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.

Disaggregation of silver nanoparticle homoaggregates in a river water matrix.

PubMed

Metreveli, George; Philippe, Allan; Schaumann, Gabriele E

2015-12-01

Silver nanoparticles (Ag NPs) could be found in aquatic systems in the near future. Although the interplay between aggregate formation and disaggregation is an important factor for mobility, bioavailability and toxicity of Ag NPs in surface waters, the factors controlling disaggregation of Ag NP homoaggregates are still unknown. In this study, we investigated the reversibility of homoaggregation of citrate coated Ag NPs in a Rhine River water matrix. We characterized the disaggregation of Ag NP homoaggregates by ionic strength reduction and addition of Suwannee River humic acid (SRHA) in the presence of strong and weak shear forces. In order to understand the disaggregation processes, we also studied the nature of homoaggregates and their formation dynamics under the influence of SRHA, Ca(2+) concentration and nanoparticle concentration. Even in the presence of SRHA and at low particle concentrations (10 μg L(-1)), aggregates formed rapidly in filtered Rhine water. The critical coagulation concentration (CCC) of Ca(2+) in reconstituted Rhine water was 1.5 mmol L(-1) and was shifted towards higher values in the presence of SRHA. Analysis of the attachment efficiency as a function of Ca(2+) concentration showed that SRHA induces electrosteric stabilization at low Ca(2+) concentrations and cation-bridging flocculation at high Ca(2+) concentrations. Shear forces in the form of mechanical shaking or ultrasound were necessary for breaking the aggregates. Without ultrasound, SRHA also induced disaggregation, but it required several days to reach a stable size of dense aggregates still larger than the primary particles. Citrate stabilized Ag NPs may be in the form of reaction limited aggregates in aquatic systems similar to the Rhine River. The size and the structure of these aggregates will be dynamic and be determined by the solution conditions. Seasonal variations in the chemical composition of natural waters can result in a sedimentation-release cycle of engineered nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Stability of volcanic ash aggregates and break-up processes.

PubMed

Mueller, Sebastian B; Kueppers, Ulrich; Ametsbichler, Jonathan; Cimarelli, Corrado; Merrison, Jonathan P; Poret, Matthieu; Wadsworth, Fabian B; Dingwell, Donald B

2017-08-07

Numerical modeling of ash plume dispersal is an important tool for forecasting and mitigating potential hazards from volcanic ash erupted during explosive volcanism. Recent tephra dispersal models have been expanded to account for dynamic ash aggregation processes. However, there are very few studies on rates of disaggregation during transport. It follows that current models regard ash aggregation as irrevocable and may therefore overestimate aggregation-enhanced sedimentation. In this experimental study, we use industrial granulation techniques to artificially produce aggregates. We subject these to impact tests and evaluate their resistance to break-up processes. We find a dependence of aggregate stability on primary particle size distribution and solid particle binder concentration. We posit that our findings could be combined with eruption source parameters and implemented in future tephra dispersal models.

Metazoan Hsp70 machines use Hsp110 to power protein disaggregation.

PubMed

Rampelt, Heike; Kirstein-Miles, Janine; Nillegoda, Nadinath B; Chi, Kang; Scholz, Sebastian R; Morimoto, Richard I; Bukau, Bernd

2012-11-05

Accumulation of aggregation-prone misfolded proteins disrupts normal cellular function and promotes ageing and disease. Bacteria, fungi and plants counteract this by solubilizing and refolding aggregated proteins via a powerful cytosolic ATP-dependent bichaperone system, comprising the AAA+ disaggregase Hsp100 and the Hsp70-Hsp40 system. Metazoa, however, lack Hsp100 disaggregases. We show that instead the Hsp110 member of the Hsp70 superfamily remodels the human Hsp70-Hsp40 system to efficiently disaggregate and refold aggregates of heat and chemically denatured proteins in vitro and in cell extracts. This Hsp110 effect relies on nucleotide exchange, not on ATPase activity, implying ATP-driven chaperoning is not required. Knock-down of nematode Caenorhabditis elegans Hsp110, but not an unrelated nucleotide exchange factor, compromises dissolution of heat-induced protein aggregates and severely shortens lifespan after heat shock. We conclude that in metazoa, Hsp70-Hsp40 powered by Hsp110 nucleotide exchange represents the crucial disaggregation machinery that reestablishes protein homeostasis to counteract protein unfolding stress.

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

Bae, Song Yi; Kim, Seulgi; Hwang, Heejin

Research highlights: {yields} Formation of the {alpha}-synuclein amyloid fibrils by [BIMbF{sub 3}Im]. {yields} Disaggregation of amyloid fibrils by epigallocatechin gallate (EGCG) and baicalein. {yields} Amyloid formation of {alpha}-synuclein tandem repeat ({alpha}-TR). -- Abstract: The aggregation of {alpha}-synuclein is clearly related to the pathogenesis of Parkinson's disease. Therefore, detailed understanding of the mechanism of fibril formation is highly valuable for the development of clinical treatment and also of the diagnostic tools. Here, we have investigated the interaction of {alpha}-synuclein with ionic liquids by using several biochemical techniques including Thioflavin T assays and transmission electron microscopy (TEM). Our data shows a rapidmore » formation of {alpha}-synuclein amyloid fibrils was stimulated by 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BIMbF{sub 3}Im], and these fibrils could be disaggregated by polyphenols such as epigallocatechin gallate (EGCG) and baicalein. Furthermore, the effect of [BIMbF{sub 3}Im] on the {alpha}-synuclein tandem repeat ({alpha}-TR) in the aggregation process was studied.« less

Using software agents to preserve individual health data confidentiality in micro-scale geographical analyses.

PubMed

Kamel Boulos, Maged N; Cai, Qiang; Padget, Julian A; Rushton, Gerard

2006-04-01

Confidentiality constraints often preclude the release of disaggregate data about individuals, which limits the types and accuracy of the results of geographical health analyses that could be done. Access to individually geocoded (disaggregate) data often involves lengthy and cumbersome procedures through review boards and committees for approval (and sometimes is not possible). Moreover, current data confidentiality-preserving solutions compatible with fine-level spatial analyses either lack flexibility or yield less than optimal results (because of confidentiality-preserving changes they introduce to disaggregate data), or both. In this paper, we present a simulation case study to illustrate how some analyses cannot be (or will suffer if) done on aggregate data. We then quickly review some existing data confidentiality-preserving techniques, and move on to explore a solution based on software agents with the potential of providing flexible, controlled (software-only) access to unmodified confidential disaggregate data and returning only results that do not expose any person-identifiable details. The solution is thus appropriate for micro-scale geographical analyses where no person-identifiable details are required in the final results (i.e., only aggregate results are needed). Our proposed software agent technique also enables post-coordinated analyses to be designed and carried out on the confidential database(s), as needed, compared to a more conventional solution based on the Web Services model that would only support a rigid, pre-coordinated (pre-determined) and rather limited set of analyses. The paper also provides an exploratory discussion of mobility, security, and trust issues associated with software agents, as well as possible directions/solutions to address these issues, including the use of virtual organizations. Successful partnerships between stakeholder organizations, proper collaboration agreements, clear policies, and unambiguous interpretations of laws and regulations are also much needed to support and ensure the success of any technological solution.

Contextualising Water Use in Residential Settings: A Survey of Non-Intrusive Techniques and Approaches

PubMed Central

Carboni, Davide; Gluhak, Alex; McCann, Julie A.; Beach, Thomas H.

2016-01-01

Water monitoring in households is important to ensure the sustainability of fresh water reserves on our planet. It provides stakeholders with the statistics required to formulate optimal strategies in residential water management. However, this should not be prohibitive and appliance-level water monitoring cannot practically be achieved by deploying sensors on every faucet or water-consuming device of interest due to the higher hardware costs and complexity, not to mention the risk of accidental leakages that can derive from the extra plumbing needed. Machine learning and data mining techniques are promising techniques to analyse monitored data to obtain non-intrusive water usage disaggregation. This is because they can discern water usage from the aggregated data acquired from a single point of observation. This paper provides an overview of water usage disaggregation systems and related techniques adopted for water event classification. The state-of-the art of algorithms and testbeds used for fixture recognition are reviewed and a discussion on the prominent challenges and future research are also included. PMID:27213397

Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates.

PubMed

Moser, Martin; Bertram, Ulf; Peter, Karlheinz; Bode, Christoph; Ruef, Johannes

2003-04-01

Platelet GPIIb/IIIa antagonists are not only used to prevent platelet aggregation, but also in combination with thrombolytic agents for the treatment of coronary thrombi. Recent data indicate a potential of abciximab alone to dissolve thrombi in vivo. We investigated the potential of abciximab, eptifibatide, and tirofiban to dissolve platelet aggregates in vitro. Adenosine diphosphate (ADP)-induced platelet aggregation could be reversed in a concentration-dependent manner by all three GPIIb/IIIa antagonists when added after the aggregation curve reached half-maximal aggregation. The concentrations chosen are comparable with in vivo plasma concentrations in clinical applications. Disaggregation reached a maximum degree of 72.4% using 0.5 microg/ml tirofiban, 91.5% using 3.75 microg/ml eptifibatide, and 48.4% using 50 microg/ml abciximab (P < 0.05, respectively). A potential fibrinolytic activity of the GPIIb/IIIa antagonists was ruled out by preincubation with aprotinin or by a plasma clot assay. A stable model Chinese hamster ovary (CHO) cell line expressing the activated form of GPIIb/IIIa was used to confirm the disaggregation capacity of GPIIb/IIIa antagonists found in platelets. Not only abciximab, but also eptifibatide and tirofiban have the potential to disaggregate newly formed platelet clusters in vitro. Because enzyme-dependent fibrinolysis does not appear to be involved, competitive removal of fibrinogen by the receptor antagonists is the most likely mechanism.

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.

Equity in health care financing in Palestine: the value-added of the disaggregate approach.

PubMed

Abu-Zaineh, Mohammad; Mataria, Awad; Luchini, Stéphane; Moatti, Jean-Paul

2008-06-01

This paper analyzes the redistributive effect and progressivity associated with the current health care financing schemes in the Occupied Palestinian Territory, using data from the first Palestinian Household Health Expenditure Survey conducted in 2004. The paper goes beyond the commonly used "aggregate summary index approach" to apply a more detailed "disaggregate approach". Such an approach is borrowed from the general economic literature on taxation, and examines redistributive and vertical effects over specific parts of the income distribution, using the dominance criterion. In addition, the paper employs a bootstrap method to test for the statistical significance of the inequality measures. While both the aggregate and disaggregate approaches confirm the pro-rich and regressive character of out-of-pocket payments, the aggregate approach does not ascertain the potential progressive feature of any of the available insurance schemes. The disaggregate approach, however, significantly reveals a progressive aspect, for over half of the population, of the government health insurance scheme, and demonstrates that the regressivity of the out-of-pocket payments is most pronounced among the worst-off classes of the population. Recommendations are advanced to improve the performance of the government insurance schemes to enhance its capacity in limiting inequalities in health care financing in the Occupied Palestinian Territory.

Destabilization of Human Insulin Fibrils by Peptides of Fruit Bromelain Derived From Ananas comosus (Pineapple).

PubMed

Das, Sromona; Bhattacharyya, Debasish

2017-12-01

Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers. These processes were followed fluorimetrically using Thioflavin T and 1-ANS, size-exclusion HPLC, dynamic light scattering, atomic force microscopy, and transmission electron microscopy. Sequences of insulin (A and B chains) and bromelain were aligned using Clustal W software to predict most probable sites of interactions. Synthetic tripeptides corresponding to the hydrophobic interactive sites of bromelain showed disaggregation of insulin suggesting specificity of interactions. The peptides GG and AAA serving as negative controls showed no potency in destabilization of aggregates. Disaggregation potency of the peptides was also observed when insulin was deposited on HepG2 liver cells where no formation of toxic oligomers occurred. Amyloidogenic des-octapeptide (B23-B30 of insulin) incapable of cell signaling showed cytotoxicity similar to insulin. This toxicity could be neutralized by bromelain derived peptides. FT-IR and far-UV circular dichroism analysis indicated that disaggregated insulin had structure distinctly different from that of its hexameric (native) or monomeric states. Based on the stoichiometry of interaction and irreversibility of disaggregation, the mechanism/s of the peptides and insulin interactions has been proposed. J. Cell. Biochem. 118: 4881-4896, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Stimulation of Cysteine-Coated CdSe/ZnS Quantum Dot Luminescence by meso-Tetrakis (p-sulfonato-phenyl) Porphyrin

NASA Astrophysics Data System (ADS)

Parra, Gustavo G.; Ferreira, Lucimara P.; Gonçalves, Pablo J.; Sizova, Svetlana V.; Oleinikov, Vladimir A.; Morozov, Vladimir N.; Kuzmin, Vladimir A.; Borissevitch, Iouri E.

2018-02-01

Interaction between porphyrins and quantum dots (QD) via energy and/or charge transfer is usually accompanied by reduction of the QD luminescence intensity and lifetime. However, for CdSe/ZnS-Cys QD water solutions, kept at 276 K during 3 months (aged QD), the significant increase in the luminescence intensity at the addition of meso-tetrakis (p-sulfonato-phenyl) porphyrin (TPPS4) has been observed in this study. Aggregation of QD during the storage provokes reduction in the quantum yield and lifetime of their luminescence. Using steady-state and time-resolved fluorescence techniques, we demonstrated that TPPS4 stimulated disaggregation of aged CdSe/ZnS-Cys QD in aqueous solutions, increasing the quantum yield of their luminescence, which finally reached that of the fresh-prepared QD. Disaggregation takes place due to increase in electrostatic repulsion between QD at their binding with negatively charged porphyrin molecules. Binding of just four porphyrin molecules per single QD was sufficient for total QD disaggregation. The analysis of QD luminescence decay curves demonstrated that disaggregation stronger affected the luminescence related with the electron-hole annihilation in the QD shell. The obtained results demonstrate the way to repair aged QD by adding of some molecules or ions to the solutions, stimulating QD disaggregation and restoring their luminescence characteristics, which could be important for QD biomedical applications, such as bioimaging and fluorescence diagnostics. On the other hand, the disaggregation is important for QD applications in biology and medicine since it reduces the size of the particles facilitating their internalization into living cells across the cell membrane.

Aggregation and Disaggregation of Senile Plaques in Alzheimer Disease

NASA Astrophysics Data System (ADS)

Cruz, L.; Urbanc, B.; Buldyrev, S. V.; Christie, R.; Gomez-Isla, T.; Havlin, S.; McNamara, M.; Stanley, H. E.; Hyman, B. T.

1997-07-01

We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to gain insights about the processes that govern Aβ peptide deposition. Our results show that plaques are complex porous structures with characteristic pore sizes. We interpret plaque morphology in the context of a new dynamical model based on competing aggregation and disaggregation processes in kinetic steady-state equilibrium with an additional diffusion process allowing Aβ deposits to diffuse over the surface of plaques.

