the recovery, biology, and life history of goliath grouper, but fine scale spatiotemporal and community level aspects of aggregation formation have not been specifically addressed. Thus, we developed a novel two-tiered survey approach using scientific echosounders and diver visual surveys to characterize the spatiotemporal aspects of goliath grouper aggregations, along with the community response to aggregations at six aggregation sites near Jupiter, Florida. Acoustic transects and diver surveys were performed near peak lunar phases throughout the spawning season to quantify fluctuations in goliath grouper density and abundance during the season; and to characterize changes in local community structure in response to aggregation formation. The results from this study are being used to inform the development of resource management plans in South Florida; and addressing these questions will generate a framework to apply a novel research technique in other regions where knowledge of reproductive behavior is absent from the peer-reviewed literature.

The amyloid interactome: Exploring protein aggregation

PubMed Central

Mastrokalou, Chara V.; Hamodrakas, Stavros J.

2017-01-01

Protein-protein interactions are the quintessence of physiological activities, but also participate in pathological conditions. Amyloid formation, an abnormal protein-protein interaction process, is a widespread phenomenon in divergent proteins and peptides, resulting in a variety of aggregation disorders. The complexity of the mechanisms underlying amyloid formation/amyloidogenicity is a matter of great scientific interest, since their revelation will provide important insight on principles governing protein misfolding, self-assembly and aggregation. The implication of more than one protein in the progression of different aggregation disorders, together with the cited synergistic occurrence between amyloidogenic proteins, highlights the necessity for a more universal approach, during the study of these proteins. In an attempt to address this pivotal need we constructed and analyzed the human amyloid interactome, a protein-protein interaction network of amyloidogenic proteins and their experimentally verified interactors. This network assembled known interconnections between well-characterized amyloidogenic proteins and proteins related to amyloid fibril formation. The consecutive extended computational analysis revealed significant topological characteristics and unraveled the functional roles of all constituent elements. This study introduces a detailed protein map of amyloidogenicity that will aid immensely towards separate intervention strategies, specifically targeting sub-networks of significant nodes, in an attempt to design possible novel therapeutics for aggregation disorders. PMID:28249044

Genetic structure of nest aggregations and drone congregations of the southeast Asian stingless bee Trigona collina.

PubMed

Cameron, E C; Franck, P; Oldroyd, B P

2004-08-01

In stingless bees, sex is determined by a single complementary sex-determining locus. This method of sex determination imposes a severe cost of inbreeding because an egg fertilized by sperm carrying the same sex allele as the egg results in a sterile diploid male. To explore how reproductive strategies may be used to avoid inbreeding in stingless bees, we studied the genetic structure of a population of 27 colonies and three drone congregations of Trigona collina in Chanthaburi, Thailand. The colonies were distributed across six nest aggregations, each aggregation located in the base of a different fig tree. Genetic analysis at eight microsatellite loci showed that colonies within aggregations were not related. Samples taken from three drone congregations showed that the males were drawn from a large number of colonies (estimated to be 132 different colonies in our largest swarm). No drone had a genotype indicating that it could have originated from the colony that it was directly outside. Combined, these results suggest that movements of drones and possibly movements of reproductive swarms among colony aggregations provide two mechanisms of inbreeding avoidance. Copyright 2004 Blackwell Publishing Ltd

Reduction and degradation of amyloid aggregates by a pulsed radio-frequency cold atmospheric plasma jet

NASA Astrophysics Data System (ADS)

Bayliss, D. L.; Walsh, J. L.; Shama, G.; Iza, F.; Kong, M. G.

2009-11-01

Surface-borne amyloid aggregates with mature fibrils are used as a non-infectious prion model to evaluate cold atmospheric plasmas (CAPs) as a prion inactivation strategy. Using a helium-oxygen CAP jet with pulsed radio-frequency (RF) excitation, amyloid aggregates deposited on freshly cleaved mica discs are reduced substantially leaving only a few spherical fragments of sub-micrometer sizes in areas directly treated by the CAP jet. Outside the light-emitting part of the CAP jet, plasma treatment results in a 'skeleton' of much reduced amyloid stacks with clear evidence of fibril fragmentation. Analysis of possible plasma species and the physical configuration of the jet-sample interaction suggests that the skeleton structures observed are unlikely to have arisen as a result of physical forces of detachment, but instead by progressive diffusion of oxidizing plasma species into porous amyloid aggregates. Composition of chemical bonds of this reduced amyloid sample is very different from that of intact amyloid aggregates. These suggest the possibility of on-site degradation by CAP treatment with little possibility of spreading contamination elsewhere , thus offering a new reaction chemistry route to protein infectivity control with desirable implications for the practical implementation of CAP-based sterilization systems.

Effects of supplemental feeding and aggregation on fecal glucocorticoid metabolite concentrations in elk

USGS Publications Warehouse

Forristal, Victoria E.; Creel, Scott; Taper, Mark L.; Scurlock, Brandon M.; Cross, Paul C.

2012-01-01

Habitat modifications and supplemental feeding artificially aggregate some wildlife populations, with potential impacts upon contact and parasite transmission rates. Less well recognized, however, is how increased aggregation may affect wildlife physiology. Crowding has been shown to induce stress responses, and increased glucocorticoid (GC) concentrations can reduce immune function and increase disease susceptibility. We investigated the effects of supplemental feeding and the aggregation that it induces on behavior and fecal glucocorticoid metabolite concentrations (fGCM) in elk (Cervus elaphus) using observational and experimental approaches. We first compared fGCM levels of elk on supplemental feedgrounds to neighboring elk populations wintering in native habitats using data from 2003 to 2008. We then experimentally manipulated the distribution of supplemental food on feedgrounds to investigate whether more widely distributed food would result in lower rates of aggression and stress hormone levels. Contrary to some expectations that fed elk may be less stressed than unfed elk during the winter, we found that elk on feedgrounds had fecal GC levels at least 31% higher than non-feedground populations. Within feedgrounds, fGCM levels were strongly correlated with local measures of elk density (r2 = 0.81). Dispersing feed more broadly, however, did not have a detectable effect on fGCM levels or aggression rates. Our results suggest that increases in aggregation associated with winter feedgrounds affects elk physiology, and the resulting increases in fGCM levels are not likely to be mitigated by management efforts that distribute the feed more widely. Additional research is needed to assess whether these increases in fGCMs directly alter parasite transmission and disease dynamics.

Predicting organic floc transport dynamics in shallow aquatic ecosystems: Insights from the field, the laboratory, and numerical modeling

USGS Publications Warehouse

Harvey, Judson W.; Noe, Gregory B.; Larsen, Laurel G.; Crimaldi, John P.

2009-01-01

Transport of particulate organic material can impact watershed sediment and nutrient budgets and can alter the geomorphologic evolution of shallow aquatic environments. Prediction of organic aggregate (“floc”) transport in these environments requires knowledge of how hydraulics and biota affect the entrainment, settling, and aggregation of particles. This study evaluated the aggregation and field transport dynamics of organic floc from a low‐gradient floodplain wetland with flow‐parallel ridges and sloughs in the Florida Everglades. Floc dynamics were evaluated in a rotating annular flume and in situ in the field. Under present managed conditions in the Everglades, floc is not entrained by mean flows but is suspended via biological production in the water column and bioturbation. Aggregation was a significant process affecting Everglades floc at high flume flow velocities (7.0 cm s−1) and during recovery from high flow; disaggregation was not significant for the tested flows. During moderate flows when floc dynamics are hydrodynamically controlled, it is possible to model floc transport using a single “operative floc diameter” that accurately predicts fluxes downstream and to the bed. In contrast, during high flows and recovery from high flows, aggregation dynamics should be simulated. When entrained by flow in open‐water sloughs, Everglades floc will be transported downstream in multiple deposition and reentrainment events but will undergo net settling when transported onto ridges of emergent vegetation. We hypothesize that net transport of material from open to vegetated areas during high flows is critical for forming and maintaining distinctive topographic patterning in the Everglades and other low‐gradient floodplains.

Enhanced Performance of Recycled Aggregate Concrete with Atomic Polymer Technology

DOT National Transportation Integrated Search

2012-06-01

The atomic polymer technology in form of mesoporous inorganic polymer (MIP) can effectively improve material durability and performance of concrete by dramatically increase inter/intragranular bond strength of concrete at nano-scale. The strategy of ...

Multitarget drug design strategy in Alzheimer's disease: focus on cholinergic transmission and amyloid-β aggregation.

PubMed

Simoni, Elena; Bartolini, Manuela; Abu, Izuddin F; Blockley, Alix; Gotti, Cecilia; Bottegoni, Giovanni; Caporaso, Roberta; Bergamini, Christian; Andrisano, Vincenza; Cavalli, Andrea; Mellor, Ian R; Minarini, Anna; Rosini, Michela

2017-06-01

Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active players of the disease. Besides the cholinesterase mainstay, the multifaceted interplay between nicotinic receptors and amyloid is actually considered to have a central role in neuroprotection. Thus, the multitarget drug-design strategy has emerged as a chance to face the disease network. By exploiting the multitarget approach, hybrid compounds have been synthesized and studied in vitro and in silico toward selected targets of the cholinergic and amyloidogenic pathways. The new molecules were able to target the cholinergic system, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit amyloid-β aggregation. The compounds emerged as a suitable starting point for a further optimization process.

Rigidity of transmembrane proteins determines their cluster shape

NASA Astrophysics Data System (ADS)

Jafarinia, Hamidreza; Khoshnood, Atefeh; Jalali, Mir Abbas

2016-01-01

Protein aggregation in cell membrane is vital for the majority of biological functions. Recent experimental results suggest that transmembrane domains of proteins such as α -helices and β -sheets have different structural rigidities. We use molecular dynamics simulation of a coarse-grained model of protein-embedded lipid membranes to investigate the mechanisms of protein clustering. For a variety of protein concentrations, our simulations under thermal equilibrium conditions reveal that the structural rigidity of transmembrane domains dramatically affects interactions and changes the shape of the cluster. We have observed stable large aggregates even in the absence of hydrophobic mismatch, which has been previously proposed as the mechanism of protein aggregation. According to our results, semiflexible proteins aggregate to form two-dimensional clusters, while rigid proteins, by contrast, form one-dimensional string-like structures. By assuming two probable scenarios for the formation of a two-dimensional triangular structure, we calculate the lipid density around protein clusters and find that the difference in lipid distribution around rigid and semiflexible proteins determines the one- or two-dimensional nature of aggregates. It is found that lipids move faster around semiflexible proteins than rigid ones. The aggregation mechanism suggested in this paper can be tested by current state-of-the-art experimental facilities.

Covalent complexes of albumin with serotonin, ketanserin and lysergic acid antagonize the activity of serotonin in human platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

VanderBerg, S.R.; Gonias, S.L.

1989-01-01

Covalent conjugates of bovine serum albumin (BSA) and 5-HT, ketanserin or d-lysergic acid were synthesized and characterized by polyacrylamide gel electrophoresis, whole blood clearance experiments in mice and aggregation studies with human platelets. Using the standard synthesis procedure, each mol of BSA bound 13.4 mol of (/sup 3/H)5-HT. Derivatization did not cause significant protein aggregation as determined by electrophoresis. All three conjugates antagonized the ability of 5-HT to amplify aggregation caused by low concentrations of ADP. The antagonist activity of each conjugate was concentration dependent; 2.6 ..mu..M 5-HT-BSA completely inhibited the aggregation caused by 13 ..mu..M 5-HT. None of themore » BSA drug conjugates, including 5-HT-BSA, amplified platelet aggregation caused by ADP in the absence of 5-HT. Aggregation by ristocetin, collagen, epinephrine or ADP alone was not significantly affected by the conjugates. Whole blood elimination experiments in mice demonstrated that the three conjugates and underivatized BSA are equally stable in the circulation. These prototypic 5-HT drug-protein conjugates may be useful for probing 5-HT/sub 2/ receptor-ligand interactions in human platelets.« less

Effect of surrogate aggregates on the thermal conductivity of concrete at ambient and elevated temperatures.

PubMed

Yun, Tae Sup; Jeong, Yeon Jong; Youm, Kwang-Soo

2014-01-01

The accurate assessment of the thermal conductivity of concretes is an important part of building design in terms of thermal efficiency and thermal performance of materials at various temperatures. We present an experimental assessment of the thermal conductivity of five thermally insulated concrete specimens made using lightweight aggregates and glass bubbles in place of normal aggregates. Four different measurement methods are used to assess the reliability of the thermal data and to evaluate the effects of the various sensor types. The concrete specimens are also assessed at every 100 °C during heating to ~800 °C. Normal concrete is shown to have a thermal conductivity of ~2.25 W m(-1) K(-1). The surrogate aggregates effectively reduce the conductivity to ~1.25 W m(-1) K(-1) at room temperature. The aggregate size is shown not to affect thermal conduction: fine and coarse aggregates each lead to similar results. Surface contact methods of assessment tend to underestimate thermal conductivity, presumably owing to high thermal resistance between the transducers and the specimens. Thermogravimetric analysis shows that the stages of mass loss of the cement paste correspond to the evolution of thermal conductivity upon heating.

Effect of Surrogate Aggregates on the Thermal Conductivity of Concrete at Ambient and Elevated Temperatures

PubMed Central

Yun, Tae Sup; Jeong, Yeon Jong; Youm, Kwang-Soo

2014-01-01

The accurate assessment of the thermal conductivity of concretes is an important part of building design in terms of thermal efficiency and thermal performance of materials at various temperatures. We present an experimental assessment of the thermal conductivity of five thermally insulated concrete specimens made using lightweight aggregates and glass bubbles in place of normal aggregates. Four different measurement methods are used to assess the reliability of the thermal data and to evaluate the effects of the various sensor types. The concrete specimens are also assessed at every 100°C during heating to ~800°C. Normal concrete is shown to have a thermal conductivity of ~2.25 W m−1 K−1. The surrogate aggregates effectively reduce the conductivity to ~1.25 W m−1 K−1 at room temperature. The aggregate size is shown not to affect thermal conduction: fine and coarse aggregates each lead to similar results. Surface contact methods of assessment tend to underestimate thermal conductivity, presumably owing to high thermal resistance between the transducers and the specimens. Thermogravimetric analysis shows that the stages of mass loss of the cement paste correspond to the evolution of thermal conductivity upon heating. PMID:24696666

Aggregation Pathways of Native-Like Ubiquitin Promoted by Single-Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium.

PubMed

Fermani, Simona; Calvaresi, Matteo; Mangini, Vincenzo; Falini, Giuseppe; Bottoni, Andrea; Natile, Giovanni; Arnesano, Fabio

2018-03-15

Ubiquitin-positive protein aggregates are biomarkers of neurodegeneration, but the molecular mechanism responsible for their formation and accumulation is still unclear. Possible aggregation pathways of human ubiquitin (hUb) promoted by both intrinsic and extrinsic factors, are here investigated. By a computational analysis, two different hUb dimers are indicated as possible precursors of amyloid-like structures, but their formation is disfavored by an electrostatic repulsion involving Glu16 and other carboxylate residues present at the dimer interface. Experimental data on the E16V mutant of hUb shows that this single-point mutation, although not affecting the overall protein conformation, promotes protein aggregation. It is sufficient to shift the same mutation by only two residues (E18V) to regain the behavior of wild-type hUb. The neutralization of Glu16 negative charge by a metal ion and a decrease of the dielectric constant of the medium by addition of trifluoroethanol (TFE), also promote hUb aggregation. The outcomes of this research have important implications for the prediction of physiological parameters that favor aggregate formation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review.

PubMed

Marx, Wolfgang; McKavanagh, Daniel; McCarthy, Alexandra L; Bird, Robert; Ried, Karin; Chan, Alexandre; Isenring, Liz

2015-01-01

The potential effect of ginger on platelet aggregation is a widely-cited concern both within the published literature and to clinicians; however, there has been no systematic appraisal of the evidence to date. Using the PRISMA guidelines, we systematically reviewed the results of clinical and observational trials regarding the effect of ginger on platelet aggregation in adults compared to either placebo or baseline data. Studies included in this review stipulated the independent variable was a ginger preparation or isolated ginger compound, and used measures of platelet aggregation as the primary outcome. Ten studies were included, comprising eight clinical trials and two observational studies. Of the eight clinical trials, four reported that ginger reduced platelet aggregation, while the remaining four reported no effect. The two observational studies also reported mixed findings. Many of the studies appraised for this review had moderate risks of bias. Methodology varied considerably between studies, notably the timeframe studied, dose of ginger used, and the characteristics of subjects recruited (e.g. healthy vs. patients with chronic diseases). The evidence that ginger affects platelet aggregation and coagulation is equivocal and further study is needed to definitively address this question.