Effects of slaking and mechanical breakdown on disaggregation and splash erosion

USDA-ARS?s Scientific Manuscript database

The contributions of different aggregate breakdown mechanisms to splash erosion are still obscure. This study was designed to investigate the effects of different soil disaggregation mechanisms on splash erosion. Loam clay soil, clay loam soil, and sandy loam soil were used in this study. Soil aggre...

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.

Viral Aggregation: Impact on Virus Behavior in the Environment.

PubMed

Gerba, Charles P; Betancourt, Walter Q

2017-07-05

Aggregates of viruses can have a significant impact on quantification and behavior of viruses in the environment. Viral aggregates may be formed in numerous ways. Viruses may form crystal like structures and aggregates in the host cell during replication or may form due to changes in environmental conditions after virus particles are released from the host cells. Aggregates tend to form near the isoelectric point of the virus, under the influence of certain salts and salt concentrations in solution, cationic polymers, and suspended organic matter. The given conditions under which aggregates form in the environment are highly dependent on the type of virus, type of salts in solution (cation, anion. monovalent, divalent) and pH. However, virus type greatly influences the conditions when aggregation/disaggregation will occur, making predictions difficult under any given set of water quality conditions. Most studies have shown that viral aggregates increase the survival of viruses in the environment and resistance to disinfectants, especially with more reactive disinfectants. The presence of viral aggregates may also result in overestimation of removal by filtration processes. Virus aggregation-disaggregation is a complex process and predicting the behavior of any individual virus is difficult under a given set of environmental circumstances without actual experimental data.

Disaggregation induced solvatochromic switch: A study of dansylated polyglycerol dendrons in binary solvent mixture

NASA Astrophysics Data System (ADS)

Subuddhi, Usharani; Vuram, Prasanna K.; Chadha, Anju; Mishra, Ashok K.

2014-07-01

A reversal in solvatochromic behaviour was observed in second and third generation glycerol based dansylated polyether dendrons in water on addition of a second solvent like methanol or acetonitrile. Below a certain percentage of the nonaqueous solvent there is a negative-solvatochromism observed and above that there is a switch to positive-solvatochromism. The negative-solvatochromism is attributed to the progressive disaggregation of the dendron aggregates by the nonaqueous solvent component. Once the disaggregation process is complete, positive-solvatochromism is exhibited by the dendron monomers. Higher the hydrophobicity of the dendron more is the amount of the second solvent required for disaggregation.

Crucial HSP70 co–chaperone complex unlocks metazoan protein disaggregation

PubMed Central

Nillegoda, Nadinath B.; Kirstein, Janine; Szlachcic, Anna; Berynskyy, Mykhaylo; Stank, Antonia; Stengel, Florian; Arnsburg, Kristin; Gao, Xuechao; Scior, Annika; Aebersold, Ruedi; Guilbride, D. Lys; Wade, Rebecca C.; Morimoto, Richard I.; Mayer, Matthias P.; Bukau, Bernd

2016-01-01

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states1,2. Healthy metazoan cells effectively eliminate intracellular protein aggregates3,4, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems5,6, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro4,7. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control. PMID:26245380

A Novel Magnetic Actuation Scheme to Disaggregate Nanoparticles and Enhance Passage across the Blood–Brain Barrier

PubMed Central

Le, Tuan-Anh; Amin, Faiz Ul; Kim, Myeong Ok

2017-01-01

The blood–brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme. PMID:29271927

A Novel Magnetic Actuation Scheme to Disaggregate Nanoparticles and Enhance Passage across the Blood-Brain Barrier.

PubMed

Hoshiar, Ali Kafash; Le, Tuan-Anh; Amin, Faiz Ul; Kim, Myeong Ok; Yoon, Jungwon

2017-12-22

The blood-brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme.

Enzymatic activity inside and outside of water-stable aggregates in soils under different land use

NASA Astrophysics Data System (ADS)

Garbuz, S. A.; Yaroslavtseva, N. V.; Kholodov, V. A.

2016-03-01

A method is presented for assessing the distribution of enzymatic activity inside and outside of water-stable aggregates. Two samples of water-stable aggregates >1 mm have been isolated from dry aggregates of 1-2 mm. To determine the enzymatic activity, a substrate has been added to one of the samples without disaggregation; the other sample has been preliminarily disaggregated. Enzymatic activity within waterstable aggregates has been assessed from the difference between the obtained results under the supposition that the penetration of substrate within the water-saturated aggregates is hampered, and enzymatic reactions occur only at the periphery. The levels and distributions of enzymatic (peroxidase, polyphenol oxidase, and catalase) activities in water-stable aggregates of soddy-podzolic soils under forest and plowland and typical chernozems of long-term field experiments have been studied. The peroxidase, polyphenol oxidase, and catalase activities of water-stable aggregates vary from 6 to 23, from 7 to 30, and from 5 to 7 mmol/(g h), respectively. The ratio between the enzymatic activities inside and outside of soil aggregates showed a higher dependence on soil type and land use, as well as on the input of organic matter and the structural state, than the general activity level in water-stable aggregates.

A rainfall disaggregation scheme for sub-hourly time scales: Coupling a Bartlett-Lewis based model with adjusting procedures

NASA Astrophysics Data System (ADS)

Kossieris, Panagiotis; Makropoulos, Christos; Onof, Christian; Koutsoyiannis, Demetris

2018-01-01

Many hydrological applications, such as flood studies, require the use of long rainfall data at fine time scales varying from daily down to 1 min time step. However, in the real world there is limited availability of data at sub-hourly scales. To cope with this issue, stochastic disaggregation techniques are typically employed to produce possible, statistically consistent, rainfall events that aggregate up to the field data collected at coarser scales. A methodology for the stochastic disaggregation of rainfall at fine time scales was recently introduced, combining the Bartlett-Lewis process to generate rainfall events along with adjusting procedures to modify the lower-level variables (i.e., hourly) so as to be consistent with the higher-level one (i.e., daily). In the present paper, we extend the aforementioned scheme, initially designed and tested for the disaggregation of daily rainfall into hourly depths, for any sub-hourly time scale. In addition, we take advantage of the recent developments in Poisson-cluster processes incorporating in the methodology a Bartlett-Lewis model variant that introduces dependence between cell intensity and duration in order to capture the variability of rainfall at sub-hourly time scales. The disaggregation scheme is implemented in an R package, named HyetosMinute, to support disaggregation from daily down to 1-min time scale. The applicability of the methodology was assessed on a 5-min rainfall records collected in Bochum, Germany, comparing the performance of the above mentioned model variant against the original Bartlett-Lewis process (non-random with 5 parameters). The analysis shows that the disaggregation process reproduces adequately the most important statistical characteristics of rainfall at wide range of time scales, while the introduction of the model with dependent intensity-duration results in a better performance in terms of skewness, rainfall extremes and dry proportions.

Dynamic structural states of ClpB involved in its disaggregation function.

PubMed

Uchihashi, Takayuki; Watanabe, Yo-Hei; Nakazaki, Yosuke; Yamasaki, Takashi; Watanabe, Hiroki; Maruno, Takahiro; Ishii, Kentaro; Uchiyama, Susumu; Song, Chihong; Murata, Kazuyoshi; Iino, Ryota; Ando, Toshio

2018-06-01

The ATP-dependent bacterial protein disaggregation machine, ClpB belonging to the AAA+ superfamily, refolds toxic protein aggregates into the native state in cooperation with the cognate Hsp70 partner. The ring-shaped hexamers of ClpB unfold and thread its protein substrate through the central pore. However, their function-related structural dynamics has remained elusive. Here we directly visualize ClpB using high-speed atomic force microscopy (HS-AFM) to gain a mechanistic insight into its disaggregation function. The HS-AFM movies demonstrate massive conformational changes of the hexameric ring during ATP hydrolysis, from a round ring to a spiral and even to a pair of twisted half-spirals. HS-AFM observations of Walker-motif mutants unveil crucial roles of ATP binding and hydrolysis in the oligomer formation and structural dynamics. Furthermore, repressed and hyperactive mutations result in significantly different oligomeric forms. These results provide a comprehensive view for the ATP-driven oligomeric-state transitions that enable ClpB to disentangle protein aggregates.

Economic growth, energy consumption and CO2 emissions in India: a disaggregated causal analysis

NASA Astrophysics Data System (ADS)

Nain, Md Zulquar; Ahmad, Wasim; Kamaiah, Bandi

2017-09-01

This study examines the long-run and short-run causal relationships among energy consumption, real gross domestic product (GDP) and CO2 emissions using aggregate and disaggregate (sectoral) energy consumption measures utilising annual data from 1971 to 2011. The autoregressive distributed lag bounds test reveals that there is a long-run relationship among the variables concerned at both aggregate and disaggregate levels. The Toda-Yamamoto causality tests, however, reveal that the long-run as well short-run causal relationship among the variables is not uniform across sectors. The weight of evidences of the study indicates that there is short-run causality from electricity consumption to economic growth, and to CO2 emissions. The results suggest that India should take appropriate cautious steps to sustain high growth rate and at the same time to control emissions of CO2. Further, energy and environmental policies should acknowledge the sectoral differences in the relationship between energy consumption and real gross domestic product.

Descriptive parameters of the erythrocyte aggregation phenomenon using a laser transmission optical chip

NASA Astrophysics Data System (ADS)

Toderi, Martín A.; Castellini, Horacio V.; Riquelme, Bibiana D.

2017-01-01

The study of red blood cell (RBC) aggregation is of great interest because of its implications for human health. Altered RBC aggregation can lead to microcirculatory problems as in vascular pathologies, such as hypertension and diabetes, due to a decrease in the erythrocyte surface electric charge and an increase in the ligands present in plasma. The process of erythrocyte aggregation was studied in stasis situation (free shear stresses), using an optical chip based on the laser transmission technique. Kinetic curves of erythrocyte aggregation under different conditions were obtained, allowing evaluation and characterization of this process. Two main characteristics of blood that influence erythrocyte aggregation were analyzed: the erythrocyte surface anionic charge (EAC) after digestion with the enzyme trypsin and plasmatic protein concentration in suspension medium using plasma dissolutions in physiological saline with human albumin. A theoretical approach was evaluated to obtain aggregation and disaggregation ratios by syllectograms data fitting. Sensible parameters (Amp100, t) regarding a reduced erythrocyte EAC were determined, and other parameters (AI, M-Index) resulted that are representative of a variation in the plasmatic protein content of the suspension medium. These results are very useful for further applications in biomedicine.

Ultratrace Detection of Nitroaromatics: Picric Acid Responsive Aggregation/Disaggregation of Self-Assembled p-Terphenylbenzimidazolium-Based Molecular Baskets.

PubMed

Sandhu, Sana; Kumar, Rahul; Singh, Prabhpreet; Mahajan, Aman; Kaur, Manmeet; Kumar, Subodh

2015-05-20

1-(p-Terphenyl)-benzimidazolium (TRIPOD-TP) molecules undergo self-assembly to form rodlike structures in aqueous medium, as shown by field-emission scanning electron microscopy, transmission electron microscopy, and dynamic light scattering studies. Upon gradual addition of picric acid (PA), these aggregates undergo an aggregation/disaggregation process to complex morphological structures (10(-12)-10(-10) M PA) and spherical aggregates (10(-9)-10(-8) M PA). These spherical aggregates undergo further dissolution to well-dispersed spheres between 10(-7)-10(-6) M PA. During fluorescence studies, these aggregates demonstrate superamplified fluorescence quenching (>97%) in the presence of 10(-5) to 0.2 equiv of the probe concentration, an unprecedented process with PA. The lowest detection limits by solution of TRIPOD-TP are 5 × 10(-13) PA, 50 × 10(-12) M 2,4-dinitrophenol, 200 × 10(-12) M 2,4,6-trinitrotoluene, and 1 nM 1-chloro-2,4-dinitrobenzene. Paper strips dipped in the solution of TRIPOD-TP demonstrate quantitative fluorescence quenching between 10(-17) and 10(-6) M PA using front-surface steady state studies and can measure as low as 2.29 × 10(-20) g/cm(2) PA.

Monetary Value of Quality-Adjusted Life Years (QALY) among Patients with Cardiovascular Disease: a Willingness to Pay Study (WTP)

PubMed Central

Moradi, Najmeh; Rashidian, Arash; Rasekh, Hamid Reza; Olyaeemanesh, Alireza; Foroughi, Mahnoosh; Mohammadi, Teymoor

2017-01-01

The aim of this study was to estimate the monetary value of a QALY among patients with heart disease and to identify its determinants. A cross-sectional survey was conducted through face-to-face interview on 196 patients with cardiovascular disease from two heart hospitals in Tehran, Iran, to estimate the value of QALY using disaggregated and aggregated approaches. The EuroQol-5 Dimension (EQ-5D) questionnaire, Visual Analogue Scale (VAS), Time Trade-Off (TTO) and contingent valuation WTP techniques were employed, first to elicit patients’ preferences and then, to estimate WTP for QALY. The association of patients’ characteristics with WTP for QALY, was assessed through Heckman selection model. The Mean willingness to pay per QALY, estimated by the disaggregated approach ranged from 2,799 to 3599 US dollars. It is higher than the values, estimated from aggregated methods (USD 2,256 to 3,137). However, in both approaches, the values were less than one Gross Domestic Product (GDP) per capita of Iran. Significant variables were: Current health state, education, age, marital status, number of comorbidities, and household’s cost group. Our results challenge two major issues: the first, is a policy challenge which concerns the WHO recommendation to use less than 3 GDP per capita as a cost-effectiveness threshold value. The second, is an analytical challenge related to patients with zero QALY gain. More scrutiny is suggested on the issue of how patients with full health state valuation should be dealt with and what arbitrary value could be included in the estimation value of QALY when the disaggregated approach used. PMID:28979338

Monetary Value of Quality-Adjusted Life Years (QALY) among Patients with Cardiovascular Disease: a Willingness to Pay Study (WTP).

PubMed

Moradi, Najmeh; Rashidian, Arash; Rasekh, Hamid Reza; Olyaeemanesh, Alireza; Foroughi, Mahnoosh; Mohammadi, Teymoor

2017-01-01

The aim of this study was to estimate the monetary value of a QALY among patients with heart disease and to identify its determinants. A cross-sectional survey was conducted through face-to-face interview on 196 patients with cardiovascular disease from two heart hospitals in Tehran, Iran, to estimate the value of QALY using disaggregated and aggregated approaches. The EuroQol-5 Dimension (EQ-5D) questionnaire, Visual Analogue Scale (VAS), Time Trade-Off (TTO) and contingent valuation WTP techniques were employed, first to elicit patients' preferences and then, to estimate WTP for QALY. The association of patients' characteristics with WTP for QALY, was assessed through Heckman selection model. The Mean willingness to pay per QALY, estimated by the disaggregated approach ranged from 2,799 to 3599 US dollars. It is higher than the values, estimated from aggregated methods (USD 2,256 to 3,137). However, in both approaches, the values were less than one Gross Domestic Product (GDP) per capita of Iran. Significant variables were: Current health state, education, age, marital status, number of comorbidities, and household's cost group. Our results challenge two major issues: the first, is a policy challenge which concerns the WHO recommendation to use less than 3 GDP per capita as a cost-effectiveness threshold value. The second, is an analytical challenge related to patients with zero QALY gain. More scrutiny is suggested on the issue of how patients with full health state valuation should be dealt with and what arbitrary value could be included in the estimation value of QALY when the disaggregated approach used.

Block-accelerated aggregation multigrid for Markov chains with application to PageRank problems

NASA Astrophysics Data System (ADS)

Shen, Zhao-Li; Huang, Ting-Zhu; Carpentieri, Bruno; Wen, Chun; Gu, Xian-Ming

2018-06-01

Recently, the adaptive algebraic aggregation multigrid method has been proposed for computing stationary distributions of Markov chains. This method updates aggregates on every iterative cycle to keep high accuracies of coarse-level corrections. Accordingly, its fast convergence rate is well guaranteed, but often a large proportion of time is cost by aggregation processes. In this paper, we show that the aggregates on each level in this method can be utilized to transfer the probability equation of that level into a block linear system. Then we propose a Block-Jacobi relaxation that deals with the block system on each level to smooth error. Some theoretical analysis of this technique is presented, meanwhile it is also adapted to solve PageRank problems. The purpose of this technique is to accelerate the adaptive aggregation multigrid method and its variants for solving Markov chains and PageRank problems. It also attempts to shed some light on new solutions for making aggregation processes more cost-effective for aggregation multigrid methods. Numerical experiments are presented to illustrate the effectiveness of this technique.

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.

Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes.

PubMed

Nillegoda, Nadinath B; Stank, Antonia; Malinverni, Duccio; Alberts, Niels; Szlachcic, Anna; Barducci, Alessandro; De Los Rios, Paolo; Wade, Rebecca C; Bukau, Bernd

2017-05-15

Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain folding to protein disaggregation. This versatility in function is achieved through a diverse family of J-protein cochaperones that select substrates for Hsp70. Substrate selection is further tuned by transient complexation between different classes of J-proteins, which expands the range of protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the prevalence and evolutionary conservation of J-protein complexation and cooperation in disaggregation. We find the emergence of a eukaryote-specific signature for interclass complexation of canonical J-proteins. Consistently, complexes exist in yeast and human cells, but not in bacteria, and correlate with cooperative action in disaggregation in vitro. Signature alterations exclude some J-proteins from networking, which ensures correct J-protein pairing, functional network integrity and J-protein specialization. This fundamental change in J-protein biology during the prokaryote-to-eukaryote transition allows for increased fine-tuning and broadening of Hsp70 function in eukaryotes.

Mapping Urban Risk: Flood Hazards, Race, & Environmental Justice In New York”

PubMed Central

Maantay, Juliana; Maroko, Andrew

2009-01-01

This paper demonstrates the importance of disaggregating population data aggregated by census tracts or other units, for more realistic population distribution/location. A newly-developed mapping method, the Cadastral-based Expert Dasymetric System (CEDS), calculates population in hyper-heterogeneous urban areas better than traditional mapping techniques. A case study estimating population potentially impacted by flood hazard in New York City compares the impacted population determined by CEDS with that derived by centroid-containment method and filtered areal weighting interpolation. Compared to CEDS, 37 percent and 72 percent fewer people are estimated to be at risk from floods city-wide, using conventional areal weighting of census data, and centroid-containment selection, respectively. Undercounting of impacted population could have serious implications for emergency management and disaster planning. Ethnic/racial populations are also spatially disaggregated to determine any environmental justice impacts with flood risk. Minorities are disproportionately undercounted using traditional methods. Underestimating more vulnerable sub-populations impairs preparedness and relief efforts. PMID:20047020

Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage.

PubMed

Green, F W; Kaplan, M M; Curtis, L E; Levine, P H

1978-01-01

In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.

Amyloid-beta aggregates formed at polar-nonpolar interfaces differ from amyloid-beta protofibrils produced in aqueous buffers.

PubMed

Nichols, Michael R; Moss, Melissa A; Reed, Dana Kim; Hoh, Jan H; Rosenberry, Terrone L

2005-07-01

The deposition of aggregated amyloid-beta (Abeta) peptides in the brain as senile plaques is a pathological hallmark of Alzheimer's disease (AD). Several lines of evidence indicate that fibrillar and, in particular, soluble aggregates of these 40- and 42-residue peptides are important in the etiology of AD. Recent studies also stress that amyloid aggregates are polymorphic and that a single polypeptide can fold into multiple amyloid conformations. Here we review our recent reports that Abeta(1-40) in vitro can form soluble aggregates with predominant beta-structures that differ in stability and morphology. One class of aggregates involved soluble Abeta protofibrils, prepared by vigorous overnight agitation of monomeric Abeta(1-40) in low ionic strength buffers. These aggregates were quite stable and disaggregated to only a limited extent on dilution. A second class of soluble Abeta aggregates was generated at polar-nonpolar interfaces. Aggregation in a two-phase system of buffer over chloroform occurred more rapidly than in buffer alone. In buffered 2% hexafluoroisopropanol (HFIP), microdroplets of HFIP were formed and the half-time for aggregation was less than 10 minutes. Like Abeta protofibrils, these interfacial aggregates showed increased thioflavin T fluorescence and were rich in beta-structure by circular dichroism. However, electron microscopy and atomic force microscopy revealed very different morphologies. The HFIP aggregates formed initial globular clusters that progressed over several days to soluble fibrous aggregates. When diluted out of HFIP these aggregates initially were very unstable and disaggregated completely within 2 minutes. However, their stability increased as they progressed to fibers. It is important to determine whether similar interfacial Abeta aggregates are produced in vivo.

α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

PubMed Central

Shield, Kristy; Riley, Clyde; Quinn, Michael A; Rice, Gregory E; Ackland, Margaret L; Ahmed, Nuzhat

2007-01-01

Background Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface. This study was designed to elucidate early inherent mechanism(s) of spheroid survival, growth and disaggregation required for peritoneal metastases Methods In this study, we determined the growth pattern and adhesive capacity of ovarian cancer cell lines (HEY and OVHS1) grown as spheroids, using the well established liquid overlay technique, and compared them to a normal ovarian cell line (IOSE29) and cancer cells grown as a monolayer. The proteolytic capacity of these spheroids was compared with cells grown as a monolayer using a gelatin zymography assay to analyze secreted MMP-2/9 in conditioned serum-free medium. The disaggregation of cancer cell line spheroids was determined on extracellular matrices (ECM) such as laminin (LM), fibronectin (FN) and collagen (CI) and the expression of α2, α3, αv, α6 and β1 interin was determined by flow cytometric analysis. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin was used to inhibit disaggregation as well as activation of MMPs in spheroids. Results We demonstrate that ovarian cancer cell lines grown as spheroids can sustain growth for 10 days while the normal ovarian cell line failed to grow beyond 2 days. Compared to cells grown as a monolayer, cancer cells grown as spheroids demonstrated no change in adhesion for up to 4 days, while IOSE29 cells had a 2–4-fold loss of adhesion within 2 days. Cancer cell spheroids disaggregated on extracellular matrices (ECM) and demonstrated enhanced expression of secreted pro-MMP2 as well as activated MMP2/MMP9 with no such activation of MMP's observed in monolayer cells. Flow cytometric analysis demonstrated enhanced expression of α2 and diminution of α6 integrin subunits in spheroids versus monolayer cells. No change in the expression of α3, αv and β1 subunits was evident. Conversely, except for αv integrin, a 1.5–7.5-fold decrease in α2, α3, α6 and β1 integrin subunit expression was observed in IOSE29 cells within 2 days. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin inhibited disaggregation as well as activation of MMPs in spheroids. Conclusion Our results suggest that enhanced expression of α2β1 integrin may influence spheroid disaggregation and proteolysis responsible for the peritoneal dissemination of ovarian carcinoma. This may indicate a new therapeutic target for the suppression of the peritoneal metastasis associated with advanced ovarian carcinomas. PMID:17567918

Modeling the reversible kinetics of neutrophil aggregation under hydrodynamic shear.

PubMed Central

Neelamegham, S; Taylor, A D; Hellums, J D; Dembo, M; Smith, C W; Simon, S I

1997-01-01

Neutrophil emigration into inflamed tissue is mediated by beta 2-integrin and L-selectin adhesion receptors. Homotypic neutrophil aggregation is also dependent on these molecules, and it provides a model system in which to study adhesion dynamics. In the current study we formulated a mathematical model for cellular aggregation in a linear shear field based on Smoluchowski's two-body collision theory. Neutrophil suspensions activated with chemotactic stimulus and sheared in a cone-plate viscometer rapidly aggregate. Over a range of shear rates (400-800 s-1), approximately 90% of the single cells were recruited into aggregates ranging from doublets to groupings larger than sextuplets. The adhesion efficiency fit to these kinetics reached maximum levels of > 70%. Formed aggregates remained intact and resistant to shear up to 120 s, at which time they spontaneously dissociated back to singlets. The rate of cell disaggregation was linearly proportional to the applied shear rate, and it was approximately 60% lower for doublets as compared to larger aggregates. By accounting for the time-dependent changes in adhesion efficiency, disaggregation rate, and the effects of aggregate geometry, we succeeded in predicting the reversible kinetics of aggregation over a wide range of shear rates and cell concentrations. The combination of viscometry with flow cytometry and mathematical analysis as presented here represents a novel approach to differentiating between the effects of hydrodynamics and the intrinsic biological processes that control cell adhesion. Images FIGURE 3 FIGURE 5 PMID:9083659

Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

NASA Astrophysics Data System (ADS)

Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

2012-02-01

Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

Overlapping and Specific Functions of the Hsp104 N Domain Define Its Role in Protein Disaggregation

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

Lee, Jungsoon; Sung, Nuri; Mercado, Jonathan M.

Hsp104 is a ring-forming protein disaggregase that rescues stress-damaged proteins from an aggregated state. To facilitate protein disaggregation, Hsp104 cooperates with Hsp70 and Hsp40 chaperones (Hsp70/40) to form a bi-chaperone system. How Hsp104 recognizes its substrates, particularly the importance of the N domain, remains poorly understood and multiple, seemingly conficting mechanisms have been proposed. Although the N domain is dispensable for protein disaggregation, it is sensitive to point mutations that abolish the function of the bacterial Hsp104 homolog in vitro, and is essential for curing yeast prions by Hsp104 overexpression in vivo. Here, we present the crystal structure of anmore » N-terminal fragment of Saccharomyces cerevisiae Hsp104 with the N domain of one molecule bound to the C-terminal helix of the neighboring D1 domain. Consistent with mimicking substrate interaction, mutating the putative substrate-binding site in a constitutively active Hsp104 variant impairs the recovery of functional protein from aggregates. We fnd that the observed substrate-binding defect can be rescued by Hsp70/40 chaperones, providing a molecular explanation as to why the N domain is dispensable for protein disaggregation when Hsp70/40 is present, yet essential for the dissolution of Hsp104-specifc substrates, such as yeast prions, which likely depends on a direct N domain interaction.« less

Overlapping and Specific Functions of the Hsp104 N Domain Define Its Role in Protein Disaggregation

DOE PAGES

Lee, Jungsoon; Sung, Nuri; Mercado, Jonathan M.; ...

2017-09-11

Hsp104 is a ring-forming protein disaggregase that rescues stress-damaged proteins from an aggregated state. To facilitate protein disaggregation, Hsp104 cooperates with Hsp70 and Hsp40 chaperones (Hsp70/40) to form a bi-chaperone system. How Hsp104 recognizes its substrates, particularly the importance of the N domain, remains poorly understood and multiple, seemingly conficting mechanisms have been proposed. Although the N domain is dispensable for protein disaggregation, it is sensitive to point mutations that abolish the function of the bacterial Hsp104 homolog in vitro, and is essential for curing yeast prions by Hsp104 overexpression in vivo. Here, we present the crystal structure of anmore » N-terminal fragment of Saccharomyces cerevisiae Hsp104 with the N domain of one molecule bound to the C-terminal helix of the neighboring D1 domain. Consistent with mimicking substrate interaction, mutating the putative substrate-binding site in a constitutively active Hsp104 variant impairs the recovery of functional protein from aggregates. We fnd that the observed substrate-binding defect can be rescued by Hsp70/40 chaperones, providing a molecular explanation as to why the N domain is dispensable for protein disaggregation when Hsp70/40 is present, yet essential for the dissolution of Hsp104-specifc substrates, such as yeast prions, which likely depends on a direct N domain interaction.« less

Direct Visualization of Aggregate Morphology and Dynamics in a Model Soil Organic–Mineral System

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

Hufschmid, Ryan; Newcomb, Christina J.; Grate, Jay W.

Interactions between mineral surfaces and organic matter are ubiquitous in soils and the environment. Through both physical and chemical mechanisms, organic-mineral assemblages prevent decomposition of soil organic matter by limiting accessibility or reducing efficacy of enzymes and microbes. To understand the mechanisms underlying organic-mineral interactions, researchers have begun to interrogate these systems at smaller length scales. Current techniques that maintain a hydrated state and allow researchers to characterize nanometer length scales are limited. Here we chose a model organic-mineral system and performed complementary imaging techniques that enable direct nanoscale observations in environmentally relevant conditions: cryogenic TEM and in-situ liquid cellmore » TEM. We observed a three-fold increase in aggregate size of goethite nanoparticles upon addition of a model organic phosphate ligand and quantification of nanoparticle orientation reveals a preference for side-to-side interactions independent of the addition of an organic ligand. Additionally, in-situ liquid cell TEM experiments provides a dynamic view of the interactions allowing us to report velocities of mineral assemblages during aggregation and disaggregation, which could potentially provide binding energetics and kinetic parameters about organic-mineral and mineral-mineral systems.« less

Command Disaggregation Attack and Mitigation in Industrial Internet of Things

PubMed Central

Zhu, Pei-Dong; Hu, Yi-Fan; Cui, Peng-Shuai; Zhang, Yan

2017-01-01

A cyber-physical attack in the industrial Internet of Things can cause severe damage to physical system. In this paper, we focus on the command disaggregation attack, wherein attackers modify disaggregated commands by intruding command aggregators like programmable logic controllers, and then maliciously manipulate the physical process. It is necessary to investigate these attacks, analyze their impact on the physical process, and seek effective detection mechanisms. We depict two different types of command disaggregation attack modes: (1) the command sequence is disordered and (2) disaggregated sub-commands are allocated to wrong actuators. We describe three attack models to implement these modes with going undetected by existing detection methods. A novel and effective framework is provided to detect command disaggregation attacks. The framework utilizes the correlations among two-tier command sequences, including commands from the output of central controller and sub-commands from the input of actuators, to detect attacks before disruptions occur. We have designed components of the framework and explain how to mine and use these correlations to detect attacks. We present two case studies to validate different levels of impact from various attack models and the effectiveness of the detection framework. Finally, we discuss how to enhance the detection framework. PMID:29065461

Command Disaggregation Attack and Mitigation in Industrial Internet of Things.