The Effect of Ginger (Zingiber officinale) on Platelet Aggregation: A Systematic Literature Review

PubMed Central

Marx, Wolfgang; McKavanagh, Daniel; McCarthy, Alexandra L.; Bird, Robert; Ried, Karin; Chan, Alexandre; Isenring, Liz

2015-01-01

Background The potential effect of ginger on platelet aggregation is a widely-cited concern both within the published literature and to clinicians; however, there has been no systematic appraisal of the evidence to date. Methods Using the PRISMA guidelines, we systematically reviewed the results of clinical and observational trials regarding the effect of ginger on platelet aggregation in adults compared to either placebo or baseline data. Studies included in this review stipulated the independent variable was a ginger preparation or isolated ginger compound, and used measures of platelet aggregation as the primary outcome. Results Ten studies were included, comprising eight clinical trials and two observational studies. Of the eight clinical trials, four reported that ginger reduced platelet aggregation, while the remaining four reported no effect. The two observational studies also reported mixed findings. Discussion Many of the studies appraised for this review had moderate risks of bias. Methodology varied considerably between studies, notably the timeframe studied, dose of ginger used, and the characteristics of subjects recruited (e.g. healthy vs. patients with chronic diseases). Conclusion The evidence that ginger affects platelet aggregation and coagulation is equivocal and further study is needed to definitively address this question. PMID:26488162

Quantitative analysis of liquid penetration kinetics and slaking of aggregates as related to solid-liquid interfacial properties

NASA Astrophysics Data System (ADS)

Goebel, Marc-O.; Woche, Susanne K.; Bachmann, Jörg

2012-06-01

SummaryAggregate stability is frequently shown to be enhanced by strong soil water repellency, however, there is limited systematic evidence on this effect for moderately (subcritically) water repellent soils. This study aimed to investigate the specific effects of interfacial properties on the liquid penetration kinetics in relation to the stability of subcritically water repellent aggregates (4-6.3 mm) from various arable and forest soils against breakdown by slaking. In contrast to many other studies, where aggregate stability was determined by wet sieving, we here assessed the stability by immersion of air-dry aggregates in water-ethanol solutions with surface tensions ranging from 30 to 70 mN m-1. This approach allowed a highly sensitive discrimination of different stability levels and the determination of breakdown kinetics also for less stable aggregates. Interfacial properties were characterized in terms of contact angle measured on crushed aggregates, θc, and calculated for intact aggregates, θi, based on infiltration measurements with water and ethanol. Aggregate stability turned out to be higher in forest soils compared to arable soils with topsoil aggregates generally found to be more stable than subsoil aggregates. For water repellent aggregates, characterized by contact angles >40° and low water infiltration rates (<0.2 mm3 s-0.5), the fraction of disrupted aggregates after 30 s of immersion was generally below 10%, whereas in case of the more wettable aggregates, characterized by contact angles <10° and higher infiltration rates (>0.25 mm3 s-0.5) more than 80% of the aggregates were disrupted. In accordance, we found a close relationship between aggregate stability and wettability with differences between θc and θi being generally small. In addition, aggregate stability turned out to be related to organic carbon content. However, correlation analysis revealed that both persistence of aggregate stability and kinetics of aggregate breakdown were more strongly affected by the contact angle, θc (r = 0.90 and r = -0.83, respectively) and θi (r = 0.89 and r = -0.76, respectively) than the organic carbon content (r = 0.62 and -0.52, respectively), suggesting that stability was primarily controlled by aggregate interfacial properties. Calculation of liquid penetrativity as a function of surface tension and contact angle clearly demonstrated the importance of both solid and liquid interfacial properties in determining the stability of subcritically water repellent aggregates against slaking.

A multi-scale assessment of animal aggregation patterns to understand increasing pathogen seroprevalence

USGS Publications Warehouse

Brennan, Angela K.; Cross, Paul C.; Higgs, Megan D.; Edwards, W. Henry; Scurlock, Brandon M.; Creel, Scott

2014-01-01

Understanding how animal density is related to pathogen transmission is important to develop effective disease control strategies, but requires measuring density at a scale relevant to transmission. However, this is not straightforward or well-studied among large mammals with group sizes that range several orders of magnitude or aggregation patterns that vary across space and time. To address this issue, we examined spatial variation in elk (Cervus canadensis) aggregation patterns and brucellosis across 10 regions in the Greater Yellowstone Area where previous studies suggest the disease may be increasing. We hypothesized that rates of increasing brucellosis would be better related to the frequency of large groups than mean group size or population density, but we examined whether other measures of density would also explain rising seroprevalence. To do this, we measured wintering elk density and group size across multiple spatial and temporal scales from monthly aerial surveys. We used Bayesian hierarchical models and 20 years of serologic data to estimate rates of increase in brucellosis within the 10 regions, and to examine the linear relationships between these estimated rates of increase and multiple measures of aggregation. Brucellosis seroprevalence increased over time in eight regions (one region showed an estimated increase from 0.015 in 1991 to 0.26 in 2011), and these rates of increase were positively related to all measures of aggregation. The relationships were weaker when the analysis was restricted to areas where brucellosis was present for at least two years, potentially because aggregation was related to disease-establishment within a population. Our findings suggest that (1) group size did not explain brucellosis increases any better than population density and (2) some elk populations may have high densities with small groups or lower densities with large groups, but brucellosis is likely to increase in either scenario. In this case, any one control method such as reducing population density or group size may not be sufficient to reduce transmission. This study highlights the importance of examining the density-transmission relationship at multiple scales and across populations before broadly applying disease control strategies.

Embryo aggregation does not improve the development of interspecies somatic cell nuclear transfer embryos in the horse.

PubMed

Gambini, Andrés; De Stéfano, Adrián; Jarazo, Javier; Buemo, Carla; Karlanian, Florencia; Salamone, Daniel Felipe

2016-09-01

The low efficiency of interspecies somatic cell nuclear transfer (iSCNT) makes it necessary to investigate new strategies to improve embryonic developmental competence. Embryo aggregation has been successfully applied to improve cloning efficiency in mammals, but it remains unclear whether it could also be beneficial for iSCNT. In this study, we first compared the effect of embryo aggregation over in vitro development and blastocyst quality of porcine, bovine, and feline zona-free (ZF) parthenogenetic (PA) embryos to test the effects of embryo aggregation on species that were later used as enucleated oocytes donors in our iSCNT study. We then assessed whether embryo aggregation could improve the in vitro development of ZF equine iSCNT embryos after reconstruction with porcine, bovine, and feline ooplasm. Bovine- and porcine-aggregated PA blastocysts had significantly larger diameters compared with nonaggregated embryos. On the other hand, feline- and bovine-aggregated PA embryos had higher blastocyst cell number. Embryo aggregation of equine-equine SCNT was found to be beneficial for embryo development as we have previously reported, but the aggregation of three ZF reconstructed embryos did not improve embryo developmental rates on iSCNT. In vitro embryo development of nonaggregated iSCNT was predominantly arrested around the stage when transcriptional activation of the embryonic genome is reported to start on the embryo of the donor species. Nevertheless, independent of embryo aggregation, equine blastocyst-like structures could be obtained in our study using domestic feline-enucleated oocytes. Taken together, these results reported that embryo aggregation enhance in vitro PA embryo development and embryo quality but effects vary depending on the species. Embryo aggregation also improves, as expected, the in vitro embryo development of equine-equine SCNT embryos; however, we did not observe positive effects on equine iSCNT embryo development. Among oocytes from domestic animals tested in our study, the feline ooplasm might be the most appropriate recipient to partially allow preimplantation embryo development of iSCNT equine embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Aggregation and disaggregation dynamics of sedimented and charged superparamagnetic micro-particles in water suspension.

PubMed

Domínguez-García, P; Pastor, J M; Rubio, M A

2011-04-01

This article presents results on the aggregation and disaggregation kinetics on a 1 μm diameter charged superparamagnetic particles dispersed in water under a constant uniaxial magnetic field in experiments with salt (KCl) added to the suspension in order to observe the behaviour of the system when the electrical properties of the particles have been screened. These particles have an electric charge and are confined between two separated 100 μm thick quartz windows, and sediment near the charged bottom wall. The electrostatic interactions that take place in this experimental setup may affect the micro-structure and colloidal stability of the suspension and thus, the dynamics of aggregation and disaggregation.

Crushed cement concrete substitution for construction aggregates; a materials flow analysis

USGS Publications Warehouse

Kelly, Thomas

1998-01-01

An analysis of the substitution of crushed cement concrete for natural construction aggregates is performed by using a materials flow diagram that tracks all material flows into and out of the cement concrete portion of the products made with cement concrete: highways, roads, and buildings. Crushed cement concrete is only one of the materials flowing into these products, and the amount of crushed cement concrete substituted influences the amount of other materials in the flow. Factors such as availability and transportation costs, as well as physical properties, that can affect stability and finishability, influence whether crushed cement concrete or construction aggregates should be used or predominate for a particular end use.

Phage display and kinetic selection of antibodies that specifically inhibit amyloid self-replication.

PubMed

Munke, Anna; Persson, Jonas; Weiffert, Tanja; De Genst, Erwin; Meisl, Georg; Arosio, Paolo; Carnerup, Anna; Dobson, Christopher M; Vendruscolo, Michele; Knowles, Tuomas P J; Linse, Sara

2017-06-20

The aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is a defining characteristic of Alzheimer's disease. Because of the complexity of this aggregation process, effective therapeutic inhibitors will need to target the specific microscopic steps that lead to the production of neurotoxic species. We introduce a strategy for generating fibril-specific antibodies that selectively suppress fibril-dependent secondary nucleation of the 42-residue form of Aβ (Aβ42). We target this step because it has been shown to produce the majority of neurotoxic species during aggregation of Aβ42. Starting from large phage display libraries of single-chain antibody fragments (scFvs), the three-stage approach that we describe includes ( i ) selection of scFvs with high affinity for Aβ42 fibrils after removal of scFvs that bind Aβ42 in its monomeric form; ( ii ) ranking, by surface plasmon resonance affinity measurements, of the resulting candidate scFvs that bind to the Aβ42 fibrils; and ( iii ) kinetic screening and analysis to find the scFvs that inhibit selectively the fibril-catalyzed secondary nucleation process in Aβ42 aggregation. By applying this approach, we have identified four scFvs that inhibit specifically the fibril-dependent secondary nucleation process. Our method also makes it possible to discard antibodies that inhibit elongation, an important factor because the suppression of elongation does not target directly the production of toxic oligomers and may even lead to its increase. On the basis of our results, we suggest that the method described here could form the basis for rationally designed immunotherapy strategies to combat Alzheimer's and related neurodegenerative diseases.

Physical and chemical effects of grain aggregates on the Palos Verdes margin, southern California

USGS Publications Warehouse

Drake, D.E.; Eganhouse, R.; McArthur, W.

2002-01-01

Large discharges of wastewater and particulate matter from the outfalls of the Los Angeles County Sanitation Districts onto the Palos Verdes shelf since 1937 have produced an effluent-affected sediment deposit characterized by low bulk density, elevated organic matter content, and a high percentage of fine silt and clay particles relative to underlying native sands and sandy silts. Comparison of the results of grain-size analyses using a gentle wet-sieving technique that preserves certain grain aggregates to the results of standard size analyses of disaggregated particles shows that high percentages (up to 50%) of the silt and clay fractions of the effluent-affected mud are incorporated in aggregates having intermediate diameters in the fine-to-medium sand size range (63-500 ??m), Scanning electron microscope images of the aggregates show that they are predominantly oval fecal pellets or irregularly shaped fragments of pellets. Deposit-feeding polychaete worms such as Capitella sp. and Mediomastus sp., abundant in the mud-rich effluent-affected sediment on Palos Verdes shelf, are probably responsible for most of the grain aggregates through fecal pellet production. Particle settling rates and densities, and the concentrations of organic carbon and p,p???-DDE, a metabolite of the hydrophobic pesticide DDT, were determined for seven grain-size fractions in the effluent-affected sediment. Fecal pellet grain densities ranged from about 1.2 to 1.5 g/cc, and their average settling rates were reduced to the equivalent of about one phi size relative to spherical quartz grains of the same diameter. However, repackaging of fine silt and clay grains into the sand-sized fecal pellets causes an effective settling rate increase of up to 3 orders of magnitude for the smallest particles incorporated in the pellets. Moreover, organic carbon and p,p???-DDE exhibit a bimodal distribution with relatively high concentrations in the finest size fraction (0-20 ??m), as expected, and a second concentration peak associated with the sand-sized fecal pellets. The repackaging of fine-grained particles along with their adsorbed chemical compounds into relatively fast-settling pellets has important implications for the mobilization and transport of the sediment and the desorption of chemicals from grain surfaces. ?? 2002 Published by Elsevier Science Ltd.

7 CFR 993.97 - Exhibit A; minimum standards.

Code of Federal Regulations, 2011 CFR

2011-01-01

... condition; (3) end cracks; (4) fermentation; (5) skin or flesh damage; (6) scab; (7) burned; (8) mold; (9... substantially affected. (3) End cracks means callous growth cracks, at the blossom end of prunes, aggregating... flavor is substantially affected. (5) Skin or flesh damage means growth cracks, splits, breaks in skin or...

The effect of fire on soil properties

Treesearch

Leonard F. DeBano

1991-01-01

Fire affects nutrient cycling and the physical, chemical, and biological properties of soils occupied by western montane forests. Combustion of litter and soil organic matter (OM) increases the availability of some nutrients, although others are volatilized (for example, N, P, S). Soil OM loss also affects cation exchange capacity, organic chelation, aggregate...

Red crown rot of Hop in Oregon caused by Phomopsis tuberivora

USDA-ARS?s Scientific Manuscript database

During July 2007, a hop grower in Marion County, Oregon reported weak growth and death of plants of cultivar Fuggle. Affected plants were aggregated within and among rows, and had underdeveloped lateral branches, uneven and weak bines, and chlorotic leaves; severely affected plants were dead. The p...

Exploiting Identical Generators in Unit Commitment

DOE PAGES

Knueven, Ben; Ostrowski, Jim; Watson, Jean -Paul

2017-12-14

Here, we present sufficient conditions under which thermal generators can be aggregated in mixed-integer linear programming (MILP) formulations of the unit commitment (UC) problem, while maintaining feasibility and optimality for the original disaggregated problem. Aggregating thermal generators with identical characteristics (e.g., minimum/maximum power output, minimum up/down-time, and cost curves) into a single unit reduces redundancy in the search space induced by both exact symmetry (permutations of generator schedules) and certain classes of mutually non-dominated solutions. We study the impact of aggregation on two large-scale UC instances, one from the academic literature and another based on real-world operator data. Our computationalmore » tests demonstrate that when present, identical generators can negatively affect the performance of modern MILP solvers on UC formulations. Further, we show that our reformation of the UC MILP through aggregation is an effective method for mitigating this source of computational difficulty.« less

Influence of Aggregate Coated with Modified Sulfur on the Properties of Cement Concrete

PubMed Central

Lee, Swoo-Heon; Hong, Ki-Nam; Park, Jae-Kyu; Ko, Jung

2014-01-01

This paper proposes the mixing design of concrete having modified sulfur-coated aggregate (MSCA) to enhance the durability of Portland cement concrete. The mechanical properties and durability of the proposed MSCA concrete were evaluated experimentally. Melting-modified sulfur was mixed with aggregate in order to coat the aggregate surface at a speed of 20 rpm for 120 s. The MSCA with modified sulfur corresponding to 5% of the cement weight did not significantly affect the flexural strength in a prism concrete beam specimen, regardless of the water-cement ratio (W/C). However, a dosage of more than 7.5% decreased the flexural strength. On the other hand, the MSCA considerably improved the resistance to the sulfuric acid and the freezing-thawing, regardless of the sulfur dosage in the MSCA. The coating modified sulfur of 5% dosage consequently led to good results for the mechanical properties and durability of MSCA concrete. PMID:28788703

Exploiting Identical Generators in Unit Commitment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knueven, Ben; Ostrowski, Jim; Watson, Jean -Paul

Here, we present sufficient conditions under which thermal generators can be aggregated in mixed-integer linear programming (MILP) formulations of the unit commitment (UC) problem, while maintaining feasibility and optimality for the original disaggregated problem. Aggregating thermal generators with identical characteristics (e.g., minimum/maximum power output, minimum up/down-time, and cost curves) into a single unit reduces redundancy in the search space induced by both exact symmetry (permutations of generator schedules) and certain classes of mutually non-dominated solutions. We study the impact of aggregation on two large-scale UC instances, one from the academic literature and another based on real-world operator data. Our computationalmore » tests demonstrate that when present, identical generators can negatively affect the performance of modern MILP solvers on UC formulations. Further, we show that our reformation of the UC MILP through aggregation is an effective method for mitigating this source of computational difficulty.« less

Incorporating Early Learning Strategies in the School Improvement Grants (SIG) Program: How Three Schools Integrated Early Childhood Strategies into School Turnaround Efforts to Improve Instruction for All Students

ERIC Educational Resources Information Center

Connors-Tadros, Lori; Dunn, Lenay; Martella, Jana; McCauley, Carlas

2015-01-01

A significant body of research shows that achievement gaps evident in persistently low-performing schools, in many instances, manifest prior to children entering kindergarten. High-quality early learning programs have proven to demonstrate positive effects on closing academic gaps both for individual children and in the aggregate for the school.…

Contrasting responses of bacterial and fungal communities to aggregate-size fractions and long-term fertilizations in soils of northeastern China.

PubMed

Liao, Hao; Zhang, Yuchen; Zuo, Qinyan; Du, Binbin; Chen, Wenli; Wei, Dan; Huang, Qiaoyun

2018-04-20

Soils, with non-uniform distribution of nutrients across different aggregate-size fractions, provide spatially heterogeneous microhabitats for microorganisms. However, very limited information is available on microbial distributions and their response to fertilizations across aggregate-size fractions in agricultural soils. Here, we examined the structures of bacterial and fungal communities across different aggregate-size fractions (2000-250 μm, 250-53 μm and <53 μm) in response to 35-years organic and/or chemical fertilization regimes in the soil of northeastern China by phospholipid fatty acid (PLFA) and high throughput sequencing (HTS) technology. Our results show that larger fractions (>53 μm), especially 250-53 μm aggregates, which contain more soil C and N, are associated with greater microbial biomass and higher fungi/bacteria ratio. We firstly reported the fungal community composition in different aggregate-size fractions by HTS technology and found more Ascomycota but less Zygomycota in larger fractions with higher C content across all fertilization regimes. Fertilization and aggregate-size fractions significantly affect the compositions of bacterial and fungal communities although their effects are different. The bacterial community is mainly driven by fertilization, especially chemical fertilizers, and is closely related to the shifts of soil P (phosphorus). The fungal community is preferentially impacted by different aggregate-size fractions and is more associated with the changes of soil C and N. The distinct responses of microbial communities suggest different mechanisms controlling the assembly of soil bacterial and fungal communities at aggregate scale. The investigations of both bacterial and fungal communities could provide a better understanding on nutrient cycling across aggregate-size fractions. Copyright © 2018. Published by Elsevier B.V.

Corrosion Behavior of Steel Reinforcement in Concrete with Recycled Aggregates, Fly Ash and Spent Cracking Catalyst

PubMed Central

Gurdián, Hebé; García-Alcocel, Eva; Baeza-Brotons, Francisco; Garcés, Pedro; Zornoza, Emilio

2014-01-01

The main strategy to reduce the environmental impact of the concrete industry is to reuse the waste materials. This research has considered the combination of cement replacement by industrial by-products, and natural coarse aggregate substitution by recycled aggregate. The aim is to evaluate the behavior of concretes with a reduced impact on the environment by replacing a 50% of cement by industrial by-products (15% of spent fluid catalytic cracking catalyst and 35% of fly ash) and a 100% of natural coarse aggregate by recycled aggregate. The concretes prepared according to these considerations have been tested in terms of mechanical strengths and the protection offered against steel reinforcement corrosion under carbonation attack and chloride-contaminated environments. The proposed concrete combinations reduced the mechanical performance of concretes in terms of elastic modulus, compressive strength, and flexural strength. In addition, an increase in open porosity due to the presence of recycled aggregate was observed, which is coherent with the changes observed in mechanical tests. Regarding corrosion tests, no significant differences were observed in the case of the resistance of these types of concretes under a natural chloride attack. In the case of carbonation attack, although all concretes did not stand the highly aggressive conditions, those concretes with cement replacement behaved worse than Portland cement concretes. PMID:28788613

Sporadic Inclusion Body Myositis: Possible pathogenesis inferred from biomarkers

PubMed Central

Weihl, Conrad C.; Pestronk, Alan

2013-01-01

Purpose of review The relevance of proteins that accumulate and aggregate in the muscle fibers of patients with sporadic inclusion body myositis (sIBM) is unknown. Many of these proteins also aggregate in other disorders, including Alzheimer’s disease, leading to speculation that sIBM pathogenesis has similarities to neurodegenerative disorders. Our review will discuss current studies on these protein biomarkers and any utility in sIBM diagnosis. Recent findings Two “classical” components of sIBM aggregates (Aβ and phospho-tau) have been re-evaluated. Three additional components of aggregates (TDP-43, p62, and LC3) have been identified. The sensitivity and specificity of these biomarkers has been explored. Two studies suggest that TDP-43 may have clinical utility in distinguishing sIBM from other inflammatory myopathies. Summary The fact that sIBM muscle accumulates multiple protein aggregates with no single protein appearing in every sIBM patient biopsy suggests that it is not presently possible to place pathogenic blame on any single protein (i.e. Aβ or TDP-43). Instead changes in protein homeostasis may lead to the accumulation of different proteins that have a propensity to aggregate in skeletal muscle. Therapies aimed at improving protein homeostasis, instead of targeting a specific protein that may or may not accumulate in all sIBM patients, could be useful future strategies for this devastating and enigmatic disorder. PMID:20664349

Distribution of Sulfate-Reducing and Methanogenic Bacteria in Anaerobic Aggregates Determined by Microsensor and Molecular Analyses

PubMed Central

Santegoeds, Cecilia M.; Damgaard, Lars Riis; Hesselink, Gijs; Zopfi, Jakob; Lens, Piet; Muyzer, Gerard; de Beer, Dirk

1999-01-01

Using molecular techniques and microsensors for H2S and CH4, we studied the population structure of and the activity distribution in anaerobic aggregates. The aggregates originated from three different types of reactors: a methanogenic reactor, a methanogenic-sulfidogenic reactor, and a sulfidogenic reactor. Microsensor measurements in methanogenic-sulfidogenic aggregates revealed that the activity of sulfate-reducing bacteria (2 to 3 mmol of S2− m−3 s−1 or 2 × 10−9 mmol s−1 per aggregate) was located in a surface layer of 50 to 100 μm thick. The sulfidogenic aggregates contained a wider sulfate-reducing zone (the first 200 to 300 μm from the aggregate surface) with a higher activity (1 to 6 mmol of S2− m−3 s−1 or 7 × 10−9 mol s−1 per aggregate). The methanogenic aggregates did not show significant sulfate-reducing activity. Methanogenic activity in the methanogenic-sulfidogenic aggregates (1 to 2 mmol of CH4 m−3 s−1 or 10−9 mmol s−1 per aggregate) and the methanogenic aggregates (2 to 4 mmol of CH4 m−3 s−1 or 5 × 10−9 mmol s−1 per aggregate) was located more inward, starting at ca. 100 μm from the aggregate surface. The methanogenic activity was not affected by 10 mM sulfate during a 1-day incubation. The sulfidogenic and methanogenic activities were independent of the type of electron donor (acetate, propionate, ethanol, or H2), but the substrates were metabolized in different zones. The localization of the populations corresponded to the microsensor data. A distinct layered structure was found in the methanogenic-sulfidogenic aggregates, with sulfate-reducing bacteria in the outer 50 to 100 μm, methanogens in the inner part, and Eubacteria spp. (partly syntrophic bacteria) filling the gap between sulfate-reducing and methanogenic bacteria. In methanogenic aggregates, few sulfate-reducing bacteria were detected, while methanogens were found in the core. In the sulfidogenic aggregates, sulfate-reducing bacteria were present in the outer 300 μm, and methanogens were distributed over the inner part in clusters with syntrophic bacteria. PMID:10508098

Generation of urban road dust from anti-skid and asphalt concrete aggregates.

PubMed

Tervahattu, Heikki; Kupiainen, Kaarle J; Räisänen, Mika; Mäkelä, Timo; Hillamo, Risto

2006-04-30

Road dust forms an important component of airborne particulate matter in urban areas. In many winter cities the use of anti-skid aggregates and studded tires enhance the generation of mineral particles. The abrasion particles dominate the PM10 during springtime when the material deposited in snow is resuspended. This paper summarizes the results from three test series performed in a test facility to assess the factors that affect the generation of abrasion components of road dust. Concentrations, mass size distribution and composition of the particles were studied. Over 90% of the particles were aluminosilicates from either anti-skid or asphalt concrete aggregates. Mineral particles were observed mainly in the PM10 fraction, the fine fraction being 12% and submicron size being 6% of PM10 mass. The PM10 concentrations increased as a function of the amount of anti-skid aggregate dispersed. The use of anti-skid aggregate increased substantially the amount of PM10 originated from the asphalt concrete. It was concluded that anti-skid aggregate grains contribute to pavement wear. The particle size distribution of the anti-skid aggregates had great impact on PM10 emissions which were additionally enhanced by studded tires, modal composition, and texture of anti-skid aggregates. The results emphasize the interaction of tires, anti-skid aggregate, and asphalt concrete pavement in the production of dust emissions. They all must be taken into account when measures to reduce road dust are considered. The winter maintenance and springtime cleaning must be performed properly with methods which are efficient in reducing PM10 dust.

Microbial activities and dissolved organic matter dynamics in oil-contaminated surface seawater from the Deepwater Horizon oil spill site.

PubMed

Ziervogel, Kai; McKay, Luke; Rhodes, Benjamin; Osburn, Christopher L; Dickson-Brown, Jennifer; Arnosti, Carol; Teske, Andreas

2012-01-01

The Deepwater Horizon oil spill triggered a complex cascade of microbial responses that reshaped the dynamics of heterotrophic carbon degradation and the turnover of dissolved organic carbon (DOC) in oil contaminated waters. Our results from 21-day laboratory incubations in rotating glass bottles (roller bottles) demonstrate that microbial dynamics and carbon flux in oil-contaminated surface water sampled near the spill site two weeks after the onset of the blowout were greatly affected by activities of microbes associated with macroscopic oil aggregates. Roller bottles with oil-amended water showed rapid formation of oil aggregates that were similar in size and appearance compared to oil aggregates observed in surface waters near the spill site. Oil aggregates that formed in roller bottles were densely colonized by heterotrophic bacteria, exhibiting high rates of enzymatic activity (lipase hydrolysis) indicative of oil degradation. Ambient waters surrounding aggregates also showed enhanced microbial activities not directly associated with primary oil-degradation (β-glucosidase; peptidase), as well as a twofold increase in DOC. Concurrent changes in fluorescence properties of colored dissolved organic matter (CDOM) suggest an increase in oil-derived, aromatic hydrocarbons in the DOC pool. Thus our data indicate that oil aggregates mediate, by two distinct mechanisms, the transfer of hydrocarbons to the deep sea: a microbially-derived flux of oil-derived DOC from sinking oil aggregates into the ambient water column, and rapid sedimentation of the oil aggregates themselves, serving as vehicles for oily particulate matter as well as oil aggregate-associated microbial communities.

Microbial Activities and Dissolved Organic Matter Dynamics in Oil-Contaminated Surface Seawater from the Deepwater Horizon Oil Spill Site

PubMed Central

Ziervogel, Kai; McKay, Luke; Rhodes, Benjamin; Osburn, Christopher L.; Dickson-Brown, Jennifer; Arnosti, Carol; Teske, Andreas

2012-01-01

The Deepwater Horizon oil spill triggered a complex cascade of microbial responses that reshaped the dynamics of heterotrophic carbon degradation and the turnover of dissolved organic carbon (DOC) in oil contaminated waters. Our results from 21-day laboratory incubations in rotating glass bottles (roller bottles) demonstrate that microbial dynamics and carbon flux in oil-contaminated surface water sampled near the spill site two weeks after the onset of the blowout were greatly affected by activities of microbes associated with macroscopic oil aggregates. Roller bottles with oil-amended water showed rapid formation of oil aggregates that were similar in size and appearance compared to oil aggregates observed in surface waters near the spill site. Oil aggregates that formed in roller bottles were densely colonized by heterotrophic bacteria, exhibiting high rates of enzymatic activity (lipase hydrolysis) indicative of oil degradation. Ambient waters surrounding aggregates also showed enhanced microbial activities not directly associated with primary oil-degradation (β-glucosidase; peptidase), as well as a twofold increase in DOC. Concurrent changes in fluorescence properties of colored dissolved organic matter (CDOM) suggest an increase in oil-derived, aromatic hydrocarbons in the DOC pool. Thus our data indicate that oil aggregates mediate, by two distinct mechanisms, the transfer of hydrocarbons to the deep sea: a microbially-derived flux of oil-derived DOC from sinking oil aggregates into the ambient water column, and rapid sedimentation of the oil aggregates themselves, serving as vehicles for oily particulate matter as well as oil aggregate-associated microbial communities. PMID:22509359

The durability of concrete containing recycled tyres as a partial replacement of fine aggregate

NASA Astrophysics Data System (ADS)

Syamir Senin, Mohamad; Shahidan, Shahiron; Syazani Leman, Alif; Othman, Nurulain; Shamsuddin, Shamrul-mar; Ibrahim, M. H. W.; Zuki, S. S. Mohd

2017-11-01

Nowadays, uncontrolled disposal of waste materials such as tyres can affect the environment. Therefore, careful management of waste disposal must be done in order to conserve the environment. Waste tyres can be use as a replacement for both fine aggregate and coarse aggregate in the production of concrete. This research was conducted to assess the durability of concrete containing recycled tyres which have been crushed into fine fragments to replace fine aggregate in the concrete mix. This study presents an overview of the use of waste rubber as a partial replacement of natural fine aggregate in a concrete mix. 36 concrete cubes measuring 100mm × 100mm × 100mm and 12 concrete cubes measuring 150mm × 150mm × 150mm were prepared and added with different percentages of rubber from recycled tyres (0%, 3%, 5% and 7%) as fine aggregate replacement. The results obtained show that the replacement of fine aggregate with 7% of rubber recorded a compressive strength of 43.7MPa while the addition of 3% of rubber in the concrete sample recorded a high compressive strength of 50.8MPa. This shows that there is a decrease in the strength and workability of concrete as the amount of rubber used a replacement for fine aggregate in concrete increases. On the other hand, the water absorption test indicated that concrete which contains rubber has better water absorption ability. In this study, 3% of rubber was found to be the optimal percentage as a partial replacement for fine aggregate in the production of concrete.

Insights into the Aggregation Mechanism of PolyQ Proteins with Different Glutamine Repeat Lengths.

PubMed

Yushchenko, Tetyana; Deuerling, Elke; Hauser, Karin

2018-04-24

Polyglutamine (polyQ) diseases, including Huntington's disease, result from the aggregation of an abnormally expanded polyQ repeat in the affected protein. The length of the polyQ repeat is essential for the disease's onset; however, the molecular mechanism of polyQ aggregation is still poorly understood. Controlled conditions and initiation of the aggregation process are prerequisites for the detection of transient intermediate states. We present an attenuated total reflection Fourier-transform infrared spectroscopic approach combined with protein immobilization to study polyQ aggregation dependent on the polyQ length. PolyQ proteins were engineered mimicking the mammalian N-terminus fragment of the Huntingtin protein and containing a polyQ sequence with the number of glutamines below (Q11), close to (Q38), and above (Q56) the disease threshold. A monolayer of the polyQ construct was chemically immobilized on the internal reflection element of the attenuated total reflection cell, and the aggregation was initiated via enzymatic cleavage. Structural changes of the polyQ sequence were monitored by time-resolved infrared difference spectroscopy. We observed faster aggregation kinetics for the longer sequences, and furthermore, we could distinguish β-structured intermediates for the different constructs, allowing us to propose aggregation mechanisms dependent on the repeat length. Q11 forms a β-structured aggregate by intermolecular interaction of stretched monomers, whereas Q38 and Q56 undergo conformational changes to various β-structured intermediates, including intramolecular β-sheets. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Impact of Cavitation, High Shear Stress and Air/Liquid Interfaces on Protein Aggregation.

PubMed

Duerkop, Mark; Berger, Eva; Dürauer, Astrid; Jungbauer, Alois

2018-03-25

The reported impact of shear stress on protein aggregation has been contradictory. At high shear rates, the occurrence of cavitation or entrapment of air is reasonable and their effects possibly misattributed to shear stress. Nine different proteins (α-lactalbumin, two antibodies, fibroblast growth factor 2, granulocyte colony stimulating factor [GCSF], green fluorescence protein [GFP], hemoglobin, human serum albumin, and lysozyme) are tested for their aggregation behavior on vapor/liquid interfaces generated by cavitation and compared it to the isolated effects of high shear stress and air/liquid interfaces generated by foaming. Cavitation induced the aggregation of GCSF by +68.9%, hemoglobin +4%, and human serum albumin +2.9%, compared to a control, whereas the other proteins do not aggregate. The protein aggregation behaviors of the different proteins at air/liquid interfaces are similar to cavitation, but the effect is more pronounced. Air-liquid interface induced the aggregation of GCSF by +94.5%, hemoglobin +35.5%, and human serum albumin (HSA) +31.1%. The results indicate that the sensitivity of a certain protein toward cavitation is very similar to air/liquid-induced aggregation. Hence, hydroxyl radicals cannot be seen as the driving force for protein aggregation when cavitation occurs. Further, high shear rates of up to 10 8  s -1 do not affect any of the tested proteins. Therefore, also within this study generated extremely high isolated shear rates cannot be considered to harm structural integrity when processing proteins. © 2018 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Assessment of optimum threshold and particle shape parameter for the image analysis of aggregate size distribution of concrete sections

NASA Astrophysics Data System (ADS)

Ozen, Murat; Guler, Murat

2014-02-01

Aggregate gradation is one of the key design parameters affecting the workability and strength properties of concrete mixtures. Estimating aggregate gradation from hardened concrete samples can offer valuable insights into the quality of mixtures in terms of the degree of segregation and the amount of deviation from the specified gradation limits. In this study, a methodology is introduced to determine the particle size distribution of aggregates from 2D cross sectional images of concrete samples. The samples used in the study were fabricated from six mix designs by varying the aggregate gradation, aggregate source and maximum aggregate size with five replicates of each design combination. Each sample was cut into three pieces using a diamond saw and then scanned to obtain the cross sectional images using a desktop flatbed scanner. An algorithm is proposed to determine the optimum threshold for the image analysis of the cross sections. A procedure was also suggested to determine a suitable particle shape parameter to be used in the analysis of aggregate size distribution within each cross section. Results of analyses indicated that the optimum threshold hence the pixel distribution functions may be different even for the cross sections of an identical concrete sample. Besides, the maximum ferret diameter is the most suitable shape parameter to estimate the size distribution of aggregates when computed based on the diagonal sieve opening. The outcome of this study can be of practical value for the practitioners to evaluate concrete in terms of the degree of segregation and the bounds of mixture's gradation achieved during manufacturing.

To what extent clay mineralogy affect soil aggregation? Insights from fractionation analyses conducted on soils under different land-uses.

NASA Astrophysics Data System (ADS)

Fernandez-Ugalde, O.; Barré, P.; Hubert, F.; Virto, I.; Girardin, C.; Ferrage, E.; Caner, L.; Chenu, C.

2012-04-01

Aggregation is a key process for soil functioning as it influences C storage, vulnerability to erosion and water holding capacity. While the influence of soil C content or tillage on aggregation has been documented, much less is known about the role of soil mineralogy. The aim of this study is to determine quantitatively if different clay minerals of a temperate soil contribute differently to aggregation and if their contribution is modulated by soil management. We compared the aggregate-size distribution of three cropping systems in a silt loam soil in Versailles (France): organic cropping system (ORG, tilled yearly), direct seeding mulch-based cropping system (DMC, tilled every 4 years), both from a long-term trial, and a nearby grassland. Soil samples from 0-5 cm were wet-sieved to 5 mm and air-dried before aggregate-size separation. For each aggregate class, fraction <2 µm was separated and analysed using X-ray diffraction. Organic C content was determined both in aggregates and <2-µm fractions. C content was lower in ORG than in the two other treatments. The proportion of large-macroaggregates (500-5000 µm) was greater in DMC and grassland; while microaggregates (50-250 µm) showed greater proportions in ORG. In the three treatments, microaggregates had the greatest amount of clays, with preferential accumulation of smectitic phases. In grassland, clays from all aggregated fractions showed more smectitic phases than free-clay fraction. The results indicate that smectitic phases contributed particularly to the microaggregates dynamics. Their contribution to aggregation was lower for larger aggregate sizes where the influence of organic matter was preponderant. Moreover, it was observed that cultivation (ORG and DMC treatments) reduced the relative enrichment of smectitic phases in stable aggregates which makes them more vulnerable to slaking erosion and alters their physico-chemical functions.

The mechanism of the polymer-induced drag reduction in blood.

PubMed

Pribush, Alexander; Hatzkelzon, Lev; Meyerstein, Dan; Meyerstein, Naomi

2013-03-01

Literature reports provide evidence that nanomolar concentrations of spaghetti-like, high molecular weight polymers decrease the hydrodynamic resistance of blood thereby improving impaired blood circulation. It has been suggested that the polymer-induced drag reduction is caused by the corralling of red blood cells (RBCs) among extended macromolecules aligned in the flow direction. This mechanism predicts that drag-reducing polymers must affect the conductivity of completely dispersed blood, time-dependent and steady state structural organization of aggregated RBCs at rest. However, experimental results obtained at the concentration of poly(ethylene oxide) (PEO, MW=4 × 10(6)) of 35 ppm show that neither the conductivity of completely dispersed blood, nor the kinetics of RBC aggregation occurring after the stoppage of flow, nor the structural organization of aggregated RBCs in the quiescent blood are affected by PEO. As these results are at odds with the "corralling" hypothesis, it is assumed that the effect of these polymers on the drag is associated with their interactions with local irregularities of disturbed laminar blood flow. Copyright © 2012 Elsevier B.V. All rights reserved.