PubMed

Xun, Peng; Zhu, Pei-Dong; Hu, Yi-Fan; Cui, Peng-Shuai; Zhang, Yan

2017-10-21

A cyber-physical attack in the industrial Internet of Things can cause severe damage to physical system. In this paper, we focus on the command disaggregation attack, wherein attackers modify disaggregated commands by intruding command aggregators like programmable logic controllers, and then maliciously manipulate the physical process. It is necessary to investigate these attacks, analyze their impact on the physical process, and seek effective detection mechanisms. We depict two different types of command disaggregation attack modes: (1) the command sequence is disordered and (2) disaggregated sub-commands are allocated to wrong actuators. We describe three attack models to implement these modes with going undetected by existing detection methods. A novel and effective framework is provided to detect command disaggregation attacks. The framework utilizes the correlations among two-tier command sequences, including commands from the output of central controller and sub-commands from the input of actuators, to detect attacks before disruptions occur. We have designed components of the framework and explain how to mine and use these correlations to detect attacks. We present two case studies to validate different levels of impact from various attack models and the effectiveness of the detection framework. Finally, we discuss how to enhance the detection framework.

Measurement of blood coagulation with considering RBC aggregation through a microchip-based light transmission aggregometer.

PubMed

Lim, Hyunjung; Nam, Jeonghun; Xue, Shubin; Shin, Sehyun

2011-01-01

Even though blood coagulation can be tested by various methods and techniques, the effect of RBC aggregation on blood coagulation is not fully understood. The present study monitored clot formation in a microchip-based light transmission aggregometer. Citrated blood samples with and without the addition of calcium ion solution were initially disaggregated by rotating a stirrer in the microchip. After abrupt stop of the rotating stirrer, the transmitted light intensity over time was recorded. The syllectogram (light intensity vs. time graph) manifested a rapid increase that is associated with RBC aggregation followed by a decrease that is associated with blood coagulation. The time to reach the peak point was used as a new index of coagulation time (CT) and ranged from 200 to 500 seconds in the present measurements. The CT was inversely proportional to the concentration of fibrinogen, which enhances RBC aggregation. In addition, the CT was inversely proportional to the hematocrit, which is similar to the case of the prothrombin time (PT), as measured by a commercial coagulometer. Thus, we carefully concluded that RBC aggregation should be considered in tests of blood coagulation.

Concurrent changes in aggregation and swelling of coal particles in solvents

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

Nishioka, M.

1995-12-31

A new method of coal swelling has been developed tinder the condition of low coal concentrations with continuous mixing of coal and solvent. The change in particle size distributions by a laser scattering procedure was used for the evaluation of coal swelling. Particle size distributions in good and poor solvents were nearly equal, but reversibly changed in good solvents from time to time. The effects of solubles and coal concentrations on the distributions were small. It was concluded that aggregate d coal particles disaggregate in good solvents, and that an increase in the particle size distribution due to swelling inmore » good solvents are compensated by a decrease in the particle size due to disaggregation. Therefore, the behavior of coal particles in solvents is controlled by aggregation in addition to coal swelling. This implies that an increase in the particle size due to coal swelling in actual processes is not so large as expected by the results obtained from the conventional coal swelling methods.« less

To Aggregate or Not and Potentially Better Questions for Clustered Data: The Need for Hierarchical Linear Modeling in CTE Research

ERIC Educational Resources Information Center

Nimon, Kim

2012-01-01

Using state achievement data that are openly accessible, this paper demonstrates the application of hierarchical linear modeling within the context of career technical education research. Three prominent approaches to analyzing clustered data (i.e., modeling aggregated data, modeling disaggregated data, modeling hierarchical data) are discussed…

Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.

PubMed

Ardah, Mustafa T; Paleologou, Katerina E; Lv, Guohua; Menon, Sindhu A; Abul Khair, Salema B; Lu, Jia-Hong; Safieh-Garabedian, Bared; Al-Hayani, Abdulmonem A; Eliezer, David; Li, Min; El-Agnaf, Omar M A

2015-02-01

Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel method for soil aggregate stability measurement by laser granulometry with sonication

NASA Astrophysics Data System (ADS)

Rawlins, B. G.; Lark, R. M.; Wragg, J.

2012-04-01

Regulatory authorities need to establish rapid, cost-effective methods to measure soil physical indicators - such as aggregate stability - which can be applied to large numbers of soil samples to detect changes of soil quality through monitoring. Limitations of sieve-based methods to measure the stability of soil macro-aggregates include: i) the mass of stable aggregates is measured, only for a few, discrete sieve/size fractions, ii) no account is taken of the fundamental particle size distribution of the sub-sampled material, and iii) they are labour intensive. These limitations could be overcome by measurements with a Laser Granulometer (LG) instrument, but this technology has not been widely applied to the quantification of aggregate stability of soils. We present a novel method to quantify macro-aggregate (1-2 mm) stability. We measure the difference between the mean weight diameter (MWD; μm) of aggregates that are stable in circulating water of low ionic strength, and the MWD of the fundamental particles of the soil to which these aggregates are reduced by sonication. The suspension is circulated rapidly through a LG analytical cell from a connected vessel for ten seconds; during this period hydrodynamic forces associated with the circulating water lead to the destruction of unstable aggregates. The MWD of stable aggregates is then measured by LG. In the next step, the aggregates - which are kept in the vessel at a minimal water circulation speed - are subject to sonication (18W for ten minutes) so the vast majority of the sample is broken down into its fundamental particles. The suspension is then recirculated rapidly through the LG and the MWD measured again. We refer to the difference between these two measurements as disaggregation reduction (DR) - the reduction in MWD on disaggregation by sonication. Soil types with more stable aggregates have larger values of DR. The stable aggregates - which are resistant to both slaking and mechanical breakdown by the hydrodynamic forces during circulation - are disrupted only by sonication. We used this method to compare macro-aggregate (1-2 mm) stability of air-dried agricultural topsoils under conventional tillage developed from two contrasting parent material types and compared the results with an alternative sieve-based technique. The first soil from the Midlands of England (developed from sedimentary mudstone; mean soil organic carbon (SOC) 2.5%) contained a substantially larger amount of illite/smectite (I/S) minerals compared to the second from the Wensum catchment in eastern England (developed from sands and glacial deposits; mean SOC=1.7%). The latter soils are prone to large erosive losses of fine sediment. Both sets of samples had been stored air-dried for 6 months prior to aggregate analyses. The mean values of DR (n=10 repeated subsample analyses) for the Midlands soil was 178μm; mean DR (n=10 repeat subsample analyses) for the Wensum soil was 30μm. The large difference in DR is most likely due to differences in soil mineralogy. The coefficient of variation of mean DR for duplicate analyses of sub-samples from the two topsoil types is around 10%. The majority of this variation is likely to be related to the difference in composition of the sub-samples. A standard, aggregated material could be included in further analyses to determine the relative magnitude of sub-sampling and analytical variance for this measurement technique. We then used the technique to investigate whether - as previously observed - variations (range 1000 - 4000 mg kg-1) in the quantity of amorphous (oxalate extractable) iron oxyhydroxides in a variety of soil samples (n=30) from the Wensum area (range SOC 1 - 2%) could account for differences in aggregate stability of these samples.

Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor.

PubMed

Lee, Jungsoon; Kim, Ji-Hyun; Biter, Amadeo B; Sielaff, Bernhard; Lee, Sukyeong; Tsai, Francis T F

2013-05-21

Heat shock protein (Hsp) 104 is a ring-forming, protein-remodeling machine that harnesses the energy of ATP binding and hydrolysis to drive protein disaggregation. Although Hsp104 is an active ATPase, the recovery of functional protein requires the species-specific cooperation of the Hsp70 system. However, like Hsp104, Hsp70 is an active ATPase, which recognizes aggregated and aggregation-prone proteins, making it difficult to differentiate the mechanistic roles of Hsp104 and Hsp70 during protein disaggregation. Mapping the Hsp70-binding sites in yeast Hsp104 using peptide array technology and photo-cross-linking revealed a striking conservation of the primary Hsp70-binding motifs on the Hsp104 middle-domain across species, despite lack of sequence identity. Remarkably, inserting a Strep-Tactin binding motif at the spatially conserved Hsp70-binding site elicits the Hsp104 protein disaggregating activity that now depends on Strep-Tactin but no longer requires Hsp70/40. Consistent with a Strep-Tactin-dependent activation step, we found that full-length Hsp70 on its own could activate the Hsp104 hexamer by promoting intersubunit coordination, suggesting that Hsp70 is an activator of the Hsp104 motor.

Light scattering method to measure red blood cell aggregation during incubation

NASA Astrophysics Data System (ADS)

Grzegorzewski, B.; Szołna-Chodór, A.; Baryła, J.; DreŻek, D.

2018-01-01

Red blood cell (RBC) aggregation can be observed both in vivo as well as in vitro. This process is a cause of alterations of blood flow in microvascular network. Enhanced RBC aggregation makes oxygen and nutrients delivery difficult. Measurements of RBC aggregation usually give a description of the process for a sample where the state of a solution and cells is well-defined and the system reached an equilibrium. Incubation of RBCs in various solutions is frequently used to study the effects of the solutions on the RBC aggregation. The aggregation parameters are compared before and after incubation while the detailed changes of the parameters during incubation remain unknown. In this paper we have proposed a method to measure red blood cell aggregation during incubation based on the well-known technique where backscattered light is used to assess the parameters of the RBC aggregation. Couette system consisting of two cylinders is adopted in the method. The incubation is observed in the Couette system. In the proposed method following sequence of rotations is adapted. Two minutes rotation is followed by two minutes stop. In this way we have obtained a time series of back scattered intensity consisting of signals respective for disaggregation and aggregation. It is shown that the temporal changes of the intensity manifest changes of RBC aggregation during incubation. To show the ability of the method to assess the effect of incubation time on RBC aggregation the results are shown for solutions that cause an increase of RBC aggregation as well as for the case where the aggregation is decreased.

Oxidized quercetin inhibits α-synuclein fibrillization.

PubMed

Zhu, Min; Han, Shubo; Fink, Anthony L

2013-04-01

α-Synucein is a small (14 kDa), abundant, intrinsically disordered presynaptic protein, whose aggregation is believed to be a critical step in Parkinson's disease (PD). Oxidative stress is reported to be a risk factor for dopamine cell degeneration in PD. Flavonoids are suggested to be important antioxidant against oxidative stress. Flavonoids were reported to inhibit fibrillization and disaggregate the preformed fibrils of α-synucein, but the molecular mechanism was still not clear. Quercetin, a well-recognized flavonoid antioxidant, was tested for its inhibition of α-synucein aggregation by thioflavin T assay, light scattering measurement, size-exclusion high performance liquid chromatography, atomic force microscopy, etc. The pre-incubated quercetin exhibited a noticeably stronger inhibition behavior to the fibril formation than that of the freshly prepared. The inhibition is significant in the presence of ortho- and para-benzenediol isomers and inconsiderable in the presence of meta-isomer. The oxidized quercetin species (i.e., chalcantrione, benzyfuranone, quercetinchinone, and other derivatives) cause stronger inhibition than quercetin does because of the elevated polarity and hydrophilicity. Presence of quercetin disaggregates α-synucein fibrils, rather than oligomers and amorphous aggregations. Instead of the antioxidant activity, the 1:1 covalent binding of quercetin with α-synucein, and the increased hydophilicity of the covalently modified α-synucein oligomers or monomers, account for the inhibition of α-synucein fibrillation. Clarification of the molecular mechanism of the inhibition and disaggregation may help to screen safer and more effective flavonoid therapeutic in combating PD. Copyright © 2012. Published by Elsevier B.V.

The UK-DALE dataset, domestic appliance-level electricity demand and whole-house demand from five UK homes.

PubMed

Kelly, Jack; Knottenbelt, William

2015-01-01

Many countries are rolling out smart electricity meters. These measure a home's total power demand. However, research into consumer behaviour suggests that consumers are best able to improve their energy efficiency when provided with itemised, appliance-by-appliance consumption information. Energy disaggregation is a computational technique for estimating appliance-by-appliance energy consumption from a whole-house meter signal. To conduct research on disaggregation algorithms, researchers require data describing not just the aggregate demand per building but also the 'ground truth' demand of individual appliances. In this context, we present UK-DALE: an open-access dataset from the UK recording Domestic Appliance-Level Electricity at a sample rate of 16 kHz for the whole-house and at 1/6 Hz for individual appliances. This is the first open access UK dataset at this temporal resolution. We recorded from five houses, one of which was recorded for 655 days, the longest duration we are aware of for any energy dataset at this sample rate. We also describe the low-cost, open-source, wireless system we built for collecting our dataset.

Inhibition of Alzheimer’s Amyloid Toxicity with a Tricyclic Pyrone Molecule In Vitro and In Vivo

PubMed Central

Hong, Hyun-Seok; Rana, Sandeep; Barrigan, Lydia; Shi, Aibin; Zhang, Yi; Zhou, Feimeng; Jin, Lee-Way; Hua, Duy H.

2009-01-01

Small amyloid β 1–42 aggregates are toxic to neurons and may be the primary toxic species in Alzheimer’s disease (AD). Methods to reduce the level of Aβ, prevent Aβ aggregation, and eliminate existing Aβ aggregates have been proposed for treatment of AD. A tricyclic pyrone named CP2 is found to prevent cell death associated with Aβ oligomers. We studied the possible mechanisms of neuroprotection by CP2. Surface plasmon resonance spectroscopy shows a direct binding of CP2 with Aβ42 oligomer. Circular dichroism spectroscopy reveals monomeric Aβ42 peptide remains as a random coil/α-helix structure in the presence of CP2 over 48 h. Atomic force microscopy (AFM) studies show CP2 exhibits similar ability to inhibit Aβ42 aggregation as that of Congo Red and curcumin. AFM closed-fluid cell study demonstrates that CP2 disaggregates Aβ42 oligomers and protofibrils. CP2 also blocks Aβ fibrillations using a protein quantification method. Treatment of 5x FAD mice, a robust Aβ42-producing animal model of AD, with a two-week course of CP2 resulted in 40% and 50% decreases in non-fibrillar and fibrillar Aβ species, respectively. Our results suggest that CP2 might be beneficial to AD patients by preventing Aβ aggregation and disaggregating existing Aβ oligomers and protofibrils. PMID:19141069

75 FR 74863 - Health Insurance Issuers Implementing Medical Loss Ratio (MLR) Requirements Under the Patient...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-01

... regarding that topic, rather than here. For example, ``aggregation'' is addressed in Sec. 158.120... would disaggregate products by type of coverage--for example, HMO, PPO, and high-deductible coverage...