Local-aggregate modeling for big data via distributed optimization: Applications to neuroimaging.

PubMed

Hu, Yue; Allen, Genevera I

2015-12-01

Technological advances have led to a proliferation of structured big data that have matrix-valued covariates. We are specifically motivated to build predictive models for multi-subject neuroimaging data based on each subject's brain imaging scans. This is an ultra-high-dimensional problem that consists of a matrix of covariates (brain locations by time points) for each subject; few methods currently exist to fit supervised models directly to this tensor data. We propose a novel modeling and algorithmic strategy to apply generalized linear models (GLMs) to this massive tensor data in which one set of variables is associated with locations. Our method begins by fitting GLMs to each location separately, and then builds an ensemble by blending information across locations through regularization with what we term an aggregating penalty. Our so called, Local-Aggregate Model, can be fit in a completely distributed manner over the locations using an Alternating Direction Method of Multipliers (ADMM) strategy, and thus greatly reduces the computational burden. Furthermore, we propose to select the appropriate model through a novel sequence of faster algorithmic solutions that is similar to regularization paths. We will demonstrate both the computational and predictive modeling advantages of our methods via simulations and an EEG classification problem. © 2015, The International Biometric Society.

Role of social interactions in dynamic patterns of resource patches and forager aggregation.

PubMed

Tania, Nessy; Vanderlei, Ben; Heath, Joel P; Edelstein-Keshet, Leah

2012-07-10

The dynamics of resource patches and species that exploit such patches are of interest to ecologists, conservation biologists, modelers, and mathematicians. Here we consider how social interactions can create unique, evolving patterns in space and time. Whereas simple prey taxis (with consumable prey) promotes spatial uniform distributions, here we show that taxis in producer-scrounger groups can lead to pattern formation. We consider two types of foragers: those that search directly ("producers") and those that exploit other foragers to find food ("scroungers" or exploiters). We show that such groups can sustain fluctuating spatiotemporal patterns, akin to "waves of pursuit." Investigating the relative benefits to the individuals, we observed conditions under which either strategy leads to enhanced success, defined as net food consumption. Foragers that search for food directly have an advantage when food patches are localized. Those that seek aggregations of group mates do better when their ability to track group mates exceeds the foragers' food-sensing acuity. When behavioral switching or reproductive success of the strategies is included, the relative abundance of foragers and exploiters is dynamic over time, in contrast with classic models that predict stable frequencies. Our work shows the importance of considering two-way interaction--i.e., how food distribution both influences and is influenced by social foraging and aggregation of predators.

To what extent clay mineralogy affects soil aggregation? Consequences for soil organic matter stabilization

NASA Astrophysics Data System (ADS)

Fernandez-Ugalde, O.; Barré, P.; Hubert, F.; Virto, I.; Chenu, C.; Ferrage, E.; Caner, L.

2012-12-01

Aggregation is a key process for soil functioning as it influences C storage, vulnerability to erosion and water holding capacity. While the influence of soil organic C on aggregation has been documented, much less is known about the role of soil mineralogy. Soils usually contain a mixture of clay minerals with contrasted surface properties, which should result on different abilities of clay minerals to aggregation. We took advantage of the intrinsic mineral heterogeneity of a temperate Luvisol to compare the role of clay minerals (illite, smectite, kaolinite, and mixed-layer illite-smectite) in aggregation. In a first step, grassland and tilled soil samples were fractionated in water in aggregate-size classes according to the hierarchical model of aggregation (Tisdall and Oades, 1982). Clay mineralogy and organic C in the aggregate-size classes were analyzed. The results showed that interstratified minerals containing swelling phases accumulated in aggregated fractions (>2 μm) compared to free clay fractions (<2 μm) in the two land-uses. The accumulation increased from large macro-aggregates (>500 μm) to micro-aggregates (50-250 μm). C concentration and C/N ratio followed the opposite trend. These results constitute a clay mineral-based evidence for the hierarchical model of aggregation, which postulates an increasing importance of the reactivity of clay minerals in the formation of micro-aggregates compared to larger aggregates. In the latter aggregates, formation relies on the physical enmeshment of particles by fungal hyphae, and root and microbial exudates. In a second step, micro-aggregates from the tilled soil samples were submitted to increasingly disaggregating treatments by sonication to evaluate the link between their water stability and clay mineralogy. Micro-aggregates with increasing stability showed an increase of interstratified minerals containing swelling phases and C concentration for low intensities of disaggregation (from 0 to 5 J mL-1). This suggests that swelling phases promote their stability. Swelling phases and organic C decreased for greater intensities of disaggregation. These results and the SEM images taken at different disaggregation intensities indicate that when increasing disaggregation intensity above 5 J mL-1, the recovered material consists on sand particles covered by physical coatings of illite and kaolinite. Our results show that different clay minerals have different contribution to soil aggregation. Swelling phases are especially important for water-stable aggregates formation, whereas illite and kaolinite can either contribute to aggregation or been coated to sand grains in "mineral aggregates", without porosity and organic C protection capability. In conclusion, soils with large proportion of swelling clay minerals have greater potential for carbon storage by occlusion in aggregates and greater resistance to erosion. Tisdall JM, Oades JM (1982) Organic matter and water-stable aggregates in soils. J Soil Sci 62: 141-163.

Optical Measurement of Cell Colonization Patterns on Individual Suspended Sediment Aggregates

NASA Astrophysics Data System (ADS)

Nguyen, Thu Ha; Tang, Fiona H. M.; Maggi, Federico

2017-10-01

Microbial processes can make substantial differences to the way in which particles settle in aquatic environments. A novel method (OMCEC, optical measurement of cell colonization) is introduced to systematically map the biological spatial distribution over individual suspended sediment aggregates settling through a water column. OMCEC was used to investigate (1) whether a carbon source concentration has an impact on cell colonization, (2) how cells colonize minerals, and (3) if a correlation between colonization patterns and aggregate geometry exists. Incubations of Saccharomyces cerevisiae and stained montmorillonite at four sucrose concentrations were tested in a settling column equipped with a full-color microparticle image velocimetry system. The acquired high-resolution images were processed to map the cell distribution on aggregates based on emission spectra separation. The likelihood of cells colonizing minerals increased with increasing sucrose concentration. Colonization patterns were classified into (i) scattered, (ii) well touched, and (iii) poorly touched, with the second being predominant. Cell clusters in well-touched patterns were found to have lower capacity dimension than those in other patterns, while the capacity dimension of the corresponding aggregates was relatively high. A strong correlation of colonization patterns with aggregate biomass fraction and properties suggests dynamic colonization mechanisms from cell attachment to minerals, to joining of isolated cell clusters, and finally cell growth over the entire aggregate. This paper introduces a widely applicable method for analyses of microbial-affected sediment dynamics and highlights the microbial control on aggregate geometry, which can improve the prediction of large-scale morphodynamics processes.

Data-driven modeling reveals cell behaviors controlling self-organization during Myxococcus xanthus development

PubMed Central

Cotter, Christopher R.; Schüttler, Heinz-Bernd; Igoshin, Oleg A.; Shimkets, Lawrence J.

2017-01-01

Collective cell movement is critical to the emergent properties of many multicellular systems, including microbial self-organization in biofilms, embryogenesis, wound healing, and cancer metastasis. However, even the best-studied systems lack a complete picture of how diverse physical and chemical cues act upon individual cells to ensure coordinated multicellular behavior. Known for its social developmental cycle, the bacterium Myxococcus xanthus uses coordinated movement to generate three-dimensional aggregates called fruiting bodies. Despite extensive progress in identifying genes controlling fruiting body development, cell behaviors and cell–cell communication mechanisms that mediate aggregation are largely unknown. We developed an approach to examine emergent behaviors that couples fluorescent cell tracking with data-driven models. A unique feature of this approach is the ability to identify cell behaviors affecting the observed aggregation dynamics without full knowledge of the underlying biological mechanisms. The fluorescent cell tracking revealed large deviations in the behavior of individual cells. Our modeling method indicated that decreased cell motility inside the aggregates, a biased walk toward aggregate centroids, and alignment among neighboring cells in a radial direction to the nearest aggregate are behaviors that enhance aggregation dynamics. Our modeling method also revealed that aggregation is generally robust to perturbations in these behaviors and identified possible compensatory mechanisms. The resulting approach of directly combining behavior quantification with data-driven simulations can be applied to more complex systems of collective cell movement without prior knowledge of the cellular machinery and behavioral cues. PMID:28533367

Affinity Electrophoresis Using Ligands Attached To Polymers

NASA Technical Reports Server (NTRS)

Van Alstine, James M.; Snyder, Robert S.; Harris, J. M.; Brooks, D. E.

1990-01-01

In new technique, reduction of electrophoretic mobilities by addition of polyethylene glycol to ligands increases electrophoretic separabilities. In immuno-affinity electrophoresis, modification of ligands extends specificity of electrophoretic separation to particles having surface electric-charge structures otherwise making them electrophoretically inseparable. Modification of antibodies by polyethylene glycol greatly reduces ability to aggregate while enhancing ability to affect electrophoretic mobilities of cells. In hydrophobic-affinity electrophoresis, addition of polyethylene glycol reduces tendency toward aggregation of cells or macromolecules.

Design of a dual-function peptide probe as a binder of angiotensin II and an inducer of silver nanoparticle aggregation for use in label-free colorimetric assays.

PubMed

Okochi, Mina; Kuboyama, Masashi; Tanaka, Masayoshi; Honda, Hiroyuki

2015-09-01

Label-free colorimetric assays using metallic nanoparticles have received much recent attention, for their application in simple and sensitive methods for detection of biomolecules. Short peptide probes that can bind to analyte biomolecules are attractive ligands in molecular nanotechnology; however, identification of biological recognition motifs is usually based on trial-and-error experiments. Herein, a peptide probe was screened for colorimetric detection of angiotensin II (Ang II) using a mechanism for non-crosslinking aggregation of silver nanoparticles (AgNPs). The dual-function peptides, which bind to the analyte and induce AgNP aggregation, were identified using a two-step strategy: (1) screening of an Ang II-binding peptide from an Ang II receptor sequence library, using SPOT technology, which enable peptides synthesis on cellulose membranes via an Fmoc method and (2) selection of peptide probes that effectively induce aggregation of AgNPs using a photolinker modified peptide array. Using the identified peptide probe, KGKNKRRR, aggregation of AgNPs was detected by observation of a pink color in the absence of Ang II, whereas AgNPs remained dispersed in the presence of Ang II (yellow). The color changes were not observed in the presence of other hormone molecules. Ang II could be detected within 15 min, with a detection limit of 10 µM, by measuring the ratio of absorbance at 400 nm and 568 nm; the signal could also be observed with the naked eye. These data suggest that the peptide identified here could be used as a probe for simple and rapid colorimetric detection of Ang II. This strategy for the identification of functional peptides shows promise for the development of colorimetric detection of various diagnostically important biomolecules. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel natural mutation AαPhe98Ile in the fibrinogen coiled-coil affects fibrinogen function.

PubMed

Riedelová-Reicheltová, Zuzana; Kotlín, Roman; Suttnar, Jiří; Geierová, Véra; Riedel, Tomáš; Májek, Pavel; Dyr, Jan Evangelista

2014-01-01

The aim of this study was to investigate the structure and function of fibrinogen obtained from a patient with normal coagulation times and idiopathic thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel heterozygous point mutation in the fibrinogen Aα chain, Phe98 to Ile, was found and designated as fibrinogen Vizovice. The mutation, which is located in the RGDF sequence (Aα 95-98) of the fibrinogen coiled-coil region, significantly affected fibrin clot morphology. Namely, the clot formed by fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen were found to be impaired. The lysis rate of Vizovice clots was almost four times slower than the lysis rate of control clots. In the presence of platelets agonists the mutant fibrinogen caused increased platelet aggregation. The data obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aα chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and platelet aggregation. They also suggest that delayed fibrinolysis, together with the abnormal fibrin network morphology and increased platelet aggregation, may be the direct cause of thrombotic complications in the patient associated with pregnancy loss.

In vitro anti-platelet effects of simple plant-derived phenolic compounds are only found at high, non-physiological concentrations.

PubMed

Ostertag, Luisa M; O'Kennedy, Niamh; Horgan, Graham W; Kroon, Paul A; Duthie, Garry G; de Roos, Baukje

2011-11-01

Bioactive polyphenols from fruits, vegetables, and beverages have anti-platelet effects and may thus affect the development of cardiovascular disease. We screened the effects of 26 low molecular weight phenolic compounds on two in vitro measures of human platelet function. After platelets had been incubated with one of 26 low molecular weight phenolic compounds in vitro, collagen-induced human platelet aggregation and in vitro TRAP-induced P-selectin expression (as marker of platelet activation) were assessed. Incubation of platelet-rich plasma from healthy volunteers with 100 μmol/L hippuric acid, pyrogallol, catechol, or resorcinol significantly inhibited collagen-induced platelet aggregation (all p<0.05; n≥15). Incubation of whole blood with concentrations of 100 μmol/L salicylic acid, p-coumaric acid, caffeic acid, ferulic acid, 4-hydroxyphenylpropionyl glycine, 5-methoxysalicylic acid, and catechol significantly inhibited TRAP-induced surface P-selectin expression (all p<0.05; n=10). Incubation with lower concentrations of phenolics affected neither platelet aggregation nor activation. As concentrations of 100 μmol/L are unlikely to be reached in the circulation, it is doubtful whether consumption of dietary phenolics in nutritionally attainable amounts plays a major role in inhibition of platelet activation and aggregation in humans. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dis-aggregation of an insoluble porphyrin in a calixarene matrix: characterization of aggregate modes by extended dipole model.

PubMed

de Miguel, Gustavo; Martín-Romero, María T; Pedrosa, José M; Muñoz, Eulogia; Pérez-Morales, Marta; Richardson, Tim H; Camacho, Luis

2008-03-21

In this paper, the different aggregation modes of a water-insoluble porphyrin (EHO) mixed with an amphiphilic calix[8]arene (C8A), at the air-water interface and in Langmuir-Blodgett (LB) film form, are analyzed as a function of the mixed composition. The strategy used to control the EHO aggregation has consisted of preparing mixed thin films containing EHO and C8A, in different ratios, at the air-water interface. Therefore, the increase of the C8A molar ratio in the mixed film diminishes the aggregation of the EHO molecules, although such an effect must be exclusively related to the dilution of the porphyrin. The reflection spectra of the mixed C8A-EHO films registered at the air-water interface, show a complex Soret band exhibiting splitting, hypochromicity and broadening features. Also, during the transfer process at high surface pressure, it has been shown that the EHO molecules are ejected from the C8A monolayer and only a fraction of porphyrin is transferred to the solid support, in spite of a complete transfer for the C8A matrix. The complex structure of the reflection spectra at the air-water interface, as well as the polarization dependence of the absorption spectra for the mixed LB films, indicate the existence of four different arrangements for the EHO hosted in the C8A matrix. The aggregate formation is governed by two factors: the attraction between the porphyrin rings which minimizes their separation, and the alkyl chain interactions, that is, hydrophobic effect and/or steric hindrance which determine and restrict the possible aggregation structures. By using the extended dipole model, the assignment of the spectral peaks observed to different EHO aggregates is shown.

Electrochemical sensors and biosensors based on less aggregated graphene.

PubMed

Bo, Xiangjie; Zhou, Ming; Guo, Liping

2017-03-15

As a novel single-atom-thick sheet of sp 2 hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial and Temporal Uncertainty of Crop Yield Aggregations

NASA Technical Reports Server (NTRS)

Porwollik, Vera; Mueller, Christoph; Elliott, Joshua; Chryssanthacopoulos, James; Iizumi, Toshichika; Ray, Deepak K.; Ruane, Alex C.; Arneth, Almut; Balkovic, Juraj; Ciais, Philippe;

Soil aggregate stability and rainfall-induced sediment transport on field plots as affected by amendment with organic matter inputs

NASA Astrophysics Data System (ADS)

Shi, Pu; Arter, Christian; Liu, Xingyu; Keller, Martin; Schulin, Rainer

2017-04-01

Aggregate stability is an important factor in soil resistance against erosion, and, by influencing the extent of sediment transport associated with surface runoff, it is thus also one of the key factors which determine on- and off-site effects of water erosion. As it strongly depends on soil organic matter, many studies have explored how aggregate stability can be improved by organic matter inputs into the soil. However, the focus of these studies has been on the relationship between aggregate stability and soil organic matter dynamics. How the effects of organic matter inputs on aggregate stability translate into soil erodibility under rainfall impacts has received much less attention. In this study, we performed field plot experiments to examine how organic matter inputs affect aggregate breakdown and surface sediment transport under field conditions in artificial rainfall events. Three pairs of plots were prepared by adding a mixture of grass and wheat straw to one of plots in each pair but not to the other, while all plots were treated in the same way otherwise. The rainfall events were applied some weeks later so that the applied organic residues had sufficient time for decomposition and incorporation into the soil. Surface runoff rate and sediment concentration showed substantial differences between the treatments with and without organic matter inputs. The plots with organic inputs had coarser and more stable aggregates and a rougher surface than the control plots without organic inputs, resulting in a higher infiltration rate and lower transport capacity of the surface runoff. Consequently, sediments exported from the amended plots were less concentrated but more enriched in suspended particles (<20 µm) than from the un-amended plots, indicating a more size-selective sediment transport. In contrast to the amended plots, there was an increase in the coarse particle fraction (> 250 µm) in the runoff from the plots with no organic matter inputs towards the end of the rainfall events due to emerging bed-load transport. The results show that a single application of organic matter can already cause a large difference in aggregate breakdown, surface sealing, and lateral sediment-associated matter transfer under rainfall impact. Furthermore, we will present terrestrial laser scanning data showing the treatment effects on soil surface structure, as well as data on carbon, phosphorus and heavy metal export associated with the translocation of the sediments.

Alternative Lipid Emulsions in the Critically Ill: A Systematic Review of the Evidence

PubMed Central

Manzanares, William; Dhaliwal, Rupinder; Jurewitsch, Brian; Stapleton, Renee D.; Jeejeebhoy, Khursheed N.; Heyland, Daren K.

2015-01-01

Introduction Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides (LCT) derived from soybean oil (SO). SO containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to SO emulsion only products. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients. Methods We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition (PN). Results A total of 12 RCTs met inclusion criteria. When the results of these RCTs that were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio RR= 0.83, 95% confidence intervals CI 0.62, 1.11, P = 0.20), in duration of ventilation (weighted mean difference, WMD −2.57, 95% CI −5.51, 0.37, P= 0.09), and in ICU length of stay (WMD −2.31, 95% CI −5.28, 0.66, P= 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR=1.13, 95% CI 0.87, 1.46, P=0.35). Conclusion Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects. PMID:23812404

Alternative lipid emulsions in the critically ill: a systematic review of the evidence.

PubMed

Manzanares, William; Dhaliwal, Rupinder; Jurewitsch, Brian; Stapleton, Renee D; Jeejeebhoy, Khursheed N; Heyland, Daren K

2013-10-01

Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to products containing SO emulsion only. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients. We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition. A total of 12 RCTs met the inclusion criteria. When the results of these RCTs were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio, RR 0.83; 95 % confidence intervals, CI 0.62, 1.11; P = 0.20), in duration of ventilation (weighted mean difference, WMD -2.57; 95 % CI -5.51, 0.37; P = 0.09), and in ICU length of stay (LOS) (WMD -2.31; 95 % CI -5.28, 0.66; P = 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR 1.13; 95 % CI 0.87, 1.46; P = 0.35). Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects.

Role of the H-bond between L53 and T56 for Aquaporin-4 epitope in Neuromyelitis Optica.

PubMed

Pisani, Francesco; Simone, Laura; Gargano, Concetta Domenica; De Bellis, Manuela; Cibelli, Antonio; Mola, Maria Grazia; Catacchio, Giacomo; Frigeri, Antonio; Svelto, Maria; Nicchia, Grazia Paola

2017-03-01

Aquaporin-4 (AQP4) is the CNS water channel organized into well-ordered protein aggregates called Orthogonal Arrays of Particles (OAPs). Neuromyelitis Optica (NMO) is an autoimmune disease caused by anti-OAP autoantibodies (AQP4-IgG). Molecular Dynamics (MD) simulations have identified an H-bond between L53 and T56 as the key for AQP4 epitope and therefore of potential interest for drug design in NMO field. In the present study, we have experimentally tested this MD-prediction using the classic mutagenesis approach. We substituted T56 with V56 and tested this mutant for AQP4 aggregates and AQP4-IgG binding. gSTED super-resolution microscopy showed that the mutation does not affect AQP4 aggregate dimension; immunofluorescence and cytofluorimetric analysis demonstrated its unaltered AQP4-IgG binding, therefore invalidating the MD-prediction. We later investigated whether AQP4, expressed in Sf9 insect and HEK-293F cells, is able to correctly aggregate before and after the purification steps usually applied to obtain AQP4 crystal. The results demonstrated that AQP4-IgG recognizes AQP4 expressed in Sf9 and HEK-293F cells by immunofluorescence even though BN-PAGE analysis showed that AQP4 forms smaller aggregates when expressed in insect cells compared to mammalian cell lines. Notably, after AQP4 purification, from both insect and HEK-293F cells, no aggregates are detectable by BN-PAGE and AQP4-IgG binding is impaired in sandwich ELISA assays. All together these results indicate that 1) the MD prediction under analysis is not supported by experimental data and 2) the procedure to obtain AQP4 crystals might affect its native architecture and, as a consequence, MD simulations. In conclusion, given the complex nature of the AQP4 epitope, MD might not be the suitable for molecular medicine advances in NMO. Copyright © 2016. Published by Elsevier B.V.

[Splash erosion of black soil with different reclamation years and its relations to soil aggregates selective characteristics].

PubMed

Zhou, Yi-Yang; Wang, En-Heng; Chen, Xiang-Wei

2009-10-01

Taking the typical black soil with a reclamation history of 8, 30, and 50 years and the un-reclaimed secondary forest land as test objects, a simulation study was made on the process of splash erosion and the selective characteristics of soil aggregates under artificial rainfall condition, with the effects of reclamation on the splash erosion in black soil region analyzed. The splash amount of reclaimed black soil was evidently higher than that of un-reclaimed secondary forest land, and increased with increasing reclamation years, with a variation range of 0.95-7.06 g x cm(-1). There was a significant exponential correlation between splash amount and splash distance, and the percentages of small size water-stable aggregates increased with increasing splash distance. The critical particle size of soil aggregates for the enrichment and depletion of splash erosion was 1.0 mm. Soil water-stable aggregates larger than 2 mm and smaller than 0.25 mm in size and soil organic matter content were the main factors affecting the splash erosion characteristics of typical black soil.

The use of lithium compounds for inhibiting alkali-aggregate reaction effects in pavement structures

NASA Astrophysics Data System (ADS)

Zapała-Sławeta, J.; Owsiak, Z.

2018-05-01

Internal corrosion of concrete caused by the reaction of reactive aggregate with sodium and potassium hydroxides from cement is a threat to the durability of concrete pavements. Traditional methods for reducing the negative effects of the reaction include the use of unreactive aggregates, low alkali cements, mineral additives or chemical admixtures, incorporated during mixing. Lowering the relative humidity of the concrete below 80% is another measure for limiting the destructive reaction. The incorporation of lithium compounds, in particular lithium nitrate and lithium hydroxide, to the concrete mix is a method of limiting alkali-silica reaction effects. The challenge is to reduce the negative effects of aggregate reactivity in members in which the reaction has occurred because the aggregate happened to be reactive. The paper presents ways of limiting the deterioration of ASR-affected concrete in road pavements and other forms of transportation infrastructure, mainly through the use of lithium compounds, i.e. lithium nitrate. Impregnation methods that allow the penetration of lithium ions into the concrete structure were characterized, as was the effectiveness of the solutions applied.

Stability of fluctuating and transient aggregates of amphiphilic solutes in aqueous binary mixtures: Studies of dimethylsulfoxide, ethanol, and tert-butyl alcohol

NASA Astrophysics Data System (ADS)

Banerjee, Saikat; Bagchi, Biman

2013-10-01

In aqueous binary mixtures, amphiphilic solutes such as dimethylsulfoxide (DMSO), ethanol, tert-butyl alcohol (TBA), etc., are known to form aggregates (or large clusters) at small to intermediate solute concentrations. These aggregates are transient in nature. Although the system remains homogeneous on macroscopic length and time scales, the microheterogeneous aggregation may profoundly affect the properties of the mixture in several distinct ways, particularly if the survival times of the aggregates are longer than density relaxation times of the binary liquid. Here we propose a theoretical scheme to quantify the lifetime and thus the stability of these microheterogeneous clusters, and apply the scheme to calculate the same for water-ethanol, water-DMSO, and water-TBA mixtures. We show that the lifetime of these clusters can range from less than a picosecond (ps) for ethanol clusters to few tens of ps for DMSO and TBA clusters. This helps explaining the absence of a strong composition dependent anomaly in water-ethanol mixtures but the presence of the same in water-DMSO and water-TBA mixtures.

Complex Behavior of Aqueous α-Cyclodextrin Solutions. Interfacial Morphologies Resulting from Bulk Aggregation.

PubMed

Hernandez-Pascacio, Jorge; Piñeiro, Ángel; Ruso, Juan M; Hassan, Natalia; Campbell, Richard A; Campos-Terán, José; Costas, Miguel

2016-07-05

The spontaneous aggregation of α-cyclodextrin (α-CD) molecules in the bulk aqueous solution and the interactions of the resulting aggregates at the liquid/air interface have been studied at 283 K using a battery of techniques: transmission electron microscopy, dynamic light scattering, dynamic surface tensiometry, Brewster angle microscopy, neutron reflectometry, and ellipsometry. We show that α-CD molecules spontaneously form aggregates in the bulk that grow in size with time. These aggregates adsorb to the liquid/air interface with their size in the bulk determining the adsorption rate. The material that reaches the interface coalesces laterally to form two-dimensional domains on the micrometer scale with a layer thickness on the nanometer scale. These processes are affected by the ages of both the bulk and the interface. The interfacial layer formed is not in fast dynamic equilibrium with the subphase as the resulting morphology is locked in a kinetically trapped state. These results reveal a surprising complexity of the parallel physical processes taking place in the bulk and at the interface of what might have seemed initially like a simple system.

Evaluation of platelet aggregability during left ventricular bypass using a MedTech MagLev VAD in a series of chronic calf experiments.

PubMed

Kimura, Taro; Yokoyama, Yoshimasa; Sakota, Daisuke; Nagaoka, Eiki; Kitao, Takashi; Takakuda, Kazuo; Takatani, Setsuo

2013-03-01

The impact of continuous flow left ventricular assist device (LVAD) pumping on platelet aggregation was investigated in animal experiments utilizing six calves. A single-use MagLev centrifugal blood pump, MedTech MagLev, was used to bypass the calves' hearts from the left atrium to the descending aorta at a flow rate of 50 ml/kg/min. The LVAD's impact on blood coagulation activities was evaluated based on the platelet aggregability, which was measured with a turbidimetric assay method during the preoperative, operative, and postoperative periods. Heparin and warfarin were used for anticoagulation, while aspirin was used for the antiplatelet therapy. A decrease in platelet aggregation immediately after the pump started was observed in the cases of successful long-term pump operation, while the absence of such a decrease might have caused coagulation-related complications to terminate the experiments. Thus, the platelet aggregability was found to be significantly affected by the pump, and its initial trend may be related to the long-term outcome of the mechanical circulatory support.

Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus.

PubMed

Rezaei-Ghaleh, Nasrollah; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

2016-07-29

Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-β (Aβ) peptide and investigate how phosphorylation at serine 8 affects the structure of Aβ aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Aβ, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Aβ phosphorylation at serine 8 causes structural changes in the N-terminal region of Aβ aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Aβ aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Granular activated carbon as nucleating agent for aerobic sludge granulation: Effect of GAC size on velocity field differences (GAC versus flocs) and aggregation behavior.

PubMed

Zhou, Jia-Heng; Zhao, Hang; Hu, Miao; Yu, Hai-Tian; Xu, Xiang-Yang; Vidonish, Julia; Alvarez, Pedro J J; Zhu, Liang

2015-12-01

Initial cell aggregation plays an important role in the formation of aerobic granules. In this study, three parallel aerobic granular sludge reactors treating low-strength wastewater were established using granular activated carbon (GAC) of different sizes as the nucleating agent. A novel visual quantitative evaluation method was used to discern how GAC size affects velocity field differences (GAC versus flocs) and aggregation behavior during sludge granulation. Results showed that sludge granulation was significantly enhanced by addition of 0.2mm GAC. However, there was no obvious improvement in granulation in reactor amended with 0.6mm GAC. Hydraulic analysis revealed that increase of GAC size enhanced the velocity field difference between flocs and GAC, which decreased the lifecycle and fraction of flocs-GAC aggregates. Overall, based on analysis of aggregation behavior, GAC of suitable sizes (0.2mm) can serve as the nucleating agent to accelerate flocs-GAC coaggregation and formation of aerobic granules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attached biofilms and suspended aggregates are distinct microbial lifestyles emanating from differing hydraulics.

PubMed

Niederdorfer, Robert; Peter, Hannes; Battin, Tom J

2016-10-03

Small-scale hydraulics affects microbial behaviour at the cell level 1 , trophic interactions in marine aggregates 2 and the physical structure and function of stream biofilms 3,4 . However, it remains unclear how hydraulics, predictably changing from small streams to large rivers, impacts the structure and biodiversity of complex microbial communities in these ecosystems. Here, we present experimental evidence unveiling hydraulics as a hitherto poorly recognized control of microbial lifestyle differentiation in fluvial ecosystems. Exposing planktonic source communities from stream and floodplain ecosystems to different hydraulic environments revealed strong selective hydraulic pressures but only minor founder effects on the differentiation of attached biofilms and suspended aggregates and their biodiversity dynamics. Key taxa with a coherent phylogenetic underpinning drove this differentiation. Only a few resident and phylogenetically related taxa formed the backbone of biofilm communities, whereas numerous resident taxa characterized aggregate communities. Our findings unveil fundamental differences between biofilms and aggregates and build the basis for a mechanistic understanding of how hydraulics drives the distribution of microbial diversity along the fluvial continuum 5-7 .

Mutagenic analysis of the nucleation propensity of oxidized Alzheimer's beta-amyloid peptide.

PubMed

Christopeit, Tony; Hortschansky, Peter; Schroeckh, Volker; Gührs, Karlheinz; Zandomeneghi, Giorgia; Fändrich, Marcus

2005-08-01

The formation of polypeptide aggregates represents a nucleated polymerization reaction in which an initial nucleation event (lag phase) is followed by the extension of newly formed nuclei into larger aggregates, including fibrils (growth phase). The efficiencies of these reactions relate to the lag time (lag phase) and to the rate of aggregation (growth phase), which can be determined from experimental aggregation curves. Here we present a mutagenic analysis in which we replace valine 18 of the Alzheimer's Abeta (1-40) peptide with 17 different amino acids and determine its effect on the lag time, and therefore, on the propensity of nucleation. Comparison with various physico-chemical properties shows that nucleation is affected in a predictable manner depending on the beta-sheet propensity and hydrophobicity of residue 18. In addition, we observe a direct proportionality between the lag time and the rate of aggregation. These data imply that the two reactions, nucleation and polymerization, are governed by very similar physicochemical principles and that they involve the formation of the same types of noncovalent interactions.

Control of binder viscosity and hygroscopicity on particle aggregation efficiency

NASA Astrophysics Data System (ADS)

Mueller, Sebastian B.; Kueppers, Ulrich; Ayris, Paul M.; Jacob, Michael; Delmelle, Pierre; Dingwell, Donald B.

2016-04-01

In the course of explosive volcanic eruptions, large amounts of ash are released into the atmosphere and may subsequently pose a threat to infrastructure, such as aviation industry. Ash plume forecasting is therefore a crucial tool for volcanic hazard mitigation but may be significantly affected by aggregation, altering the aerodynamic properties of particles. Models struggle with the implementation of aggregation since external conditions promoting aggregation have not been completely understood; in a previous study we have shown the rapid generation of ash aggregates through liquid bonding via the use of fluidization bed technology and further defined humidity and temperature ranges necessary to trigger aggregation. Salt (NaCl) was required for the recovery of stable aggregates, acting as a cementation agent and granting aggregate cohesion. A numerical model was used to explain the physics behind particle aggregation mechanisms and further predicted a dependency of aggregation efficiency on liquid binder viscosity. In this study we proof the effect of viscosity on particle aggregation. HCl and H2SO4 solutions were diluted to various concentrations resulting in viscosities between 1 and 2 mPas. Phonolitic and rhyolitic ash samples as well as soda-lime glass beads (serving as analogue material) were fluidized in the ProCell Lab® of Glatt Ingenieurtechnik GmbH and treated with the acids via a bottom-spray technique. Chemically driven interaction between acid liquids and surfaces of the three used materials led to crystal precipitation. Salt crystals (e.g. NaCl) have been confirmed through scanning electron microscopy (SEM) and leachate analysis. Both volcanic ash samples as well as the glass beads showed a clear dependency of aggregation efficiency on viscosity of the sprayed HCl solution. Spraying H2SO4 provoked a collapse of the fluidized bed and no aggregation has been observed. This is accounted by the high hygroscopicity of H2SO4. Dissolving CaCl2 (known to be a highly hygroscopic salt) in de-ionized water yielded comparable results without observable aggregation. In case of successful aggregation, concentration of salts has been found to be in the range of published values. We conclude that non-hygroscopic salt crystal precipitation from an aqueous liquid interacting with the glass phase in volcanic ash is a very efficient way to produce cohesive ash aggregates that can survive external forces acting during transport and sedimentation.

Technology Solutions Case Study: Capillary Break Beneath a Slab: Polyethylene Sheeting over Aggregate, Southwestern Pennsylvania

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2014-07-01

In this project, Building America team IBACOS worked with a builder of single- and multifamily homes in southwestern Pennsylvania (climate zone 5) to understand its methods of successfully using polyethylene sheeting over aggregate as a capillary break beneath the slab in new construction. This builder’s homes vary in terms of whether they have crawlspaces or basements. However, in both cases, the strategy protects the home from water intrusion via capillary action (e.g., water wicking into cracks and spaces in the slab), thereby helping to preserve the durability of the home.

Models and Methods of Aggregating Linguistic Information in Multi-criteria Hierarchical Quality Assessment Systems

NASA Astrophysics Data System (ADS)

Azarnova, T. V.; Titova, I. A.; Barkalov, S. A.

2018-03-01

The article presents an algorithm for obtaining an integral assessment of the quality of an organization from the perspective of customers, based on the method of aggregating linguistic information on a multilevel hierarchical system of quality assessment. The algorithm is of a constructive nature, it provides not only the possibility of obtaining an integral evaluation, but also the development of a quality improvement strategy based on the method of linguistic decomposition, which forms the minimum set of areas of work with clients whose quality change will allow obtaining the required level of integrated quality assessment.

Self-assembly of active amphiphilic Janus particles

NASA Astrophysics Data System (ADS)

Mallory, S. A.; Alarcon, F.; Cacciuto, A.; Valeriani, C.

2017-12-01

In this article, we study the phenomenology of a two dimensional dilute suspension of active amphiphilic Janus particles. We analyze how the morphology of the aggregates emerging from their self-assembly depends on the strength and the direction of the active forces. We systematically explore and contrast the phenomenologies resulting from particles with a range of attractive patch coverages. Finally, we illustrate how the geometry of the colloids and the directionality of their interactions can be used to control the physical properties of the assembled active aggregates and suggest possible strategies to exploit self-propulsion as a tunable driving force for self-assembly.

Molecular mechanisms of protein aggregation from global fitting of kinetic models.