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.

Using Maximum Likelihood Statistical Methods and Pigment Flux Data to Constrain Particle Exchange and Organic Matter Remineralization Rate Constants in the Mediterranean Sea

NASA Astrophysics Data System (ADS)

Wang, W.; Lee, C.; Cochran, K. K.; Armstrong, R. A.

2016-02-01

Sinking particles play a pivotal role transferring material from the surface to the deeper ocean via the "biological pump". To quantify the extent to which these particles aggregate and disaggregate, and thus affect particle settling velocity, we constructed a box model to describe organic matter cycling. The box model was fit to chloropigment data sampled in the 2005 MedFlux project using Indented Rotating Sphere sediment traps operating in Settling Velocity (SV) mode. Because of the very different pigment compositions of phytoplankton and fecal pellets, chloropigments are useful as proxies to record particle exchange. The maximum likelihood statistical method was used to estimate particle aggregation, disaggregation, and organic matter remineralization rate constants. Eleven settling velocity categories collected by SV sediment traps were grouped into two sinking velocity classes (fast- and slow-sinking) to decrease the number of parameters that needed to be estimated. Organic matter degradation rate constants were estimated to be 1.2, 1.6, and 1.1 y^-1, which are equivalent to degradation half-lives of 0.60, 0.45, and 0.62 y^-1, at 313, 524, and 1918 m, respectively. Rate constants of chlorophyll a degradation to pheopigments (pheophorbide, pheophytin, and pyropheophorbide) were estimated to be 0.88, 0.93, and 1.2 y^-1, at 313, 524, and 1918 m, respectively. Aggregation rate constants varied little with depth, with the highest value being 0.07 y^-1 at 524 m. Disaggregation rate constants were highest at 524 m (14 y^-1) and lowest at 1918 m (9.6 y^-1)

Agent Based Simulation Design for Aggregation and Disaggregation

DTIC Science & Technology

2011-12-01

of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB... PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18...theo- retical analysis) finding conditions under which aggregation equations might be reasonably valid (requires theo- retical analysis

Mapping disease at an approximated individual level using aggregate data: a case study of mapping New Hampshire birth defects.

PubMed

Shi, Xun; Miller, Stephanie; Mwenda, Kevin; Onda, Akikazu; Reese, Judy; Onega, Tracy; Gui, Jiang; Karagas, Margret; Demidenko, Eugene; Moeschler, John

2013-09-06

Limited by data availability, most disease maps in the literature are for relatively large and subjectively-defined areal units, which are subject to problems associated with polygon maps. High resolution maps based on objective spatial units are needed to more precisely detect associations between disease and environmental factors. We propose to use a Restricted and Controlled Monte Carlo (RCMC) process to disaggregate polygon-level location data to achieve mapping aggregate data at an approximated individual level. RCMC assigns a random point location to a polygon-level location, in which the randomization is restricted by the polygon and controlled by the background (e.g., population at risk). RCMC allows analytical processes designed for individual data to be applied, and generates high-resolution raster maps. We applied RCMC to the town-level birth defect data for New Hampshire and generated raster maps at the resolution of 100 m. Besides the map of significance of birth defect risk represented by p-value, the output also includes a map of spatial uncertainty and a map of hot spots. RCMC is an effective method to disaggregate aggregate data. An RCMC-based disease mapping maximizes the use of available spatial information, and explicitly estimates the spatial uncertainty resulting from aggregation.

Epigallocatechin-3-gallate (EGCG)-stabilized selenium nanoparticles coated with Tet-1 peptide to reduce amyloid-β aggregation and cytotoxicity.

PubMed

Zhang, Jingnan; Zhou, Xianbo; Yu, Qianqian; Yang, Licong; Sun, Dongdong; Zhou, Yanhui; Liu, Jie

2014-06-11

Alzheimer's disease (AD), the most common neurodegenerative disease, is caused by an accumulation of amyloid-β (Aβ) plaque deposits in the brains. Evidence is increasingly showing that epigallocatechin-3-gallate (EGCG) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. In order to better understand the process of Aβ aggregation and amyloid fibril disaggregation and reduce the cytotoxicity of EGCG at high doses, we attached EGCG onto the surface of selenium nanoparticles (EGCG@Se). Given the low delivery efficiency of EGCG@Se to the targeted cells and the involvement of selenoprotein in antioxidation and neuroprotection, which are the key factors for preventing the onset and progression of AD, we synthesized EGCG-stabilized selenium nanoparticles coated with Tet-1 peptide (Tet-1-EGCG@Se, a synthetic selenoprotein analogue), considering the affinity of Tet-1 peptide to neurons. We revealed that Tet-1-EGCG@Se can effectively inhibit Aβ fibrillation and disaggregate preformed Aβ fibrils into nontoxic aggregates. In addition, we found that both EGCG@Se and Tet-1-EGCG@Se can label Aβ fibrils with a high affinity, and Tet-1 peptides can significantly enhance the cellular uptake of Tet-1-EGCG@Se in PC12 cells rather than in NIH/3T3 cells.

The aggregated unfitted finite element method for elliptic problems

NASA Astrophysics Data System (ADS)

Badia, Santiago; Verdugo, Francesc; Martín, Alberto F.

2018-07-01

Unfitted finite element techniques are valuable tools in different applications where the generation of body-fitted meshes is difficult. However, these techniques are prone to severe ill conditioning problems that obstruct the efficient use of iterative Krylov methods and, in consequence, hinders the practical usage of unfitted methods for realistic large scale applications. In this work, we present a technique that addresses such conditioning problems by constructing enhanced finite element spaces based on a cell aggregation technique. The presented method, called aggregated unfitted finite element method, is easy to implement, and can be used, in contrast to previous works, in Galerkin approximations of coercive problems with conforming Lagrangian finite element spaces. The mathematical analysis of the new method states that the condition number of the resulting linear system matrix scales as in standard finite elements for body-fitted meshes, without being affected by small cut cells, and that the method leads to the optimal finite element convergence order. These theoretical results are confirmed with 2D and 3D numerical experiments.

Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

PubMed

Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

2017-08-01

Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.

A methodology for finding the optimal iteration number of the SIRT algorithm for quantitative Electron Tomography.

PubMed

Okariz, Ana; Guraya, Teresa; Iturrondobeitia, Maider; Ibarretxe, Julen

2017-02-01

The SIRT (Simultaneous Iterative Reconstruction Technique) algorithm is commonly used in Electron Tomography to calculate the original volume of the sample from noisy images, but the results provided by this iterative procedure are strongly dependent on the specific implementation of the algorithm, as well as on the number of iterations employed for the reconstruction. In this work, a methodology for selecting the iteration number of the SIRT reconstruction that provides the most accurate segmentation is proposed. The methodology is based on the statistical analysis of the intensity profiles at the edge of the objects in the reconstructed volume. A phantom which resembles a a carbon black aggregate has been created to validate the methodology and the SIRT implementations of two free software packages (TOMOJ and TOMO3D) have been used. Copyright © 2016 Elsevier B.V. All rights reserved.

An economic analysis of disaggregation of space assets: Application to GPS

NASA Astrophysics Data System (ADS)

Hastings, Daniel E.; La Tour, Paul A.

2017-05-01

New ideas, technologies and architectural concepts are emerging with the potential to reshape the space enterprise. One of those new architectural concepts is the idea that rather than aggregating payloads onto large very high performance buses, space architectures should be disaggregated with smaller numbers of payloads (as small as one) per bus and the space capabilities spread across a correspondingly larger number of systems. The primary rationale is increased survivability and resilience. The concept of disaggregation is examined from an acquisition cost perspective. A mixed system dynamics and trade space exploration model is developed to look at long-term trends in the space acquisition business. The model is used to examine the question of how different disaggregated GPS architectures compare in cost to the well-known current GPS architecture. A generation-over-generation examination of policy choices is made possible through the application of soft systems modeling of experience and learning effects. The assumptions that are allowed to vary are: design lives, production quantities, non-recurring engineering and time between generations. The model shows that there is always a premium in the first generation to be paid to disaggregate the GPS payloads. However, it is possible to construct survivable architectures where the premium after two generations is relatively low.

Physical Properties of Human Whole Salivary Mucin:A Dynamic Light Scattering Study

NASA Astrophysics Data System (ADS)

Mahajan, Manish; Kumar, Vijay; Saraswat, Mayank; Yadav, Savita; Shukla, N. K.; Singh, T. P.

2008-04-01

Human salivary mucin, a primary mucous membrane coating glycoprotein forms the first line of defense against adverse environments, attributed to the complex formation between mucin subunits and non mucin species. Aim of the study was to emphasize the effect of pH, denaturants (guanidinum hydrochloride, urea) and detergents (CHAPS, TRITON X -100, SDS on human whole salivary mucin. Hydrodynamic size distribution was measured using DLS. It was observed that aggregation was due to increase in hydrophobic interactions, believed to be accomplished by unfolding of the protein core. Whereas, the detergents which solubilize the proteins by decreasing hydrophobicity lead to disaggregation of mucin into smaller fragments. Mucin subjected to tobacco extract and upon subsequent addition of nicotine was found to have a disaggregating effect on it, suggesting nicotine may be one of the factors responsible for the disaggregating effect of tobacco on mucin, an important carcinogenetic mechanism.

Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro.

PubMed

Rane, Jitendra Subhash; Bhaumik, Prasenjit; Panda, Dulal

2017-01-01

The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.

The UK-DALE dataset, domestic appliance-level electricity demand and whole-house demand from five UK homes

PubMed Central

Kelly, Jack; Knottenbelt, William

2015-01-01

Many countries are rolling out smart electricity meters. These measure a home’s total power demand. However, research into consumer behaviour suggests that consumers are best able to improve their energy efficiency when provided with itemised, appliance-by-appliance consumption information. Energy disaggregation is a computational technique for estimating appliance-by-appliance energy consumption from a whole-house meter signal. To conduct research on disaggregation algorithms, researchers require data describing not just the aggregate demand per building but also the ‘ground truth’ demand of individual appliances. In this context, we present UK-DALE: an open-access dataset from the UK recording Domestic Appliance-Level Electricity at a sample rate of 16 kHz for the whole-house and at 1/6 Hz for individual appliances. This is the first open access UK dataset at this temporal resolution. We recorded from five houses, one of which was recorded for 655 days, the longest duration we are aware of for any energy dataset at this sample rate. We also describe the low-cost, open-source, wireless system we built for collecting our dataset. PMID:25984347

The UK-DALE dataset, domestic appliance-level electricity demand and whole-house demand from five UK homes

NASA Astrophysics Data System (ADS)

Kelly, Jack; Knottenbelt, William

2015-03-01

Many countries are rolling out smart electricity meters. These measure a home’s total power demand. However, research into consumer behaviour suggests that consumers are best able to improve their energy efficiency when provided with itemised, appliance-by-appliance consumption information. Energy disaggregation is a computational technique for estimating appliance-by-appliance energy consumption from a whole-house meter signal. To conduct research on disaggregation algorithms, researchers require data describing not just the aggregate demand per building but also the ‘ground truth’ demand of individual appliances. In this context, we present UK-DALE: an open-access dataset from the UK recording Domestic Appliance-Level Electricity at a sample rate of 16 kHz for the whole-house and at 1/6 Hz for individual appliances. This is the first open access UK dataset at this temporal resolution. We recorded from five houses, one of which was recorded for 655 days, the longest duration we are aware of for any energy dataset at this sample rate. We also describe the low-cost, open-source, wireless system we built for collecting our dataset.

A portable microfluidic system for rapid measurement of the erythrocyte sedimentation rate.

PubMed

Isiksacan, Ziya; Erel, Ozcan; Elbuken, Caglar

2016-11-29

The erythrocyte sedimentation rate (ESR) is a frequently used 30 min or 60 min clinical test for screening of several inflammatory conditions, infections, trauma, and malignant diseases, as well as non-inflammatory conditions including prostate cancer and stroke. Erythrocyte aggregation (EA) is a physiological process where erythrocytes form face-to-face linear structures, called rouleaux, at stasis or low shear rates. In this work, we proposed a method for ESR measurement from EA. We developed a microfluidic opto-electro-mechanical system, using which we experimentally showed a significant correlation (R 2 = 0.86) between ESR and EA. The microfluidic system was shown to measure ESR from EA using fingerprick blood in 2 min. 40 μl of whole blood is filled in a disposable polycarbonate cartridge which is illuminated with a near infrared emitting diode. Erythrocytes were disaggregated under the effect of a mechanical shear force using a solenoid pinch valve. Following complete disaggregation, transmitted light through the cartridge was measured using a photodetector for 1.5 min. The intensity level is at its lowest at complete disaggregation and highest at complete aggregation. We calculated ESR from the transmitted signal profile. We also developed another microfluidic cartridge specifically for monitoring the EA process in real-time during ESR measurement. The presented system is suitable for ultrafast, low-cost, and low-sample volume measurement of ESR at the point-of-care.

The Challenge of City-Level Data-Gathering for Implementing SDG 11 in Africa

NASA Astrophysics Data System (ADS)

Elias, P. O.

2017-12-01

Implementing sustainable development goal 11 in Africa which includes measuring and monitoring social and economic welfare indicators at the city-level requires data of the best quality. In recent years, there have been progress in national statistics and censuses survey yet data gathering in many African countries are not accurate, timely, disaggregated and widely usable. This often diminish the capability of governments to tackle urban development challenges, which are particularly exacerbated by inequality, poverty and uncontrolled development especially in cities. To support knowledge driven decisions and policies there is need to improve data-gathering systems about health, education, and safety, economy and poverty, land, housing and environment, trade and commerce, population and demography. Also, the underlying dynamics, processes, distributions, patterns, trends or disparities inherent in African cities require the breaking down of aggregated data into their component parts or smaller units, which underscores urban data revolution towards achieving SDG 11. In Africa, the process of bringing together diverse data communities to embrace a diverse range of data sources, tools, and innovative technologies, to provide disaggregated data for decision-making, service delivery and citizen engagement is still emerging. Several factors are inhibiting urban data revolution and need to be overturned before we can provide more evidence, more data and more certainty for decision makers towards achieving urban development targets and sustainable cities for Africa. The paper examines the challenge of city-level data-gathering for implementing SDG 11 in Africa. Specifically, it examines the role of cities in implementing SDG 11 in Africa and the need to disaggregate data at city-level; it assesses existing data sources, compilation and dissemination channels as well as the challenges of deploying innovative techniques and strategies including digital and social media platforms and concludes with suggesting sustainable options for evolving cutting-edge strategies for integrating diverse data communities for responsible city-level data-gathering that is reliable, timely, disaggregated and widely usable.

A discrete three-layer stack aggregate of a linear porphyrin tetramer: solution-phase structure elucidation by NMR and X-ray scattering.