PubMed

Meisl, Georg; Kirkegaard, Julius B; Arosio, Paolo; Michaels, Thomas C T; Vendruscolo, Michele; Dobson, Christopher M; Linse, Sara; Knowles, Tuomas P J

2016-02-01

The elucidation of the molecular mechanisms by which soluble proteins convert into their amyloid forms is a fundamental prerequisite for understanding and controlling disorders that are linked to protein aggregation, such as Alzheimer's and Parkinson's diseases. However, because of the complexity associated with aggregation reaction networks, the analysis of kinetic data of protein aggregation to obtain the underlying mechanisms represents a complex task. Here we describe a framework, using quantitative kinetic assays and global fitting, to determine and to verify a molecular mechanism for aggregation reactions that is compatible with experimental kinetic data. We implement this approach in a web-based software, AmyloFit. Our procedure starts from the results of kinetic experiments that measure the concentration of aggregate mass as a function of time. We illustrate the approach with results from the aggregation of the β-amyloid (Aβ) peptides measured using thioflavin T, but the method is suitable for data from any similar kinetic experiment measuring the accumulation of aggregate mass as a function of time; the input data are in the form of a tab-separated text file. We also outline general experimental strategies and practical considerations for obtaining kinetic data of sufficient quality to draw detailed mechanistic conclusions, and the procedure starts with instructions for extensive data quality control. For the core part of the analysis, we provide an online platform (http://www.amylofit.ch.cam.ac.uk) that enables robust global analysis of kinetic data without the need for extensive programming or detailed mathematical knowledge. The software automates repetitive tasks and guides users through the key steps of kinetic analysis: determination of constraints to be placed on the aggregation mechanism based on the concentration dependence of the aggregation reaction, choosing from several fundamental models describing assembly into linear aggregates and fitting the chosen models using an advanced minimization algorithm to yield the reaction orders and rate constants. Finally, we outline how to use this approach to investigate which targets potential inhibitors of amyloid formation bind to and where in the reaction mechanism they act. The protocol, from processing data to determining mechanisms, can be completed in <1 d.

Model-based analyses to compare health and economic outcomes of cancer control: inclusion of disparities.

PubMed

Goldie, Sue J; Daniels, Norman

2011-09-21

Disease simulation models of the health and economic consequences of different prevention and treatment strategies can guide policy decisions about cancer control. However, models that also consider health disparities can identify strategies that improve both population health and its equitable distribution. We devised a typology of cancer disparities that considers types of inequalities among black, white, and Hispanic populations across different cancers and characteristics important for near-term policy discussions. We illustrated the typology in the specific example of cervical cancer using an existing disease simulation model calibrated to clinical, epidemiological, and cost data for the United States. We calculated average reduction in cancer incidence overall and for black, white, and Hispanic women under five different prevention strategies (Strategies A1, A2, A3, B, and C) and estimated average costs and life expectancy per woman, and the cost-effectiveness ratio for each strategy. Strategies that may provide greater aggregate health benefit than existing options may also exacerbate disparities. Combining human papillomavirus vaccination (Strategy A2) with current cervical cancer screening patterns (Strategy A1) resulted in an average reduction of 69% in cancer incidence overall but a 71.6% reduction for white women, 68.3% for black women, and 63.9% for Hispanic women. Other strategies targeting risk-based screening to racial and ethnic minorities reduced disparities among racial subgroups and resulted in more equitable distribution of benefits among subgroups (reduction in cervical cancer incidence, white vs. Hispanic women, 69.7% vs. 70.1%). Strategies that employ targeted risk-based screening and new screening algorithms, with or without vaccination (Strategies B and C), provide excellent value. The most effective strategy (Strategy C) had a cost-effectiveness ratio of $28,200 per year of life saved when compared with the same strategy without vaccination. We identify screening strategies for cervical cancer that provide greater aggregate health benefit than existing options, offer excellent cost-effectiveness, and have the biggest positive impact in worst-off groups. The typology proposed here may also be useful in research and policy decisions when trade-offs between fairness and cost-effectiveness are unavoidable.

Model-Based Analyses to Compare Health and Economic Outcomes of Cancer Control: Inclusion of Disparities

PubMed Central

Daniels, Norman

2011-01-01

Background Disease simulation models of the health and economic consequences of different prevention and treatment strategies can guide policy decisions about cancer control. However, models that also consider health disparities can identify strategies that improve both population health and its equitable distribution. Methods We devised a typology of cancer disparities that considers types of inequalities among black, white, and Hispanic populations across different cancers and characteristics important for near-term policy discussions. We illustrated the typology in the specific example of cervical cancer using an existing disease simulation model calibrated to clinical, epidemiological, and cost data for the United States. We calculated average reduction in cancer incidence overall and for black, white, and Hispanic women under five different prevention strategies (Strategies A1, A2, A3, B, and C) and estimated average costs and life expectancy per woman, and the cost-effectiveness ratio for each strategy. Results Strategies that may provide greater aggregate health benefit than existing options may also exacerbate disparities. Combining human papillomavirus vaccination (Strategy A2) with current cervical cancer screening patterns (Strategy A1) resulted in an average reduction of 69% in cancer incidence overall but a 71.6% reduction for white women, 68.3% for black women, and 63.9% for Hispanic women. Other strategies targeting risk-based screening to racial and ethnic minorities reduced disparities among racial subgroups and resulted in more equitable distribution of benefits among subgroups (reduction in cervical cancer incidence, white vs Hispanic women, 69.7% vs 70.1%). Strategies that employ targeted risk-based screening and new screening algorithms, with or without vaccination (Strategies B and C), provide excellent value. The most effective strategy (Strategy C) had a cost-effectiveness ratio of $28 200 per year of life saved when compared with the same strategy without vaccination. Conclusions We identify screening strategies for cervical cancer that provide greater aggregate health benefit than existing options, offer excellent cost-effectiveness, and have the biggest positive impact in worst-off groups. The typology proposed here may also be useful in research and policy decisions when trade-offs between fairness and cost-effectiveness are unavoidable. PMID:21900120

The effect of reduced street lighting on road casualties and crime in England and Wales: controlled interrupted time series analysis.

PubMed

Steinbach, Rebecca; Perkins, Chloe; Tompson, Lisa; Johnson, Shane; Armstrong, Ben; Green, Judith; Grundy, Chris; Wilkinson, Paul; Edwards, Phil

2015-11-01

Many local authorities in England and Wales have reduced street lighting at night to save money and reduce carbon emissions. There is no evidence to date on whether these reductions impact on public health. We quantified the effect of 4 street lighting adaptation strategies (switch off, part-night lighting, dimming and white light) on casualties and crime in England and Wales. Observational study based on analysis of geographically coded police data on road traffic collisions and crime in 62 local authorities. Conditional Poisson models were used to analyse longitudinal changes in the counts of night-time collisions occurring on affected roads during 2000-2013, and crime within census Middle Super Output Areas during 2010-2013. Effect estimates were adjusted for regional temporal trends in casualties and crime. There was no evidence that any street lighting adaptation strategy was associated with a change in collisions at night. There was significant statistical heterogeneity in the effects on crime estimated at police force level. Overall, there was no evidence for an association between the aggregate count of crime and switch off (RR 0.11; 95% CI 0.01 to 2.75) or part-night lighting (RR 0.96; 95% CI 0.86 to 1.06). There was weak evidence for a reduction in the aggregate count of crime and dimming (RR 0.84; 95% CI 0.70 to 1.02) and white light (RR 0.89; 95% CI 0.77 to 1.03). This study found little evidence of harmful effects of switch off, part-night lighting, dimming, or changes to white light/LEDs on road collisions or crime in England and Wales. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Analysis of familial aggregation of ovarian and breast cancer in patients with ovarian cancer].

PubMed

Ichikawa, Y; Nishida, M; Sugita, M; Arisawa, Y; Satoh, T; Oki, A; Kohno, K; Shigemitsu, S; Tsunoda, H; Kubo, T

1995-09-01

In 118 patients with common epithelial ovarian tumors (carcinomas and tumors of borderline malignancy) treated at Tsukuba University Hospital and Tsukuba-Gakuen Hospital, family histories of ovarian and breast cancer were obtained from medical records or in interviews, and familial aggregation of these cancers was examined. 1. A positive family history was found in 10 patients (8.5%). The high incidences of familial ovarian cancer and ovarian cancer in patients who were previously affected with breast cancer were statistically significant. 2. Patients with serous adenocarcinoma showed a significantly greater rate of positive family history than those with mucinous adenocarcinoma. 3. No significant correlation was seen between the clinical stage and a positive family history. 4. Every patient except one with a positive family history had onset of ovarian cancer after menopause. The age at onset for familial ovarian cancer cases was younger than that for the patients' relatives who were affected previously. 5. There were 14 healthy women considered to be at high risk for ovarian cancer among 5 familial ovarian and 2 familial ovarian and breast cancer aggregations. These preliminary findings suggest that screening for early ovarian cancer should be conducted in high risk relatives of familial cancer patients and women affected with breast cancer previously. More detailed studies are needed to define the occurrence of familial or hereditary ovarian and breast cancers in Japan.

Linking Intra-Aggregate Pore Size Distribution with Organic Matter Decomposition Status, Evidence from FTIR and X-Ray Tomography

NASA Astrophysics Data System (ADS)

Toosi, E. R.; Quigley, M.; Kravchenko, A. N.

2014-12-01

It has been reported that conversion of intensively cultivated lands to less disturbed systems enhances soil OM storage capacity, primarily through OM stabilization in macroaggregates. We hypothesized that the potential for OM stabilization inside macro-aggregates is influenced by presence and abundance of intra-aggregate pores. Pores determine microbial access to OM and regulate diffusion of solution/gases within aggregates which drives microbial functioning. We investigated the influence of longterm disturbance intensity on soil OM composition and its relation to pore size distribution within macroaggregates. We used quantitative FTIR to determine OM decomposition status and X-ray micro-tomography to assess pore size distribution in macroaggregates as affected by management and landuse. Macroaggregates 4-6 mm in size where selected from topsoil under long term conventional tillage (CT), cover-crop (CC), and native succession vegetation (NS) treatments at Kellogg Biological Station, Michigan. Comparison of main soil OM functional groups suggested that with increasing disturbance intensity, the proportion of aromatic and carboxylic/carbohydrates associated compounds increased and it was concomitant with a decrease in the proportion of aliphatic associated compounds and lignin derivatives. Further, FTIR-based decomposition indices revealed that overall decomposition status of macroaggregates followed the pattern of CT > CC ≈ NS. X-ray micro-tomography findings suggested that greater OM decomposition within the macroaggregates was associated with i) greater percent of pores >13 micron in size within the aggregates, as well as ii) greater proportion of small to medium pores (13-110 micron). The results develop previous findings, suggesting that shift in landuse or management indirectly affects soil OM stabilization through alteration of pore size distribution within macroaggregates that itself, is coupled with OM decomposition status.

Influence of mechanical cell salvage on red blood cell aggregation, deformability, and 2,3-diphosphoglycerate in patients undergoing cardiac surgery with cardiopulmonary bypass.

PubMed

Gu, Y John; Vermeijden, Wytze J; de Vries, Adrianus J; Hagenaars, J Ans M; Graaff, Reindert; van Oeveren, Willem

2008-11-01

Mechanical cell salvage is increasingly used during cardiac surgery. Although this procedure is considered safe, it is unknown whether it affects the red blood cell (RBC) function, especially the RBC aggregation, deformability, and the contents of 2,3-diphosphoglycerate (2,3-DPG). This study examines the following: (1) whether the cell salvage procedure influences RBC function; and (2) whether retransfusion of the salvaged blood affects RBC function in patients. Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly allocated to a cell saver group (n = 20) or a control group (n = 20). In the cell saver group, the blood aspirated from the wound area and the residual blood from the heart-lung machine were processed with a continuous-flow cell saver before retransfusion. In the control group this blood was retransfused without processing. The RBC aggregation and deformability were measured with a laser-assisted optical rotational cell analyzer and 2,3,-DPG by conventional laboratory test. The cell saver procedure did not influence the RBC aggregation but significantly reduced the RBC deformability (p = 0.007) and the content of RBC 2,3-DPG (p = 0.032). However, in patients receiving the processed blood, their intraoperative and postoperative RBC aggregation, deformability, and 2,3-DPG content did not differ from those of the control patients. Both groups of patients had a postoperative drop of RBC function as a result of hemodilution. The mechanical cell salvage procedure reduces the RBC deformability and the cell 2,3-DPG content. Retransfusion of the processed blood by cell saver does not further compromise the RBC function in patients undergoing cardiac surgery with cardiopulmonary bypass.

Primate cathelicidin orthologues display different structures and membrane interactions.

PubMed

Morgera, Francesca; Vaccari, Lisa; Antcheva, Nikolinka; Scaini, Denis; Pacor, Sabrina; Tossi, Alessandro

2009-02-01

The human cathelicidin LL-37 displays both direct antibacterial activities and the capacity to modulate host-cell activities. These depend on structural characteristics that are subject to positive selection for variation, as observed in a previous analysis of the CAMP gene (encoding LL-37) in primates. The altered balance between cationic and anionic residues in different primate orthologues affects intramolecular salt-bridging and influences the stability of the helical conformation and tendency to aggregate in solution of the peptide. In the present study, we have analysed the effects of these structural variations on membrane interactions for human LL-37, rhesus RL-37 and orang-utan LL-37, using several complementary biophysical and biochemical methods. CD and ATR (attenuated total reflection)-FTIR (Fourier-transform IR) spectroscopy on model membranes indicate that RL-37, which is monomeric and unstructured in bulk solution [F-form (free form)], and human LL-37, which is partly structured and probably aggregated [A-form (aggregated form)], bind biological membranes in different manners. RL-37 may insert more deeply into the lipid bilayer than LL-37, which remains aggregated. AFM (atomic force microscopy) performed on the same supported bilayer as used for ATR-FTIR measurements suggests a carpet-like mode of permeabilization for RL37 and formation of more defined worm-holes for LL-37. Comparison of data from the biological activity on bacterial cells with permeabilization of model membranes indicates that the structure/aggregation state also affects the trajectory of the peptides from bulk solution through the outer cell-wall layers to the membrane. The results of the present study suggest that F-form cathelicidin orthologues may have evolved to have primarily a direct antimicrobial defensive capacity, whereas the A-forms have somewhat sacrificed this to gain host-cell modulating functions.

Comparative Analysis of the Conformation, Aggregation, Interaction, and Fibril Morphologies of Human α-, β-, and γ-Synuclein Proteins.

PubMed

Jain, Manish Kumar; Singh, Priyanka; Roy, Sneha; Bhat, Rajiv

2018-06-13

The human synuclein (syn) family is comprised of α-, β-, and γ-syn proteins. α-syn has the highest propensity for aggregation, and its aggregated forms accumulate in Lewy bodies (LB) and Lewy neurites, which are involved in Parkinson's disease (PD). β- and γ-syn are absent in LB, and their exact role is still enigmatic. β-syn does not form aggregates under physiological conditions (pH 7.4), while γ-syn is associated with neural and non-neural diseases like breast cancer. Because of their similar regional distribution in the brain, natively unfolded structure, and high degree of sequence homology, studying the effect of the environment on their conformation, interactions, fibrillation, and fibril morphologies has become important. Our studies show that high temperatures, low pH values, and high concentrations increase the rate of fibrillation of α- and γ-syn, while β-syn forms fibrils only at low pH. Fibril morphologies are strongly dependent on the immediate environment of the proteins. The high molar ratio of β-syn inhibits the fibrillation in α- and γ-syn. However, preformed seed fibrils of β- and γ-syn do not affect fibrillation of α-syn. Surface plasmon resonance data show that interactions between α- and β-syn, β- and γ-syn, and α- and γ-syn are weak to moderate in nature and can be physiologically significant in counteracting several adverse conditions in the cells that trigger their aggregation. These studies could be helpful in understanding collective human synuclein behavior in various protein environments and in the modulation of the homeostasis between β-syn and healthy versus corrupt α- and γ-syn that can potentially affect PD pathology.

Enhancement of particle aggregation in the presence of organic matter during neutralization of acid drainage in a stream confluence and its effect on arsenic immobilization.

PubMed

Arce, Guillermo; Montecinos, Mauricio; Guerra, Paula; Escauriaza, Cristian; Coquery, Marina; Pastén, Pablo

2017-08-01

Acid drainage (AD) is an important environmental concern that impacts water quality. The formation of reactive Fe and Al oxyhydroxides during the neutralization of AD at river confluences is a natural attenuation process. Although it is known that organic matter (OM) can affect the aggregation of Fe and Al oxyhydroxides and the sorption of As onto their surfaces, the role of OM during the neutralization of AD at river confluences has not been studied. Field and experimental approaches were used to understand this role, using the Azufre River (pH 2) - Caracarani River (pH 8.6) confluence (northern Chile) as model system. Field measurements of organic carbon revealed a 10-15% loss of OM downstream the confluence, which was attributed to associations with Fe and Al oxyhydroxides that settle in the river bed. Laboratory mixtures of AD water with synthetic Caracarani waters under varying conditions of pH, concentration and type of OM revealed that OM promoted the aggregation of Fe oxyhydroxides without reducing As sorption, enhancing the removal of As at slightly acidic conditions (pH ∼4.5). At acidic conditions (pH ∼3), aggregation of OM - metal complexes at high OM concentrations could become the main removal mechanism. One type of OM promoted bimodal particle size distributions with larger mean sizes, possibly increasing the settling velocity of aggregates. This work contributes to a better understanding of the role of OM in AD affected basins, showing that the presence of OM during processes of neutralization of AD can enhance the removal of toxic elements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using surveillance data to inform a SUID reduction strategy in Massachusetts.