PubMed

Hutin, Marie; Sprafke, Johannes K; Odell, Barbara; Anderson, Harry L; Claridge, Tim D W

2013-08-28

Formation of stacked aggregates can dramatically alter the properties of aromatic π-systems, yet the solution-phase structure elucidation of these aggregates is often impossible because broad distributions of species are formed, giving uninformative spectroscopic data. Here, we show that a butadiyne-linked zinc porphyrin tetramer forms a remarkably well-defined aggregate, consisting of exactly three molecules, in a parallel stacked arrangement (in chloroform at room temperature; concentration 1 mM-0.1 μM). The aggregate has a mass of 14.7 kDa. Unlike most previously reported aggregates, it gives sharp NMR resonances and aggregation is in slow exchange on the NMR time scale. The structure was elucidated using a range of NMR techniques, including diffusion-editing, (1)H-(29)Si HMBC, (1)H-(1)H COSY, TOCSY and NOESY, and (1)H-(13)C edited HSQC spectroscopy. Surprisingly, the (1)H-(1)H COSY spectrum revealed many long-range residual dipolar couplings (RDCs), and detailed analysis of magnetic field-induced (1)H-(13)C RDCs provided further evidence for the structural model. The size and shape of the aggregate is supported by small-angle X-ray scattering (SAXS) data. It adopts a geometry that maximizes van der Waals contact between the porphyrins, while avoiding clashes between side chains. The need for interdigitation of the side chains prevents formation of stacks consisting of more than three layers. Although a detailed analysis has only been carried out for one compound (the tetramer), comparison with the NMR spectra of other oligomers indicates that they form similar three-layer stacks. In all cases, aggregation can be prevented by addition of pyridine, although at low pyridine concentrations, disaggregation takes many hours to reach equilibrium.

Exploring how organic matter controls structural transformations in natural aquatic nanocolloidal dispersions.

PubMed

King, Stephen M; Jarvie, Helen P

2012-07-03

The response of the dispersion nanostructure of surface river bed sediment to the controlled removal and readdition of natural organic matter (NOM), in the absence and presence of background electrolyte, was examined using the technique of small-angle neutron scattering (SANS). Partial NOM removal induced aggregation of the mineral particles, but more extensive NOM removal restored colloidal stability. When peat humic acid (PHA) was added to a NOM-deficient sediment concentration-related structural transformations were observed: at 255 mg/L PHA aggregation of the nanocolloid was actually enhanced, but at 380 mg/L PHA disaggregation and colloidal stability were promoted. The addition of 2 mM CaCl(2) induced mild aggregation in the native sediment but not in sediments with added PHA, suggesting that the native NOM and the PHA respond differently to changes in ionic strength. A first attempt at using SANS to directly characterize the thickness and coverage of an adsorbed PHA layer in a natural nanocolloid is also presented. The results are discussed in the context of a hierarchical aquatic colloidal nanostructure, and the implications for contemporary studies of the role of dissolved organic carbon (DOC) in sustaining the transport of colloidal iron in upland catchments.

Spatial and temporal disaggregation of transport-related carbon dioxide emissions in Bogota - Colombia

NASA Astrophysics Data System (ADS)

Hernandez-Gonzalez, L. A.; Jimenez Pizarro, R.; Néstor Y. Rojas, N. Y.

2011-12-01

As a result of rapid urbanization during the last 60 years, 75% of the Colombian population now lives in cities. Urban areas are net sources of greenhouse gases (GHG) and contribute significantly to national GHG emission inventories. The development of scientifically-sound GHG mitigation strategies require accurate GHG source and sink estimations. Disaggregated inventories are effective mitigation decision-making tools. The disaggregation process renders detailed information on the distribution of emissions by transport mode, and the resulting a priori emissions map allows for optimal definition of sites for GHG flux monitoring, either by eddy covariance or inverse modeling techniques. Fossil fuel use in transportation is a major source of carbon dioxide (CO2) in Bogota. We present estimates of CO2 emissions from road traffic in Bogota using the Intergovernmental Panel on Climate Change (IPCC) reference method, and a spatial and temporal disaggregation method. Aggregated CO2 emissions from mobile sources were estimated from monthly and annual fossil fuel (gasoline, diesel and compressed natural gas - CNG) consumption statistics, and estimations of bio-ethanol and bio-diesel use. Although bio-fuel CO2 emissions are considered balanced over annual (or multi-annual) agricultural cycles, we included them since CO2 generated by their combustion would be measurable by a net flux monitoring system. For the disaggregation methodology, we used information on Bogota's road network classification, mean travel speed and trip length for each vehicle category and road type. The CO2 emission factors were taken from recent in-road measurements for gasoline- and CNG-powered vehicles and also estimated from COPERT IV. We estimated emission factors for diesel from surveys on average trip length and fuel consumption. Using IPCC's reference method, we estimate Bogota's total transport-related CO2 emissions for 2008 (reference year) at 4.8 Tg CO2. The disaggregation method estimation is 16% lower, mainly due to uncertainty in activity factors. With only 4% of Bogota's fleet, diesel use accounts for 42% of the CO2 emissions. The emissions are almost evenly shared between public (9% of the fleet) and private transport. Peak emissions occur at 8 a.m. and 6 p.m. with maximum values over a densely industrialized area at the northwest of Bogota. This investigation allowed estimating the relative contribution of fuel and vehicle categories to spatially- and temporally-resolved CO2 emissions. Fuel consumption time series indicate a near-stabilization trend on energy consumption for transportation, which is unexpected taking into account the sustained economic and vehicle fleet growth in Bogota. The comparison of the disaggregation methodology with the IPCC methodology contributes to the analysis of possible error sources on activity factor estimations. This information is very useful for uncertainty estimation and adjustment of primary air pollutant emissions inventories.

Manpower Planning: A Research Bibliography and Supplement. Bulletin 45 and Supplement I.

ERIC Educational Resources Information Center

Keaveny, Timothy J.; Herman, Georgianna

This bibliography is composed of 260 citations ranging in date from 1942 to 1967, but emphasizing the 1960 to 1967 period. Listings are arranged alphabetically according to author under the general divisions of Introduction to Manpower Planning, Aggregate Manpower Planning, Disaggregate Manpower Planning, Foreign Manpower Planning, Manpower…

Essays on Technology and Forecasting in Macroeconomics

ERIC Educational Resources Information Center

Samuels, Jon Devin

2012-01-01

The three chapters in this dissertation use disaggregated models and data to provide new insights on well-established questions in macroeconomics. In the first chapter, to analyze how productivity impacts the business cycle, I model aggregate production with a production possibility frontier that accommodates sector-and factor-biased productivity.…

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

Li, Rong; Wu, Yongquan, E-mail: yqwu@shu.edu.cn; Xiao, Junjiang

We observed homogeneous nucleation process of supercooled liquid Fe by molecular dynamics simulations. Using bond-orientational order parameters together with Voronoi polyhedron method, we characterized local structure, calculated the volume of Voronoi polyhedra of atoms and identified the structure and density fluctuations. We monitored the formation of nucleus and analyzed its inner structure. The birth and growth of the pre-nucleus and nucleus are accompanied with aggregating and disaggregating processes in the time scale of femtosecond. Only the initial solid-like clusters (ISLC), ranging from 1 to 7 atoms, pop up directly from liquid. The relation between the logarithm of number of clustersmore » and the cluster size was found to be linear for ISLCs and was observed to be parabolic for all solid-like clusters (SLC) due to aggregating and disaggregating effects. The nucleus and pre-nuclei mainly consist of body centered cubic (BCC) and hexagonal close packed atoms, while the BCC atoms tend to be located at the surface. Medium-range structure fluctuations induce the birth of ISLCs, benefit the aggregation of embryos and remarkably promote the nucleation. But density fluctuations contribute little to nucleation. The lifetime of most icosahedral-like atoms (ICO) is shorter than 0.7 ps. No obvious relationship was found between structure/density fluctuations and the appearance of ICO atoms.« less

Advertising media and cigarette demand.

PubMed

Goel, Rajeev K

2011-01-01

Using state-level panel data for the USA spanning three decades, this research estimates the demand for cigarettes. The main contribution lies in studying the effects of cigarette advertising disaggregated across five qualitatively different groups. Results show cigarette demand to be near unit elastic, the income effects to be generally insignificant and border price effects and habit effects to be significant. Regarding advertising effects, aggregate cigarette advertising has a negative effect on smoking. Important differences across advertising media emerge when cigarette advertising is disaggregated. The effects of public entertainment and Internet cigarette advertising are stronger than those of other media. Anti-smoking messages accompanying print cigarette advertising seem relatively more effective. Implications for smoking control policy are discussed.

TiO2 nanoparticles aggregation and disaggregation in presence of alginate and Suwannee River humic acids. pH and concentration effects on nanoparticle stability.

PubMed

Loosli, Frédéric; Le Coustumer, Philippe; Stoll, Serge

2013-10-15

The behavior of manufactured TiO2 nanoparticles is studied in a systematic way in presence of alginate and Suwannee River humic acids at variable concentrations. TiO2 nanoparticles aggregation, disaggregation and stabilization are investigated using dynamic light scattering and electrophoretic experiments allowing the measurement of z-average hydrodynamic diameters and zeta potential values. Stability of the TiO2 nanoparticles is discussed by considering three pH-dependent electrostatic scenarios. In the first scenario, when pH is below the TiO2 nanoparticle point of zero charge, nanoparticles exhibit a positively charged surface whereas alginate and Suwannee River humic acids are negatively charged. Fast adsorption at the TiO2 nanoparticles occurs, promotes surface charge neutralization and aggregation. By increasing further alginate and Suwannee River humic acids concentrations charge inversion and stabilization of TiO2 nanoparticles are obtained. In the second electrostatic scenario, at the surface charge neutralization pH, TiO2 nanoparticles are rapidly forming aggregates. Adsorption of alginate and Suwannee River humic acids on aggregates leads to their partial fragmentation. In the third electrostatic scenario, when nanoparticles, alginate and Suwannee River humic acids are negatively charged, only a small amount of Suwannee River humic acids is adsorbed on TiO2 nanoparticles surface. It is found that the fate and behavior of individual and aggregated TiO2 nanoparticles in presence of environmental compounds are mainly driven by the complex interplay between electrostatic attractive and repulsive interactions, steric and van der Waals interactions, as well as concentration ratio. Results also suggest that environmental aquatic concentration ranges of humic acids and biopolymers largely modify the stability of aggregated or dispersed TiO2 nanoparticles. Copyright © 2013 Elsevier Ltd. All rights reserved.

From Sub-basin to Grid Scale Soil Moisture Disaggregation in SMART, A Semi-distributed Hydrologic Modeling Framework

NASA Astrophysics Data System (ADS)

Ajami, H.; Sharma, A.

2016-12-01

A computationally efficient, semi-distributed hydrologic modeling framework is developed to simulate water balance at a catchment scale. The Soil Moisture and Runoff simulation Toolkit (SMART) is based upon the delineation of contiguous and topologically connected Hydrologic Response Units (HRUs). In SMART, HRUs are delineated using thresholds obtained from topographic and geomorphic analysis of a catchment, and simulation elements are distributed cross sections or equivalent cross sections (ECS) delineated in first order sub-basins. ECSs are formulated by aggregating topographic and physiographic properties of the part or entire first order sub-basins to further reduce computational time in SMART. Previous investigations using SMART have shown that temporal dynamics of soil moisture are well captured at a HRU level using the ECS delineation approach. However, spatial variability of soil moisture within a given HRU is ignored. Here, we examined a number of disaggregation schemes for soil moisture distribution in each HRU. The disaggregation schemes are either based on topographic based indices or a covariance matrix obtained from distributed soil moisture simulations. To assess the performance of the disaggregation schemes, soil moisture simulations from an integrated land surface-groundwater model, ParFlow.CLM in Baldry sub-catchment, Australia are used. ParFlow is a variably saturated sub-surface flow model that is coupled to the Common Land Model (CLM). Our results illustrate that the statistical disaggregation scheme performs better than the methods based on topographic data in approximating soil moisture distribution at a 60m scale. Moreover, the statistical disaggregation scheme maintains temporal correlation of simulated daily soil moisture while preserves the mean sub-basin soil moisture. Future work is focused on assessing the performance of this scheme in catchments with various topographic and climate settings.

Trehalose and Magnesium Chloride Exert a Common Anti-amyloidogenic Effect Towards Hen Egg White Lysozyme.

PubMed

Chatterjee, Rupsa; Kolli, Vidyalatha; Sarkar, Nandini

2017-04-01

Many degenerative disorder such as Parkinsons, Alzheimers, Huntingtons disease, etc are caused due to the deposition of amyloid fibrils, formed due to the ordered aggregation of misfolded/unfolded proteins. Misfolded or unfolded proteins aggregate mostly through hydrophobic interactions which are unexposed in native state, but become exposed upon unfolding. To counteract amyloid related diseases, inhibition of the protein self assembly into fibril is a potential therapeutic strategy. The study aims at investigating the effect of selected compounds, namely trehalose and magnesium chloride hexahydrate towards inhibition and disaggregation of amyloid fibrils using Hen Egg White Lysozyme as a model. We further attempted to understand the mechanism of action with the help of various biophysical, microscopic as well as computational studies. A common mechanism of action was identified where the selected compounds exert their anti-amyloidogenic effects by altering HEWL conformations characterized by reduction in the beta sheet content and decrease in exposed hydrophobic surfaces. The altered conformation seems to have lesser amyloidogenic propensity leading to inhibition as well as disaggregation of amyloids.

Origin destination disaggregation using fratar biproportional least squares estimation for truck forecasting.

DOT National Transportation Integrated Search

2009-02-01

This working paper describes a group of techniques for disaggregating origin-destination tables : for truck forecasting that makes explicit use of observed traffic on a network. Six models within : the group are presented, each of which uses nonlinea...

Disaggregation and Refinement of System Dynamics Models via Agent-based Modeling

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

Nutaro, James J; Ozmen, Ozgur; Schryver, Jack C

System dynamics models are usually used to investigate aggregate level behavior, but these models can be decomposed into agents that have more realistic individual behaviors. Here we develop a simple model of the STEM workforce to illuminate the impacts that arise from the disaggregation and refinement of system dynamics models via agent-based modeling. Particularly, alteration of Poisson assumptions, adding heterogeneity to decision-making processes of agents, and discrete-time formulation are investigated and their impacts are illustrated. The goal is to demonstrate both the promise and danger of agent-based modeling in the context of a relatively simple model and to delineate themore » importance of modeling decisions that are often overlooked.« less

Dynamic bioprocessing and microfluidic transport control with smart magnetic nanoparticles in laminar-flow devices

PubMed Central

Lai, James J.; Nelson, Kjell; Nash, Michael A.; Hoffman, Allan S.; Yager, Paul; Stayton, Patrick S.