PubMed

Treadway, Nicole J; Diop, Hafsatou; Lu, Emily; Nelson, Kerrie; Hackman, Holly; Howland, Jonathan

2014-12-01

Non-supine infant sleep positions put infants at risk for sudden unexpected infant death (SUID). Disparities in safe sleep practices are associated with maternal income and race/ethnicity. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) is a nutrition supplement program for low-income (≤185% Federal Poverty Level) pregnant and postpartum women. Currently in Massachusetts, approximately 40% of pregnant/postpartum women are WIC clients. To inform the development of a SUID intervention strategy, the Massachusetts Department of Public Health (MDPH) investigated the association between WIC status and infant safe sleep practices among postpartum Massachusetts mothers using data from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. PRAMS is an ongoing statewide health surveillance system of new mothers conducted by the MDPH in collaboration with the Centers for Disease Control and Prevention (CDC). PRAMS includes questions about infant sleep position and mothers' prenatal WIC status. Risk Ratio (RR) and 95 percent confidence intervals (CI) were calculated for infant supine sleep positioning by WIC enrollment, yearly and in aggregate (2007-2010). The aggregate (2007-2010) weighted sample included 276,252 women (weighted n ≈ 69,063 women/year; mean survey response rate 69%). Compared to non-WIC mothers, WIC mothers were less likely to usually or always place their infants in supine sleeping positions [RR = 0.81 (95% CI: 0.80, 0.81)]. Overall, significant differences were found for each year (2007, 2008, 2009, 2010), and in aggregate (2007-2010) by WIC status. Massachusetts WIC mothers more frequently placed their babies in non-supine positions than non-WIC mothers. While this relationship likely reflects the demographic factors associated with safe sleep practices (e.g., maternal income and race/ethnicity), the finding informed the deployment of an intervention strategy for SUID prevention. Given WIC's statewide infrastructure and the large proportion of pregnant/postpartum women in Massachusetts that are enrolled in WIC, a WIC-based safe sleep intervention may be an effective SUID reduction strategy with potential national application.

Cu(II) promotes amyloid pore formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hangyu, E-mail: hangyuz@uw.edu; Rochet, Jean-Christophe; Stanciu, Lia A.

2015-08-14

The aggregation of α-synuclein is associated with dopamine neuron death in Parkinson's disease. There is controversy in the field over the question of which species of the aggregates, fibrils or protofibrils, are toxic. Moreover, compelling evidence suggested the exposure to heavy metals to be a risk of PD. Nevertheless, the mechanism of metal ions in promoting PD remains unclear. In this research, we investigated the structural basis of Cu(II) induced aggregation of α-synuclein. Using transmission electron microscopy experiments, Cu(II) was found to promote in vitro aggregation of α-synuclein by facilitating annular protofibril formation rather than fibril formation. Furthermore, neuroprotective baicalein disaggregatedmore » annular protofibrils accompanied by considerable decrease of β-sheet content. These results strongly support the hypothesis that annular protofibrils are the toxic species, rather than fibrils, thereby inspiring us to search novel therapeutic strategies for the suppression of the toxic annular protofibril formation. - Highlights: • Cu(II) promoted the annular protofibril formation of α-synuclein in vitro. • Cu(II) postponed the in vitro fibrillization of α-synuclein. • Neuroprotective baicalein disaggregated annular protofibrils.« less

Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide

NASA Astrophysics Data System (ADS)

Cohen, Samuel I. A.; Cukalevski, Risto; Michaels, Thomas C. T.; Šarić, Andela; Törnquist, Mattias; Vendruscolo, Michele; Dobson, Christopher M.; Buell, Alexander K.; Knowles, Tuomas P. J.; Linse, Sara

2018-05-01

Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer's disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.

Aggregate Formation of Oligonucleotides that Assist Molecular Imaging for Tracking of the Oxygen Status in Tumor Tissue.

PubMed

Yoshihara, Kazuki; Takagi, Kohei; Son, Aoi; Kurihara, Ryohsuke; Tanabe, Kazuhito

2017-08-17

The use of DNA aggregates could be a promising strategy for the molecular imaging of biological functions. Herein, phosphorescent oligodeoxynucleotides were designed with the aim of visualizing oxygen fluctuation in tumor cells. DNA-ruthenium conjugates (DRCs) that consisted of oligodeoxynucleotides, a phosphorescent ruthenium complex, a pyrene unit for high oxygen responsiveness, and a nitroimidazole unit as a tumor-targeting unit were prepared. In general, oligonucleotides have low cell permeability because of their own negative charges; however, the DRC formed aggregates in aqueous solution due to the hydrophobic pyrene and nitroimidazole groups, and smoothly penetrated the cellular membrane to accumulate in tumor cells in a hypoxia-selective manner. The oxygen-dependent phosphorescence of DRC in cells was also observed. In vivo experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue that was transplanted into the left leg of mice, and showed that oxygen fluctuations in tumor tissue could be monitored by tracking of the phosphorescence emission of DRC. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide.

PubMed

Cohen, Samuel I A; Cukalevski, Risto; Michaels, Thomas C T; Šarić, Anđela; Törnquist, Mattias; Vendruscolo, Michele; Dobson, Christopher M; Buell, Alexander K; Knowles, Tuomas P J; Linse, Sara

2018-05-01

Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer's disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.

Effects of UVA irradiation, aryl azides, and reactive oxygen species on the orthogonal inactivation of the human immunodeficiency virus (HIV-1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belanger, Julie M.; Raviv, Yossef; Viard, Mathias

2011-08-15

Previously we reported that hydrophobic aryl azides partition into hydrophobic regions of the viral membrane of enveloped viruses and inactivate the virus upon UVA irradiation for 2 min. Prolonged irradiation (15 min) resulted in viral protein aggregation as visualized via Western blot analysis, due to reactive oxygen species (ROS) formation, with preservation of the surface antigenic epitopes. Herein, we demonstrate that these aggregates show detergent resistance and that this property may be useful towards the creation of a novel orthogonal virus inactivation strategy for use in preparing experimental vaccines. When ROS-modified HIV virus preparations were treated with 1% Triton X-100,more » there was an increase in the percent of viral proteins (gp41, p24) in the viral pellet after ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of these detergent-resistant pellets shows some recognizable virus fragments, and immunoprecipitation studies of the gp41 aggregates suggest the aggregation is covalent in nature, involving short-range interactions.« less

1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside: A new powerful antioxidant and inhibitor of Aβ42 aggregation isolated from the leaves of Lawsonia inermis.

PubMed

Dhouafli, Zohra; Ben Jannet, Hichem; Mahjoub, Borhane; Leri, Manuela; Guillard, Jérôme; Saidani Tounsi, Moufida; Stefani, Massimo; Hayouni, El Akrem

2017-12-29

Mounting evidence indicates free radicals as toxic species causing damage to human cells leading to the pathogenesis of many diseases such as neurodegenerative disease. Plant derived antioxidants are considered as promising strategy to prevent free radical toxicity. In this study, the crude extract (CE), 50%MeOH, Petroleum Ether (PE) and Ethyl acetate (EA) fractions of Lawsonia inermis leaves were investigated for their antioxidant activity and their ability to counteract amyloid-β 42 (Aβ 42 ) aggregation. Elution of the most bioactive fraction (EA) on silica gel column chromatography led to six sub-fractions. The most active sub-fraction (1) was further resolved on silica gel column chromatography. A new compound with powerful antioxidant and anti-Aβ 42 aggregation properties was purified and characterised by spectroscopic methods as 1,2,4-trihydroxynaphthalene-2-O-β-D-glucopyranoside (THNG). This finding suggests that the antioxidant and anti-Aβ 42 aggregation activities of L. inermis leaves are strongly correlated to this compound.

The specific role of fungal community structure on soil aggregation and carbon sequestration: results from long-term field study in a paddy soil

NASA Astrophysics Data System (ADS)

Murugan, Rajasekaran; Kumar, Sanjay

2015-04-01

Soil aggregate stability is a crucial soil property that affects soil biota, biogeochemical processes and C sequestration. The relationship between soil aggregate stability and soil C cycling is well known but the influence of specific fungal community structure on this relationship is largely unknown in paddy soils. The aim of the present study was to evaluate the long-term fertilisation (mineral fertiliser-MIN; farmyard manure-FYM; groundnut oil cake-GOC) effects on soil fungal community shifts associated with soil aggregates under rice-monoculture (RRR) and rice-legume-rice (RLR) systems. Fungal and bacterial communities were characterized using phospholipid fatty acids, and glucosamine and muramic acid were used as biomarkers for fungal and bacterial residues, respectively. Microbial biomass C and N, fungal biomass and residues were significantly higher in the organic fertiliser treatments than in the MIN treatment, for all aggregate sizes under both crop rotation systems. In general, fungal/bacterial biomass ratio and fungal residue C/bacterial residue C ratio were significantly higher in macroaggregate fractions (> 2000 and 250-2000 μm) than in microaggregate fractions (53-250 and <53 μm). In both crop rotation systems, the long-term application of FYM and GOC led to increased accumulation of saprotrophic fungi (SF) in aggregate fractions > 2000 μm. In contrast, we found that arbuscular mycorrhizal fungi (AMF) was surprisingly higher in aggregate fractions > 2000 μm than in aggregate fraction 250-2000 μm under MIN treatment. The RLR system showed significantly higher AMF biomass and fungal residue C/ bacterial residue C ratio in both macroaggregate fractions compared to the RRR system. The strong relationships between SF, AMF and water stable aggregates shows the specific contribution of fungi community on soil aggregate stability. Our results highlight the fact that changes within fungal community structure play an important role in shaping the soil aggregate stability and C sequestration in tropical agricultural ecosystems.

Platelet aggregation caused by a partially purified jellyfish toxin from Carybdea rastonii.

PubMed

Azuma, H; Sekizaki, S; Satoh, A; Nakajima, T; Ishikawa, M

1986-01-01

A partially purified toxin (pCrTX) was obtained from the tentacles of the jellyfish, Carybdea rastonii. When pCrTX (3 X 10(-8) - 3 X 10(-7) g/ml) was added to citrated platelet-rich plasma, aggregation was produced in a concentration-dependent manner. Scanning electron microscopic examination revealed that both pCrTX and collagen produced aggregates of platelets possessing many pseudopods. The concentration which produced 50% aggregation for pCrTX was 1.8 X 10(-7) g/ml, as compared to 2.3 X 10(-6) g/ml for collagen. The pCrTX-induced aggregation was only slightly inhibited by indomethacin and quinacrine in concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. pCrTX was less active in washed platelets suspended in Ca2+ free medium, whereas the pCrTX-induced aggregation was significantly augmented in the presence of Ca2+. The augmentation of aggregation by Ca2+ was only slightly attenuated by pretreatment with 100 microM verapamil. pCrTX significantly increased the concentration of cytoplasmic free Ca2+ ([Ca2+]i) and depolarized the platelet membrane in concentrations that produced aggregation. The increase in [Ca2+]i caused by pCrTX was little affected by verapamil. The depolarization by pCrTX was unchanged in the presence or absence of Ca2+, or by sodium or potassium transport inhibitors. The movement of 22Na+ into platelets was significantly increased by pCrTX. This increase in the movement of 22N+ into platelets was unaffected by tetrodotoxin. On the other hand, pCrTX-induced aggregation, depolarization and the increase in [Ca2+]i were all significantly attenuated in low Na+ medium. These results suggest that pCrTX causes a massive depolarization by increasing cation permeability indiscriminately and this generalized depolarization permits an inward movement of calcium down an electrochemical gradient which, in turn triggers platelet aggregation.

Recycling of construction debris as aggregate in the Mid-Atlantic Region, USA

USGS Publications Warehouse

Robinson, G.R.; Menzie, W.D.; Hyun, H.

2004-01-01

Reclaimed asphalt pavement (RAP) and portland cement concrete (RPCC) are abundant and available substitutes for natural aggregate in many areas. This paper presents an overview of factors that affect recycled aggregate cost, availability, and engineering performance, and the results of a survey of business practices in the Mid-Atlantic region. For RAP, processing costs are less than those for virgin natural aggregate. Use of efficient asphalt pavement stripping technology, on-site reclamation, and linked two-way transport of asphalt debris and processed asphalt paving mix between asphalt mix plants and paving sites has led to extensive recycling of asphalt pavement in the Mid-Atlantic region of the US. Most of the sites that recycle asphalt pavement (RAP) are located in or near urban areas close to important transportation corridors. RPCC is a viable aggregate source in urban settings where unit costs for processed aggregate from RPCC and natural aggregate are comparable. Disposal fees charged at RPCC recycling sites help defray processing costs and the significantly lower tipping fees at recycling sites versus landfill disposal sites encourage recycling of construction debris as aggregate. Construction contractors and construction debris recycling centers, many of which have the ability to crush and process concrete debris at the job site, produce most RPCC. Production of RPCC aggregate from construction debris that is processed on site using portable equipment moved to the construction site eliminates transportation costs for aggregate and provides an economic incentive for RPCC use. Processing costs, quality and performance issues, and lack of large quantities where needed limit RPCC use. Most RPCC suppliers in the Mid-Atlantic area are located in counties with population densities greater than 400 people/km2 (1036 people/mile2) and that have high unit-value costs and limited local availability of natural aggregate. ?? 2004 Published by Elsevier B.V.

Comparing the information seeking strategies of residents, nurse practitioners, and physician assistants in critical care settings

PubMed Central

Kannampallil, Thomas G; Jones, Laura K; Patel, Vimla L; Buchman, Timothy G; Franklin, Amy

2014-01-01

Objective Critical care environments are information-intensive environments where effective decisions are predicated on successfully finding and using the ‘right information at the right time’. We characterize the differences in processes and strategies of information seeking between residents, nurse practitioners (NPs), and physician assistants (PAs). Method We conducted an exploratory study in the cardiothoracic intensive care units of two large academic hospitals within the same healthcare system. Clinicians (residents (n=5), NPs (n=5), and PAs (n=5)) were shadowed as they gathered information on patients in preparation for clinical rounds. Information seeking activities on 96 patients were collected over a period of 3 months (NRes=37, NNP=24, NPA=35 patients). The sources of information and time spent gathering the information at each source were recorded. Exploratory data analysis using probabilistic sequential approaches was used to analyze the data. Results Residents predominantly used a patient-based information seeking strategy in which all relevant information was aggregated for one patient at a time. In contrast, NPs and PAs primarily utilized a source-based information seeking strategy in which similar (or equivalent) information was aggregated for multiple patients at a time (eg, X-rays for all patients). Conclusions The differences in the information seeking strategies are potentially a result of the differences in clinical training, strategies of managing cognitive load, and the nature of the use of available health IT tools. Further research is needed to investigate the effects of these differences on clinical and process outcomes. PMID:24619926

Smartphone-Based Indoor Localization with Bluetooth Low Energy Beacons

PubMed Central

Zhuang, Yuan; Yang, Jun; Li, You; Qi, Longning; El-Sheimy, Naser

2016-01-01

Indoor wireless localization using Bluetooth Low Energy (BLE) beacons has attracted considerable attention after the release of the BLE protocol. In this paper, we propose an algorithm that uses the combination of channel-separate polynomial regression model (PRM), channel-separate fingerprinting (FP), outlier detection and extended Kalman filtering (EKF) for smartphone-based indoor localization with BLE beacons. The proposed algorithm uses FP and PRM to estimate the target’s location and the distances between the target and BLE beacons respectively. We compare the performance of distance estimation that uses separate PRM for three advertisement channels (i.e., the separate strategy) with that use an aggregate PRM generated through the combination of information from all channels (i.e., the aggregate strategy). The performance of FP-based location estimation results of the separate strategy and the aggregate strategy are also compared. It was found that the separate strategy can provide higher accuracy; thus, it is preferred to adopt PRM and FP for each BLE advertisement channel separately. Furthermore, to enhance the robustness of the algorithm, a two-level outlier detection mechanism is designed. Distance and location estimates obtained from PRM and FP are passed to the first outlier detection to generate improved distance estimates for the EKF. After the EKF process, the second outlier detection algorithm based on statistical testing is further performed to remove the outliers. The proposed algorithm was evaluated by various field experiments. Results show that the proposed algorithm achieved the accuracy of <2.56 m at 90% of the time with dense deployment of BLE beacons (1 beacon per 9 m), which performs 35.82% better than <3.99 m from the Propagation Model (PM) + EKF algorithm and 15.77% more accurate than <3.04 m from the FP + EKF algorithm. With sparse deployment (1 beacon per 18 m), the proposed algorithm achieves the accuracies of <3.88 m at 90% of the time, which performs 49.58% more accurate than <8.00 m from the PM + EKF algorithm and 21.41% better than <4.94 m from the FP + EKF algorithm. Therefore, the proposed algorithm is especially useful to improve the localization accuracy in environments with sparse beacon deployment. PMID:27128917

Smartphone-Based Indoor Localization with Bluetooth Low Energy Beacons.

PubMed

Zhuang, Yuan; Yang, Jun; Li, You; Qi, Longning; El-Sheimy, Naser

2016-04-26

Indoor wireless localization using Bluetooth Low Energy (BLE) beacons has attracted considerable attention after the release of the BLE protocol. In this paper, we propose an algorithm that uses the combination of channel-separate polynomial regression model (PRM), channel-separate fingerprinting (FP), outlier detection and extended Kalman filtering (EKF) for smartphone-based indoor localization with BLE beacons. The proposed algorithm uses FP and PRM to estimate the target's location and the distances between the target and BLE beacons respectively. We compare the performance of distance estimation that uses separate PRM for three advertisement channels (i.e., the separate strategy) with that use an aggregate PRM generated through the combination of information from all channels (i.e., the aggregate strategy). The performance of FP-based location estimation results of the separate strategy and the aggregate strategy are also compared. It was found that the separate strategy can provide higher accuracy; thus, it is preferred to adopt PRM and FP for each BLE advertisement channel separately. Furthermore, to enhance the robustness of the algorithm, a two-level outlier detection mechanism is designed. Distance and location estimates obtained from PRM and FP are passed to the first outlier detection to generate improved distance estimates for the EKF. After the EKF process, the second outlier detection algorithm based on statistical testing is further performed to remove the outliers. The proposed algorithm was evaluated by various field experiments. Results show that the proposed algorithm achieved the accuracy of <2.56 m at 90% of the time with dense deployment of BLE beacons (1 beacon per 9 m), which performs 35.82% better than <3.99 m from the Propagation Model (PM) + EKF algorithm and 15.77% more accurate than <3.04 m from the FP + EKF algorithm. With sparse deployment (1 beacon per 18 m), the proposed algorithm achieves the accuracies of <3.88 m at 90% of the time, which performs 49.58% more accurate than <8.00 m from the PM + EKF algorithm and 21.41% better than <4.94 m from the FP + EKF algorithm. Therefore, the proposed algorithm is especially useful to improve the localization accuracy in environments with sparse beacon deployment.