2010-01-01

In the absence of applied forces, the transport of molecules and particulate reagents across laminar flowstreams in microfluidic devices is dominated by the diffusivities of the transported species. While the differential diffusional properties between smaller and larger diagnostic targets and reagents have been exploited for bioseparation and assay applications, there are limitations to methods that depend on these intrinsic size differences. Here a new strategy is described for exploiting the sharply reversible change in size and magnetophoretic mobility of “smart” magnetic nanoparticles (mNPs) to perform bioseparation and target isolation under continuous flow processing conditions. The isolated 5 nm mNPs do not exhibit significant magnetophoretic velocities, but do exhibit high magnetophoretic velocities when aggregated by the action of a pH-responsive polymer coating. A simple external magnet is used to magnetophorese the aggregated mNPs that have captured a diagnostic target from a lower pH laminar flowstream (pH 7.3) to a second higher pH flowstream (pH 8.4) that induces rapid mNP dis-aggregation. In this second disaggregated state and flowstream, the mNPs continue to flow past the magnet rather than being immobilized at the channel surface near the magnet. This stimuli-responsive reagent system has been shown to transfer 81% of a model protein target from an input flowstream to a second flowstream in a continuous flow H-filter device. PMID:19568666

Dynamic bioprocessing and microfluidic transport control with smart magnetic nanoparticles in laminar-flow devices.

PubMed

Lai, James J; Nelson, Kjell E; Nash, Michael A; Hoffman, Allan S; Yager, Paul; Stayton, Patrick S

2009-07-21

In the absence of applied forces, the transport of molecules and particulate reagents across laminar flowstreams in microfluidic devices is dominated by the diffusivities of the transported species. While the differential diffusional properties between smaller and larger diagnostic targets and reagents have been exploited for bioseparation and assay applications, there are limitations to methods that depend on these intrinsic size differences. Here a new strategy is described for exploiting the sharply reversible change in size and magnetophoretic mobility of "smart" magnetic nanoparticles (mNPs) to perform bioseparation and target isolation under continuous flow processing conditions. The isolated 5 nm mNPs do not exhibit significant magnetophoretic velocities, but do exhibit high magnetophoretic velocities when aggregated by the action of a pH-responsive polymer coating. A simple external magnet is used to magnetophorese the aggregated mNPs that have captured a diagnostic target from a lower pH laminar flowstream (pH 7.3) to a second higher pH flowstream (pH 8.4) that induces rapid mNP disaggregation. In this second dis-aggregated state and flowstream, the mNPs continue to flow past the magnet rather than being immobilized at the channel surface near the magnet. This stimuli-responsive reagent system has been shown to transfer 81% of a model protein target from an input flowstream to a second flowstream in a continuous flow H-filter device.

Iterative direct inversion: An exact complementary solution for inverting fault-slip data to obtain palaeostresses

NASA Astrophysics Data System (ADS)

Mostafa, Mostafa E.

2005-10-01

The present study shows that reconstructing the reduced stress tensor (RST) from the measurable fault-slip data (FSD) and the immeasurable shear stress magnitudes (SSM) is a typical iteration problem. The result of direct inversion of FSD presented by Angelier [1990. Geophysical Journal International 103, 363-376] is considered as a starting point (zero step iteration) where all SSM are assigned constant value ( λ=√{3}/2). By iteration, the SSM and RST update each other until they converge to fixed values. Angelier [1990. Geophysical Journal International 103, 363-376] designed the function upsilon ( υ) and the two estimators: relative upsilon (RUP) and (ANG) to express the divergence between the measured and calculated shear stresses. Plotting individual faults' RUP at successive iteration steps shows that they tend to zero (simulated data) or to fixed values (real data) at a rate depending on the orientation and homogeneity of the data. FSD of related origin tend to aggregate in clusters. Plots of the estimators ANG versus RUP show that by iteration, labeled data points are disposed in clusters about a straight line. These two new plots form the basis of a technique for separating FSD into homogeneous clusters.

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.

26 CFR 1.410(b)-7 - Definition of plan and rules governing plan disaggregation and aggregation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... year. (e) Determination of plans in testing group for average benefit percentage test—(1) In general... qualifiedseparatelineofbu5ine55 basis. The plans in the testing group used to determine whether Plan F satisfies the average..., DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock...

26 CFR 1.410(b)-7 - Definition of plan and rules governing plan disaggregation and aggregation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... same plan year. (e) Determination of plans in testing group for average benefit percentage test—(1) In... qualifiedseparatelineofbu5ine55 basis. The plans in the testing group used to determine whether Plan F satisfies the average..., DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit...

An Alternative Approach to the Operation of Multinational Reservoir Systems: Application to the Amistad & Falcon System (Lower Rio Grande/Rí-o Bravo)

NASA Astrophysics Data System (ADS)

Serrat-Capdevila, A.; Valdes, J. B.

2005-12-01

An optimization approach for the operation of international multi-reservoir systems is presented. The approach uses Stochastic Dynamic Programming (SDP) algorithms, both steady-state and real-time, to develop two models. In the first model, the reservoirs and flows of the system are aggregated to yield an equivalent reservoir, and the obtained operating policies are disaggregated using a non-linear optimization procedure for each reservoir and for each nation water balance. In the second model a multi-reservoir approach is applied, disaggregating the releases for each country water share in each reservoir. The non-linear disaggregation algorithm uses SDP-derived operating policies as boundary conditions for a local time-step optimization. Finally, the performance of the different approaches and methods is compared. These models are applied to the Amistad-Falcon International Reservoir System as part of a binational dynamic modeling effort to develop a decision support system tool for a better management of the water resources in the Lower Rio Grande Basin, currently enduring a severe drought.

Photoisomerisation and light-induced morphological switching of a polyoxometalate-azobenzene hybrid.

PubMed

Markiewicz, Grzegorz; Pakulski, Dawid; Galanti, Agostino; Patroniak, Violetta; Ciesielski, Artur; Stefankiewicz, Artur R; Samorì, Paolo

2017-06-29

The functionalization of a spherical Keplerate-type polyoxometalate {Mo 72 V 30 } with a cationic azobenzene surfactant has been achieved through ionic self-assembly. The photoisomerisation reaction of this complex, which emerges in a light-triggered aggregation-disaggregation process, has been followed by 1 H NMR spectroscopy, dynamic light scattering, absorption spectroscopy and scanning electron microscopy analyses.

A pretreatment method for grain size analysis of red mudstones

NASA Astrophysics Data System (ADS)

Jiang, Zaixing; Liu, Li'an

2011-11-01

Traditional sediment disaggregation methods work well for loose mud sediments, but not for tightly cemented mudstones by ferric oxide minerals. In this paper, a new pretreatment method for analyzing the grain size of red mudstones is presented. The experimental samples are Eocene red mudstones from the Dongying Depression, Bohai Bay Basin. The red mudstones are composed mainly of clay minerals, clastic sediments and ferric oxides that make the mudstones red and tightly compacted. The procedure of the method is as follows. Firstly, samples of the red mudstones were crushed into fragments with a diameter of 0.6-0.8 mm in size; secondly, the CBD (citrate-bicarbonate-dithionite) treatment was used to remove ferric oxides so that the cementation of intra-aggregates and inter-aggregates became weakened, and then 5% dilute hydrochloric acid was added to further remove the cements; thirdly, the fragments were further ground with a rubber pestle; lastly, an ultrasonicator was used to disaggregate the samples. After the treatment, the samples could then be used for grain size analysis or for other geological analyses of sedimentary grains. Compared with other pretreatment methods for size analysis of mudstones, this proposed method is more effective and has higher repeatability.

Crime Seasonality: Examining the Temporal Fluctuations of Property Crime in Cities With Varying Climates.

PubMed

Linning, Shannon J; Andresen, Martin A; Brantingham, Paul J

2017-12-01

This study investigates whether crime patterns fluctuate periodically throughout the year using data containing different property crime types in two Canadian cities with differing climates. Using police report data, a series of ordinary least squares (OLS; Vancouver, British Columbia) and negative binomial (Ottawa, Ontario) regressions were employed to examine the corresponding temporal patterns of property crime in Vancouver (2003-2013) and Ottawa (2006-2008). Moreover, both aggregate and disaggregate models were run to examine whether different weather and temporal variables had a distinctive impact on particular offences. Overall, results suggest that cities that experience greater variations in weather throughout the year have more distinct increases of property offences in the summer months and that different climate variables affect certain crime types, thus advocating for disaggregate analysis in the future.

Demand modelling of passenger air travel: An analysis and extension, volume 2

NASA Technical Reports Server (NTRS)

Jacobson, I. D.

1978-01-01

Previous intercity travel demand models in terms of their ability to predict air travel in a useful way and the need for disaggregation in the approach to demand modelling are evaluated. The viability of incorporating non-conventional factors (i.e. non-econometric, such as time and cost) in travel demand forecasting models are determined. The investigation of existing models is carried out in order to provide insight into their strong points and shortcomings. The model is characterized as a market segmentation model. This is a consequence of the strengths of disaggregation and its natural evolution to a usable aggregate formulation. The need for this approach both pedagogically and mathematically is discussed. In addition this volume contains two appendices which should prove useful to the non-specialist in the area.

Development of an Asset Value Map for Disaster Risk Assessment in China by Spatial Disaggregation Using Ancillary Remote Sensing Data.

PubMed

Wu, Jidong; Li, Ying; Li, Ning; Shi, Peijun

2018-01-01

The extent of economic losses due to a natural hazard and disaster depends largely on the spatial distribution of asset values in relation to the hazard intensity distribution within the affected area. Given that statistical data on asset value are collected by administrative units in China, generating spatially explicit asset exposure maps remains a key challenge for rapid postdisaster economic loss assessment. The goal of this study is to introduce a top-down (or downscaling) approach to disaggregate administrative-unit level asset value to grid-cell level. To do so, finding the highly correlated "surrogate" indicators is the key. A combination of three data sets-nighttime light grid, LandScan population grid, and road density grid, is used as ancillary asset density distribution information for spatializing the asset value. As a result, a high spatial resolution asset value map of China for 2015 is generated. The spatial data set contains aggregated economic value at risk at 30 arc-second spatial resolution. Accuracy of the spatial disaggregation reflects redistribution errors introduced by the disaggregation process as well as errors from the original ancillary data sets. The overall accuracy of the results proves to be promising. The example of using the developed disaggregated asset value map in exposure assessment of watersheds demonstrates that the data set offers immense analytical flexibility for overlay analysis according to the hazard extent. This product will help current efforts to analyze spatial characteristics of exposure and to uncover the contributions of both physical and social drivers of natural hazard and disaster across space and time. © 2017 Society for Risk Analysis.

Some methodological issues in the longitudinal analysis of demographic data.

PubMed

Krishinan, P

1982-12-01

Most demographic data are macro (or aggregate) in nature. Some relevant methodological issues are presented here in a time series study using aggregate data. The micro-macro distinction is relative. Time enters into the micro and macro variables in different ways. A simple micro model of rural-urban migration is given. Method 1 is to assume homogeneity in behavior. Method 2 is a Bayesian estimation. A discusssion of the results follows. Time series models of aggregate data are given. The nature of the model--predictive or explanatory--must be decided on. Explanatory models in longitudinal studies have been developed. Ways to go to the micro level from the macro are discussed. The aggregation-disaggregation problem in demography is not similar to that in econometrics. To understand small populations, separate micro level data have to be collected and analyzed and appropriate models developed. Both types of models have their uses.

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

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

Measurement of the temperature-dependent threshold shear-stress of red blood cell aggregation.

PubMed

Lim, Hyun-Jung; Nam, Jeong-Hun; Lee, Yong-Jin; Shin, Sehyun

2009-09-01

Red blood cell (RBC) aggregation is becoming an important hemorheological parameter, which typically exhibits temperature dependence. Quite recently, a critical shear-stress was proposed as a new dimensional index to represent the aggregative and disaggregative behaviors of RBCs. The present study investigated the effect of the temperature on the critical shear-stress that is required to keep RBC aggregates dispersed. The critical shear-stress was measured at various temperatures (4, 10, 20, 30, and 37 degrees C) through the use of a transient microfluidic aggregometry. The critical shear-stress significantly increased as the blood temperature lowered, which accorded with the increase in the low-shear blood viscosity with the lowering of the temperature. Furthermore, the critical shear-stress also showed good agreement with the threshold shear-stress, as measured in a rotational Couette flow. These findings assist in rheologically validating the critical shear-stress, as defined in the microfluidic aggregometry.

Regulation of Protein Secretion Through Controlled Aggregation in the Endoplasmic Reticulum

NASA Astrophysics Data System (ADS)

Rivera, Victor M.; Wang, Xiurong; Wardwell, Scott; Courage, Nancy L.; Volchuk, Allen; Keenan, Terence; Holt, Dennis A.; Gilman, Michael; Orci, Lelio; Cerasoli, Frank; Rothman, James E.; Clackson, Tim

2000-02-01

A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.

A generic method for improving the spatial interoperability of medical and ecological databases.

PubMed

Ghenassia, A; Beuscart, J B; Ficheur, G; Occelli, F; Babykina, E; Chazard, E; Genin, M

2017-10-03

The availability of big data in healthcare and the intensive development of data reuse and georeferencing have opened up perspectives for health spatial analysis. However, fine-scale spatial studies of ecological and medical databases are limited by the change of support problem and thus a lack of spatial unit interoperability. The use of spatial disaggregation methods to solve this problem introduces errors into the spatial estimations. Here, we present a generic, two-step method for merging medical and ecological databases that avoids the use of spatial disaggregation methods, while maximizing the spatial resolution. Firstly, a mapping table is created after one or more transition matrices have been defined. The latter link the spatial units of the original databases to the spatial units of the final database. Secondly, the mapping table is validated by (1) comparing the covariates contained in the two original databases, and (2) checking the spatial validity with a spatial continuity criterion and a spatial resolution index. We used our novel method to merge a medical database (the French national diagnosis-related group database, containing 5644 spatial units) with an ecological database (produced by the French National Institute of Statistics and Economic Studies, and containing with 36,594 spatial units). The mapping table yielded 5632 final spatial units. The mapping table's validity was evaluated by comparing the number of births in the medical database and the ecological databases in each final spatial unit. The median [interquartile range] relative difference was 2.3% [0; 5.7]. The spatial continuity criterion was low (2.4%), and the spatial resolution index was greater than for most French administrative areas. Our innovative approach improves interoperability between medical and ecological databases and facilitates fine-scale spatial analyses. We have shown that disaggregation models and large aggregation techniques are not necessarily the best ways to tackle the change of support problem.

Study of interaction of hypericin and its pharmaceutical preparation by fluorescence techniques.

PubMed

Liu, Jun; Saw, Constance Lay Lay; Olivo, Malini; Sudhaharan, Thankiah; Ahmed, Sohail; Heng, Paul Wan Sia; Wohland, Thorsten

2009-01-01

We report the detection of interactions between a photosensitizer, hypericin (HY), and its solvent system prepared with a formulation additive, polyvinylpyrrolidone (PVP), a commonly used pharmaceutical excipient. Fluorescence correlation spectroscopy (FCS) and fluorescence lifetime imaging microscopy (FLIM) were used to study aggregation and binding of HY in the presence of PVP. Digitized fluorescence endoscopic imaging (DFEI) was used to study the effect of the pharmaceutical formulation in the in vivo tumor implanted chick chorioallantoic membrane (CAM) model. The results presented reveal the coordination of HY-PVP binding, HY disaggregation in the presence of PVP, and strengthened HY tumor uptake selectivity. PVP is thus suggested as a potential adjuvant to previously investigated N-methyl pyrrolidone (NMP) in the HY delivery system as well as a replacement for the conventionally used albumin in the HY bladder instillation fluids preparation for clinical use.

Spatial configuration trends in coastal Louisiana from 1985 to 2010

USGS Publications Warehouse

Couvillion, Brady; Fischer, Michelle; Beck, Holly J.; Sleavin, William J.

2016-01-01

From 1932 to 2010, coastal Louisiana has experienced a net loss of 4877 km2 of wetlands. As the area of these wetlands has changed, so too has the spatial configuration of the landscape. The resulting landscape is a mosaic of patches of wetlands and open water. This study examined the spatial and temporal variability of trajectories of landscape configuration and the relation of those patterns to the trajectories of land change in wetlands during a 1985–2010 observation period. Spatial configuration was quantified using multi-temporal satellite imagery and an aggregation index (AI). The results of this analysis indicate that coastal Louisiana experienced a reduction in the AI of coastal wetlands of 1.07 %. In general, forested wetland and fresh marsh types displayed the highest aggregation and stability. The remaining marsh types, (intermediate, brackish, and saline) all experienced disaggregation during the time period, with increasing severity of disaggregation along an increasing salinity gradient. Finally, a correlation (r 2 = 0.5562) was found between AI and the land change rate for the subsequent period, indicating that fragmentation can increase the vulnerability of wetlands to further wetland loss. These results can help identify coastal areas which are susceptible to future wetland loss.

[Effect of dilution on aggregation of nanoparticles of polycarboxylic derivative of fullerene C60].

PubMed

Bobylev, A G; Pen'kov, N V; Troshin, P A; Gudkov, S V

2015-01-01

In this work, we investigated the effect of dilution on aggregation of nanoparticles of the polycarboxylic derivative of fullerene C60. It is shown that the diminution of the concentration of PCDF-1 in aqueous medium leads to a decreased amount of aggregates of fullerene and an increased amount of single molecules. This can potentially interfere with the biological activity of a compound on one molecule basis. Addition of organic and inorganic salts to the aqueous medium with fullerene derivative leads to intense disaggregation of PCDF-1. The data obtained suggest an explanation of non-stoichiometric nature of neutralization of reactive oxygen species by derivatives of fullerenes, as well as provide new insight into the physical meaning of the work on the impact of nanoparticles at ultra-low concentrations on biological objects.

Stapled Golgi cisternae remain in place as cargo passes through the stack

PubMed Central

Lavieu, Gregory; Zheng, Hong; Rothman, James E

2013-01-01

We have designed a membrane ‘staple’, which consists of membrane-anchored repeats of the trans-aggregating FM domain that face the lumen of the secretory pathway. In the presence of the disaggregating drug these proteins transit the secretory pathway. When the drug is removed these proteins form electron-dense plaques which we term staples. Unexpectedly, when initially positioned within the cis-Golgi, staples remained at the cis face of the Golgi even after many hours. By contrast, soluble FM-aggregates transited the Golgi. Staples and soluble aggregates placed in cis-Golgi cisternae therefore have different fates. Whereas the membrane staples are located in the flattened, stacked central regions of the cisternae, the soluble aggregates are in the dilated rims. This suggests that while the cisternae are static on the time scale of protein traffic, the dilated rims are mobile and progress in the cis → trans direction via a mechanism that we term ‘Rim Progression’. DOI: http://dx.doi.org/10.7554/eLife.00558.001 PMID:23755362

Scanning electron microscopy study of adhesion in sea urchin blastulae. M.S. Thesis

NASA Technical Reports Server (NTRS)

Crowther, Susan D.

1988-01-01

The dissociation supernatant (DS) isolated by disaggregating Strongylocentrotus purpuratus blastulae in calcium- and magnesium-free seawater specifically promotes reaggregation of S. purpuratus blastula cells. The purpose of this study was to use scanning electron microscopy to examine the gross morphology of aggregates formed in the presence of DS to see if it resembles adhesion in partially dissociated blastulae. A new reaggregation procedure developed here, using large volumes of cell suspension and a large diameter of rotation, was utilized to obtain sufficient quantities of aggregates for scanning electron microscopy. The results indicate that aggregates formed in the presence of DS resemble partially dissociated intact embryos in terms of the direct cell-cell adhesion observed. DS did not cause aggregation to form as a result of the entrapment of cells in masses of extracellular material. These studies provide the groundwork for further studies using transmission electron microscopy to more precisely define the adhesive contacts made by cells in the presence of the putative adhesion molecules present in DS.

Energy prediction using spatiotemporal pattern networks

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

Jiang, Zhanhong; Liu, Chao; Akintayo, Adedotun

This paper presents a novel data-driven technique based on the spatiotemporal pattern network (STPN) for energy/power prediction for complex dynamical systems. Built on symbolic dynamical filtering, the STPN framework is used to capture not only the individual system characteristics but also the pair-wise causal dependencies among different sub-systems. To quantify causal dependencies, a mutual information based metric is presented and an energy prediction approach is subsequently proposed based on the STPN framework. To validate the proposed scheme, two case studies are presented, one involving wind turbine power prediction (supply side energy) using the Western Wind Integration data set generated bymore » the National Renewable Energy Laboratory (NREL) for identifying spatiotemporal characteristics, and the other, residential electric energy disaggregation (demand side energy) using the Building America 2010 data set from NREL for exploring temporal features. In the energy disaggregation context, convex programming techniques beyond the STPN framework are developed and applied to achieve improved disaggregation performance.« less

Maximal aggregation of polynomial dynamical systems

PubMed Central

Cardelli, Luca; Tschaikowski, Max

2017-01-01

Ordinary differential equations (ODEs) with polynomial derivatives are a fundamental tool for understanding the dynamics of systems across many branches of science, but our ability to gain mechanistic insight and effectively conduct numerical evaluations is critically hindered when dealing with large models. Here we propose an aggregation technique that rests on two notions of equivalence relating ODE variables whenever they have the same solution (backward criterion) or if a self-consistent system can be written for describing the evolution of sums of variables in the same equivalence class (forward criterion). A key feature of our proposal is to encode a polynomial ODE system into a finitary structure akin to a formal chemical reaction network. This enables the development of a discrete algorithm to efficiently compute the largest equivalence, building on approaches rooted in computer science to minimize basic models of computation through iterative partition refinements. The physical interpretability of the aggregation is shown on polynomial ODE systems for biochemical reaction networks, gene regulatory networks, and evolutionary game theory. PMID:28878023

Application of Chromophoric Dissolved Organic Matter Absorbance and Excitation-Emission Matrix Fluorescence Spectra (EEMS) to Investigate Clay-Organic Matter Flocculation Processes in Riverine-Estuarine Systems

NASA Astrophysics Data System (ADS)

Smith, J. P.; Reed, A. H.; Boyd, T. J.

2016-12-01

Changes in hydrodynamic shear, variations in ionic strength (salinity), and to a lesser degree pH, along the salinity gradient influences clay-organic matter (OM) flocculation, disaggregation and particle size distributions with depth in natural river-estuarine waters. The scale and rate of aggregation and disaggregation of specific clay-OM flocs assemblages under different hydrodynamic and physiochemical conditions in estuaries or coastal river systems is an area of ongoing research. Chromophoric dissolved organic matter (CDOM) is the fraction of the DOM pool that absorbs and/or emits light at discrete wavelengths when excited. The CDOM absorbance and Excitation Emission Matrix (EEM) fluorescence spectra in natural waters can potentially be used to investigate clay-OM interactions and implications for formation kinetics, size, strength, and settling velocities of cohesive particulate aggregates (flocs and suspended sediments) as they respond to hydrodynamic shear under different physiochemical conditions. Size characteristics of particulate matter and sediment samples collected from the Misa River in Italy in 2014 were compared to the optical properties of the water column to identify potential OM components/constituents influencing flocculation processes in riverine-estuarine systems. The EEMs results were coupled with a parallel factor analysis (PARAFAC) model to associate previously identified EEMS regions of CDOM components to those found in the waters of this study and identify the main OM components/constituents influencing the multi-way variance of the EEMS data. Initial results from the Misa River and subsequent studies show a difference in dominant DOM types by salinity, clay-OM composition, and flow conditions that may be indicative of system specific particle flocculation and disaggregation under different hydrodynamic regimes. These results suggest that the CDOM absorbance and EEMS fluorescence spectra in natural waters can potentially be used to qualify the influence of OM on the flocculation and sedimentation of clay particulates in river-estuarine systems under different physiochemical and hydrodynamic conditions.

Structural mechanisms of chaperone mediated protein disaggregation

PubMed Central

Sousa, Rui

2014-01-01

The ClpB/Hsp104 and Hsp70 classes of molecular chaperones use ATP hydrolysis to dissociate protein aggregates and complexes, and to move proteins through membranes. ClpB/Hsp104 are members of the AAA+ family of proteins which form ring-shaped hexamers. Loops lining the pore in the ring engage substrate proteins as extended polypeptides. Interdomain rotations and conformational changes in these loops coupled to ATP hydrolysis unfold and pull proteins through the pore. This provides a mechanism that progressively disrupts local secondary and tertiary structure in substrates, allowing these chaperones to dissociate stable aggregates such as β-sheet rich prions or coiled coil SNARE complexes. While the ClpB/Hsp104 mechanism appears to embody a true power-stroke in which an ATP powered conformational change in one protein is directly coupled to movement or structural change in another, the mechanism of force generation by Hsp70s is distinct and less well understood. Both active power-stroke and purely passive mechanisms in which Hsp70 captures spontaneous fluctuations in a substrate have been proposed, while a third proposed mechanism—entropic pulling—may be able to generate forces larger than seen in ATP-driven molecular motors without the conformational coupling required for a power-stroke. The disaggregase activity of these chaperones is required for thermotolerance, but unrestrained protein complex/aggregate dissociation is potentially detrimental. Disaggregating chaperones are strongly auto-repressed, and are regulated by co-chaperones which recruit them to protein substrates and activate the disaggregases via mechanisms involving either sequential transfer of substrate from one chaperone to another and/or simultaneous interaction of substrate with multiple chaperones. By effectively subjecting substrates to multiple levels of selection by multiple chaperones, this may insure that these potent disaggregases are only activated in the appropriate context. PMID:25988153

NPP4 is a procoagulant enzyme on the surface of vascular endothelium

PubMed Central

Albright, Ronald A.; Chang, William C.; Robert, Donna; Ornstein, Deborah L.; Cao, Wenxiang; Liu, Lynn; Redick, Meredith E.; Young, J. Isaac; De La Cruz, Enrique M.

2012-01-01

Ap3A is a platelet-dense granule component released into the extracellular space during the second wave of platelet aggregation on activation. Here, we identify an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4), as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and secretion. We demonstrate that NPP4 is present on the surface of vascular endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Platelet aggregation assays with citrated platelet-rich plasma reveal that the primary and secondary waves of aggregation and dense granule release are strongly induced by nanomolar NPP4 in a concentration-dependent manner in the presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation followed by rapid disaggregation. NPP2 and an active site NPP4 mutant, neither of which appreciably hydrolyzes Ap3A, have no effect on platelet aggregation and secretion. Finally, by using ADP receptor blockade we confirm that NPP4 mediates platelet aggregation via release of ADP from Ap3A and activation of ADP receptors. Collectively, these studies define the biologic and enzymatic basis for NPP4 and Ap3A activity in platelet aggregation in vitro and suggest that NPP4 promotes hemostasis in vivo by augmenting ADP-mediated platelet aggregation at the site of vascular injury. PMID:22995898

Carbon quantum dots-based recyclable real-time fluorescence assay for alkaline phosphatase with adenosine triphosphate as substrate.

PubMed

Qian, Zhaosheng; Chai, Lujing; Tang, Cong; Huang, Yuanyuan; Chen, Jianrong; Feng, Hui

2015-03-03

A convenient, reliable, and highly sensitive real-time assay for alkaline phosphatase (ALP) activity in the continuous and recyclable way is established on the basis of aggregation and disaggregation of carbon quantum dots (CQDs) through the competitive assay approach. CQDs and adenosine triphosphate (ATP) were used as the fluorescent indicator and substrate for ALP activity assessment, respectively. Richness of carboxyl groups on the surface of CQDs enables their severe aggregation triggered by cerium ions, which results in effective fluorescence quenching. Under the catalytic hydrolysis of ALP, ATP can be rapidly transformed to phosphate ions. Stronger affinity of phosphate ions to cerium ions than carboxyl groups is taken advantage of to achieve fluorescence recovery induced by redispersion of CQDs in the presence of ALP and ATP. Quantitative evaluation of ALP activity in a broad range from 4.6 to 383.3 U/L with the detection limit of 1.4 U/L can be realized in this way, which endows the assay with high enough sensitivity for practical detection in human serum. The assay can be used in a recyclable way for more than three times since the generated product CePO4 as a precipitate can be easily removed from the standard assay system. This strategy broadens the sensing application of fluorescent CQDs with excellent biocompatibility and provides an example based on disaggregation in optical probe development.

Convective aggregation in realistic convective-scale simulations

NASA Astrophysics Data System (ADS)

Holloway, Christopher E.

2017-06-01

To investigate the real-world relevance of idealized-model convective self-aggregation, five 15 day cases of real organized convection in the tropics are simulated. These include multiple simulations of each case to test sensitivities of the convective organization and mean states to interactive radiation, interactive surface fluxes, and evaporation of rain. These simulations are compared to self-aggregation seen in the same model configured to run in idealized radiative-convective equilibrium. Analysis of the budget of the spatial variance of column-integrated frozen moist static energy shows that control runs have significant positive contributions to organization from radiation and negative contributions from surface fluxes and transport, similar to idealized runs once they become aggregated. Despite identical lateral boundary conditions for all experiments in each case, systematic differences in mean column water vapor (CWV), CWV distribution shape, and CWV autocorrelation length scale are found between the different sensitivity runs, particularly for those without interactive radiation, showing that there are at least some similarities in sensitivities to these feedbacks in both idealized and realistic simulations (although the organization of precipitation shows less sensitivity to interactive radiation). The magnitudes and signs of these systematic differences are consistent with a rough equilibrium between (1) equalization due to advection from the lateral boundaries and (2) disaggregation due to the absence of interactive radiation, implying disaggregation rates comparable to those in idealized runs with aggregated initial conditions and noninteractive radiation. This points to a plausible similarity in the way that radiation feedbacks maintain aggregated convection in both idealized simulations and the real world.