Leveraging Human-environment Systems in Residential Buildings for Aggregate Energy Efficiency and Sustainability

NASA Astrophysics Data System (ADS)

Xu, Xiaoqi

Reducing the energy consumed in the built environment is a key objective in many sustainability initiatives. Existing energy saving methods have consisted of physical interventions to buildings and/or behavioral modifications of occupants. However, such methods may not only suffer from their own disadvantages, e.g. high cost and transient effect, but also lose aggregate energy saving potential due to the oftentimes-associated single-building-focused view and an isolated examination of occupant behaviors. This dissertation attempts to overcome the limitations of traditional energy saving research and practical approaches, and enhance residential building energy efficiency and sustainability by proposing innovative energy strategies from a holistic perspective of the aggregate human-environment systems. This holistic perspective features: (1) viewing buildings as mutual influences in the built environment, (2) leveraging both the individual and contextualized social aspects of occupant behaviors, and (3) incorporating interactions between the built environment and human behaviors. First, I integrate three interlinked components: buildings, residents, and the surrounding neighborhood, and quantify the potential energy savings to be gained from renovating buildings at the inter-building level and leveraging neighborhood-contextualized occupant social networks. Following the confirmation of both the inter-building effect among buildings and occupants' interpersonal influence on energy conservation, I extend the research further by examining the synergy that may exist at the intersection between these "engineered" building networks and "social" peer networks, focusing specifically on the additional energy saving potential that could result from interactions between the two components. Finally, I seek to reach an alignment of the human and building environment subsystems by matching the thermostat preferences of each household with the thermal conditions within their apartment, and develop the Energy Saving Alignment Strategy to be considered in public housing assignment policy. This strategy and the inter-building level energy management strategies developed in my preceding research possess large-scale cost-effectiveness and may engender long-lasting influence compared with existing energy saving approaches. Building from the holistic framework of coupled human-environment systems, the findings of this research will advance knowledge of energy efficiency in the built environment and lead to the development of novel strategies to conserve energy in residential buildings.

Strategies to suppress hydrogen-consuming microorganisms affect macro and micro scale structure and microbiology of granular sludge.

PubMed

Abreu, A A; Alves, J I; Pereira, M A; Sousa, D Z; Alves, M M

2011-08-01

Treatment of anaerobic granules with heat and two chemical treatments, contacting with 2-bromoethanesulfonate (BES) and with BES + Chloroform, were applied to suppress hydrogen-consuming microorganisms. Three mesophilic expanded granular sludge bed (EGSB) reactors-R(Heat), R(BES), and R(BES + Chlo)--were inoculated with the treated sludges and fed with synthetic sugar-based wastewater (5 g(COD) L(-1), HRT 20-12 h). Morphological integrity of granules and bacterial communities were assessed by quantitative image analysis and 16S rRNA gene based techniques, respectively. Hydrogen production in R(Heat) was under 300 mL H(2) L(-1) day(-1), with a transient peak of 1,000 mL H(2) L(-1) day(-1) after decreasing HRT. In R(BES + Chlo) hydrogen production rate did not exceed 300 mL H(2) L(-1) day(-1) and there was granule fragmentation, release of free filaments from aggregates, and decrease of granule density. In R(BES), there was an initial period with unstable hydrogen production, but a pulse of BES triggered its production rate to 700 ± 200 mL H(2) L(-1) day(-1). This strategy did not affect granules structure significantly. Bacteria branching within Clostridiaceae and Ruminococcaceae were present in this sludge. This work demonstrates that, methods applied to suppress H(2)-consuming microorganisms can cause changes in the macro- and microstructure of granular sludge, which can be incompatible with the operation of high-rate reactors. Copyright © 2011 Wiley Periodicals, Inc.

Effect of Ibuprofen Dose on Platelet Aggregation and Coagulation in Blood Samples From Pigs

DTIC Science & Technology

2015-03-01

is not known and would be more of an issue with chronic misuse of the drug. Aspirin is another widely used NSAID. Despite similar anti-inflammatory...analgesic, and antipyretic effects, different profiles of actions have been observed in Aspirin and ibupro- fen. At equivalent effective doses of...ibuprofen (2,400 mg/day, equivalent to 3 + in this study) and aspirin (3,900 mg/day), liver function and platelet aggregation are more adversely affected by

Mobility Enhancement of Red Blood Cells with Biopolymers

NASA Astrophysics Data System (ADS)

Tahara, Daiki; Oikawa, Noriko; Kurita, Rei

2016-03-01

Adhesion of red blood cells (RBC) to substrates are one of crucial problems for a blood clot. Here we investigate the mobility of RBC between two glass substrates in saline with polymer systems. We find that RBCs are adhered to the glass substrate with PEG, however the mobility steeply increases with fibrinogen and dextran, which are biopolymers. We also find that the mobility affects an aggregation dynamics of RBCs, which is related with diseases such as influenza, blood clot and so on. The Brownian motion helps to increase probability of contact with each other and to find a more stable condition of the aggregation. Thus the biopolymers play important roles not only for preventing the adhesion but also for the aggregation.

Effects of ionic strength and sugars on the aggregation propensity of monoclonal antibodies: influence of colloidal and conformational stabilities.

PubMed

Saito, Shuntaro; Hasegawa, Jun; Kobayashi, Naoki; Tomitsuka, Toshiaki; Uchiyama, Susumu; Fukui, Kiichi

2013-05-01

To develop a general strategy for optimizing monoclonal antibody (MAb) formulations. Colloidal stabilities of four representative MAbs solutions were assessed based on the second virial coefficient (B 2) at 20°C and 40°C, and net charges at different NaCl concentrations, and/or in the presence of sugars. Conformational stabilities were evaluated from the unfolding temperatures. The aggregation propensities were determined at 40°C and after freeze-thawing. The electrostatic potential of antibody surfaces was simulated for the development of rational formulations. Similar B 2 values were obtained at 20°C and 40°C, implying little dependence on temperature. B 2 correlated quantitatively with aggregation propensities at 40°C. The net charge partly correlated with colloidal stability. Salts stabilized or destabilized MAbs, depending on repulsive or attractive interactions. Sugars improved the aggregation propensity under freeze-thaw stress through improved conformational stability. Uneven and even distributions of potential surfaces were attributed to attractive and strong repulsive electrostatic interactions. Assessment of colloidal stability at the lowest ionic strength is particularly effective for the development of formulations. If necessary, salts are added to enhance the colloidal stability. Sugars further improved aggregation propensities by enhancing conformational stability. These behaviors are rationally predictable according to the surface potentials of MAbs.

Glutathione-facilitated design and fabrication of gold nanoparticle-based logic gates and keypad lock.

PubMed

Huang, Zhenzhen; Wang, Haonan; Yang, Wensheng

2014-07-21

In this paper, we describe how we developed a simple design and fabrication method for logic gates and a device by using a commercially available tripeptide, namely glutathione (GSH), together with metal ions and disodium ethylenediaminetetraacetate (EDTA) to control the dispersion and aggregation of gold nanoparticles (NPs). With the fast adsorption of GSH on gold NPs and the strong coordination of GSH with metal ions, the addition of GSH and Pb(2+) ions immediately resulted in the aggregation of gold NPs, giving rise to an AND function. Either Pb(2+) or Ba(2+) ions induced the aggregation of gold NPs in the presence of GSH, supporting an OR gate. Based on the fact that EDTA has a strong capacity to bind metal ions, thus preventing the aggregation of gold NPs, an INHIBIT gate was also fabricated. More interestingly, we found that the addition sequence of GSH and Hg(2+) ions influenced the aggregation of gold NPs in a controlled manner, which was used to design a sequential logic gate and a three-input keypad lock for potential use in information security. The GSH strategy addresses concerns of low cost, simple fabrication, versatile design and easy operation, and offers a promising platform for the development of functional logic systems.

Reevaluation of the role of the polar groups of collagen in the platelet-collagen interaction.

PubMed Central

Chesney, C. M.; Pifer, D. D.; Crofford, L. J.; Huch, K. M.

1983-01-01

Chemical modification of collagen is a tool for exploring the platelet-collagen interaction. Since collagen must polymerize prior to the initiation of platelet aggregation and secretion, modification must be shown to affect platelet-collagen interaction and not collagen-collagen interaction. To address this point, the authors carried out the following chemical modifications on soluble monomeric collagen and preformed fibrillar collagen in parallel: 1) N-and O-acetylation, 2) esterification of the carboxyl groups, 3) succinylation of the free amino groups, 4) esterification of succinylated collagen. Intrinsic viscosity studies of the modified soluble collagens were consistent with normal triple helix conformation. Electron microscopy revealed all modified fibrillar collagen to maintain a fibrillar structure. Platelet aggregation and secretion of 14C-serotonin and platelet factor 4 by soluble and fibrillar collagen, respectively, were studied in human platelet-rich plasma. Neutralization of polar groups by 1) totally abolished aggregation and secretion by both collagens, while blocking acidic groups 2) resulted in enhanced aggregation and secretion by both soluble and fibrillar collagen. Blockage of amino groups by 3) abolished aggregation and secretion by both collagens. Esterified succinylated collagen 4) caused aggregation and secretion at relatively high collagen concentrations. These data support the theory that positive groups of collagen are important in platelet-collagen interaction. Images Figure 1 PMID:6881287

Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation

PubMed Central

Mahjoubi, Najmeh; Fazeli, Mohammad Reza; Dinarvand, Rassoul; Khoshayand, Mohammad Reza; Fazeli, Ahmad; Taghavian, Mohammad; Rastegar, Hossein

2015-01-01

Purpose: Aggregation suppressing additives have been used to stabilize proteins during manufacturing and storage. Interferonβ-1b is prone to aggregation because of being non-glycosylated. Aggregation behavior of albumin-free formulations of recombinant IFNβ-1b was explored using additives such as n-dodecyl-β-D-maltoside, Tween 20, arginine, glycine, trehalose and sucrose at different pH. Methods: Fractional factorial design was applied to select major factors affecting aggregation in solutions. Box-Behnken technique was used to optimize the best concentration of additives and protein. Results: Quadratic model was the best fitted model for particle size, OD350 and OD280/OD260. The optimal conditions of 0.2% n-Dodecyl-β-D-maltoside, 70 mM arginine, 189 mM trehalose and protein concentration of 0.50 mg/ml at pH 4 were achieved. A potency value of 91% ± 5% was obtained for the optimized formulation. Conclusion: This study shows that the combination of n-Dodecyl-β-D-maltoside, arginine and trehalose would demonstrate a significant stabilizing and anti-aggregating effect on the liquid formulation of interferonβ-1b. It can not only reduce the manufacturing costs but will also ease patient compliance. PMID:26819922

Genetic variation in aggregation behaviour and interacting phenotypes in Drosophila.

PubMed

Philippe, Anne-Sophie; Jeanson, Raphael; Pasquaretta, Cristian; Rebaudo, Francois; Sueur, Cedric; Mery, Frederic

2016-03-30

Aggregation behaviour is the tendency for animals to group together, which may have important consequences on individual fitness. We used a combination of experimental and simulation approaches to study how genetic variation and social environment interact to influence aggregation dynamics in Drosophila To do this, we used two different natural lines of Drosophila that arise from a polymorphism in the foraging gene (rovers and sitters). We placed groups of flies in a heated arena. Flies could freely move towards one of two small, cooler refuge areas. In groups of the same strain, sitters had a greater tendency to aggregate. The observed behavioural variation was based on only two parameters: the probability of entering a refuge and the likelihood of choosing a refuge based on the number of individuals present. We then directly addressed how different strains interact by mixing rovers and sitters within a group. Aggregation behaviour of each line was strongly affected by the presence of the other strain, without changing the decision rules used by each. Individuals obeying local rules shaped complex group dynamics via a constant feedback loop between the individual and the group. This study could help to identify the circumstances under which particular group compositions may improve individual fitness through underlying aggregation mechanisms under specific environmental conditions. © 2016 The Author(s).

Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

PubMed Central

Stefani, Massimo; Rigacci, Stefania

2013-01-01

Amyloid aggregation is a hallmark of several degenerative diseases affecting the brain or peripheral tissues, whose intermediates (oligomers, protofibrils) and final mature fibrils display different toxicity. Consequently, compounds counteracting amyloid aggregation have been investigated for their ability (i) to stabilize toxic amyloid precursors; (ii) to prevent the growth of toxic oligomers or speed that of fibrils; (iii) to inhibit fibril growth and deposition; (iv) to disassemble preformed fibrils; and (v) to favor amyloid clearance. Natural phenols, a wide panel of plant molecules, are one of the most actively investigated categories of potential amyloid inhibitors. They are considered responsible for the beneficial effects of several traditional diets being present in green tea, extra virgin olive oil, red wine, spices, berries and aromatic herbs. Accordingly, it has been proposed that some natural phenols could be exploited to prevent and to treat amyloid diseases, and recent studies have provided significant information on their ability to inhibit peptide/protein aggregation in various ways and to stimulate cell defenses, leading to identify shared or specific mechanisms. In the first part of this review, we will overview the significance and mechanisms of amyloid aggregation and aggregate toxicity; then, we will summarize the recent achievements on protection against amyloid diseases by many natural phenols. PMID:23765219

Evaluation of the effects of amyloid β aggregation from seaweed extracts by a microliter-scale high-throughput screening system with a quantum dot nanoprobe.

PubMed

Ogara, Toshiki; Takahashi, Tomohito; Yasui, Hajime; Uwai, Koji; Tokuraku, Kiyotaka

2015-07-01

Inhibitors of amyloid β (Aβ) aggregation have the potential to serve as lead compounds for anti-Alzheimer's disease (AD) agents because Aβ aggregation is a key step in AD pathogenesis. Recently, we developed a novel microliter-scale high-throughput screening (MSHTS) system for Aβ aggregation inhibitors that applied fluorescence microscopic analysis with quantum dot nanoprobes, and attempted to comprehensively screen the inhibitors from spices using this system (Ishigaki et al., PLoS One, 8, e72992, 2013). In this study, we tried to evaluate the inhibitory activities of 11 seaweed extracts on Aβ aggregation using the MSHTS system. The half-maximal effective concentration (EC50) of the ethanolic extracts from all seaweeds exceeded 4.9 mg/ml, indicating that the extracts inhibit Aβ aggregation although this activity was significantly lower than that displayed by members of the Lamiaceae, a family of herbal spices that showed highest activity among 52 spices tested in our 2013 study. On the other hand, the EC50 of boiling water extracts was 0.013-0.42 mg/ml which was comparable with the EC50 of the extracts from the Lamiaceae family. These results suggest that the extraction efficiency of the inhibitors by boiling water extraction was higher than that by ethanolic extraction. Moreover, analysis of fluorescence micrographs, which were obtained from the MSHTS system, revealed that the morphology of the Aβ aggregates coincubated with boiling water extracts differed from control aggregates, suggesting that the MSHTS system is also useful for screening substances that affect the morphology of aggregates. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Aggregation of asbestos fibers in water: role of solution chemistry

NASA Astrophysics Data System (ADS)

Wu, L.; Ortiz, C. P.; Jerolmack, D. J.

2016-12-01

Aggregation kinetics and stability of colloidal particles have been extensively studied using bulk techniques such as dynamic light scattering; these techniques involve large ensembles of particles and interpretation of results is difficult when particles are non-spherical and poorly characterized, as is always the case with non-ideal natural hazardous materials such as asbestos fibers. These difficulties hinder greatly progress on fundamental understanding of whether the classic colloidal aggregation theories can be applied to natural materials and how the heterogeneity of particles (e.g., shape) affects the colloidal aggregation kinetics and structure. By using in-situ microscopy and particle tracking techniques, we were able to observe the particle-by-particle growth of aggregated formed by elongated particles (synthetic glass rods and natural asbestos fibers) and demonstrated the rod-shaped geometry induced novel structures and growth dynamics that challenge existing theory. In this study, we continue to use asbestos as model system of elongated colloidal contaminant, and investigate the effects of changing solution chemistry (e.g., ionic strength, pH, and natural organic matter (NOM)), on growth dynamics and aggregates structure. The results show that aggregate growth curves are self-similar with a characteristic timescale that increases with increasing pH. By varying ionic strength for fixed pH values, we determine that the ccc is sensitive to pH. Fractal dimension decreases slightly with increasing pH and decreasing ionic strength, indicating that stronger inter-particle repulsion create sparser aggregates; however, the magnitude of the solution chemistry effects is much smaller than that of colloid shape. In monovalent solutions, regardless of their concentration, HA drastically reduces the aggregation kinetics of asbestos fiber. This work may lead to enhanced prediction of the colloidal contaminants' mobility in the environment, bioavailability, and toxicity to organisms.

A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy

PubMed Central

Schwab, Karima; Frahm, Silke; Horsley, David; Rickard, Janet E.; Melis, Valeria; Goatman, Elizabeth A.; Magbagbeolu, Mandy; Douglas, Morag; Leith, Michael G.; Baddeley, Thomas C.; Storey, John M. D.; Riedel, Gernot; Wischik, Claude M.; Harrington, Charles R.; Theuring, Franz

2018-01-01

α-Synuclein (α-Syn) aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson’s disease (PD). We have tested whether N,N,N′,N′-tetramethyl-10H-phenothiazine-3,7-diaminium bis(hydromethanesulfonate) (leuco-methylthioninium bis(hydromethanesulfonate); LMTM), a tau aggregation inhibitor, affects α-Syn aggregation in vitro and in vivo. Both cellular and transgenic models in which the expression of full-length human α-Syn (h-α-Syn) fused with a signal sequence peptide to promote α-Syn aggregation were used. Aggregated α-Syn was observed following differentiation of N1E-115 neuroblastoma cells transfected with h-α-Syn. The appearance of aggregated α-Syn was inhibited by LMTM, with an EC50 of 1.1 μM, with minimal effect on h-α-Syn mRNA levels being observed. Two independent lines of mice (L58 and L62) transgenic for the same fusion protein accumulated neuronal h-α-Syn that, with aging, developed into fibrillary inclusions characterized by both resistance to proteinase K (PK)-cleavage and their ability to bind thiazin red. There was a significant decrease in α-Syn-positive neurons in multiple brain regions following oral treatment of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg MT/kg. The early aggregates of α-Syn and the late-stage fibrillar inclusions were both susceptible to inhibition by LMTM, a treatment that also resulted in the rescue of movement and anxiety-related traits in these mice. The results suggest that LMTM may provide a potential disease modification therapy in PD and other synucleinopathies through the inhibition of α-Syn aggregation. PMID:29375308